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Conserved domains on  [gi|215274225|sp|Q5VST9|]
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RecName: Full=Obscurin; AltName: Full=Obscurin-RhoGEF; AltName: Full=Obscurin-myosin light chain kinase; Short=Obscurin-MLCK

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 6465-6721 2.54e-173

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 534.08  E-value: 2.54e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14107     1 HSVYEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14107    81 SSEELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSPTREDIKICDFGFAQEITPSEHQFSKY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd14107   161 GSPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSWDTPEITHLSEDAKDFIKRVLQP 240

                         250
                  ....*....|....*..
gi 215274225 6705 APQARPSAAQCLSHPWF 6721
Cdd:cd14107   241 DPEKRPSASECLSHEWF 257
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 7668-7924 2.68e-171

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 528.33  E-value: 2.68e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14110     1 TEKTYAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKF 7827
Cdd:cd14110    81 CSGPELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14110   161 GDYVETMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRCYAGLSGGAVNFLKSTLCA 240

                         250
                  ....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWL 7924
Cdd:cd14110   241 KPWGRPTASECLQNPWL 257
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 5882-6006 5.41e-78

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270059  Cd Length: 125  Bit Score: 255.16  E-value: 5.41e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5882 LMENYPGTLQALGEPIRQGHFIVWEGAPGARMPWKGHNRHVFLFRNHLVICKPRRDSRTDTVSYVFRNMMKLSSIDLNDQ 5961
Cdd:cd13239     1 LIENYPAPLQALGEPIRQGHFTVWEEAPEVKTSSRGHHRHVFLFKNCVVICKPKRDSRTDTVTYVFKNKMKLSDIDVKDT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 5962 VEGDDRAFEVWQEREDSVRKYLLQARTAIIKSSWVKEICGIQQRL 6006
Cdd:cd13239    81 VEGDDRSFGLWHEHRGSVRKYTLQARSAIIKSSWLKDLRDLQQRL 125
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1538-1619 4.77e-37

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


:

Pssm-ID: 409559  Cd Length: 82  Bit Score: 136.22  E-value: 4.77e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1538 QPASREVQAEAGTSATLSCEVAQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKAGDQRLSFHL 1617
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1618 HV 1619
Cdd:cd20967    81 FV 82
SH3_Obscurin_like cd12025
Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein ...
 5602-5664 5.68e-36

Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212958  Cd Length: 63  Bit Score: 132.70  E-value: 5.68e-36
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 5602 FDIYVVTADYLPLGAEQDAITLREGQYVEVLDAAHPLRWLVRTKPTKSSPSRQGWVSPAYLDR 5664
Cdd:cd12025     1 FDVYIVTADYTPDGADTEAIPLEEGQYVEVLDSAHPLKWLVRTKPTKSSPPRQGWVSPAYLEK 63
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1630-1711 3.66e-32

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 122.35  E-value: 3.66e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1630 QPAHREVQAEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEAGGQQLSFRL 1709
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1710 QV 1711
Cdd:cd20967    81 FV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 894-975 1.33e-31

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 120.81  E-value: 1.33e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  894 QLARRKLQAEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEAGGQRLSFHL 973
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225  974 DV 975
Cdd:cd20967    81 FV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1446-1527 4.28e-31

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 119.27  E-value: 4.28e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1446 QPVHREVQAQAGASTTLSCEVAQAQTEVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEAGSQRLSFHL 1525
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1526 HV 1527
Cdd:cd20967    81 FV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1354-1435 2.19e-30

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 117.34  E-value: 2.19e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1354 QLAHRKVQAEAGAIATLSCEVAQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEAGGQRLSFSL 1433
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1434 DV 1435
Cdd:cd20967    81 FV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1267-1343 4.58e-30

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 116.57  E-value: 4.58e-30
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1267 EVRTEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEAGGQRLSFHLDV 1343
Cdd:cd20967     6 AVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1170-1251 9.58e-30

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 115.42  E-value: 9.58e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1170 QSVHNEVQAEAGTTAMLSCEVAQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEAGGQRVSFQL 1249
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1250 HI 1251
Cdd:cd20967    81 FV 82
I-set pfam07679
Immunoglobulin I-set domain;
10-99 4.14e-29

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 113.89  E-value: 4.14e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIG 89
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 215274225    90 EAFAAVGLQV 99
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1078-1159 2.46e-28

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 111.57  E-value: 2.46e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1078 QSVHNEVQAEAGASAMLSCEVAQAQTEVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEAGGQRVSFHL 1157
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1158 HI 1159
Cdd:cd20967    81 FV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 986-1067 2.24e-26

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 105.79  E-value: 2.24e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  986 QVAHSEVQAEAGASATLSCEVAQAQTEVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEARGQRVSFRL 1065
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1066 HI 1067
Cdd:cd20967    81 FV 82
I-set pfam07679
Immunoglobulin I-set domain;
5126-5216 1.01e-24

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 101.57  E-value: 1.01e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDqQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  5206 GVSSTKAELRV 5216
Cdd:pfam07679   80 GEAEASAELTV 90
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 6014-6104 1.18e-24

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


:

Pssm-ID: 409563  Cd Length: 93  Bit Score: 101.39  E-value: 1.18e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLT-GVDSGQYMCFAASA 6092
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATNQ 81

                          90
                  ....*....|..
gi 215274225 6093 AGNCSTLGKILV 6104
Cdd:cd20971    82 GGSVSGTASLEV 93
I-set pfam07679
Immunoglobulin I-set domain;
6357-6446 9.66e-21

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 90.01  E-value: 9.66e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6357 PSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 215274225  6437 QVLCKAELLV 6446
Cdd:pfam07679   81 EAEASAELTV 90
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 5697-5875 6.08e-19

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


:

Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 88.13  E-value: 6.08e-19
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCphVPIAVAGQKAVIFRNVRDIGRFHSSFLQELQQC--DTDDDVAM---CF 5771
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKE--LKLLSPNELETLFGNIEEIYEFHRDFLDELEERieEWDDSVERigdVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5772 IKNQAAFEQYLEFLVGRVQAESVVVSTAIQEFYKKYAEEALLAgdpSQPPPPPLQHYLEQPVERVQRYQALLKELIRNKA 5851
Cdd:smart00325   79 LKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESS---PQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155

                           170       180
                    ....*....|....*....|....
gi 215274225   5852 RNRQNCALLEQAYAVVSALPQRAE 5875
Cdd:smart00325  156 EDHEDREDLKKALKAIKELANQVN 179
I-set pfam07679
Immunoglobulin I-set domain;
110-201 5.40e-18

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 82.31  E-value: 5.40e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEpdGPRVRVEELGEASALRIRAARPRDGGTYEVRAENP 189
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS--SDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 215274225   190 LGAASAAAALVV 201
Cdd:pfam07679   79 AGEAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
248-328 1.36e-17

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 81.15  E-value: 1.36e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQeNFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLVV 327
Cdd:pfam07679   11 EVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGG-TYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89


                   .
gi 215274225   328 V 328
Cdd:pfam07679   90 V 90
I-set pfam07679
Immunoglobulin I-set domain;
7463-7548 1.44e-17

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 81.15  E-value: 1.44e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATlKNFQLLTILVVVAEDLGVYTCSVSNAL 7542
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSA 79


                   ....*.
gi 215274225  7543 GTVTTT 7548
Cdd:pfam07679   80 GEAEAS 85
I-set pfam07679
Immunoglobulin I-set domain;
5260-5350 2.82e-17

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 80.38  E-value: 2.82e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:pfam07679    1 PKFTQKPKDVEVQEGES-ARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  5340 GAAYSSARLLV 5350
Cdd:pfam07679   80 GEAEASAELTV 90
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 4523-4608 5.80e-17

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


:

Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 79.46  E-value: 5.80e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4523 PDPPEDAEVVARSSHTVTLSWAAPmSDGGGGLCGYRVEVKEGATGQWRLCH-ELVPGPECVVDGLAPGETYRFRVAAVGP 4601
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPP-EDDGGPITGYVVEYREKGSGDWKEVEvTPGSETSYTLTGLKPGTEYEFRVRAVNG 79


                  ....*..
gi 215274225 4602 VGAGEPV 4608
Cdd:cd00063    80 GGESPPS 86
I-set pfam07679
Immunoglobulin I-set domain;
4898-4988 6.03e-17

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 79.22  E-value: 6.03e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGdGTCSLLITGLDRADAGCYTCQVSNKF 4977
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  4978 GQVTHSACVVV 4988
Cdd:pfam07679   80 GEAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
2470-2553 2.89e-16

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 77.30  E-value: 2.89e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2470 VLTRPLEPKTGRELQSVVLSCDFR--PAPKaVQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA----G 2543
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtPDPE-VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  2544 SAHSSTEVTV 2553
Cdd:pfam07679   81 EAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
6108-6197 3.95e-16

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 76.91  E-value: 3.95e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPrsGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|
gi 215274225  6188 LGSARASAEL 6197
Cdd:pfam07679   79 AGEAEASAEL 88
I-set pfam07679
Immunoglobulin I-set domain;
3890-3974 1.07e-14

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 73.06  E-value: 1.07e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCTC----G 3964
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3965 SQATSATLTV 3974
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 5371-5466 4.40e-14

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 71.13  E-value: 4.40e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDtPGYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQP-----LRSS-DRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74

                           90
                   ....*....|....*.
gi 215274225  5451 ASNAAGQALCSASLHV 5466
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3097-3177 5.82e-13

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 5.82e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3097 VFSRELTDATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA---GGA 3172
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsAGE 81


                   ....*
gi 215274225  3173 CSSSI 3177
Cdd:pfam07679   82 AEASA 86
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2648-2731 6.48e-13

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 6.48e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2648 VFLKALDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV----GS 2722
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 215274225  2723 EETRARVRV 2731
Cdd:pfam07679   82 AEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3186-3269 9.66e-13

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 67.28  E-value: 9.66e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3186 RFQEALKDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC----SFGD 3260
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGE 81


                   ....*....
gi 215274225  3261 QTTSATLTV 3269
Cdd:pfam07679   82 AEASAELTV 90
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 515-602 9.83e-13

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


:

Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 67.52  E-value: 9.83e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  515 PPVDPVVKARMESSVILSWSPPPHGERPvtIDGYLVEKKKLGTYTWIRChEAEWVATPELTVADVAEEGNFQFRVSALNS 594
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDDGGP--ITGYVVEYREKGSGDWKEV-EVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79


                  ....*...
gi 215274225  595 FGQSPYLE 602
Cdd:cd00063    80 GGESPPSE 87
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2167-2250 1.48e-12

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 66.90  E-value: 1.48e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2167 SFSRPLQDVVTTEKEKVTLECELS-RPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAHD---- 2241
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNsage 81


                   ....*....
gi 215274225  2242 AQSSASVKV 2250
Cdd:pfam07679   82 AEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3803-3885 2.77e-12

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 66.13  E-value: 2.77e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3803 RFIEDVKNQEAREGATAVLQCELSkAAP---VEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVC----G 3875
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3876 QERTSATLTV 3885
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3363-3445 3.71e-12

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 65.74  E-value: 3.71e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3363 HFIGRLRHQESIEGATATLRCELSkAAP---VEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVC----G 3435
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3436 EERTSATLTV 3445
Cdd:pfam07679   81 EAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2834-2911 4.20e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.60  E-value: 4.20e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2834 EDQWVAPGEDVELRCELSRAGTP-VHWLKDR-KAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEAS----KSTA 2907
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSsgsaSSGT 81


                    ....
gi 215274225   2908 SLHV 2911
Cdd:smart00410   82 TLTV 85
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1900-1983 5.64e-12

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 65.36  E-value: 5.64e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1900 KFMSGLSTVVAEEGGEATFQCVVS----PSdvaVVWFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEG- 1974
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtpdPE---VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNs 78

                           90
                   ....*....|..
gi 215274225  1975 ---ASSSAALRV 1983
Cdd:pfam07679   79 ageAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3715-3797 6.53e-12

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 64.97  E-value: 6.53e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3715 KFIEGLRNEEATEGDTATLWCELSkAAP---VEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVC----G 3787
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3788 QERTSATLTV 3797
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2918-3000 8.33e-12

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 64.59  E-value: 8.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2918 FTEELTNLQVEEKGTAVFTCK-TEHPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC----DIGQA 2992
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTvTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEA 82


                   ....*...
gi 215274225  2993 QSRAQLLV 3000
Cdd:pfam07679   83 EASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3539-3621 2.60e-11

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 63.43  E-value: 2.60e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3539 RFIEDVKNQEAREGATAVLQCELnSAAP---VEWRKGSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCVC----G 3611
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTV-TGTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3612 QERTSAMLTV 3621
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2293-2374 1.33e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 61.12  E-value: 1.33e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2293 VRPLRDKIAMEKHRGVLECQVSRASA-QVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDA----GDVK 2367
Cdd:pfam07679    4 TQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAE 83


                   ....*..
gi 215274225  2368 TSAQFFV 2374
Cdd:pfam07679   84 ASAELTV 90
Atrophin-1 super family cl38111
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 6801-7076 2.14e-10

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


The actual alignment was detected with superfamily member pfam03154:

Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 68.26  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6801 APFARAKSLPP--SPVTHSPLLHPRGFLRPSASLPEEAEASERSTEAPAPPASPEGAGPPAAQGCVprhsvirslfyhQA 6878
Cdd:pfam03154  198 GPTPSAPSVPPqgSPATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSP------------QP 265

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6879 GESPE-HGALAPGSrrhparrrHLLKGGyiagalpglrEPLMEHRVLEEEAAReeqatllakaPSFETALRLPASGTHLA 6957
Cdd:pfam03154  266 LPQPSlHGQMPPMP--------HSLQTG----------PSHMQHPVPPQPFPL----------TPQSSQSQVPPGPSPAA 317

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6958 PGHSHSLEHDSPSTPRPSSEACGEAQRLPSAPSG--------GAPIRDMGHPQGSKQLPSTGG----------------- 7012
Cdd:pfam03154  318 PGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSmphikpppTTPIPQLPNPQSHKHPPHLSGpspfqmnsnlppppalk 397

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7013 --------HPGTA-----------QPERPSPDSPWGQPAPFCHPKQGSA--PQEGCSPHPAVAPCPPGSFPPGSCKEApL 7071
Cdd:pfam03154  398 plsslsthHPPSAhppplqlmpqsQQLPPPPAQPPVLTQSQSLPPPAAShpPTSGLHQVPSQSPFPQHPFVPGGPPPI-T 476


                   ....*
gi 215274225  7072 VPSSP 7076
Cdd:pfam03154  477 PPSGP 481
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3275-3357 4.76e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 59.58  E-value: 4.76e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3275 QFIGKLRNKEATEGATATLRCELSkAAP---VEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVC----G 3347
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3348 EERTSASLTI 3357
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 335-418 4.90e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 59.58  E-value: 4.90e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   335 FKKRLQDLEVREKESATFLCEV---PQPSTEaaWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYIC--ETPEG 409
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVtgtPDPEVS--WFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvaTNSAG 80

                           90
                   ....*....|
gi 215274225   410 SRTV-AELAV 418
Cdd:pfam07679   81 EAEAsAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 4069-4154 8.05e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 58.79  E-value: 8.05e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4069 KFKTRLQSleqETGDIARLCCQLSDAesGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACVTGGQKT 4148
Cdd:cd20967     2 KAQPAVQV---SKGHKIRLTVELADP--DAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKC 76


                  ....*.
gi 215274225 4149 AASLRV 4154
Cdd:cd20967    77 SFELFV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3627-3709 1.07e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 58.81  E-value: 1.07e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3627 KFTEGLRNEEATEGATAVLRCELS-KMAP-VEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLC----MCGK 3700
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGE 81


                   ....*....
gi 215274225  3701 ERTSAMLTV 3709
Cdd:pfam07679   82 AEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1716-1793 2.08e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 58.04  E-value: 2.08e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1716 PQISERPcrrEPLVVKEHEDIILTATLATPSAATVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:pfam07679    1 PKFTQKP---KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 711-791 3.73e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 56.87  E-value: 3.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  711 AAAREVLARLHEEAQLLAELSDQAAAVTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECVSRGGRIAYQLS 790
Cdd:cd20967     2 KAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELF 81


                  .
gi 215274225  791 V 791
Cdd:cd20967    82 V 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3451-3533 5.45e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 56.88  E-value: 5.45e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3451 KFTEGLRNEEAVEGATAMLWCELSKVAP--VEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVC----GQ 3524
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 215274225  3525 ERTSATLTI 3533
Cdd:pfam07679   82 AEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 807-883 6.32e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 56.48  E-value: 6.32e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  807 VDAVAGGPAQFECETSEAHVHVHWYKDGMELGHSGeRFLQEDVGTRHRLVAATVTRQDEGTYSCRVGEDSVDFRLRV 883
Cdd:cd20967     7 VQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSS-KVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2560-2642 1.83e-08

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 55.34  E-value: 1.83e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2560 VTGPLQDAEATEEGWASFSCELS-HEDEEVEWSLNGMPLYNDSFHEISHKGRRHTLVLKSIQRADAGI--VRA--SSLKV 2634
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKytCVAtnSAGEA 82


                   ....*...
gi 215274225  2635 STSARLEV 2642
Cdd:pfam07679   83 EASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1810-1893 2.08e-08

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 54.96  E-value: 2.08e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1810 KFCRLLEPVCGELGGTVTLACELS----PacaEVVWRCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVC----E 1881
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtpdP---EVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnS 78

                           90
                   ....*....|..
gi 215274225  1882 SRDDHTSAQLTV 1893
Cdd:pfam07679   79 AGEAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3980-4050 3.38e-08

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 54.57  E-value: 3.38e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  3980 RFLRELQHQEVDEGGTAHLCCELSraGA---SVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC 4050
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT--GTpdpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4169-4245 4.46e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.05  E-value: 4.46e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4169 EVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRIHTLRLKGVTPEDAGT----VSFHLGNHASSAQLT 4244
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGTTLT 84


                    .
gi 215274225   4245 V 4245
Cdd:smart00410   85 V 85
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 4248-4336 1.41e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.41e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4248 PEVTIlePLQDVQLSEGQDASFQCrlsRASGQ---EARWALGGVPLQANEMNDITVEQGTlHLLTLHKVTLEDAG----T 4320
Cdd:pfam07679    1 PKFTQ--KPKDVEVQEGESARFTC---TVTGTpdpEVSWFKDGQPLRSSDRFKVTYEGGT-YTLTISNVQPDDSGkytcV 74

                           90
                   ....*....|....*.
gi 215274225  4321 VSFHVGTCSSEAQLKV 4336
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2738-2822 1.64e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.64e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2738 ITKRLKTMEVLEGESCSFECVLSheSASDP-AMWTVGGKTVGSSSRFQATRQGRKYILVVREAAPSDAGE----VVFSVR 2812
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVT--GTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKytcvATNSAG 80

                           90
                   ....*....|
gi 215274225  2813 GLTSKASLIV 2822
Cdd:pfam07679   81 EAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 427-505 8.37e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20967:

Pssm-ID: 472250  Cd Length: 82  Bit Score: 50.32  E-value: 8.37e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  427 PRKTAVRV--GDTAMFCVELAVPVGPVHWLRNQEEVVAGGRVAISAEGTRHTLTISQCCLEDVGQVAFMAGDCQTSTQFC 504
Cdd:cd20967     2 KAQPAVQVskGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELF 81


                  .
gi 215274225  505 V 505
Cdd:cd20967    82 V 82
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1990-2069 9.55e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd20951:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 94  Bit Score: 50.50  E-value: 9.55e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1990 FKKKLEPQTVEERSSVTLEVELT-RPWPELRWTRNATALAP---GKNVEIHAEGARHRLVLHNVGFADRGFFGCETPDDK 2065
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPssiPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIH 82


                  ....
gi 215274225 2066 TQAK 2069
Cdd:cd20951    83 GEAS 86
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4630-4695 6.02e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.89  E-value: 6.02e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   4630 PESRQVAAGEDVSLELEVVAEAGEVI-WHK-GMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVtWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTC 68
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3012-3091 8.48e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.50  E-value: 8.48e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3012 EDVDVQEGSSATFRCRISPANYEPVHWFLDKTPLHANELNEIDAQPGGYHVLTLRQLALKDSGTIYFEA----GDQRASA 3087
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3088 ALRV 3091
Cdd:smart00410   82 TLTV 85
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 7557-7635 3.53e-05

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


:

Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 45.68  E-value: 3.53e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7557 PSSSPCPDIGEVYADGVLLVWKPVESYGPVTYIVQCSLE----GGSWTTLASDIFDCCYLTSKLSRGGTYTFRTACVSKA 7632
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEyreeGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 215274225   7633 GMG 7635
Cdd:smart00060   81 GEG 83
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 617-673 1.86e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 43.79  E-value: 1.86e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225   617 TPLKAVQAVEGGEVTFSV------DLTVasagEWFLDGQALKASSVYEIHCDRTRHTLTIREV 673
Cdd:pfam07679    5 QKPKDVEVQEGESARFTCtvtgtpDPEV----SWFKDGQPLRSSDRFKVTYEGGTYTLTISNV 63
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2078-2161 1.77e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 41.09  E-value: 1.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2078 RLVRGLQAVEAREQGTATMEVQlshadVDG------SWTRDGLRFQQGPTCHLAVRGPMHTLTLSGLRPEDSGLMVFKAE 2151
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCT-----VTGtpdpevSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 215274225  2152 G----VHTSARLVV 2161
Cdd:pfam07679   77 NsageAEASAELTV 90
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 4342-4427 9.17e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member pfam07679:

Pssm-ID: 472250 [Multi-domain]  Cd Length: 90  Bit Score: 39.16  E-value: 9.17e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4342 VVRGLENVEALEGGEALFECQLS---QPEVaahTWLLDDEPVHTSEnaEVVFFENGLRHLLLLKNLRPQDS----CRVTF 4414
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTgtpDPEV---SWFKDGQPLRSSD--RFKVTYEGGTYTLTISNVQPDDSgkytCVATN 77

                           90
                   ....*....|...
gi 215274225  4415 LAGDMVTSAFLTV 4427
Cdd:pfam07679   78 SAGEAEASAELTV 90
 
Name Accession Description Interval E-value
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 6465-6721 2.54e-173

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 534.08  E-value: 2.54e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14107     1 HSVYEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14107    81 SSEELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSPTREDIKICDFGFAQEITPSEHQFSKY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd14107   161 GSPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSWDTPEITHLSEDAKDFIKRVLQP 240

                         250
                  ....*....|....*..
gi 215274225 6705 APQARPSAAQCLSHPWF 6721
Cdd:cd14107   241 DPEKRPSASECLSHEWF 257
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 7668-7924 2.68e-171

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 528.33  E-value: 2.68e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14110     1 TEKTYAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKF 7827
Cdd:cd14110    81 CSGPELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14110   161 GDYVETMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRCYAGLSGGAVNFLKSTLCA 240

                         250
                  ....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWL 7924
Cdd:cd14110   241 KPWGRPTASECLQNPWL 257
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 6468-6721 1.00e-79

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 265.55  E-value: 1.00e-79
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT--RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKkdRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCE 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6546 SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFSQYG 6625
Cdd:smart00220   81 GGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDE--DGHVKLADFGLARQLDPGEKLTTFVG 158

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRA 6705
Cdd:smart00220  159 TPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKD 238

                           250
                    ....*....|....*.
gi 215274225   6706 PQARPSAAQCLSHPWF 6721
Cdd:smart00220  239 PEKRLTAEEALQHPFF 254
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 5882-6006 5.41e-78

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270059  Cd Length: 125  Bit Score: 255.16  E-value: 5.41e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5882 LMENYPGTLQALGEPIRQGHFIVWEGAPGARMPWKGHNRHVFLFRNHLVICKPRRDSRTDTVSYVFRNMMKLSSIDLNDQ 5961
Cdd:cd13239     1 LIENYPAPLQALGEPIRQGHFTVWEEAPEVKTSSRGHHRHVFLFKNCVVICKPKRDSRTDTVTYVFKNKMKLSDIDVKDT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 5962 VEGDDRAFEVWQEREDSVRKYLLQARTAIIKSSWVKEICGIQQRL 6006
Cdd:cd13239    81 VEGDDRSFGLWHEHRGSVRKYTLQARSAIIKSSWLKDLRDLQQRL 125
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 7680-7924 4.02e-48

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 174.64  E-value: 4.02e-48
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7680 RGRFSVVRQCWEKASGRALAAKIIPYH--PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:smart00220    9 EGSFGKVYLARDKKTGKLVAIKVIKKKkiKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLL 88

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFKDY---LETM 7834
Cdd:smart00220   89 KKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLD-----PGEKLTTFvgtPEYM 163

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7835 APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG-ARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGRP 7913
Cdd:smart00220  164 APEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDqLLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKDPEKRL 243

                           250
                    ....*....|.
gi 215274225   7914 CASSCLQCPWL 7924
Cdd:smart00220  244 TAEEALQHPFF 254
Pkinase pfam00069
Protein kinase domain;
6468-6721 8.72e-46

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 166.65  E-value: 8.72e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT---RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKIKkkkDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLhylhshgvlhldiKPSNILMVhparedikICdfgfaqnitpaelqfsqy 6624
Cdd:pfam00069   81 EGGSLFDLLSEKGAFSEREAKFIMKQILEGL-------------ESGSSLTT--------FV------------------ 121

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPmAAHLSEDAKDFIKATLQR 6704
Cdd:pfam00069  122 GTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPEL-PSNLSEEAKDLLKKLLKK 200

                          250
                   ....*....|....*..
gi 215274225  6705 APQARPSAAQCLSHPWF 6721
Cdd:pfam00069  201 DPSKRLTATQALQHPWF 217
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
6468-6902 5.31e-45

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 173.27  E-value: 5.31e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:COG0515     9 YRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARerfrREARALARLNHPNIVRVYDVGEEDGRPYLVMEY 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQ 6623
Cdd:COG0515    89 VEGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGR--VKLIDFGIARALGGATLTQTG 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 Y--GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:COG0515   167 TvvGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSELRPDLPPALDAIVLRA 246

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6702 LQRAPQARPSAAQ--------CLSHPWFLKSMPAEEAHFINTKQLKFLLARSRWQRSLmsykSILVMRSIPELLRGPPDS 6773
Cdd:COG0515   247 LAKDPEERYQSAAelaaalraVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA----AAAAAAAAAAAAAAAAAA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6774 PSLGVARHLCRDTGGSSSSSSSSDNELAPFARAKSLPPSPVTHSPLLHPRGFLRPSASLPEEAEASERSTEAPAPPASPE 6853
Cdd:COG0515   323 PAAAAAAAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAA 402

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 6854 GAGPPAAQGCVPRHSVIRSLFYHQAGESPEHGALAPGSRRHPARRRHLL 6902
Cdd:COG0515   403 AAAAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAA 451
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1538-1619 4.77e-37

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 136.22  E-value: 4.77e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1538 QPASREVQAEAGTSATLSCEVAQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKAGDQRLSFHL 1617
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1618 HV 1619
Cdd:cd20967    81 FV 82
SH3_Obscurin_like cd12025
Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein ...
 5602-5664 5.68e-36

Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212958  Cd Length: 63  Bit Score: 132.70  E-value: 5.68e-36
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 5602 FDIYVVTADYLPLGAEQDAITLREGQYVEVLDAAHPLRWLVRTKPTKSSPSRQGWVSPAYLDR 5664
Cdd:cd12025     1 FDVYIVTADYTPDGADTEAIPLEEGQYVEVLDSAHPLKWLVRTKPTKSSPPRQGWVSPAYLEK 63
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 6463-6721 2.15e-35

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 140.72  E-value: 2.15e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFyEVKEEIGRGVFGFVKRVQHKGNK----ILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:PTZ00263   16 KLSDF-EMGETLGTGSFGRVRIAKHKGTGeyyaIKCLKKREILKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVY 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITpaE 6618
Cdd:PTZ00263   95 FLLEFVVGGELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLL--DNKGHVKVTDFGFAKKVP--D 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRV---SWsspmaahLSEDAK 6695
Cdd:PTZ00263  171 RTFTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLkfpNW-------FDGRAR 243

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6696 DFIKATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:PTZ00263  244 DLVKGLLQTDHTKRlgtlkGGVADVKNHPYF 274
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1630-1711 3.66e-32

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 122.35  E-value: 3.66e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1630 QPAHREVQAEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEAGGQQLSFRL 1709
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1710 QV 1711
Cdd:cd20967    81 FV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 894-975 1.33e-31

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 120.81  E-value: 1.33e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  894 QLARRKLQAEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEAGGQRLSFHL 973
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225  974 DV 975
Cdd:cd20967    81 FV 82
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
7677-7913 2.29e-31

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 132.44  E-value: 2.29e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKII-PYHPKDKTAV---LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:COG0515    14 LLGRGGMGVVYLARDLRLGRPVALKVLrPELAADPEARerfRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGES 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLE 7832
Cdd:COG0515    94 LADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPG 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL-QRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:COG0515   174 YMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELlRAHLREPPPPPSELRPDLPPALDAIVLRALAKDPEE 253


                  ..
gi 215274225 7912 RP 7913
Cdd:COG0515   254 RY 255
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1446-1527 4.28e-31

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 119.27  E-value: 4.28e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1446 QPVHREVQAQAGASTTLSCEVAQAQTEVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEAGSQRLSFHL 1525
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1526 HV 1527
Cdd:cd20967    81 FV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1354-1435 2.19e-30

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 117.34  E-value: 2.19e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1354 QLAHRKVQAEAGAIATLSCEVAQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEAGGQRLSFSL 1433
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1434 DV 1435
Cdd:cd20967    81 FV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1267-1343 4.58e-30

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 116.57  E-value: 4.58e-30
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1267 EVRTEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEAGGQRLSFHLDV 1343
Cdd:cd20967     6 AVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1170-1251 9.58e-30

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 115.42  E-value: 9.58e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1170 QSVHNEVQAEAGTTAMLSCEVAQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEAGGQRVSFQL 1249
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1250 HI 1251
Cdd:cd20967    81 FV 82
Pkinase pfam00069
Protein kinase domain;
7677-7924 1.78e-29

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 119.66  E-value: 1.78e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:pfam00069    6 KLGSGSFGTVYKAKHRDTGKIVAIKKIKKEkikKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGGSL 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7754 LPCLAERASYSESEVKDYLWQMLSAtqylhnqhilhldlrsenmiiteynllkvvdLGNAQSLSQEKVLPsdkfkDYlet 7833
Cdd:pfam00069   86 FDLLSEKGAFSEREAKFIMKQILEG-------------------------------LESGSSLTTFVGTP-----WY--- 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7834 MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGRP 7913
Cdd:pfam00069  127 MAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLKKLLKKDPSKRL 206

                          250
                   ....*....|.
gi 215274225  7914 CASSCLQCPWL 7924
Cdd:pfam00069  207 TATQALQHPWF 217
I-set pfam07679
Immunoglobulin I-set domain;
10-99 4.14e-29

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 113.89  E-value: 4.14e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIG 89
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 215274225    90 EAFAAVGLQV 99
Cdd:pfam07679   81 EAEASAELTV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1078-1159 2.46e-28

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 111.57  E-value: 2.46e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1078 QSVHNEVQAEAGASAMLSCEVAQAQTEVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEAGGQRVSFHL 1157
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1158 HI 1159
Cdd:cd20967    81 FV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 986-1067 2.24e-26

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 105.79  E-value: 2.24e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  986 QVAHSEVQAEAGASATLSCEVAQAQTEVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEARGQRVSFRL 1065
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1066 HI 1067
Cdd:cd20967    81 FV 82
I-set pfam07679
Immunoglobulin I-set domain;
5126-5216 1.01e-24

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 101.57  E-value: 1.01e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDqQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  5206 GVSSTKAELRV 5216
Cdd:pfam07679   80 GEAEASAELTV 90
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 6014-6104 1.18e-24

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 101.39  E-value: 1.18e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLT-GVDSGQYMCFAASA 6092
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATNQ 81

                          90
                  ....*....|..
gi 215274225 6093 AGNCSTLGKILV 6104
Cdd:cd20971    82 GGSVSGTASLEV 93
I-set pfam07679
Immunoglobulin I-set domain;
6357-6446 9.66e-21

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 90.01  E-value: 9.66e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6357 PSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 215274225  6437 QVLCKAELLV 6446
Cdd:pfam07679   81 EAEASAELTV 90
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 5126-5216 4.97e-19

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 85.24  E-value: 4.97e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 215274225 5206 GVSSTKAELRV 5216
Cdd:cd05744    81 GENSFNAELVV 91
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 5697-5875 6.08e-19

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 88.13  E-value: 6.08e-19
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCphVPIAVAGQKAVIFRNVRDIGRFHSSFLQELQQC--DTDDDVAM---CF 5771
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKE--LKLLSPNELETLFGNIEEIYEFHRDFLDELEERieEWDDSVERigdVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5772 IKNQAAFEQYLEFLVGRVQAESVVVSTAIQEFYKKYAEEALLAgdpSQPPPPPLQHYLEQPVERVQRYQALLKELIRNKA 5851
Cdd:smart00325   79 LKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESS---PQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155

                           170       180
                    ....*....|....*....|....
gi 215274225   5852 RNRQNCALLEQAYAVVSALPQRAE 5875
Cdd:smart00325  156 EDHEDREDLKKALKAIKELANQVN 179
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 5697-5873 4.37e-18

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 85.81  E-value: 4.37e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCphVPIAVAGQKAVIFRNVRDIGRFHSSFLQELQQC-----DTDDDVAMCF 5771
Cdd:cd00160     4 VIKELLQTERNYVRDLKLLVEVFLKPLDKE--LLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewdKSGPRIGDVF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5772 IKNQAAFEQYLEFLVGRVQAESVV-----VSTAIQEFYKKYaeeallagdPSQPPPPPLQHYLEQPVERVQRYQALLKEL 5846
Cdd:cd00160    82 LKLAPFFKIYSEYCSNHPDALELLkklkkFNKFFQEFLEKA---------ESECGRLKLESLLLKPVQRLTKYPLLLKEL 152

                         170       180
                  ....*....|....*....|....*..
gi 215274225 5847 IRNKARNRQNCALLEQAYAVVSALPQR 5873
Cdd:cd00160   153 LKHTPDGHEDREDLKKALEAIKEVASQ 179
I-set pfam07679
Immunoglobulin I-set domain;
110-201 5.40e-18

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 82.31  E-value: 5.40e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEpdGPRVRVEELGEASALRIRAARPRDGGTYEVRAENP 189
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS--SDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 215274225   190 LGAASAAAALVV 201
Cdd:pfam07679   79 AGEAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
248-328 1.36e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 81.15  E-value: 1.36e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQeNFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLVV 327
Cdd:pfam07679   11 EVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGG-TYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89


                   .
gi 215274225   328 V 328
Cdd:pfam07679   90 V 90
I-set pfam07679
Immunoglobulin I-set domain;
7463-7548 1.44e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 81.15  E-value: 1.44e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATlKNFQLLTILVVVAEDLGVYTCSVSNAL 7542
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSA 79


                   ....*.
gi 215274225  7543 GTVTTT 7548
Cdd:pfam07679   80 GEAEAS 85
I-set pfam07679
Immunoglobulin I-set domain;
5260-5350 2.82e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 80.38  E-value: 2.82e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:pfam07679    1 PKFTQKPKDVEVQEGES-ARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  5340 GAAYSSARLLV 5350
Cdd:pfam07679   80 GEAEASAELTV 90
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 4523-4608 5.80e-17

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 79.46  E-value: 5.80e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4523 PDPPEDAEVVARSSHTVTLSWAAPmSDGGGGLCGYRVEVKEGATGQWRLCH-ELVPGPECVVDGLAPGETYRFRVAAVGP 4601
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPP-EDDGGPITGYVVEYREKGSGDWKEVEvTPGSETSYTLTGLKPGTEYEFRVRAVNG 79


                  ....*..
gi 215274225 4602 VGAGEPV 4608
Cdd:cd00063    80 GGESPPS 86
I-set pfam07679
Immunoglobulin I-set domain;
4898-4988 6.03e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 79.22  E-value: 6.03e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGdGTCSLLITGLDRADAGCYTCQVSNKF 4977
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  4978 GQVTHSACVVV 4988
Cdd:pfam07679   80 GEAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 20-99 1.38e-16

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 78.32  E-value: 1.38e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225     20 VVSVGKDATLSCQIVGNPTPQVSWEKD-QQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIGEAFAAVGLQ 98
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQgGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84


                    .
gi 215274225     99 V 99
Cdd:smart00410   85 V 85
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 5697-5873 1.87e-16

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 80.81  E-value: 1.87e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCPHVPiavAGQKAVIFRNVRDIGRFHSS-FLQELQQC-DTDDDVAMCFIKN 5774
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSES---EEEIKTIFSNIEEIYELHRQlLLEELLKEwISIQRIGDIFLKF 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5775 QAAFEQYLEFLVGRVQAESVVvsTAIQEFYKKYAEEALLAGDPSQPPPPPLQHYLEQPVERVQRYQALLKELIRNKARNR 5854
Cdd:pfam00621   78 APGFKVYSTYCSNYPKALKLL--KKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDH 155

                          170
                   ....*....|....*....
gi 215274225  5855 QNCALLEQAYAVVSALPQR 5873
Cdd:pfam00621  156 PDYEDLKKALEAIKEVAKQ 174
I-set pfam07679
Immunoglobulin I-set domain;
2470-2553 2.89e-16

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 77.30  E-value: 2.89e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2470 VLTRPLEPKTGRELQSVVLSCDFR--PAPKaVQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA----G 2543
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtPDPE-VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  2544 SAHSSTEVTV 2553
Cdd:pfam07679   81 EAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
6108-6197 3.95e-16

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 76.91  E-value: 3.95e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPrsGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|
gi 215274225  6188 LGSARASAEL 6197
Cdd:pfam07679   79 AGEAEASAEL 88
I-set pfam07679
Immunoglobulin I-set domain;
6014-6106 1.12e-15

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 75.76  E-value: 1.12e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHiLIEDPDGSCALILDSLTGVDSGQYMCFAASAA 6093
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRF-KVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|...
gi 215274225  6094 GNCSTlgKILVQV 6106
Cdd:pfam07679   80 GEAEA--SAELTV 90
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 4523-4605 1.60e-15

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 74.96  E-value: 1.60e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4523 PDPPEDAEVVARSSHTVTLSWAAPMSDGGGG-LCGYRVEvKEGATGQWRLCHELVPGPECVVDGLAPGETYRFRVAAVGP 4601
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGyIVGYRVE-YREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 215274225   4602 VGAG 4605
Cdd:smart00060   80 AGEG 83
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 6107-6199 5.11e-15

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 73.77  E-value: 5.11e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6107 PPRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEprSGLLVLVIRAASKEDLGLYECELVN 6186
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQE--GDLHSLIIAEAFEEDTGRYSCLATN 78

                          90
                  ....*....|...
gi 215274225 6187 RLGSARASAELRI 6199
Cdd:cd20972    79 SVGSDTTSAEIFV 91
I-set pfam07679
Immunoglobulin I-set domain;
3890-3974 1.07e-14

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 73.06  E-value: 1.07e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCTC----G 3964
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3965 SQATSATLTV 3974
Cdd:pfam07679   81 EAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 5133-5216 1.28e-14

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 72.54  E-value: 1.28e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5133 QNQEVQDGYPVSFDCVVTGQPMPSVRWFKDG-KLLEEDDHYMINEDQqGGHQLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSG-STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   5212 AELRV 5216
Cdd:smart00410   81 TTLTV 85
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 6362-6446 1.32e-14

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 72.61  E-value: 1.32e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6362 TIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTY-SLVLRHVASKDAGVYTCLAQNTGGQVLC 6440
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                  ....*.
gi 215274225 6441 KAELLV 6446
Cdd:cd20973    83 SAELTV 88
I-set pfam07679
Immunoglobulin I-set domain;
1176-1251 2.29e-14

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 71.90  E-value: 2.29e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1176 VQAEAGTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSC----EAGGQRVSFQLH 1250
Cdd:pfam07679   10 VEVQEGESARFTCTVtGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAELT 89


                   .
gi 215274225  1251 I 1251
Cdd:pfam07679   90 V 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 6364-6446 4.18e-14

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 71.00  E-value: 4.18e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6364 EDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVD-STRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGGQVLCKA 6442
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAeSGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 215274225   6443 ELLV 6446
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
5371-5466 4.40e-14

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 71.13  E-value: 4.40e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDtPGYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQP-----LRSS-DRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74

                           90
                   ....*....|....*.
gi 215274225  5451 ASNAAGQALCSASLHV 5466
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 7681-7866 6.22e-14

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 77.17  E-value: 6.22e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHP----KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:PTZ00263   29 GSFGRVRIAKHKGTGEYYAIKCLKKREilkmKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVGGELFTH 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqEKVLPSDKFKDYLetmAP 7836
Cdd:PTZ00263  109 LRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVP-DRTFTLCGTPEYL---AP 184

                         170       180       190
                  ....*....|....*....|....*....|
gi 215274225 7837 ELLEGQGAVPQTDIWAIGVTAFIMLsAEYP 7866
Cdd:PTZ00263  185 EVIQSKGHGKAVDWWTMGVLLYEFI-AGYP 213
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 10-94 1.01e-13

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 70.66  E-value: 1.01e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPV-----AAGARFRLAQDGDLYRLTILDLALG--DSGQYVC 82
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkdDPRSHRIVLPSGSLFFLRVVHGRKGrsDEGVYVC 80

                          90
                  ....*....|..
gi 215274225   83 RARNAIGEAFAA 94
Cdd:cd07693    81 VAHNSLGEAVSR 92
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 5382-5466 1.12e-13

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 69.84  E-value: 1.12e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5382 VKKGSSITFSVKVEGRPVPTVHWLREEAErgvlWIGPDtPGYTVASSAQQHSLVLLDVGRQHQGTYTCIASNAAGQALCS 5461
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPEVTWYKQGGK----LLAES-GRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   5462 ASLHV 5466
Cdd:smart00410   81 TTLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 6120-6199 2.61e-13

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 68.69  E-value: 2.61e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6120 VEGEDAQFTCTIEGAPYPQIRWYKDGA-LLTTGNKFQtlSEPRSGLLVLVIRAASKEDLGLYECELVNRLGSARASAELR 6198
Cdd:smart00410    7 KEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFS--VSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84


                    .
gi 215274225   6199 I 6199
Cdd:smart00410   85 V 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 116-201 2.66e-13

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 68.69  E-value: 2.66e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    116 PTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGpRVRVEELGEASALRIRAARPRDGGTYEVRAENPLGAASA 195
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESG-RFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*.
gi 215274225    196 AAALVV 201
Cdd:smart00410   80 GTTLTV 85
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 5260-5350 2.99e-13

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 68.76  E-value: 2.99e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRLaKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKV-RLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 215274225 5340 GAAYSSARLLV 5350
Cdd:cd20972    81 GSDTTSAEIFV 91
I-set pfam07679
Immunoglobulin I-set domain;
3097-3177 5.82e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 5.82e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3097 VFSRELTDATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA---GGA 3172
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsAGE 81


                   ....*
gi 215274225  3173 CSSSI 3177
Cdd:pfam07679   82 AEASA 86
I-set pfam07679
Immunoglobulin I-set domain;
1541-1608 5.99e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 5.99e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  1541 SREVQAEAGTSATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA 1608
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
I-set pfam07679
Immunoglobulin I-set domain;
2648-2731 6.48e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 6.48e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2648 VFLKALDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV----GS 2722
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 215274225  2723 EETRARVRV 2731
Cdd:pfam07679   82 AEASAELTV 90
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 4901-4988 8.56e-13

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 67.60  E-value: 8.56e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4901 SHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKFGQV 4980
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80


                  ....*...
gi 215274225 4981 THSACVVV 4988
Cdd:cd20973    81 TCSAELTV 88
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 114-188 8.94e-13

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 67.53  E-value: 8.94e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  114 LRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDgPRVRVEELGeaSALRIRAARPRDGGTYEVRAEN 188
Cdd:cd20970     7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFN-TRYIVRENG--TTLTIRNIRRSDMGIYLCIASN 78
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 248-328 9.66e-13

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 67.52  E-value: 9.66e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLVV 327
Cdd:cd05744    11 EVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAELV 90


                  .
gi 215274225  328 V 328
Cdd:cd05744    91 V 91
I-set pfam07679
Immunoglobulin I-set domain;
3186-3269 9.66e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 67.28  E-value: 9.66e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3186 RFQEALKDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC----SFGD 3260
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGE 81


                   ....*....
gi 215274225  3261 QTTSATLTV 3269
Cdd:pfam07679   82 AEASAELTV 90
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 515-602 9.83e-13

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 67.52  E-value: 9.83e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  515 PPVDPVVKARMESSVILSWSPPPHGERPvtIDGYLVEKKKLGTYTWIRChEAEWVATPELTVADVAEEGNFQFRVSALNS 594
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDDGGP--ITGYVVEYREKGSGDWKEV-EVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79


                  ....*...
gi 215274225  595 FGQSPYLE 602
Cdd:cd00063    80 GGESPPSE 87
I-set pfam07679
Immunoglobulin I-set domain;
2167-2250 1.48e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 66.90  E-value: 1.48e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2167 SFSRPLQDVVTTEKEKVTLECELS-RPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAHD---- 2241
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNsage 81


                   ....*....
gi 215274225  2242 AQSSASVKV 2250
Cdd:pfam07679   82 AEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
3803-3885 2.77e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 66.13  E-value: 2.77e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3803 RFIEDVKNQEAREGATAVLQCELSkAAP---VEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVC----G 3875
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3876 QERTSATLTV 3885
Cdd:pfam07679   81 EAEASAELTV 90
fn3 pfam00041
Fibronectin type III domain;
4524-4607 3.37e-12

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 65.51  E-value: 3.37e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4524 DPPEDAEVVARSSHTVTLSWAAPmSDGGGGLCGYRVEVKE-GATGQWRlcHELVPGPE--CVVDGLAPGETYRFRVAAVG 4600
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPP-PDGNGPITGYEVEYRPkNSGEPWN--EITVPGTTtsVTLTGLKPGTEYEVRVQAVN 77


                   ....*..
gi 215274225  4601 PVGAGEP 4607
Cdd:pfam00041   78 GGGEGPP 84
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 248-328 3.49e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.60  E-value: 3.49e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    248 TVTEGKHARLSCYVTGEPKPETVWKKDG-QLVTEGRRHVVYEDAQeNFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLV 326
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGS-TSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83


                    ..
gi 215274225    327 VV 328
Cdd:smart00410   84 TV 85
I-set pfam07679
Immunoglobulin I-set domain;
3363-3445 3.71e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 65.74  E-value: 3.71e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3363 HFIGRLRHQESIEGATATLRCELSkAAP---VEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVC----G 3435
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3436 EERTSATLTV 3445
Cdd:pfam07679   81 EAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2834-2911 4.20e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.60  E-value: 4.20e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2834 EDQWVAPGEDVELRCELSRAGTP-VHWLKDR-KAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEAS----KSTA 2907
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSsgsaSSGT 81


                    ....
gi 215274225   2908 SLHV 2911
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
2829-2911 4.29e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 65.36  E-value: 4.29e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2829 IIKPLEDQWVAPGEDVELRCELSraGTP---VHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEAS-- 2903
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVT--GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSag 80

                           90
                   ....*....|
gi 215274225  2904 --KSTASLHV 2911
Cdd:pfam07679   81 eaEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3809-3885 4.82e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.22  E-value: 4.82e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3809 KNQEAREGATAVLQCELSKAAP--VEWRK-GSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVC----GQERTSA 3881
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3882 TLTV 3885
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
1900-1983 5.64e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 65.36  E-value: 5.64e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1900 KFMSGLSTVVAEEGGEATFQCVVS----PSdvaVVWFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEG- 1974
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtpdPE---VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNs 78

                           90
                   ....*....|..
gi 215274225  1975 ---ASSSAALRV 1983
Cdd:pfam07679   79 ageAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 6024-6095 6.33e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 64.83  E-value: 6.33e-12
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225   6024 TAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFAASAAGN 6095
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76
I-set pfam07679
Immunoglobulin I-set domain;
3715-3797 6.53e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 64.97  E-value: 6.53e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3715 KFIEGLRNEEATEGDTATLWCELSkAAP---VEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVC----G 3787
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3788 QERTSATLTV 3797
Cdd:pfam07679   81 EAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2479-2553 7.84e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 64.83  E-value: 7.84e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2479 TGRELQSVVLSCDFRPAPKA-VQWYKDD-TPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA----GSAHSSTEVT 2552
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLT 84


                    .
gi 215274225   2553 V 2553
Cdd:smart00410   85 V 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3897-3974 8.31e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 64.45  E-value: 8.31e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3897 QSLQAEEGSTATLQCELS-EPTATVVWSKGGLQ-LQANGRREPRLQGCTAELVLQDLQREDTGEYTCTC----GSQATSA 3970
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3971 TLTV 3974
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
2918-3000 8.33e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 64.59  E-value: 8.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2918 FTEELTNLQVEEKGTAVFTCK-TEHPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC----DIGQA 2992
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTvTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEA 82


                   ....*...
gi 215274225  2993 QSRAQLLV 3000
Cdd:pfam07679   83 EASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4905-4988 1.52e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 63.68  E-value: 1.52e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4905 GDTEAQVGDALRLECVVASKADVRARWLKDGVE-LTDGRHHHIDQLGdGTCSLLITGLDRADAGCYTCQVSNKFGQVTHS 4983
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSG-STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   4984 ACVVV 4988
Cdd:smart00410   81 TTLTV 85
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 5371-5466 1.63e-11

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 63.98  E-value: 1.63e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAERGVLWIGPDtpgYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGK---YKIESEYGVHVLHIRRVTVEDSAVYSAV 77

                          90
                  ....*....|....*.
gi 215274225 5451 ASNAAGQALCSASLHV 5466
Cdd:cd20951    78 AKNIHGEASSSASVVV 93
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 7470-7548 1.66e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 63.68  E-value: 1.66e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7470 SDETVVLGQSVTLACQVSAQPAAQATWSKDGA-PLESSSRVLISATLKNFQlLTILVVVAEDLGVYTCSVSNALGTVTTT 7548
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSRSGSTST-LTISNVTPEDSGTYTCAATNSSGSASSG 80
I-set pfam07679
Immunoglobulin I-set domain;
1634-1711 1.68e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 63.82  E-value: 1.68e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1634 REVQAEAGASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSC----EAGGQQLSFR 1708
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAE 87


                   ...
gi 215274225  1709 LQV 1711
Cdd:pfam07679   88 LTV 90
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 7463-7551 1.90e-11

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 63.57  E-value: 1.90e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVV-LGQSVTLACQVSAQPAAQATWSKDGAPLESSSRvliSATLKNFQlLTILVVVAEDLGVYTCSVSNA 7541
Cdd:cd20978     1 PKFIQKPEKNVVVkGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPME---RATVEDGT-LTIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|
gi 215274225 7542 LGTVTTTGVL 7551
Cdd:cd20978    77 IGDIYTETLL 86
I-set pfam07679
Immunoglobulin I-set domain;
3539-3621 2.60e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 63.43  E-value: 2.60e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3539 RFIEDVKNQEAREGATAVLQCELnSAAP---VEWRKGSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCVC----G 3611
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTV-TGTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3612 QERTSAMLTV 3621
Cdd:pfam07679   81 EAEASAELTV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2838-2911 2.62e-11

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 63.03  E-value: 2.62e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 2838 VAPGEDVELRCELSRAGTPVHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEASKSTASLHV 2911
Cdd:cd20967     9 VSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
1358-1424 2.87e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 63.05  E-value: 2.87e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1358 RKVQAEAGAIATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3192-3269 4.32e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 62.52  E-value: 4.32e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3192 KDLEVLEGGAATLRCVLSSVAAPVKWCY--GNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC----SFGDQTTSA 3265
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYkqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaatnSSGSASSGT 81


                    ....
gi 215274225   3266 TLTV 3269
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
1084-1159 5.26e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 62.27  E-value: 5.26e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1084 VQAEAGASAMLSCEVAQAQT-EVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSC----EAGGQRVSFHLH 1158
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAELT 89


                   .
gi 215274225  1159 I 1159
Cdd:pfam07679   90 V 90
I-set pfam07679
Immunoglobulin I-set domain;
898-964 5.79e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 62.27  E-value: 5.79e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   898 RKLQAEAGASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3545-3621 7.11e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 61.75  E-value: 7.11e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3545 KNQEAREGATAVLQCELNSAAP--VEWRK-GSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCVC----GQERTSA 3617
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3618 MLTV 3621
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
2293-2374 1.33e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 61.12  E-value: 1.33e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2293 VRPLRDKIAMEKHRGVLECQVSRASA-QVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDA----GDVK 2367
Cdd:pfam07679    4 TQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAE 83


                   ....*..
gi 215274225  2368 TSAQFFV 2374
Cdd:pfam07679   84 ASAELTV 90
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
6468-6667 1.49e-10

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 68.28  E-value: 1.49e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRG----VfgfvkrvqHKGN----------KILCA-----AKFIpLRSRTRAQAyrerdiLAALSHPLVTGLL 6528
Cdd:NF033483    9 YEIGERIGRGgmaeV--------YLAKdtrldrdvavKVLRPdlardPEFV-ARFRREAQS------AASLSHPNIVSVY 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6529 DQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKIC 6606
Cdd:NF033483   74 DVGEDGGIPYIVMEYVDGRTLKDYIREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILI----TKDgrVKVT 149

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6607 DFGFA-----QNITpaelQFSQ-YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES 6667
Cdd:NF033483  150 DFGIAralssTTMT----QTNSvLGTVHYLSPEQARGGTVDARSDIYSLGIVLYEMLTGRPPFDGDS 212
I-set pfam07679
Immunoglobulin I-set domain;
1273-1332 1.80e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 60.73  E-value: 1.80e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  1273 GASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:pfam07679   15 GESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2655-2731 2.00e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 60.60  E-value: 2.00e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2655 DLSAEERGTLALQCEVS-DPEAHVVWRKDGVQ-LGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV----GSEETRAR 2728
Cdd:smart00410    3 SVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTT 82


                    ...
gi 215274225   2729 VRV 2731
Cdd:smart00410   83 LTV 85
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 6801-7076 2.14e-10

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 68.26  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6801 APFARAKSLPP--SPVTHSPLLHPRGFLRPSASLPEEAEASERSTEAPAPPASPEGAGPPAAQGCVprhsvirslfyhQA 6878
Cdd:pfam03154  198 GPTPSAPSVPPqgSPATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSP------------QP 265

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6879 GESPE-HGALAPGSrrhparrrHLLKGGyiagalpglrEPLMEHRVLEEEAAReeqatllakaPSFETALRLPASGTHLA 6957
Cdd:pfam03154  266 LPQPSlHGQMPPMP--------HSLQTG----------PSHMQHPVPPQPFPL----------TPQSSQSQVPPGPSPAA 317

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6958 PGHSHSLEHDSPSTPRPSSEACGEAQRLPSAPSG--------GAPIRDMGHPQGSKQLPSTGG----------------- 7012
Cdd:pfam03154  318 PGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSmphikpppTTPIPQLPNPQSHKHPPHLSGpspfqmnsnlppppalk 397

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7013 --------HPGTA-----------QPERPSPDSPWGQPAPFCHPKQGSA--PQEGCSPHPAVAPCPPGSFPPGSCKEApL 7071
Cdd:pfam03154  398 plsslsthHPPSAhppplqlmpqsQQLPPPPAQPPVLTQSQSLPPPAAShpPTSGLHQVPSQSPFPQHPFVPGGPPPI-T 476


                   ....*
gi 215274225  7072 VPSSP 7076
Cdd:pfam03154  477 PPSGP 481
I-set pfam07679
Immunoglobulin I-set domain;
3275-3357 4.76e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.58  E-value: 4.76e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3275 QFIGKLRNKEATEGATATLRCELSkAAP---VEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVC----G 3347
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3348 EERTSASLTI 3357
Cdd:pfam07679   81 EAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
335-418 4.90e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.58  E-value: 4.90e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   335 FKKRLQDLEVREKESATFLCEV---PQPSTEaaWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYIC--ETPEG 409
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVtgtPDPEVS--WFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvaTNSAG 80

                           90
                   ....*....|
gi 215274225   410 SRTV-AELAV 418
Cdd:pfam07679   81 EAEAsAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3721-3797 5.57e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 59.44  E-value: 5.57e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3721 RNEEATEGDTATLWCELSKAAP--VEWRK-GHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVC----GQERTSA 3793
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3794 TLTV 3797
Cdd:smart00410   82 TLTV 85
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2666-2720 6.16e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 58.88  E-value: 6.16e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2666 LQCEVS-DPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV 2720
Cdd:cd00096     3 LTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2924-3000 6.84e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 59.06  E-value: 6.84e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2924 NLQVEEKGTAVFTCKTE-HPAATVTWRK-GLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC----DIGQAQSRAQ 2997
Cdd:smart00410    3 SVTVKEGESVTLSCEASgSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaatnSSGSASSGTT 82


                    ...
gi 215274225   2998 LLV 3000
Cdd:smart00410   83 LTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1906-1983 7.25e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 59.06  E-value: 7.25e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1906 STVVAEEGGEATFQCVVSPSDVAVV-WFRDGA-LLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEG----ASSSA 1979
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVtWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNssgsASSGT 81


                    ....
gi 215274225   1980 ALRV 1983
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
992-1056 7.53e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.19  E-value: 7.53e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225   992 VQAEAGASATLSCEVAQAQT-EVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEA 1056
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 4069-4154 8.05e-10

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 58.79  E-value: 8.05e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4069 KFKTRLQSleqETGDIARLCCQLSDAesGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACVTGGQKT 4148
Cdd:cd20967     2 KAQPAVQV---SKGHKIRLTVELADP--DAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKC 76


                  ....*.
gi 215274225 4149 AASLRV 4154
Cdd:cd20967    77 SFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
3627-3709 1.07e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 58.81  E-value: 1.07e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3627 KFTEGLRNEEATEGATAVLRCELS-KMAP-VEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLC----MCGK 3700
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGE 81


                   ....*....
gi 215274225  3701 ERTSAMLTV 3709
Cdd:pfam07679   82 AEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3106-3181 1.22e-09

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 58.29  E-value: 1.22e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3106 TITEGEDLTLVCETSTCDIPVC-WTKDG-KTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA--GGACSSSIVRVH 3181
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVtWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnSSGSASSGTTLT 84
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2486-2542 1.48e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 57.72  E-value: 1.48e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 2486 VVLSCDFRPAPKA-VQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA 2542
Cdd:cd00096     1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
I-set pfam07679
Immunoglobulin I-set domain;
1716-1793 2.08e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 58.04  E-value: 2.08e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1716 PQISERPcrrEPLVVKEHEDIILTATLATPSAATVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:pfam07679    1 PKFTQKP---KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3108-3180 2.29e-09

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 57.64  E-value: 2.29e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 3108 TEGEDLTLVCETSTCDIPVCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEAGGACSSSIVRV 3180
Cdd:cd20967    10 SKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 5267-5350 2.36e-09

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 57.52  E-value: 2.36e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5267 RDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDG-QPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMGAAYSS 5345
Cdd:smart00410    2 PSVTVKEGES-VTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   5346 ARLLV 5350
Cdd:smart00410   81 TTLTV 85
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 711-791 3.73e-09

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 56.87  E-value: 3.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  711 AAAREVLARLHEEAQLLAELSDQAAAVTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECVSRGGRIAYQLS 790
Cdd:cd20967     2 KAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELF 81


                  .
gi 215274225  791 V 791
Cdd:cd20967    82 V 82
I-set pfam07679
Immunoglobulin I-set domain;
3451-3533 5.45e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 56.88  E-value: 5.45e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3451 KFTEGLRNEEAVEGATAMLWCELSKVAP--VEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVC----GQ 3524
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 215274225  3525 ERTSATLTI 3533
Cdd:pfam07679   82 AEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
1450-1527 6.07e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 56.50  E-value: 6.07e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1450 REVQAQAGASTTLSCEVAQAQT-EVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSC----EAGSQRLSFH 1524
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAE 87


                   ...
gi 215274225  1525 LHV 1527
Cdd:pfam07679   88 LTV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 807-883 6.32e-09

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 56.48  E-value: 6.32e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  807 VDAVAGGPAQFECETSEAHVHVHWYKDGMELGHSGeRFLQEDVGTRHRLVAATVTRQDEGTYSCRVGEDSVDFRLRV 883
Cdd:cd20967     7 VQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSS-KVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
4511-4603 6.91e-09

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 63.10  E-value: 6.91e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4511 AVASArLTVLGLPDPPEDAEVVARSSHTVTLSWAAPMSdggGGLCGYRVEVKEGATGQWRLCHELVPGPECVVDGLAPGE 4590
Cdd:COG3401   316 NVVSV-TTDLTPPAAPSGLTATAVGSSSITLSWTASSD---ADVTGYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPGT 391

                          90
                  ....*....|...
gi 215274225 4591 TYRFRVAAVGPVG 4603
Cdd:COG3401   392 TYYYKVTAVDAAG 404
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2170-2250 1.08e-08

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 55.71  E-value: 1.08e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2170 RPLQDVVTTEK-EKVTLECELSRPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAHDAQSSASV 2248
Cdd:cd20967     1 KKAQPAVQVSKgHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 2249 KV 2250
Cdd:cd20967    81 FV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3894-3974 1.24e-08

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 55.33  E-value: 1.24e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3894 EPLQ-SLQAEEGSTATLQCELSEPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCTCGSQATSATL 3972
Cdd:cd20967     1 KKAQpAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 3973 TV 3974
Cdd:cd20967    81 FV 82
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3633-3709 1.55e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 55.20  E-value: 1.55e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3633 RNEEATEGATAVLRCELSKMAP--VEWWK-GHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLCMC----GKERTSA 3705
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3706 MLTV 3709
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
2560-2642 1.83e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 55.34  E-value: 1.83e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2560 VTGPLQDAEATEEGWASFSCELS-HEDEEVEWSLNGMPLYNDSFHEISHKGRRHTLVLKSIQRADAGI--VRA--SSLKV 2634
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKytCVAtnSAGEA 82


                   ....*...
gi 215274225  2635 STSARLEV 2642
Cdd:pfam07679   83 EASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1541-1619 1.96e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.82  E-value: 1.96e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1541 SREVQAEAGTSATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA----GDQRLS 1614
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSG 80


                    ....*
gi 215274225   1615 FHLHV 1619
Cdd:smart00410   81 TTLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
1810-1893 2.08e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 54.96  E-value: 2.08e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1810 KFCRLLEPVCGELGGTVTLACELS----PacaEVVWRCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVC----E 1881
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtpdP---EVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnS 78

                           90
                   ....*....|..
gi 215274225  1882 SRDDHTSAQLTV 1893
Cdd:pfam07679   79 AGEAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1176-1240 2.15e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.82  E-value: 2.15e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   1176 VQAEAGTTAMLSCEVAQ-PQTEVTWYKDG-KKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:smart00410    4 VTVKEGESVTLSCEASGsPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 809-883 3.33e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.43  E-value: 3.33e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    809 AVAGGPAQFECE-TSEAHVHVHWYKDGMELGHSGERFLQEDVGTRHRLVAATVTRQDEGTYSCRV----GEDSVDFRLRV 883
Cdd:smart00410    6 VKEGESVTLSCEaSGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
3980-4050 3.38e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 54.57  E-value: 3.38e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  3980 RFLRELQHQEVDEGGTAHLCCELSraGA---SVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC 4050
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT--GTpdpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4169-4245 4.46e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.05  E-value: 4.46e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4169 EVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRIHTLRLKGVTPEDAGT----VSFHLGNHASSAQLT 4244
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGTTLT 84


                    .
gi 215274225   4245 V 4245
Cdd:smart00410   85 V 85
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 515-598 4.49e-08

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 53.77  E-value: 4.49e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    515 PPVDPVVKARMESSVILSWSPPPHGERPVTIDGYLVEKKKLGTyTWIRCHEAewVATPELTVADVAEEGNFQFRVSALNS 594
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGS-EWKEVNVT--PSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 215274225    595 FGQS 598
Cdd:smart00060   80 AGEG 83
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 335-405 5.02e-08

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 53.96  E-value: 5.02e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  335 FKKRLQDLEVREKESATFLCEVP-QPSTEAAWFKEE---TRLWASAKYGIEEEGTERRLTVRNVSADDDAVYICE 405
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGvpiDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAV 77
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3812-3885 5.86e-08

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 53.40  E-value: 5.86e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3812 EAREGATAVLQCELSKA-APVEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVCGQERTSATLTV 3885
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
4068-4154 7.90e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 53.42  E-value: 7.90e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4068 PKFKTRLQSLEQETGDIARLCCQLSdAESGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACV----T 4143
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVatnsA 79

                           90
                   ....*....|.
gi 215274225  4144 GGQKTAASLRV 4154
Cdd:pfam07679   80 GEAEASAELTV 90
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3540-3621 9.39e-08

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 53.27  E-value: 9.39e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3540 FIEDVKNQEAREGATAVLQCELnSAAPV---EWRKGSETLRDGD-RYSLRQDGTkceLQIRGLAMADTGEYSCVC----G 3611
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQA-TGEPVptiSWLKDGVPLLGKDeRITTLENGS---LQIKGAEKSDTGEYTCVAlnlsG 77

                          90
                  ....*....|
gi 215274225 3612 QERTSAMLTV 3621
Cdd:cd20952    78 EATWSAVLDV 87
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3989-4063 1.37e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 52.63  E-value: 1.37e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3989 EVDEGGTAHLCCELSRAGASVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTCDTGHTQSMASLSV 4063
Cdd:cd20967     8 QVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
4248-4336 1.41e-07

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.41e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4248 PEVTIlePLQDVQLSEGQDASFQCrlsRASGQ---EARWALGGVPLQANEMNDITVEQGTlHLLTLHKVTLEDAG----T 4320
Cdd:pfam07679    1 PKFTQ--KPKDVEVQEGESARFTC---TVTGTpdpEVSWFKDGQPLRSSDRFKVTYEGGT-YTLTISNVQPDDSGkytcV 74

                           90
                   ....*....|....*.
gi 215274225  4321 VSFHVGTCSSEAQLKV 4336
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3724-3797 1.60e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 52.24  E-value: 1.60e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3724 EATEGDTATLWCELSKA-APVEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVCGQERTSATLTV 3797
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
2738-2822 1.64e-07

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.64e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2738 ITKRLKTMEVLEGESCSFECVLSheSASDP-AMWTVGGKTVGSSSRFQATRQGRKYILVVREAAPSDAGE----VVFSVR 2812
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVT--GTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKytcvATNSAG 80

                           90
                   ....*....|
gi 215274225  2813 GLTSKASLIV 2822
Cdd:pfam07679   81 EAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2173-2250 2.11e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 52.12  E-value: 2.11e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2173 QDVVTTEKEKVTLECELS-RPNVDVRWLKDGVE-LRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAH----DAQSSA 2246
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATnssgSASSGT 81


                    ....
gi 215274225   2247 SVKV 2250
Cdd:smart00410   82 TLTV 85
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3284-3357 2.11e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.86  E-value: 2.11e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3284 EATEGATATLRCELSKA-APVEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVCGEERTSASLTI 3357
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 2289-2374 3.03e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 51.81  E-value: 3.03e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2289 PVTLVRPLRDKIAMEKHRGVLECQVS-RASAQVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDA---- 2363
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLAtnsv 80

                          90
                  ....*....|.
gi 215274225 2364 GDVKTSAQFFV 2374
Cdd:cd20972    81 GSDTTSAEIFV 91
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3460-3533 3.34e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.47  E-value: 3.34e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3460 EAVEGATAMLWCELSKV-APVEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVCGQERTSATLTI 3533
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1268-1332 3.54e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.35  E-value: 3.54e-07
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   1268 VRTEAGASATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:smart00410    4 VTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1084-1148 4.26e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.35  E-value: 4.26e-07
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   1084 VQAEAGASAMLSCEVAQA-QTEVTWYKDG-KKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:smart00410    4 VTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1726-1793 4.26e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.35  E-value: 4.26e-07
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   1726 EPLVVKEHEDIILTATLATPSAATVTWLKDGVE-IRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 990-1057 4.56e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.97  E-value: 4.56e-07
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    990 SEVQAEAGASATLSCEVAQA-QTEVMWYKDG-KKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEAR 1057
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAT 71
fn3 pfam00041
Fibronectin type III domain;
515-600 4.91e-07

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 50.88  E-value: 4.91e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   515 PPVDPVVKARMESSVILSWSPPPHGERPvtIDGYLVEKKKLGTYT-WIRCHEAEwvATPELTVADVAEEGNFQFRVSALN 593
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGP--ITGYEVEYRPKNSGEpWNEITVPG--TTTSVTLTGLKPGTEYEVRVQAVN 77


                   ....*..
gi 215274225   594 SFGQSPY 600
Cdd:pfam00041   78 GGGEGPP 84
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2297-2375 4.93e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.97  E-value: 4.93e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2297 RDKIAMEKHRGVLECQVS-RASAQVRWFK-GSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDAGDVKTSAQFFV 2374
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    .
gi 215274225   2375 E 2375
Cdd:smart00410   82 T 82
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1634-1711 6.24e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.58  E-value: 6.24e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1634 REVQAEAGASATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEA----GGQQLSF 1707
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   1708 RLQV 1711
Cdd:smart00410   82 TLTV 85
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1900-1980 7.96e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 50.66  E-value: 7.96e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1900 KFMSGLSTVVAEEGGEATFQCVVSPSDVAVV-WFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEGASSS 1978
Cdd:cd20972     3 QFIQKLRSQEVAEGSKVRLECRVTGNPTPVVrWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVGS 82


                  ..
gi 215274225 1979 AA 1980
Cdd:cd20972    83 DT 84
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1821-1893 8.05e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 50.32  E-value: 8.05e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 1821 ELGGTVTLACELSPACAEVVWRCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVCESRDDHTSAQLTV 1893
Cdd:cd20967    10 SKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 427-505 8.37e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 50.32  E-value: 8.37e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  427 PRKTAVRV--GDTAMFCVELAVPVGPVHWLRNQEEVVAGGRVAISAEGTRHTLTISQCCLEDVGQVAFMAGDCQTSTQFC 504
Cdd:cd20967     2 KAQPAVQVskGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELF 81


                  .
gi 215274225  505 V 505
Cdd:cd20967    82 V 82
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1736-1793 9.01e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 49.64  E-value: 9.01e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1736 IILTATLATPSAATVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3372-3445 9.50e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 50.32  E-value: 9.50e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3372 ESIEGATATLRCELSKA-APVEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVCGEERTSATLTV 3445
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1990-2069 9.55e-07

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 50.50  E-value: 9.55e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1990 FKKKLEPQTVEERSSVTLEVELT-RPWPELRWTRNATALAP---GKNVEIHAEGARHRLVLHNVGFADRGFFGCETPDDK 2065
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPssiPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIH 82


                  ....
gi 215274225 2066 TQAK 2069
Cdd:cd20951    83 GEAS 86
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3986-4063 1.04e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.20  E-value: 1.04e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3986 QHQEVDEGGTAHLCCELS-RAGASVEWRKGSLQ-LFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC----DTGHTQSMA 4059
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaatnSSGSASSGT 81


                    ....
gi 215274225   4060 SLSV 4063
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
425-489 1.26e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 49.95  E-value: 1.26e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225   425 KLPRKTAVRVGDTAMF-CVELAVPVGPVHWLRNQEEVVAGGRVAISAEGTRHTLTISQCCLEDVGQ 489
Cdd:pfam07679    5 QKPKDVEVQEGESARFtCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGK 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1820-1895 1.31e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.81  E-value: 1.31e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   1820 GELGGTVTLACELSPACAEVVW--RCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVCESRDDHTSAQLTVSV 1895
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPEVTwyKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3375-3445 1.56e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.43  E-value: 1.56e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   3375 EGATATLRCELSKAAP--VEWRK-GRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVC----GEERTSATLTV 3445
Cdd:smart00410    8 EGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 340-405 1.64e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.43  E-value: 1.64e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225    340 QDLEVREKESATFLCEVPQ-PSTEAAWFKEETR-LWASAKYGIEEEGTERRLTVRNVSADDDAVYICE 405
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGsPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCA 69
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1358-1424 2.08e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.43  E-value: 2.08e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   1358 RKVQAEAGAIATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
I-set pfam07679
Immunoglobulin I-set domain;
737-779 2.45e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 49.18  E-value: 2.45e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 215274225   737 VTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECV 779
Cdd:pfam07679   32 VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3636-3709 2.79e-06

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 48.78  E-value: 2.79e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3636 EATEGATAVLRCELSKM-APVEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLCMCGKERTSAMLTV 3709
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
807-883 3.23e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 48.79  E-value: 3.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   807 VDAVAGGPAQFECETSEAHV-HVHWYKDGMELgHSGERFLQEDVGTRHRLVAATVTRQDEGTYSCRV----GEDSVDFRL 881
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDpEVSWFKDGQPL-RSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAEASAEL 88


                   ..
gi 215274225   882 RV 883
Cdd:pfam07679   89 TV 90
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 3189-3269 3.93e-06

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 48.72  E-value: 3.93e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3189 EALKDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAML-ELVVRNLRPQDSGRYSC----SFGDQT 3262
Cdd:cd20973     2 QTLRDKEVVEGSAARFDCKVEGYPDPeVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCkavnSLGEAT 81


                  ....*..
gi 215274225 3263 TSATLTV 3269
Cdd:cd20973    82 CSAELTV 88
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3457-3533 5.36e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 48.27  E-value: 5.36e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3457 RNEEAVEGATAMLWCELSKVAP--VEWRK-GPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVC----GQERTSA 3529
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3530 TLTI 3533
Cdd:smart00410   82 TLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4630-4695 6.02e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.89  E-value: 6.02e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   4630 PESRQVAAGEDVSLELEVVAEAGEVI-WHK-GMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVtWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTC 68
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 898-964 7.04e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.89  E-value: 7.04e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225    898 RKLQAEAGASATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3281-3357 7.61e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.50  E-value: 7.61e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3281 RNKEATEGATATLRCELSKAAP--VEWRK-GSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVC----GEERTSA 3353
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3354 SLTI 3357
Cdd:smart00410   82 TLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3012-3091 8.48e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.50  E-value: 8.48e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3012 EDVDVQEGSSATFRCRISPANYEPVHWFLDKTPLHANELNEIDAQPGGYHVLTLRQLALKDSGTIYFEA----GDQRASA 3087
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3088 ALRV 3091
Cdd:smart00410   82 TLTV 85
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
494-633 1.39e-05

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 52.31  E-value: 1.39e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  494 AGDCQTSTQFCVSAPRKPPLqPPVDPVVKARMESSVILSWSPPPHGErpvtIDGYLVEKKK--LGTYTWIrcheAEwVAT 571
Cdd:COG3401   215 GGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVTESD----ATGYRVYRSNsgDGPFTKV----AT-VTT 284

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  572 PELTVADVAEEGNFQFRVSALNSFG----QSPYLEfpGTVHLAPKLAVrTPLKAVqAVEGGEVTFS 633
Cdd:COG3401   285 TSYTDTGLTNGTTYYYRVTAVDAAGnesaPSNVVS--VTTDLTPPAAP-SGLTAT-AVGSSSITLS 346
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 4634-4695 1.77e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 46.47  E-value: 1.77e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 4634 QVAAGEDVSLELEVVAEAGEVIWHKGMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:cd20967     8 QVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQC 69
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2933-2987 1.90e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 46.17  E-value: 1.90e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2933 AVFTCKTE-HPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC 2987
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTC 56
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1450-1527 2.66e-05

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 45.96  E-value: 2.66e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1450 REVQAQAGASTTLSCEVAQA-QTEVMWYKDG-KKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEA----GSQRLSF 1523
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   1524 HLHV 1527
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
4161-4245 2.88e-05

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 46.10  E-value: 2.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4161 IVRGLVDAEVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRiHTLRLKGVTPEDAG----TVSFHLGN 4236
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGT-YTLTISNVQPDDSGkytcVATNSAGE 81


                   ....*....
gi 215274225  4237 HASSAQLTV 4245
Cdd:pfam07679   82 AEASAELTV 90
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 7557-7635 3.53e-05

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 45.68  E-value: 3.53e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7557 PSSSPCPDIGEVYADGVLLVWKPVESYGPVTYIVQCSLE----GGSWTTLASDIFDCCYLTSKLSRGGTYTFRTACVSKA 7632
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEyreeGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 215274225   7633 GMG 7635
Cdd:smart00060   81 GEG 83
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 2564-2642 4.16e-05

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 45.56  E-value: 4.16e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2564 LQDAEATEEGWASFSCELS-HEDEEVEWSLNGMPLYNDSFHE-ISHKGRRHTLVLKSIQRADAGIVRASSL----KVSTS 2637
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKVSgLPTPDLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTCIARnragENSFN 86


                  ....*
gi 215274225 2638 ARLEV 2642
Cdd:cd05744    87 AELVV 91
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4082-4154 1.01e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 44.42  E-value: 1.01e-04
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   4082 GDIARLCCQLSDAESgAVVQWLKEGVELHA-GPKYEMRSQGATRELLIHQLEAKDTGEYACV---TGGQKTA-ASLRV 4154
Cdd:smart00410    9 GESVTLSCEASGSPP-PEVTWYKQGGKLLAeSGRFSVSRSGSTSTLTISNVTPEDSGTYTCAatnSSGSASSgTTLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
4630-4695 1.09e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 44.56  E-value: 1.09e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  4630 PESRQVAAGEDVSLELEVVAE-AGEVIWHKGMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTpDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
7757-7866 1.29e-04

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 49.02  E-value: 1.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQ------EKVLPSdkfKDY 7830
Cdd:NF033483   98 IREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSttmtqtNSVLGT---VHY 174

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 215274225 7831 LetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:NF033483  175 L---SPEQARGGTVDARSDIYSLGIVLYEMLTGRPP 207
I-set pfam07679
Immunoglobulin I-set domain;
3011-3091 1.36e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 44.17  E-value: 1.36e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3011 LEDVDVQEGSSATFRCRISpANYEP-VHWFLDKTPLHANELNEIDAQpGGYHVLTLRQLALKDSGtIYF-----EAGDQR 3084
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVT-GTPDPeVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSG-KYTcvatnSAGEAE 83


                   ....*..
gi 215274225  3085 ASAALRV 3091
Cdd:pfam07679   84 ASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
617-673 1.86e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 43.79  E-value: 1.86e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225   617 TPLKAVQAVEGGEVTFSV------DLTVasagEWFLDGQALKASSVYEIHCDRTRHTLTIREV 673
Cdd:pfam07679    5 QKPKDVEVQEGESARFTCtvtgtpDPEV----SWFKDGQPLRSSDRFKVTYEGGTYTLTISNV 63
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 4162-4245 4.17e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.87  E-value: 4.17e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4162 VRGLVDAEVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRIHTLRLKGVTPEDAGTVSFHLGNHAS-- 4239
Cdd:cd05744     4 LQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGen 83


                  ....*...
gi 215274225 4240 --SAQLTV 4245
Cdd:cd05744    84 sfNAELVV 91
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 427-488 6.27e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 42.11  E-value: 6.27e-04
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225    427 PRKTAVRVGDTAMF-CVELAVPVGPVHWLRN-QEEVVAGGRVAISAEGTRHTLTISQCCLEDVG 488
Cdd:smart00410    1 PPSVTVKEGESVTLsCEASGSPPPEVTWYKQgGKLLAESGRFSVSRSGSTSTLTISNVTPEDSG 64
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3006-3091 6.59e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.48  E-value: 6.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3006 HIIEDLEDVDVQEGSSATFRCRISPANYEPVHWFLDKTPLHANELNEIDAQPGGYHVLTLRQLALKDSGtIYF-----EA 3080
Cdd:cd05744     2 HFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAG-IYTciarnRA 80

                          90
                  ....*....|.
gi 215274225 3081 GDQRASAALRV 3091
Cdd:cd05744    81 GENSFNAELVV 91
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1995-2060 9.31e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.40  E-value: 9.31e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  1995 EPQTVEERSSVTLEVELT-RPWPELRWTRNATALAPGKNVEIHAEGARHRLVLHNVGFADRGFFGCE 2060
Cdd:pfam13927    9 SSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2575-2642 1.11e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 41.34  E-value: 1.11e-03
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225   2575 ASFSCELS-HEDEEVEWSLNG--MPLYNDSFHeISHKGRRHTLVLKSIQRADAGI----VRASSLKVSTSARLEV 2642
Cdd:smart00410   12 VTLSCEASgSPPPEVTWYKQGgkLLAESGRFS-VSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGTTLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4257-4336 1.51e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 40.95  E-value: 1.51e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4257 QDVQLSEGQDASFQCRLSRASGQEARWALGGVPLQANEMNDITVEQGTLHLLTLHKVTLEDAGT----VSFHVGTCSSEA 4332
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGT 81


                    ....
gi 215274225   4333 QLKV 4336
Cdd:smart00410   82 TLTV 85
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 4256-4336 1.54e-03

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 41.33  E-value: 1.54e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4256 LQDVQLSEGQDASFQCRLSRASGQEARWALGGVPLQANEMNDITVEQGTLHLLTLHKVTLEDAGTVSF----HVGTCSSE 4331
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCiarnRAGENSFN 86


                  ....*
gi 215274225 4332 AQLKV 4336
Cdd:cd05744    87 AELVV 91
I-set pfam07679
Immunoglobulin I-set domain;
2078-2161 1.77e-03

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 41.09  E-value: 1.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2078 RLVRGLQAVEAREQGTATMEVQlshadVDG------SWTRDGLRFQQGPTCHLAVRGPMHTLTLSGLRPEDSGLMVFKAE 2151
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCT-----VTGtpdpevSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 215274225  2152 G----VHTSARLVV 2161
Cdd:pfam07679   77 NsageAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2743-2822 1.79e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 40.95  E-value: 1.79e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2743 KTMEVLEGESCSFECVLSheSASDPAMW--TVGGKTVGSSSRFQATRQGRKYILVVREAAPSDAG----EVVFSVRGLTS 2816
Cdd:smart00410    2 PSVTVKEGESVTLSCEAS--GSPPPEVTwyKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGtytcAATNSSGSASS 79


                    ....*.
gi 215274225   2817 KASLIV 2822
Cdd:smart00410   80 GTTLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1995-2072 3.48e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 40.18  E-value: 3.48e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1995 EPQTVEERSSVTLEVELTRPW-PELRWTRNA-TALAPGKNVEIHAEGARHRLVLHNVGFADRGFFGCET----PDDKTQA 2068
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPpPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   2069 KLTV 2072
Cdd:smart00410   82 TLTV 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 714-792 6.07e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 39.41  E-value: 6.07e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    714 REVLARLHEEAQLLAELSDQAAA-VTWLKDG-RTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECVSRGGRIAYQLSV 791
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    .
gi 215274225    792 Q 792
Cdd:smart00410   82 T 82
I-set pfam07679
Immunoglobulin I-set domain;
4342-4427 9.17e-03

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 39.16  E-value: 9.17e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4342 VVRGLENVEALEGGEALFECQLS---QPEVaahTWLLDDEPVHTSEnaEVVFFENGLRHLLLLKNLRPQDS----CRVTF 4414
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTgtpDPEV---SWFKDGQPLRSSD--RFKVTYEGGTYTLTISNVQPDDSgkytCVATN 77

                           90
                   ....*....|...
gi 215274225  4415 LAGDMVTSAFLTV 4427
Cdd:pfam07679   78 SAGEAEASAELTV 90
 
Name Accession Description Interval E-value
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 6465-6721 2.54e-173

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 534.08  E-value: 2.54e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14107     1 HSVYEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14107    81 SSEELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSPTREDIKICDFGFAQEITPSEHQFSKY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd14107   161 GSPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSWDTPEITHLSEDAKDFIKRVLQP 240

                         250
                  ....*....|....*..
gi 215274225 6705 APQARPSAAQCLSHPWF 6721
Cdd:cd14107   241 DPEKRPSASECLSHEWF 257
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 7668-7924 2.68e-171

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 528.33  E-value: 2.68e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14110     1 TEKTYAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKF 7827
Cdd:cd14110    81 CSGPELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14110   161 GDYVETMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRCYAGLSGGAVNFLKSTLCA 240

                         250
                  ....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWL 7924
Cdd:cd14110   241 KPWGRPTASECLQNPWL 257
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
 6474-6720 1.64e-124

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 393.56  E-value: 1.64e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd14006     1 LGRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELLDRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGSPEFVSPE 6633
Cdd:cd14006    81 AERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADRPSPQIKIIDFGLARKLNPGEELKEIFGTPEFVAPE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6634 IIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAA 6713
Cdd:cd14006   161 IVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLANISACRVDFSEEYFSSVSQEAKDFIRKLLVKEPRKRPTAQ 240


                  ....*..
gi 215274225 6714 QCLSHPW 6720
Cdd:cd14006   241 EALQHPW 247
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
 7678-7923 9.69e-112

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 356.96  E-value: 9.69e-112
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14006     1 LGRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELLDRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE--YNLLKVVDLGNAQSLSQEKVLpsDKFKDYLETMA 7835
Cdd:cd14006    81 AERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADrpSPQIKIIDFGLARKLNPGEEL--KEIFGTPEFVA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7836 PELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYA-GLSGGAVAFLRSTLCAQPWGRPC 7914
Cdd:cd14006   159 PEIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLANISACRVDFSEEYFsSVSQEAKDFIRKLLVKEPRKRPT 238


                  ....*....
gi 215274225 7915 ASSCLQCPW 7923
Cdd:cd14006   239 AQEALQHPW 247
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 6467-6721 4.53e-87

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 286.80  E-value: 4.53e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSs 6546
Cdd:cd14108     3 YYDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTELCH- 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGS 6626
Cdd:cd14108    82 EELLERITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMADQKTDQVRICDFGNAQELTPNEPQYCKYGT 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDF-IKATLQRa 6705
Cdd:cd14108   162 PEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRTTLMNIRNYNVAFEESMFKDLCREAKGFiIKVLVSD- 240

                         250
                  ....*....|....*.
gi 215274225 6706 pQARPSAAQCLSHPWF 6721
Cdd:cd14108   241 -RLRPDAEETLEHPWF 255
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 6468-6721 1.00e-79

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 265.55  E-value: 1.00e-79
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT--RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKkdRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCE 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6546 SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFSQYG 6625
Cdd:smart00220   81 GGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDE--DGHVKLADFGLARQLDPGEKLTTFVG 158

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRA 6705
Cdd:smart00220  159 TPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKD 238

                           250
                    ....*....|....*.
gi 215274225   6706 PQARPSAAQCLSHPWF 6721
Cdd:smart00220  239 PEKRLTAEEALQHPFF 254
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
 6467-6720 4.97e-78

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 260.87  E-value: 4.97e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05117     1 KYELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARE-DIKICDFGFAQNITPAELQFS 6622
Cdd:cd05117    81 CTGGELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDsPIKIIDFGLAKIFEEGEKLKT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATL 6702
Cdd:cd05117   161 VCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFDSPEWKNVSEEAKDLIKRLL 240

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd05117   241 VVDPKKRLTAAEALNHPW 258
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 5882-6006 5.41e-78

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270059  Cd Length: 125  Bit Score: 255.16  E-value: 5.41e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5882 LMENYPGTLQALGEPIRQGHFIVWEGAPGARMPWKGHNRHVFLFRNHLVICKPRRDSRTDTVSYVFRNMMKLSSIDLNDQ 5961
Cdd:cd13239     1 LIENYPAPLQALGEPIRQGHFTVWEEAPEVKTSSRGHHRHVFLFKNCVVICKPKRDSRTDTVTYVFKNKMKLSDIDVKDT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 5962 VEGDDRAFEVWQEREDSVRKYLLQARTAIIKSSWVKEICGIQQRL 6006
Cdd:cd13239    81 VEGDDRSFGLWHEHRGSVRKYTLQARSAIIKSSWLKDLRDLQQRL 125
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
 6474-6720 3.98e-72

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 243.67  E-value: 3.98e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT-RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDR 6552
Cdd:cd14103     1 LGRGKFGTVYRCVEKATGKELAAKFIKCRKAKdREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGELFER 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6553 LYRKG-VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGSPEFVS 6631
Cdd:cd14103    81 VVDDDfELTERDCILFMRQICEGVQYMHKQGILHLDLKPENILCVSRTGNQIKIIDFGLARKYDPDKKLKVLFGTPEFVA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6632 PEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPS 6711
Cdd:cd14103   161 PEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWDFDDEAFDDISDEAKDFISKLLVKDPRKRMS 240


                  ....*....
gi 215274225 6712 AAQCLSHPW 6720
Cdd:cd14103   241 AAQCLQHPW 249
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 7670-7924 2.61e-70

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 238.57  E-value: 2.61e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14111     3 KPYTFLDEKARGRFGVIRRCRENATGKNFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFCS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKD 7829
Cdd:cd14111    83 GKELLHSLIDRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNPLSLRQLGRRTG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7830 YLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQP 7909
Cdd:cd14111   163 TLEYMAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAKILVAKFDAFKLYPNVSQSASLFLKKVLSSYP 242

                         250
                  ....*....|....*
gi 215274225 7910 WGRPCASSCLQCPWL 7924
Cdd:cd14111   243 WSRPTTKDCFAHAWL 257
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 6460-6721 4.47e-69

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 235.71  E-value: 4.47e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6460 HRRKLHSFYEV-KEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR---TRAQAYRERDILA-ALSHPLVTGLLDQFETR 6534
Cdd:cd14106     1 STENINEVYTVeSTPLGRGKFAVVRKCIHKETGKEYAAKFLRKRRRgqdCRNEILHEIAVLElCKDCPRVVNLHEVYETR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHP-AREDIKICDFGFAQN 6613
Cdd:cd14106    81 SELILILELAAGGELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEfPLGDIKLCDFGISRV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSED 6693
Cdd:cd14106   161 IGEGEEIREILGTPDYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQETFLNISQCNLDFPEELFKDVSPL 240

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14106   241 AIDFIKRLLVKDPEKRLTAKECLEHPWL 268
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
 6468-6720 1.32e-64

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 222.01  E-value: 1.32e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP---LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14003     2 YELGKTLGEGSFGKVKLARHKLTGEKVAIKIIDkskLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14003    82 SGGELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILL--DKNGNLKIIDFGLSNEFRGGSLLKTFC 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswssPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd14003   160 GTPAYAAPEVLLGRKYdGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKY----PIPSHLSPDARDLIRRMLV 235

                         250
                  ....*....|....*..
gi 215274225 6704 RAPQARPSAAQCLSHPW 6720
Cdd:cd14003   236 VDPSKRITIEEILNHPW 252
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
 6463-6720 2.26e-63

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 219.28  E-value: 2.26e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR----SR---TRAQAYRERDILAALSHPLVTGLLDQFETRK 6535
Cdd:cd14105     2 NVEDFYDIGEELGSGQFAVVKKCREKSTGLEYAAKFIKKRrskaSRrgvSREDIEREVSILRQVLHPNIITLHDVFENKT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 TLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM----VHPARedIKICDFGFA 6611
Cdd:cd14105    82 DVVLILELVAGGELFDFLAEKESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLldknVPIPR--IKLIDFGLA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLS 6691
Cdd:cd14105   160 HKIEDGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVNYDFDDEYFSNTS 239

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14105   240 ELAKDFIRQLLVKDPRKRMTIQESLRHPW 268
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
 6467-6721 1.47e-60

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 210.90  E-value: 1.47e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL-RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd14114     3 HYDILEELGTGAFGVVHRCTERATGNNFAAKFIMTpHESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKG-VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14114    83 GGELFERIAAEHyKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTKRSNEVKLIDFGLATHLDPKESVKVTT 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVleGRVSWSSPMAA--HLSEDAKDFIKATL 6702
Cdd:cd14114   163 GTAEFAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDDETLRNV--KSCDWNFDDSAfsGISEEAKDFIRKLL 240

                         250
                  ....*....|....*....
gi 215274225 6703 QRAPQARPSAAQCLSHPWF 6721
Cdd:cd14114   241 LADPNKRMTIHQALEHPWL 259
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 6466-6721 2.44e-60

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 210.22  E-value: 2.44e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd14113     7 SFYSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMAD 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVH-PAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14113    87 QGRLLDYVVRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQsLSKPTIKLADFGDAVQLNTTYYIHQLL 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd14113   167 GSPEFAAPEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDESVEETCLNICRLDFSFPDDYFKGVSQKAKDFVCFLLQM 246

                         250
                  ....*....|....*..
gi 215274225 6705 APQARPSAAQCLSHPWF 6721
Cdd:cd14113   247 DPAKRPSAALCLQEQWL 263
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 6460-6721 5.58e-59

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 206.70  E-value: 5.58e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6460 HRRKLHSFYEV-KEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR---TRAQAYRERDIL-AALSHPLVTGLLDQFETR 6534
Cdd:cd14198     1 SMDNFNNFYILtSKELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRgqdCRAEILHEIAVLeLAKSNPRVVNLHEVYETT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLY--RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM--VHPArEDIKICDFGF 6610
Cdd:cd14198    81 SEIILILEYAAGGEIFNLCVpdLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLssIYPL-GDIKIVDFGM 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 AQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHL 6690
Cdd:cd14198   160 SRKIGHACELREIMGTPEYLAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLNISQVNVDYSEETFSSV 239

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6691 SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14198   240 SQLATDFIQKLLVKNPEKRPTAEICLSHSWL 270
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
 6462-6720 3.43e-58

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 204.42  E-value: 3.43e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6462 RKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR----SR---TRAQAYRERDILAALSHPLVTGLLDQFETR 6534
Cdd:cd14196     1 QKVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRqsraSRrgvSREEIEREVSILRQVLHPNIITLHDVYENR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV--HPAREDIKICDFGFAQ 6612
Cdd:cd14196    81 TDVVLILELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLdkNIPIPHIKLIDFGLAH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 NITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSE 6692
Cdd:cd14196   161 EIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSHTSE 240

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14196   241 LAKDFIRKLLVKETRKRLTIQEALRHPW 268
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
 6464-6720 4.60e-57

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 201.02  E-value: 4.60e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR----SR---TRAQAYRERDILAALSHPLVTGLLDQFETRKT 6536
Cdd:cd14194     3 VDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRrtksSRrgvSREDIEREVSILKEIQHPNVITLHEVYENKTD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV--HPAREDIKICDFGFAQNI 6614
Cdd:cd14194    83 VILILELVAGGELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLdrNVPKPRIKIIDFGLAHKI 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDA 6694
Cdd:cd14194   163 DFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYFSNTSALA 242

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6695 KDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14194   243 KDFIRRLLVKDPKKRMTIQDSLQHPW 268
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
 6468-6722 5.05e-57

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 200.39  E-value: 5.05e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14007     2 FEIGKPLGKGKFGNVYLAREKKSGFIVALKVISksqlQKSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILEY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAqNITPAELQFSQ 6623
Cdd:cd14007    82 APNGELYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGS--NGELKLADFGWS-VHAPSNRRKTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKATLQ 6703
Cdd:cd14007   159 CGTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPS----SVSPEAKDLISKLLQ 234

                         250
                  ....*....|....*....
gi 215274225 6704 RAPQARPSAAQCLSHPWFL 6722
Cdd:cd14007   235 KDPSKRLSLEQVLNHPWIK 253
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
 6467-6720 9.00e-57

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 200.61  E-value: 9.00e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR----SR---TRAQAYRERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd14195     6 HYEMGEELGSGQFAIVRKCREKGTGKEYAAKFIKKRrlssSRrgvSREEIEREVNILREIQHPNIITLHDIFENKTDVVL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED--IKICDFGFAQNITPA 6617
Cdd:cd14195    86 ILELVSGGELFDFLAEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNprIKLIDFGIAHKIEAG 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDF 6697
Cdd:cd14195   166 NEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSELAKDF 245

                         250       260
                  ....*....|....*....|...
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14195   246 IRRLLVKDPKKRMTIAQSLEHSW 268
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
 6471-6721 1.81e-56

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 198.99  E-value: 1.81e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6471 KEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR-SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14190     9 KEVLGGGKFGKVHTCTEKRTGLKLAAKVINKQnSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVEGGEL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGSPE 6628
Cdd:cd14190    89 FERIVDEDYhLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCVNRTGHQVKIIDFGLARRYNPREKLKVNFGTPE 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQA 6708
Cdd:cd14190   169 FLSPEVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNWYFDEETFEHVSDEAKDFVSNLIIKERSA 248

                         250
                  ....*....|...
gi 215274225 6709 RPSAAQCLSHPWF 6721
Cdd:cd14190   249 RMSATQCLKHPWL 261
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
 6468-6721 6.00e-56

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 198.63  E-value: 6.00e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQayrERDILAALS-HPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd14091     2 YEIKEEIGKGSYSVCKRCIHKATGKEYAVKIIDKSKRDPSE---EIEILLRYGqHPNIITLRDVYDDGNSVYLVTELLRG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAR--EDIKICDFGFAQNITpAE---LQF 6621
Cdd:cd14091    79 GELLDRILRQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADESGdpESLRICDFGFAKQLR-AEnglLMT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYgSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFA---GESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFI 6698
Cdd:cd14091   158 PCY-TANFVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFAsgpNDTPEVILARIGSGKIDLSGGNWDHVSDSAKDLV 236

                         250       260
                  ....*....|....*....|...
gi 215274225 6699 KATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14091   237 RKMLHVDPSQRPTAAQVLQHPWI 259
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
 6467-6721 8.43e-56

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 197.15  E-value: 8.43e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd14191     3 FYDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFKAYSAKEKENIRqEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14191    83 GGELFERIIDEDFeLTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTKIKLIDFGLARRLENAGSLKVLF 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd14191   163 GTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISNLLKK 242

                         250
                  ....*....|....*..
gi 215274225 6705 APQARPSAAQCLSHPWF 6721
Cdd:cd14191   243 DMKARLTCTQCLQHPWL 259
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
 6466-6721 1.04e-55

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 197.11  E-value: 1.04e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEV--KEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRS-RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14192     2 SYYAVcpHEVLGGGRFGQVHKCTELSTGLTLAAKIIKVKGaKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQF 6621
Cdd:cd14192    82 YVDGGELFDRITDESYqLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCVNSTGNQIKIIDFGLARRYKPREKLK 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:cd14192   162 VNFGTPEFLAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETDAETMNNIVNCKWDFDAEAFENLSEEAKDFISRL 241

                         250       260
                  ....*....|....*....|
gi 215274225 6702 LQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14192   242 LVKEKSCRMSATQCLKHEWL 261
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
 6468-6721 1.08e-53

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 190.88  E-value: 1.08e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY-RERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd05122     2 FEILEKIGKGGFGVVYKARHKKTGQIVAIKKINLESKEKKESIlNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFSQYG 6625
Cdd:cd05122    82 GSLKDLLkNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDG--EVKLIDFGLSAQLSDGKTRNTFVG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVisylsltcsspfagesdraTLLNVLEGRV--SWSSPMAAHL------------- 6690
Cdd:cd05122   160 TPYWMAPEVIQGKPYGFKADIWSLGI-------------------TAIEMAEGKPpySELPPMKALFliatngppglrnp 220

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 6691 ---SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd05122   221 kkwSKEFKDFLKKCLQKDPEKRPTAEQLLKHPFI 254
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 6474-6720 1.26e-53

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 190.56  E-value: 1.26e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd14115     1 IGRGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDGRLLDYL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM-VHPAREDIKICDFGFAQNITPAELQFSQYGSPEFVSP 6632
Cdd:cd14115    81 MNHDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIdLRIPVPRVKLIDLEDAVQISGHRHVHHLLGNPEFAAP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6633 EIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLegRVSWSSPMA--AHLSEDAKDFIKATLQRAPQARP 6710
Cdd:cd14115   161 EVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDESKEETCINVC--RVDFSFPDEyfGDVSQAARDFINVILQEDPRRRP 238

                         250
                  ....*....|
gi 215274225 6711 SAAQCLSHPW 6720
Cdd:cd14115   239 TAATCLQHPW 248
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 6473-6721 2.83e-53

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 190.53  E-value: 2.83e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQAYRERDI--LAAL----SHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd14197    16 ELGRGKFAVVRKCVEKDSGKEFAAKF--MRKRRKGQDCRMEIIheIAVLelaqANPWVINLHEVYETASEMILVLEYAAG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLY--RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAR-EDIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14197    94 GEIFNQCVadREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPlGDIKIVDFGLSRILKNSEELREI 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd14197   174 MGTPEYVAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGDDKQETFLNISQMNVSYSEEEFEHLSESAIDFIKTLLI 253

                         250
                  ....*....|....*...
gi 215274225 6704 RAPQARPSAAQCLSHPWF 6721
Cdd:cd14197   254 KKPENRATAEDCLKHPWL 271
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
 6468-6725 7.21e-53

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 189.30  E-value: 7.21e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14104     2 YMIAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFISGV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGS 6626
Cdd:cd14104    82 DIFERITTARFeLNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRRGSYIKIIEFGQSRQLKPGDKFRLQYTS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAP 6706
Cdd:cd14104   162 AEFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEYAFDDEAFKNISIEALDFVDRLLVKER 241

                         250
                  ....*....|....*....
gi 215274225 6707 QARPSAAQCLSHPWFLKSM 6725
Cdd:cd14104   242 KSRMTAQEALNHPWLKQGM 260
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
 6466-6720 1.55e-52

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 187.81  E-value: 1.55e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEE--IGRGVFGFVKRVQHKGNKILCAAKFIPLRS-RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14193     2 SYYNVNKEeiLGGGRFGQVHKCEEKSSGLKLAAKIIKARSqKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQF 6621
Cdd:cd14193    82 YVDGGELFDRIIDENYnLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSREANQVKIIDFGLARRYKPREKLR 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:cd14193   162 VNFGTPEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILACQWDFEDEEFADISEEAKDFISKL 241

                         250
                  ....*....|....*....
gi 215274225 6702 LQRAPQARPSAAQCLSHPW 6720
Cdd:cd14193   242 LIKEKSWRMSASEALKHPW 260
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6464-6720 1.62e-52

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 187.58  E-value: 1.62e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDI--LAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14083     1 IRDKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDKKALKGKEDSLENEIavLRKIKHPNIVQLLDIYESKSHLYLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPArED--IKICDFGFAQNITPAEL 6619
Cdd:cd14083    81 ELVTGGELFDRIVEKGSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLYYSPD-EDskIMISDFGLSKMEDSGVM 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QfSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIK 6699
Cdd:cd14083   160 S-TACGTPGYVAPEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDSKLFAQILKAEYEFDSPYWDDISDSAKDFIR 238

                         250       260
                  ....*....|....*....|.
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14083   239 HLMEKDPNKRYTCEQALEHPW 259
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
 6468-6720 4.38e-52

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 186.59  E-value: 4.38e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14087     3 YDIKALIGRGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFA--QNITPAELQFSQY 6624
Cdd:cd14087    83 ELFDRIIAKGSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYYHPGPDSkIMITDFGLAstRKKGPNCLMKTTC 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFagESDRATLL--NVLEGRVSWSSPMAAHLSEDAKDFIKATL 6702
Cdd:cd14087   163 GTPEYIAPEILLRKPYTQSVDMWAVGVIAYILLSGTMPF--DDDNRTRLyrQILRAKYSYSGEPWPSVSNLAKDFIDRLL 240

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd14087   241 TVNPGERLSATQALKHPW 258
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 6474-6721 4.22e-51

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 183.10  E-value: 4.22e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05123     1 LGKGSFGKVLLVRKKDTGKLYAMKVLRkkeiIKRKEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPGGEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpareD----IKICDFGFA-QNITPAELQFSQY 6624
Cdd:cd05123    81 FSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILL------DsdghIKLTDFGLAkELSSDGDRTYTFC 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKATLQR 6704
Cdd:cd05123   155 GTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPE----YVSPEAKSLISGLLQK 230

                         250       260
                  ....*....|....*....|
gi 215274225 6705 APQARPSA--AQCL-SHPWF 6721
Cdd:cd05123   231 DPTKRLGSggAEEIkAHPFF 250
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
 6474-6719 5.75e-51

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 181.31  E-value: 5.75e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT--RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLD 6551
Cdd:cd00180     1 LGKGSFGKVYKARDKETGKKVAVKVIPKEKLKklLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6552 RL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAEL---QFSQYGSP 6627
Cdd:cd00180    81 LLkENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGT--VKLADFGLAKDLDSDDSllkTTGGTTPP 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVIsylsltcsspfagesdratLLNVlegrvswsspmaahlsEDAKDFIKATLQRAPQ 6707
Cdd:cd00180   159 YYAPPELLGGRYYGPKVDIWSLGVI-------------------LYEL----------------EELKDLIRRMLQYDPK 203

                         250
                  ....*....|..
gi 215274225 6708 ARPSAAQCLSHP 6719
Cdd:cd00180   204 KRPSAKELLEHL 215
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
 6468-6714 6.14e-51

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 183.17  E-value: 6.14e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL----RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14014     2 YRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPelaeDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14014    82 VEGGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGR--VKLTDFGIARALGDSGLTQTG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 --YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:cd14014   160 svLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQEAPPPPSPLNPDVPPALDAIILRA 239

                         250
                  ....*....|...
gi 215274225 6702 LQRAPQARPSAAQ 6714
Cdd:cd14014   240 LAKDPEERPQSAA 252
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6464-6720 6.38e-51

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 183.94  E-value: 6.38e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDI--LAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14169     1 INSVYELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKALRGKEAMVENEIavLRRINHENIVSLEDIYESPTHLYLAM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQnITPAELQ 6620
Cdd:cd14169    81 ELVTGGELFDRIIERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYATPFEDSkIMISDFGLSK-IEAQGML 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14169   160 STACGTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAEYEFDSPYWDDISESAKDFIRH 239

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14169   240 LLERDPEKRFTCEQALQHPW 259
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
 6468-6719 1.54e-50

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 181.89  E-value: 1.54e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR---SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd08215     2 YEKIRVIGKGSFGSAYLVRRKSDGKLYVLKEIDLSnmsEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 S----SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFA-QNITPAEL 6619
Cdd:cd08215    82 DggdlAQKIKKQKKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLT--KDGVVKLGDFGISkVLESTTDL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIK 6699
Cdd:cd08215   160 AKTVVGTPYYLSPELCENKPYNYKSDIWALGCVLYELCTLKHPFEANNLPALVYKIVKGQY---PPIPSQYSSELRDLVN 236

                         250       260
                  ....*....|....*....|
gi 215274225 6700 ATLQRAPQARPSAAQCLSHP 6719
Cdd:cd08215   237 SMLQKDPEKRPSANEILSSP 256
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6468-6720 1.88e-49

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 179.07  E-value: 1.88e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDI--LAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd14167     5 YDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKALEGKETSIENEIavLHKIKHPNIVALDDIYESGGHLYLIMQLVS 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNiLMVHPARED--IKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14167    85 GGELFDRIVEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPEN-LLYYSLDEDskIMISDFGLSKIEGSGSVMSTA 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd14167   164 CGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFDSPYWDDISDSAKDFIQHLME 243

                         250
                  ....*....|....*..
gi 215274225 6704 RAPQARPSAAQCLSHPW 6720
Cdd:cd14167   244 KDPEKRFTCEQALQHPW 260
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
 6468-6721 2.11e-49

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 178.52  E-value: 2.11e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14099     3 YRRGKFLGKGGFAKCYEVTDMSTGKVYAGKVVPksslTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPA-ELQFS 6622
Cdd:cd14099    83 CSNGSLMELLKRRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFL--DENMNVKIGDFGLAARLEYDgERKKT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQ-QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAAHLSEDAKDFIKAT 6701
Cdd:cd14099   161 LCGTPNYIAPEVLEkKKGHSFEVDIWSLGVILYTLLVGKPPFETSDVKETYKRIKKNEYSF--PSHLSISDEAKDLIRSM 238

                         250       260
                  ....*....|....*....|
gi 215274225 6702 LQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14099   239 LQPDPTKRPSLDEILSHPFF 258
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
 6467-6721 7.87e-49

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 176.93  E-value: 7.87e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEE-IGRGVFGFVKRVQHKGNKILCAAKFIPLRSrtraQAYRERDILAALSHPLVTGLLDQFET-RKTLILILELC 6544
Cdd:cd14109     4 LYEIGEEdEKRAAQGAPFHVTERSTGRNFLAQLRYGDP----FLMREVDIHNSLDHPNIVQMHDAYDDeKLAVTVIDNLA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SS-EELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDIKICDFGFAQNITPAELQFS 6622
Cdd:cd14109    80 STiELVRDNLLPgKDYYTERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILL---QDDKLKLADFGQSRRLLRGKLTTL 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATL 6702
Cdd:cd14109   157 IYGSPEFVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWSFDSSPLGNISDDARDFIKKLL 236

                         250
                  ....*....|....*....
gi 215274225 6703 QRAPQARPSAAQCLSHPWF 6721
Cdd:cd14109   237 VYIPESRLTVDEALNHPWF 255
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 6468-6720 8.11e-49

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 176.94  E-value: 8.11e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14111     5 YTFLDEKARGRFGVIRRCRENATGKNFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFCSGK 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNIlMVHPAREdIKICDFGFAQNITPAEL-QFSQY-G 6625
Cdd:cd14111    85 ELLHSLIDRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNI-MVTNLNA-IKIVDFGSAQSFNPLSLrQLGRRtG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwSSPMAAHLSEDAKDFIKATLQRA 6705
Cdd:cd14111   163 TLEYMAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAKILVAKFD-AFKLYPNVSQSASLFLKKVLSSY 241

                         250
                  ....*....|....*
gi 215274225 6706 PQARPSAAQCLSHPW 6720
Cdd:cd14111   242 PWSRPTTKDCFAHAW 256
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
 6468-6721 3.38e-48

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 175.62  E-value: 3.38e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRS---------RTRAQAYRERDILAALS-HPLVTGLLDQFETRKTL 6537
Cdd:cd14093     5 YEPKEILGRGVSSTVRRCIEKETGQEFAVKIIDITGeksseneaeELREATRREIEILRQVSgHPNIIELHDVFESPTFI 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPA 6617
Cdd:cd14093    85 FLVFELCRKGELFDYLTEVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLD--DNLNVKISDFGFATRLDEG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNPVSEAS------DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLS 6691
Cdd:cd14093   163 EKLRELCGTPGYLAPEVLKCSMYDNAPgygkevDMWACGVIMYTLLAGCPPFWHRKQMVMLRNIMEGKYEFGSPEWDDIS 242

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14093   243 DTAKDLISKLLVVDPKKRLTAEEALEHPFF 272
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 7680-7924 4.02e-48

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 174.64  E-value: 4.02e-48
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7680 RGRFSVVRQCWEKASGRALAAKIIPYH--PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:smart00220    9 EGSFGKVYLARDKKTGKLVAIKVIKKKkiKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLL 88

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFKDY---LETM 7834
Cdd:smart00220   89 KKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLD-----PGEKLTTFvgtPEYM 163

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7835 APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG-ARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGRP 7913
Cdd:smart00220  164 APEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDqLLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKDPEKRL 243

                           250
                    ....*....|.
gi 215274225   7914 CASSCLQCPWL 7924
Cdd:smart00220  244 TAEEALQHPFF 254
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
 6468-6721 9.14e-48

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 173.98  E-value: 9.14e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14081     3 YRLGKTLGKGQTGLVKLAKHCVTGQKVAIKIVNkeklSKESVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVLEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14081    83 VSGGELFDYLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLL--DEKNNIKIADFGMASLQPEGSLLETS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATL 6702
Cdd:cd14081   161 CGSPHYACPEVIKGEKYdGRKADIWSCGVILYALLVGALPFDDDNLRQLLEKVKRGVFH----IPHFISPDAQDLLRRML 236

                         250
                  ....*....|....*....
gi 215274225 6703 QRAPQARPSAAQCLSHPWF 6721
Cdd:cd14081   237 EVNPEKRITIEEIKKHPWF 255
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
 6468-6719 1.24e-47

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 173.21  E-value: 1.24e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY---RERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14002     3 YHVLELIGEGSFGKVYKGRRKYTGQVVALKFIPKRGKSEKELRnlrQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEeLLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQF-SQ 6623
Cdd:cd14002    83 QGE-LFQILEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILI--GKGGVVKLCDFGFARAMSCNTLVLtSI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESdRATLLN-VLEGRVSWSSPMaahlSEDAKDFIKATL 6702
Cdd:cd14002   160 KGTPLYMAPELVQEQPYDHTADLWSLGCILYELFVGQPPFYTNS-IYQLVQmIVKDPVKWPSNM----SPEFKSFLQGLL 234

                         250
                  ....*....|....*..
gi 215274225 6703 QRAPQARPSAAQCLSHP 6719
Cdd:cd14002   235 NKDPSKRLSWPDLLEHP 251
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6468-6720 3.49e-47

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 173.38  E-value: 3.49e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14086     3 YDLKEELGKGAFSVVRRCVQKSTGQEFAAKIIntkKLSARDHQKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARE-DIKICDFGFA---QNITPAELQ 6620
Cdd:cd14086    83 TGGELFEDIVAREFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASKSKGaAVKLADFGLAievQGDQQAWFG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSqyGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14086   163 FA--GTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLINQ 240

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14086   241 MLTVNPAKRITAAEALKHPW 260
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
 7674-7923 6.10e-47

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 171.51  E-value: 6.10e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd05117     4 LGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELCTG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT---EYNLLKVVDLGNAqslsqeKVLPSDKF 7827
Cdd:cd05117    84 GELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLAskdPDSPIKIIDFGLA------KIFEEGEK 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 kdyLET-------MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVA 7899
Cdd:cd05117   158 ---LKTvcgtpyyVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFdSPEWKNVSEEAKD 234

                         250       260
                  ....*....|....*....|....
gi 215274225 7900 FLRSTLCAQPWGRPCASSCLQCPW 7923
Cdd:cd05117   235 LIKRLLVVDPKKRLTAAEALNHPW 258
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6462-6720 6.77e-47

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 172.48  E-value: 6.77e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6462 RKLHSFYEVkeeIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd14166     2 RETFIFMEV---LGSGAFSEVYLVKQRSTGKLYALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYESTTHYYLV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQnITPAEL 6619
Cdd:cd14166    79 MQLVSGGELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYLTPDENSkIMITDFGLSK-MEQNGI 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIK 6699
Cdd:cd14166   158 MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYYEFESPFWDDISESAKDFIR 237

                         250       260
                  ....*....|....*....|.
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14166   238 HLLEKNPSKRYTCEKALSHPW 258
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
 6472-6721 1.39e-46

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 170.39  E-value: 1.39e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAY-RERDILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd06606     6 ELLGKGSFGSVYLALNLDTGELMAVKEVELsgDSEEELEALeREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGS 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA---QNITPAELQFSQYG 6625
Cdd:cd06606    86 LASLLKKFGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGV--VKLADFGCAkrlAEIATGEGTKSLRG 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMG--VISYlsLTCSSPFAGESDRATLLNVLeGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd06606   164 TPYWMAPEVIRGEGYGRAADIWSLGctVIEM--ATGKPPWSELGNPVAALFKI-GSSGEPPPIPEHLSEEAKDFLRKCLQ 240

                         250
                  ....*....|....*...
gi 215274225 6704 RAPQARPSAAQCLSHPWF 6721
Cdd:cd06606   241 RDPKKRPTADELLQHPFL 258
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 6468-6720 6.67e-46

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 168.56  E-value: 6.67e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14110     5 YAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSGP 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAEL----QFSQ 6623
Cdd:cd14110    85 ELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNL--LKIVDLGNAQPFNQGKVlmtdKKGD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPefVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAhLSEDAKDFIKATLQ 6703
Cdd:cd14110   163 YVET--MAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRCYAG-LSGGAVNFLKSTLC 239

                         250
                  ....*....|....*..
gi 215274225 6704 RAPQARPSAAQCLSHPW 6720
Cdd:cd14110   240 AKPWGRPTASECLQNPW 256
Pkinase pfam00069
Protein kinase domain;
6468-6721 8.72e-46

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 166.65  E-value: 8.72e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT---RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKIKkkkDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLhylhshgvlhldiKPSNILMVhparedikICdfgfaqnitpaelqfsqy 6624
Cdd:pfam00069   81 EGGSLFDLLSEKGAFSEREAKFIMKQILEGL-------------ESGSSLTT--------FV------------------ 121

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPmAAHLSEDAKDFIKATLQR 6704
Cdd:pfam00069  122 GTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPEL-PSNLSEEAKDLLKKLLKK 200

                          250
                   ....*....|....*..
gi 215274225  6705 APQARPSAAQCLSHPWF 6721
Cdd:pfam00069  201 DPSKRLTATQALQHPWF 217
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
 6468-6721 1.01e-45

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 167.79  E-value: 1.01e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR---ERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd06627     2 YQLGDLIGRGAFGSVYKGLNLNTGEFVAIKQISLEKIPKSDLKSvmgEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQ-FSQ 6623
Cdd:cd06627    82 ENGSLASIIKKFGKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILT--TKDGLVKLADFGVATKLNEVEKDeNSV 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRvswSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd06627   160 VGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQPMAALFRIVQDD---HPPLPENISPELRDFLLQCFQ 236

                         250
                  ....*....|....*...
gi 215274225 6704 RAPQARPSAAQCLSHPWF 6721
Cdd:cd06627   237 KDPTLRPSAKELLKHPWL 254
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
 6468-6720 1.71e-45

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 167.95  E-value: 1.71e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN------KILCAAKFIPLRSRTRAQAYR---ERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:cd14084     8 YIMSRTLGSGACGEVKLAYDKSTckkvaiKIINKRKFTIGSRREINKPRNietEIEILKKLSHPCIIKIEDFFDAEDDYY 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQNITPA 6617
Cdd:cd14084    88 IVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSQEEEClIKITDFGLSKILGET 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQ---QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLN-VLEGRVSWSSPMAAHLSED 6693
Cdd:cd14084   168 SLMKTLCGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEEYTQMSLKEqILSGKYTFIPKAWKNVSEE 247

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14084   248 AKDLVKKMLVVDPSRRPSIEEALEHPW 274
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6464-6751 4.30e-45

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 167.92  E-value: 4.30e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDI--LAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14168     8 IKKIFEFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKALKGKESSIENEIavLRKIKHENIVALEDIYESPNHLYLVM 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQNITPAELQ 6620
Cdd:cd14168    88 QLVSGGELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYFSQDEESkIMISDFGLSKMEGKGDVM 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14168   168 STACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKADYEFDSPYWDDISDSAKDFIRN 247

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6701 TLQRAPQARPSAAQCLSHPWFL-KSMPAEEAHFINTKQLKFLLARSRWQRSL 6751
Cdd:cd14168   248 LMEKDPNKRYTCEQALRHPWIAgDTALCKNIHESVSAQIRKNFAKSKWRQAF 299
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
6468-6902 5.31e-45

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 173.27  E-value: 5.31e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:COG0515     9 YRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARerfrREARALARLNHPNIVRVYDVGEEDGRPYLVMEY 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQ 6623
Cdd:COG0515    89 VEGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGR--VKLIDFGIARALGGATLTQTG 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 Y--GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:COG0515   167 TvvGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSELRPDLPPALDAIVLRA 246

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6702 LQRAPQARPSAAQ--------CLSHPWFLKSMPAEEAHFINTKQLKFLLARSRWQRSLmsykSILVMRSIPELLRGPPDS 6773
Cdd:COG0515   247 LAKDPEERYQSAAelaaalraVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA----AAAAAAAAAAAAAAAAAA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6774 PSLGVARHLCRDTGGSSSSSSSSDNELAPFARAKSLPPSPVTHSPLLHPRGFLRPSASLPEEAEASERSTEAPAPPASPE 6853
Cdd:COG0515   323 PAAAAAAAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAA 402

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 6854 GAGPPAAQGCVPRHSVIRSLFYHQAGESPEHGALAPGSRRHPARRRHLL 6902
Cdd:COG0515   403 AAAAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAA 451
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
 7680-7924 9.58e-44

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 162.01  E-value: 9.58e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIP-YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP-CL 7757
Cdd:cd14103     3 RGKFGTVYRCVEKATGKELAAKFIKcRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGELFErVV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSEN-MIIT-EYNLLKVVDLGNAQslsqeKVLPSDKFKdYL---- 7831
Cdd:cd14103    83 DDDFELTERDCILFMRQICEGVQYMHKQGILHLDLKPENiLCVSrTGNQIKIIDFGLAR-----KYDPDKKLK-VLfgtp 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSseGARDLQRglrkgLVRLSR--------CYAGLSGGAVAFLRS 7903
Cdd:cd14103   157 EFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFM--GDNDAET-----LANVTRakwdfddeAFDDISDEAKDFISK 229

                         250       260
                  ....*....|....*....|.
gi 215274225 7904 TLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14103   230 LLVKDPRKRMSAAQCLQHPWL 250
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
 6457-6722 2.93e-43

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 164.04  E-value: 2.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6457 KQSHRRKLH--SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRAQAYRERDILAAL-SHPLVTGLLDQFET 6533
Cdd:cd14176     8 QQLHRNSIQftDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKII---DKSKRDPTEEIEILLRYgQHPNIITLKDVYDD 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPA--REDIKICDFGFA 6611
Cdd:cd14176    85 GKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESgnPESIRICDFGFA 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAE-LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAG---ESDRATLLNVLEGRVSWSSPMA 6687
Cdd:cd14176   165 KQLRAENgLLMTPCYTANFVAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFANgpdDTPEEILARIGSGKFSLSGGYW 244

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 215274225 6688 AHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFL 6722
Cdd:cd14176   245 NSVSDTAKDLVSKMLHVDPHQRLTAALVLRHPWIV 279
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
 6474-6720 3.14e-43

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 160.47  E-value: 3.14e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14009     1 IGRGSFATVWKGRHKQTGEVVAIKEISRKKLNKKlqeNLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHP-AREDIKICDFGFAQNITPAELQFSQYGSPEF 6629
Cdd:cd14009    81 QYIRKRGRLPEAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSgDDPVLKIADFGFARSLQPASMAETLCGSPLY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6630 VSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQAR 6709
Cdd:cd14009   161 MAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVQLLRNIERSDAVIPFPIAAQLSPDCKDLLRRLLRRDPAER 240

                         250
                  ....*....|.
gi 215274225 6710 PSAAQCLSHPW 6720
Cdd:cd14009   241 ISFEEFFAHPF 251
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
 6468-6721 1.26e-42

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 159.27  E-value: 1.26e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHK--GNKILCAAKFIplrSRTRAQAY-------RERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:cd14080     2 YRLGKTIGEGSYSKVKLAEYTksGLKEKVACKII---DKKKAPKDflekflpRELEILRKLRHPNIIQVYSIFERGSKVF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPAE 6618
Cdd:cd14080    79 IFMEYAEHGDLLEYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLD--SNNNVKLSDFGFARLCPDDD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQ-FSQ-Y-GSPEFVSPEIIQQNPVS-EASDIWAMGVISYLSLTCSSPFaGESDRATLL-NVLEGRVSWSSPMaAHLSED 6693
Cdd:cd14080   157 GDvLSKtFcGSAAYAAPEILQGIPYDpKKYDIWSLGVILYIMLCGSMPF-DDSNIKKMLkDQQNRKVRFPSSV-KKLSPE 234

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14080   235 CKDLIDQLLEPDPTKRATIEEILNHPWL 262
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
 6468-6721 2.00e-42

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 159.30  E-value: 2.00e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN------KIlCAAKFIpLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd05581     3 FKFGKPLGEGSYSTVVLAKEKETgkeyaiKV-LDKRHI-IKEKKVKYVTIEKEVLSRLAHPGIVKLYYTFQDESKLYFVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQ-------NI 6614
Cdd:cd05581    81 EYAPNGDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMH--IKITDFGTAKvlgpdssPE 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQY-----------GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWS 6683
Cdd:cd05581   159 STKGDADSQIaynqaraasfvGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEYEFP 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 215274225 6684 spmaAHLSEDAKDFIKATLQRAPQARPSAA------QCLSHPWF 6721
Cdd:cd05581   239 ----ENFPPDAKDLIQKLLVLDPSKRLGVNenggydELKAHPFF 278
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
 6468-6743 5.73e-42

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 158.65  E-value: 5.73e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd14175     3 YVVKETIGVGSYSVCKRCVHKATNMEYAVKVI---DKSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKHVYLVTELMRG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPA--REDIKICDFGFAQNITPAE-LQFSQ 6623
Cdd:cd14175    80 GELLDKILRQKFFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVDESgnPESLRICDFGFAKQLRAENgLLMTP 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFA---GESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14175   160 CYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFAngpSDTPEEILTRIGSGKFTLSGGNWNTVSDAAKDLVSK 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 6701 TLQRAPQARPSAAQCLSHPWFLK--SMPAEEAHFINTKQLKFLLA 6743
Cdd:cd14175   240 MLHVDPHQRLTAKQVLQHPWITQkdKLPQSQLNHQDVQLVKGAMA 284
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
 6468-6720 6.75e-42

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 157.10  E-value: 6.75e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQAY---RERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14095     2 YDIGRVIGDGNFAVVKECRDKATDKEYALKIID-KAKCKGKEHmieNEVAILRRVKHPNIVQLIEEYDTDTELYLVMELV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNiLMVHPaRED----IKICDFGFAQNITpaELQ 6620
Cdd:cd14095    81 KGGDLFDAITSSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPEN-LLVVE-HEDgsksLKLADFGLATEVK--EPL 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLL--NVLEGRVSWSSPMAAHLSEDAKDFI 6698
Cdd:cd14095   157 FTVCGTPTYVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDRDQEELfdLILAGEFEFLSPYWDNISDSAKDLI 236

                         250       260
                  ....*....|....*....|..
gi 215274225 6699 KATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14095   237 SRMLVVDPEKRYSAGQVLDHPW 258
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
 6468-6720 1.42e-41

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 156.48  E-value: 1.42e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRV--QHKGN----KILCAAKFIpLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14098     2 YQIIDRLGSGTFAEVKKAveVETGKmraiKQIVKRKVA-GNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQF 6621
Cdd:cd14098    81 EYVEGGDLMDFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDPVIVKISDFGLAKVIHTGTFLV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEAS------DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAK 6695
Cdd:cd14098   161 TFCGTMAYLAPEILMSKEQNLQGgysnlvDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGRYTQPPLVDFNISEEAI 240

                         250       260
                  ....*....|....*....|....*
gi 215274225 6696 DFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14098   241 DFILRLLDVDPEKRMTAAQALDHPW 265
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 6468-6721 1.61e-41

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 155.47  E-value: 1.61e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDIL----AALSHPLVTGLLDQFETR--KTLILIL 6541
Cdd:cd05118     1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLkhlnDVEGHPNIVKLLDVFEHRggNHLCLVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSsEELLD--RLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPaREDIKICDFGFAQNITPAEL 6619
Cdd:cd05118    81 ELMG-MNLYEliKDYPRGL-PLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLE-LGQLKLADFGLARSFTSPPY 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 qfSQYGSP-EFVSPEII-QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE--GrvswsspmaahlSEDAK 6695
Cdd:cd05118   158 --TPYVATrWYRAPEVLlGAKPYGSSIDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVRllG------------TPEAL 223

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6696 DFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd05118   224 DLLSKMLKYDPAKRITASQALAHPYF 249
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
 6474-6721 7.92e-41

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 154.25  E-value: 7.92e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIpLRSRTRAQAY----------------RERDILAALSHPLVTGL---LDQFETR 6534
Cdd:cd14008     1 LGRGSFGKVKLALDTETGQLYAIKIF-NKSRLRKRREgkndrgkiknalddvrREIAIMKKLDHPNIVRLyevIDDPESD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KtLILILELCSSEELLDRLY--RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQ 6612
Cdd:cd14008    80 K-LYLVLEYCEGGPVMELDSgdRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLT--ADGTVKISDFGVSE 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 NIT--PAELQFSQyGSPEFVSPEIIQQNPVS---EASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswSSPMA 6687
Cdd:cd14008   157 MFEdgNDTLQKTA-GTPAFLAPELCDGDSKTysgKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQND--EFPIP 233

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 6688 AHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14008   234 PELSPELKDLLRRMLEKDPEKRITLKEIKEHPWV 267
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 7677-7924 1.20e-40

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 153.51  E-value: 1.20e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd14107     9 EIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSSEELLDR 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSEN--MIITEYNLLKVVDLGNAQslsqeKVLPSD-KFKDY--L 7831
Cdd:cd14107    89 LFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNilMVSPTREDIKICDFGFAQ-----EITPSEhQFSKYgsP 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSR-CYAGLSGGAVAFLRSTLCAQPW 7910
Cdd:cd14107   164 EFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSWDTpEITHLSEDAKDFIKRVLQPDPE 243

                         250
                  ....*....|....
gi 215274225 7911 GRPCASSCLQCPWL 7924
Cdd:cd14107   244 KRPSASECLSHEWF 257
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
 6474-6721 2.21e-40

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 152.76  E-value: 2.21e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRS--RTRAQA--YRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05572     1 LGVGGFGRVELVQLKSKGRTFALKCVKKRHivQTRQQEhiFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQYGSPEF 6629
Cdd:cd05572    81 WTILRDRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGY--VKLVDFGFAKKLGSGRKTWTFCGTPEY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6630 VSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDR--ATLLNVLEGRVSWSSPmaAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05572   159 VAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGDDEDpmKIYNIILKGIDKIEFP--KYIDKNAKNLIKQLLRRNPE 236

                         250
                  ....*....|....*....
gi 215274225 6708 AR-----PSAAQCLSHPWF 6721
Cdd:cd05572   237 ERlgylkGGIRDIKKHKWF 255
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
 6468-6722 2.87e-40

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 153.63  E-value: 2.87e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd14178     5 YEIKEDIGIGSYSVCKRCVHKATSTEYAVKII---DKSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKFVYLVMELMRG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPA--REDIKICDFGFAQNITPAE-LQFSQ 6623
Cdd:cd14178    82 GELLDRILRQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYMDESgnPESIRICDFGFAKQLRAENgLLMTP 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD---RATLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14178   162 CYTANFVAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFANGPDdtpEEILARIGSGKYALSGGNWDSISDAAKDIVSK 241

                         250       260
                  ....*....|....*....|..
gi 215274225 6701 TLQRAPQARPSAAQCLSHPWFL 6722
Cdd:cd14178   242 MLHVDPHQRLTAPQVLRHPWIV 263
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
 7680-7860 4.57e-40

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 150.11  E-value: 4.57e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIP--YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd00180     3 KGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASY-SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLET-MA 7835
Cdd:cd00180    83 KENKGPlSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPYyAP 162

                         170       180
                  ....*....|....*....|....*
gi 215274225 7836 PELLEGQGAVPQTDIWAIGVTAFIM 7860
Cdd:cd00180   163 PELLGGRYYGPKVDIWSLGVILYEL 187
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
 6469-6720 1.16e-39

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 150.82  E-value: 1.16e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06623     4 ERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHVdgDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHS-HGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFSQY- 6624
Cdd:cd06623    84 GSLADLLKKVGKIPEPVLAYIARQILKGLDYLHTkRHIIHRDIKPSNLLINS--KGEVKIADFGISKVLENTLDQCNTFv 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF--AGESDRATLLNVLEGRVSWSSPmAAHLSEDAKDFIKATL 6702
Cdd:cd06623   162 GTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFlpPGQPSFFELMQAICDGPPPSLP-AEEFSPEFRDFISACL 240

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd06623   241 QKDPKKRPSAAELLQHPF 258
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
 6462-6721 1.33e-39

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 151.28  E-value: 1.33e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6462 RKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR---------TRAQAYRERDILAALS-HPLVTGLLDQF 6531
Cdd:cd14181     6 KEFYQKYDPKEVIGRGVSSVVRRCVHRHTGQEFAVKIIEVTAErlspeqleeVRSSTLKEIHILRQVSgHPSIITLIDSY 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6532 ETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA 6611
Cdd:cd14181    86 ESSTFIFLVFDLMRRGELFDYLTEKVTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILL--DDQLHIKLSDFGFS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAELQFSQYGSPEFVSPEII-----QQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSP 6685
Cdd:cd14181   164 CHLEPGEKLRELCGTPGYLAPEILkcsmdETHPgYGKEVDLWACGVILFTLLAGSPPFWHRRQMLMLRMIMEGRYQFSSP 243

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 215274225 6686 MAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14181   244 EWDDRSSTVKDLISRLLVVDPEIRLTAEQALQHPFF 279
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 7675-7924 1.93e-39

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 150.19  E-value: 1.93e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7675 QTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA---VLREYEALK-GLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14106    13 STPLGRGKFAVVRKCIHKETGKEYAAKFLRKRRRGQDCrneILHEIAVLElCKDCPRVVNLHEVYETRSELILILELAAG 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT-EYNL--LKVVDLGNAQSLSqekvlPSDKF 7827
Cdd:cd14106    93 GELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTsEFPLgdIKLCDFGISRVIG-----EGEEI 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVsseGARDLQrglrKGLVRLSRC--------YAGLSGG 7896
Cdd:cd14106   168 REILGTpdyVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPF---GGDDKQ----ETFLNISQCnldfpeelFKDVSPL 240

                         250       260
                  ....*....|....*....|....*...
gi 215274225 7897 AVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14106   241 AIDFIKRLLVKDPEKRLTAKECLEHPWL 268
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
 6468-6721 3.02e-39

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 150.42  E-value: 3.02e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05580     3 FEFLKTLGTGSFGRVRLVKHKDSGKYYALKILKkakiIKLKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpareD----IKICDFGFAQNItpAEL 6619
Cdd:cd05580    83 VPGGELFSLLRRSGRFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLL------DsdghIKITDFGFAKRV--KDR 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIK 6699
Cdd:cd05580   155 TYTLCGTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFPS----FFDPDAKDLIK 230

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6700 ATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05580   231 RLLVVDLTKRlgnlkNGVEDIKNHPWF 257
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
 6468-6719 3.69e-39

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 149.10  E-value: 3.69e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRS---RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd08529     2 FEILNKLGKGSFGVVYKVVRKVDGRVYALKQIDISRmsrKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRL--YRKGVVTEAEV-KVYIQQLVeGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITP-AELQ 6620
Cdd:cd08529    82 ENGDLHSLIksQRGRPLPEDQIwKFFIQTLL-GLSHLHSKKILHRDIKSMNIFL--DKGDNVKIGDLGVAKILSDtTNFA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKA 6700
Cdd:cd08529   159 QTIVGTPYYLSPELCEDKPYNEKSDVWALGCVLYELCTGKHPFEAQNQGALILKIVRGKY---PPISASYSQDLSQLIDS 235

                         250
                  ....*....|....*....
gi 215274225 6701 TLQRAPQARPSAAQCLSHP 6719
Cdd:cd08529   236 CLTKDYRQRPDTTELLRNP 254
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 6464-6746 7.48e-39

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 149.59  E-value: 7.48e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14085     1 LEDFFEIESELGRGATSVVYRCRQKGTQKPYAVKK--LKKTVDKKIVRtEIGVLLRLSHPNIIKLKEIFETPTEISLVLE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQnITPAELQF 6621
Cdd:cd14085    79 LVTGGELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATPAPDApLKIADFGLSK-IVDQQVTM 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQY-GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGE-SDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIK 6699
Cdd:cd14085   158 KTVcGTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDErGDQYMFKRILNCDYDFVSPWWDDVSLNAKDLVK 237

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPWfLKSMPAEEAHFINT-KQLKFLLARSR 6746
Cdd:cd14085   238 KLIVLDPKKRLTTQQALQHPW-VTGKAANFAHMDTAqKKLQEFNARRK 284
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
 6474-6721 1.14e-38

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 148.13  E-value: 1.14e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA----QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05579     1 ISRGAYGRVYLAKKKSTGDLYAIKVIKKRDMIRKnqvdSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFG----------------FAQN 6613
Cdd:cd05579    81 YSLLENVGALDEDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILIDANGH--LKLTDFGlskvglvrrqiklsiqKKSN 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAAHLSED 6693
Cdd:cd05579   159 GAPEKEDRRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEW--PEDPEVSDE 236

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6694 AKDFIKATLQRAPQARP---SAAQCLSHPWF 6721
Cdd:cd05579   237 AKDLISKLLTPDPEKRLgakGIEEIKNHPFF 267
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
 6467-6720 1.17e-38

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 147.79  E-value: 1.17e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQ---AYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14185     1 HYEIGRTIGDGNFAVVKECRHWNENQEYAMKIID-KSKLKGKedmIESEILIIKSLSHPNIVKLFEVYETEKEIYLILEY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPA--REDIKICDFGFAQNIT-PAelq 6620
Cdd:cd14185    80 VRGGDLFDAIIESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHNPdkSTTLKLADFGLAKYVTgPI--- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF-AGESDRATLLNVLE-GRVSWSSPMAAHLSEDAKDFI 6698
Cdd:cd14185   157 FTVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFrSPERDQEELFQIIQlGHYEFLPPYWDNISEAAKDLI 236

                         250       260
                  ....*....|....*....|..
gi 215274225 6699 KATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14185   237 SRLLVVDPEKRYTAKQVLQHPW 258
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
 6468-6721 6.37e-38

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 146.47  E-value: 6.37e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07829     1 YEKLEKLGEGTYGVVYKAKDKKTGEIVALKKIRLDNEEEgipSTALREISLLKELKHPNIVKLLDVIHTENKLYLVFEYC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SS--EELLDRlyRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFs 6622
Cdd:cd07829    81 DQdlKKYLDK--RPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINR--DGVLKLADFGLARAFGIPLRTY- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 qygSPEFVS-----PEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLL----------------------- 6673
Cdd:cd07829   156 ---THEVVTlwyraPEILLGSKHySTAVDIWSVGCIFAELITGKPLFPGDSEIDQLFkifqilgtpteeswpgvtklpdy 232

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6674 ---------NVLEGRVSWsspmaahLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07829   233 kptfpkwpkNDLEKVLPR-------LDPEGIDLLSKMLQYNPAKRISAKEALKHPYF 282
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
 6468-6721 6.78e-38

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 145.52  E-value: 6.78e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRA-QAY------RERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd14162     2 YIVGKTLGHGSYAVVKKAYSTKHKCKVAIKIV---SKKKApEDYlqkflpREIEVIKGLKHPNLICFYEAIETTSRVYII 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNIT---PA 6617
Cdd:cd14162    79 MELAENGDLLDYIRKNGALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLL--DKNNNLKITDFGFARGVMktkDG 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQY--GSPEFVSPEIIQQNPVS-EASDIWAMGVISYLSLTCSSPFaGESDRATLLNVLEGRVSWSSpmAAHLSEDA 6694
Cdd:cd14162   157 KPKLSETycGSYAYASPEILRGIPYDpFLSDIWSMGVVLYTMVYGRLPF-DDSNLKVLLKQVQRRVVFPK--NPTVSEEC 233

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6695 KDFIKATLQRAPqARPSAAQCLSHPWF 6721
Cdd:cd14162   234 KDLILRMLSPVK-KRITIEEIKRDPWF 259
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 6468-6720 1.16e-37

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 144.85  E-value: 1.16e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14663     2 YELGRTLGEGTFAKVKFARNTKTGESVAIKIIDkeqvAREGMVEQIKREIAIMKLLRHPNIVELHEVMATKTKIFFVMEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGF---AQNITPAELQ 6620
Cdd:cd14663    82 VTGGELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLL--DEDGNLKISDFGLsalSEQFRQDGLL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEA-SDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswssPMAAHLSEDAKDFIK 6699
Cdd:cd14663   160 HTTCGTPNYVAPEVLARRGYDGAkADIWSCGVILFVLLAGYLPFDDENLMALYRKIMKGEF----EYPRWFSPGAKSLIK 235

                         250       260
                  ....*....|....*....|.
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14663   236 RILDPNPSTRITVEQIMASPW 256
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
 6468-6720 1.55e-37

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 144.62  E-value: 1.55e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA----QAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14186     3 FKVLNLLGKGSFACVYRARSLHTGLEVAIKMIDKKAMQKAgmvqRVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNIT-PAELQF 6621
Cdd:cd14186    83 CHNGEMSRYLkNRKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLT--RNMNIKIADFGLATQLKmPHEKHF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKAT 6701
Cdd:cd14186   161 TMCGTPNYISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPFDTDTVKNTLNKVVLADYE----MPAFLSREAQDLIHQL 236

                         250
                  ....*....|....*....
gi 215274225 6702 LQRAPQARPSAAQCLSHPW 6720
Cdd:cd14186   237 LRKNPADRLSLSSVLDHPF 255
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
 6468-6721 1.93e-37

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 144.32  E-value: 1.93e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05578     2 FQILRVIGKGSFGKVCIVQKKDTKKMFAMKYMNkqkcIEKDSVRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd05578    82 LLGGDLRYHLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILL--DEQGHVHITDFNIATKLTDGTLATST 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESdRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd05578   160 SGTKPYMAPEVFMRAGYSFAVDWWSLGVTAYEMLRGKRPYEIHS-RTSIEEIRAKFETASVLYPAGWSEEAIDLINKLLE 238

                         250
                  ....*....|....*....
gi 215274225 6704 RAPQARPSAAQCLS-HPWF 6721
Cdd:cd05578   239 RDPQKRLGDLSDLKnHPYF 257
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 7678-7923 2.01e-37

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 143.95  E-value: 2.01e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14115     1 IGRGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDGRLLDYL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT---EYNLLKVVDLGNAQSLSQEK----VLPSDKFKdy 7830
Cdd:cd14115    81 MNHDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDlriPVPRVKLIDLEDAVQISGHRhvhhLLGNPEFA-- 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 letmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQrglrKGLVRLSRC-----YAGLSGGAVAFLRSTL 7905
Cdd:cd14115   159 ----APEVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDESKEETC----INVCRVDFSfpdeyFGDVSQAARDFINVIL 230

                         250
                  ....*....|....*...
gi 215274225 7906 CAQPWGRPCASSCLQCPW 7923
Cdd:cd14115   231 QEDPRRRPTAATCLQHPW 248
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
 6472-6720 2.32e-37

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 143.58  E-value: 2.32e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHK-GNKILCAAKFIPLRSRTRAQA---YRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14121     1 EKLGSGTYATVYKAYRKsGAREVVAVKCVSKSSLNKASTenlLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd14121    81 DLSRFIRSRRTLPESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSRYNPVLKLADFGFAQHLKPNDEAHSLRGSP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESdratlLNVLEGRVsWSS-----PMAAHLSEDAKDFIKATL 6702
Cdd:cd14121   161 LYMAPEMILKKKYDARVDLWSVGVILYECLFGRAPFASRS-----FEELEEKI-RSSkpieiPTRPELSADCRDLLLRLL 234

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd14121   235 QRDPDRRISFEEFFAHPF 252
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1538-1619 4.77e-37

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 136.22  E-value: 4.77e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1538 QPASREVQAEAGTSATLSCEVAQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKAGDQRLSFHL 1617
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1618 HV 1619
Cdd:cd20967    81 FV 82
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
 7677-7924 7.08e-37

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 142.72  E-value: 7.08e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPY-HPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14114     9 ELGTGAFGVVHRCTERATGNNFAAKFIMTpHESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLSGGELFE 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLA-ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT--EYNLLKVVDLGNAQSLSQEKVLPSDkfKDYLE 7832
Cdd:cd14114    89 RIAaEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTtkRSNEVKLIDFGLATHLDPKESVKVT--TGTAE 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSseGARDLQRglrkgLVRLSRC--------YAGLSGGAVAFLRST 7904
Cdd:cd14114   167 FAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFA--GENDDET-----LRNVKSCdwnfddsaFSGISEEAKDFIRKL 239

                         250       260
                  ....*....|....*....|
gi 215274225 7905 LCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14114   240 LLADPNKRMTIHQALEHPWL 259
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
 6468-6720 7.59e-37

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 143.62  E-value: 7.59e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd14177     6 YELKEDIGVGSYSVCKRCIHRATNMEFAVKII---DKSKRDPSEEIEILMRYgQHPNIITLKDVYDDGRYVYLVTELMKG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNIL-MVHPARED-IKICDFGFAQNITPAE-LQFSQ 6623
Cdd:cd14177    83 GELLDRILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILyMDDSANADsIRICDFGFAKQLRGENgLLLTP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFA-GESD--RATLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14177   163 CYTANFVAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFAnGPNDtpEEILLRIGSGKFSLSGGNWDTVSDAAKDLLSH 242

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14177   243 MLHVDPHQRYTAEQVLKHSW 262
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
 7677-7923 1.11e-36

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 141.89  E-value: 1.11e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPyhpKDK------TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14003     7 TLGEGSFGKVKLARHKLTGEKVAIKIID---KSKlkeeieEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYASG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEkVLPSDKFKDY 7830
Cdd:cd14003    84 GELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFG----LSNE-FRGGSLLKTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 LET---MAPELLEGQG-AVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRcyaGLSGGAVAFLRSTLC 7906
Cdd:cd14003   159 CGTpayAAPEVLLGRKyDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPS---HLSPDARDLIRRMLV 235

                         250
                  ....*....|....*..
gi 215274225 7907 AQPWGRPCASSCLQCPW 7923
Cdd:cd14003   236 VDPSKRITIEEILNHPW 252
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 7677-7924 1.31e-36

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 142.04  E-value: 1.31e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd14113    14 ELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRLLDY 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQ----EKVLPSDKFKd 7829
Cdd:cd14113    94 VVRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQSLskpTIKLADFGDAVQLNTtyyiHQLLGSPEFA- 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7830 yletmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGL-RKGLVRLSRCYAGLSGGAVAFLRSTLCAQ 7908
Cdd:cd14113   173 -----APEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDESVEETCLNIcRLDFSFPDDYFKGVSQKAKDFVCFLLQMD 247

                         250
                  ....*....|....*.
gi 215274225 7909 PWGRPCASSCLQCPWL 7924
Cdd:cd14113   248 PAKRPSAALCLQEQWL 263
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 7669-7924 1.46e-36

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 141.58  E-value: 1.46e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd14108     1 TDYYDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTELC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SgPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE--YNLLKVVDLGNAQSLSQEKvlpsDK 7826
Cdd:cd14108    81 H-EELLERITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMADqkTDQVRICDFGNAQELTPNE----PQ 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDY--LETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVAFLRS 7903
Cdd:cd14108   156 YCKYgtPEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRTTLMNIRNYNVAFeESMFKDLCREAKGFIIK 235

                         250       260
                  ....*....|....*....|.
gi 215274225 7904 TLcAQPWGRPCASSCLQCPWL 7924
Cdd:cd14108   236 VL-VSDRLRPDAEETLEHPWF 255
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
 6468-6720 1.58e-36

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 141.92  E-value: 1.58e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRAQAY------RERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14097     3 YTFGRKLGQGSFGVVIEATHKETQTKWAIKKI---NREKAGSSavklleREVDILKHVNHAHIIHLEEVFETPKRMYLVM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM----VHPA-REDIKICDFGFA---QN 6613
Cdd:cd14097    80 ELCEDGELKELLLRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVkssiIDNNdKLNIKVTDFGLSvqkYG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQfSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSED 6693
Cdd:cd14097   160 LGEDMLQ-ETCGTPIYMAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEEKLFEEIRKGDLTFTQSVWQSVSDA 238

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14097   239 AKNVLQQLLKVDPAHRMTASELLDNPW 265
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
 6467-6721 3.21e-36

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 140.61  E-value: 3.21e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP---LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14071     1 FYDIERTIGKGNFAVVKLARHRITKTEVAIKIIDksqLDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14071    81 ASNGEIFDYLAQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLL--DANMNIKIADFGFSNFFKPGELLKTW 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQ-QNPVSEASDIWAMGVISYLsLTCSS-PFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKAT 6701
Cdd:cd14071   159 CGSPPYAAPEVFEgKEYEGPQLDIWSLGVVLYV-LVCGAlPFDGSTLQTLRDRVLSGRFR----IPFFMSTDCEHLIRRM 233

                         250       260
                  ....*....|....*....|
gi 215274225 6702 LQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14071   234 LVLDPSKRLTIEQIKKHKWM 253
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
 7677-7924 4.32e-36

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 140.70  E-value: 4.32e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPK-------DKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14105    12 ELGSGQFAVVKKCREKSTGLEYAAKFIKKRRSkasrrgvSREDIEREVSILRQVLHPNIITLHDVFENKTDVVLILELVA 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL----LKVVDLGNAQslsqeKVLPSD 7825
Cdd:cd14105    92 GGELFDFLAEKESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAH-----KIEDGN 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVAFL 7901
Cdd:cd14105   167 EFKNIFGTpefVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVNYDFdDEYFSNTSELAKDFI 246

                         250       260
                  ....*....|....*....|...
gi 215274225 7902 RSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14105   247 RQLLVKDPRKRMTIQESLRHPWI 269
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
 6461-6746 5.37e-36

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 141.32  E-value: 5.37e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6461 RRKL--HSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTL 6537
Cdd:cd06644     5 RRDLdpNEVWEIIGELGDGAFGKVYKAKNKETGALAAAKVIETKSEEELEDYMvEIEILATCNHPYIVKLLGAFYWDGKL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEEL------LDRlyrkgVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGF- 6610
Cdd:cd06644    85 WIMIEFCPGGAVdaimleLDR-----GLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDG--DIKLADFGVs 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 AQNITPAELQFSQYGSPEFVSPEII-----QQNPVSEASDIWAMGvISYLSLTCSSPFAGESDRATLLNvlegRVSWSSP 6685
Cdd:cd06644   158 AKNVKTLQRRDSFIGTPYWMAPEVVmcetmKDTPYDYKADIWSLG-ITLIEMAQIEPPHHELNPMRVLL----KIAKSEP 232

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6686 ----MAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPwFLKSMpaeeahfINTKQLKFLLARSR 6746
Cdd:cd06644   233 ptlsQPSKWSMEFRDFLKTALDKHPETRPSAAQLLEHP-FVSSV-------TSNRPLRELVAEAK 289
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
 6468-6721 5.38e-36

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 140.82  E-value: 5.38e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR----------SRTRAQAYRERDILAALS-HPLVTGLLDQFETRKT 6536
Cdd:cd14182     5 YEPKEILGRGVSSVVRRCIHKPTRQEYAVKIIDITgggsfspeevQELREATLKEIDILRKVSgHPNIIQLKDTYETNTF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITP 6616
Cdd:cd14182    85 FFLVFDLMKKGELFDYLTEKVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILL--DDDMNIKLTDFGFSCQLDP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQ--QNPVSE----ASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHL 6690
Cdd:cd14182   163 GEKLREVCGTPGYLAPEIIEcsMDDNHPgygkEVDMWSTGVIMYTLLAGSPPFWHRKQMLMLRMIMSGNYQFGSPEWDDR 242

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6691 SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14182   243 SDTVKDLISRFLVVQPQKRYTAEEALAHPFF 273
SH3_Obscurin_like cd12025
Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein ...
 5602-5664 5.68e-36

Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212958  Cd Length: 63  Bit Score: 132.70  E-value: 5.68e-36
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 5602 FDIYVVTADYLPLGAEQDAITLREGQYVEVLDAAHPLRWLVRTKPTKSSPSRQGWVSPAYLDR 5664
Cdd:cd12025     1 FDVYIVTADYTPDGADTEAIPLEEGQYVEVLDSAHPLKWLVRTKPTKSSPPRQGWVSPAYLEK 63
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
 6474-6721 6.52e-36

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 141.77  E-value: 6.52e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQ-----HKGN----KILCAAKFIPLRSRTrAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd05584     4 LGKGGYGKVFQVRkttgsDKGKifamKVLKKASIVRNQKDT-AHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILEYL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-QNITPAELQFSQ 6623
Cdd:cd05584    83 SGGELFMHLEREGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPENILLDAQGH--VKLTDFGLCkESIHDGTVTHTF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQ 6703
Cdd:cd05584   161 CGTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLN----LPPYLTNEARDLLKKLLK 236

                         250       260
                  ....*....|....*....|...
gi 215274225 6704 RAPQAR----PS-AAQCLSHPWF 6721
Cdd:cd05584   237 RNVSSRlgsgPGdAEEIKAHPFF 259
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
 6468-6720 7.54e-36

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 139.47  E-value: 7.54e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQH--KGNKIlcAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14074     5 YDLEETLGRGHFAVVKLARHvfTGEKV--AVKVIdktKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpAREDIKICDFGFAQNITPAELQF 6621
Cdd:cd14074    83 LGDGGDMYDYIMKHENgLNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFE-KQGLVKLTDFGFSNKFQPGEKLE 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKA 6700
Cdd:cd14074   162 TSCGSLAYSAPEILLGDEYdAPAVDIWSLGVILYMLVCGQPPFQEANDSETLTMIMDCKYT----VPAHVSPECKDLIRR 237

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14074   238 MLIRDPKKRASLEEIENHPW 257
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
 6466-6743 1.03e-35

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 139.88  E-value: 1.03e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd06611     5 DIWEIIGELGDGAFGKVYKAQHKETGLFAAAKIIQIESEEELEDFMvEIDILSECKHPNIVGLYEAYFYENKLWILIEFC 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SS---EELLDRLYRkgVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpARE-DIKICDFGF-AQNITPAEL 6619
Cdd:cd06611    85 DGgalDSIMLELER--GLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILL---TLDgDVKLADFGVsAKNKSTLQK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEII-----QQNPVSEASDIWAMGvISYLSLT-CSSPFAGESDRATLLNVLEGrvswSSPMAA---HL 6690
Cdd:cd06611   160 RDTFIGTPYWMAPEVVacetfKDNPYDYKADIWSLG-ITLIELAqMEPPHHELNPMRVLLKILKS----EPPTLDqpsKW 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6691 SEDAKDFIKATLQRAPQARPSAAQCLSHPWFlksmpaeeAHFINTKQLKFLLA 6743
Cdd:cd06611   235 SSSFNDFLKSCLVKDPDDRPTAAELLKHPFV--------SDQSDNKAIKDLLA 279
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 6472-6724 2.05e-35

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 140.13  E-value: 2.05e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRtRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14092    12 EALGDGSFSVCRKCVHKKTGQEFAVKIV---SR-RLDTSREVQLLRLCqGHPNIVKLHEVFQDELHTYLVMELLRGGELL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARE-DIKICDFGFAQnITPAELQFS------Q 6623
Cdd:cd14092    88 ERIRKKKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDDDaEIKIVDFGFAR-LKPENQPLKtpcftlP 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSpEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAG----ESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIK 6699
Cdd:cd14092   167 YAAPEVLK-QALSTQGYDESCDLWSLGVILYTMLSGQVPFQSpsrnESAAEIMKRIKSGDFSFDGEEWKNVSSEAKSLIQ 245

                         250       260
                  ....*....|....*....|....*
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPWFLKS 6724
Cdd:cd14092   246 GLLTVDPSKRLTMSELRNHPWLQGS 270
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 6463-6721 2.15e-35

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 140.72  E-value: 2.15e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFyEVKEEIGRGVFGFVKRVQHKGNK----ILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:PTZ00263   16 KLSDF-EMGETLGTGSFGRVRIAKHKGTGeyyaIKCLKKREILKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVY 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITpaE 6618
Cdd:PTZ00263   95 FLLEFVVGGELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLL--DNKGHVKVTDFGFAKKVP--D 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRV---SWsspmaahLSEDAK 6695
Cdd:PTZ00263  171 RTFTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLkfpNW-------FDGRAR 243

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6696 DFIKATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:PTZ00263  244 DLVKGLLQTDHTKRlgtlkGGVADVKNHPYF 274
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 7663-7924 2.32e-35

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 138.53  E-value: 2.32e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7663 AQPLPSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---KTAVLREYEALKGLR-HPHLAQLHAAYLSP 7738
Cdd:cd14197     2 SEPFQERYSLSPGRELGRGKFAVVRKCVEKDSGKEFAAKFMRKRRKGqdcRMEIIHEIAVLELAQaNPWVINLHEVYETA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7739 RHLVLILELCSGPELL-PCLAER-ASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLL---KVVDLGNA 7813
Cdd:cd14197    82 SEMILVLEYAAGGEIFnQCVADReEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPLgdiKIVDFGLS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7814 QSLSQekvlpSDKFKDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEgarDLQRGLRKgLVRLSRCY 7890
Cdd:cd14197   162 RILKN-----SEELREIMgtpEYVAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGD---DKQETFLN-ISQMNVSY 232

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 215274225 7891 AG-----LSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14197   233 SEeefehLSESAIDFIKTLLIKKPENRATAEDCLKHPWL 271
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
 6474-6719 3.05e-35

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 137.92  E-value: 3.05e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPL------RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd06632     8 LGSGSFGSVYEGFNGDTGDFFAVKEVSLvdddkkSRESVKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGG 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd06632    88 SIHKLLQRYGAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGV--VKLADFGMAKHVEAFSFAKSFKGSP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEII--QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVleGRVSWSSPMAAHLSEDAKDFIKATLQRA 6705
Cdd:cd06632   166 YWMAPEVImqKNSGYGLAVDIWSLGCTVLEMATGKPPWSQYEGVAAIFKI--GNSGELPPIPDHLSPDAKDFIRLCLQRD 243

                         250
                  ....*....|....
gi 215274225 6706 PQARPSAAQCLSHP 6719
Cdd:cd06632   244 PEDRPTASQLLEHP 257
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
 6468-6721 3.29e-35

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270725 [Multi-domain]  Cd Length: 350  Bit Score: 140.50  E-value: 3.29e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05573     3 FEVIKVIGRGAFGEVWLVRDKDTGQVYAMKILrksDMLKREQIAHVRaERDILADADSPWIVRLHYAFQDEDHLYLVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV---HparedIKICDFG----------- 6609
Cdd:cd05573    83 MPGGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDadgH-----IKLADFGlctkmnksgdr 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6610 -----------FAQNITPAE--------LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRA 6670
Cdd:cd05573   158 esylndsvntlFQDNVLARRrphkqrrvRAYSAVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSDSLVE 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6671 TLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd05573   238 TYSKIMNWKESLVFPDDPDVSPEAIDLIRRLLCDPEDRLGSAEEIKAHPFF 288
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
 6468-6727 3.30e-35

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 140.06  E-value: 3.30e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05599     3 FEPLKVIGRGAFGEVRLVRKKDTGHVYAMKKLRksemLEKEQVAHVRAERDILAEADNPWVVKLYYSFQDEENLYLIMEF 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd05599    83 LPGGDMMTLLMKKDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLL--DARGHIKLSDFGLCTGLKKSHLAYST 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd05599   161 VGTPDYIAPEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQETCRKIMNWRETLVFPPEVPISPEAKDLIERLLC 240

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 6704 RAPQ--ARPSAAQCLSHPWF-------LKSMPA 6727
Cdd:cd05599   241 DAEHrlGANGVEEIKSHPFFkgvdwdhIRERPA 273
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
 6474-6709 1.58e-34

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 137.53  E-value: 1.58e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFG---FVKRVQHKGNKILCAAKFIP---LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd05582     3 LGQGSFGkvfLVRKITGPDAGTLYAMKVLKkatLKVRDRVRTKMERDILADVNHPFIVKLHYAFQTEGKLYLILDFLRGG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGS 6626
Cdd:cd05582    83 DLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILL--DEDGHIKLTDFGLSkESIDHEKKAYSFCGT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQRAP 6706
Cdd:cd05582   161 VEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLG----MPQFLSPEAQSLLRALFKRNP 236


                  ...
gi 215274225 6707 QAR 6709
Cdd:cd05582   237 ANR 239
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
 6468-6720 1.68e-34

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 137.29  E-value: 1.68e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN------KILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14094     5 YELCEVIGKGPFSVVRRCIHRETgqqfavKIVDVAKFTSSPGLSTEDLKREASICHMLKHPHIVELLETYSSDGMLYMVF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 E------LCSseELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpARED----IKICDFGFA 6611
Cdd:cd14094    85 EfmdgadLCF--EIVKRADAGFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLL---ASKEnsapVKLGGFGVA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAELQFS-QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRaTLLNVLEGRVSWSSPMAAHL 6690
Cdd:cd14094   160 IQLGESGLVAGgRVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRQWSHI 238

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6691 SEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14094   239 SESAKDLVRRMLMLDPAERITVYEALNHPW 268
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
 6468-6721 2.08e-34

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 135.47  E-value: 2.08e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN------KILCAAKFIPLRSRTRAQayRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14079     4 YILGKTLGVGSFGKVKLAEHELTghkvavKILNRQKIKSLDMEEKIR--REIQILKLFRHPHIIRLYEVIETPTDIFMVM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQF 6621
Cdd:cd14079    82 EYVSGGELFDYIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDS--NMNVKIADFGLSNIMRDGEFLK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPV--SEAsDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGrvswSSPMAAHLSEDAKDFIK 6699
Cdd:cd14079   160 TSCGSPNYAAPEVISGKLYagPEV-DVWSCGVILYALLCGSLPFDDEHIPNLFKKIKSG----IYTIPSHLSPGARDLIK 234

                         250       260
                  ....*....|....*....|..
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14079   235 RMLVVDPLKRITIPEIRQHPWF 256
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 6468-6720 2.80e-34

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 136.41  E-value: 2.80e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFV-KRVQHKGNKILCAAKFIP--------LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:cd14096     3 YRLINKIGEGAFSNVyKAVPLRNTGKPVAIKVVRkadlssdnLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM---------VHPARED------- 6602
Cdd:cd14096    83 IVLELADGGEIFHQIVRLTYFSEDLSRHVITQVASAVKYLHEIGVVHRDIKPENLLFepipfipsiVKLRKADddetkvd 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 ---------------IKICDFGFAQNITPAELQfSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES 6667
Cdd:cd14096   163 egefipgvggggigiVKLADFGLSKQVWDSNTK-TPCGTVGYTAPEVVKDERYSKKVDMWALGCVLYTLLCGFPPFYDES 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6668 DRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14096   242 IETLTEKISRGDYTFLSPWWDEISKSAKDLISHLLTVDPAKRYDIDEFLAHPW 294
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
 6468-6720 2.87e-34

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 135.16  E-value: 2.87e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQAY---RERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14184     3 YKIGKVIGDGNFAVVKECVERSTGKEFALKIID-KAKCCGKEHlieNEVSILRRVKHPNIIMLIEEMDTPAELYLVMELV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV-HP-AREDIKICDFGFAqNITPAELqFS 6622
Cdd:cd14184    82 KGGDLFDAITSSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCeYPdGTKSLKLGDFGLA-TVVEGPL-YT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLL--NVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14184   160 VCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNLQEDLfdQILLGKLEFPSPYWDNITDSAKELISH 239

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14184   240 MLQVNVEARYTAEQILSHPW 259
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
 6467-6720 3.43e-34

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 135.54  E-value: 3.43e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd06643     6 FWEIVGELGDGAFGKVYKAQNKETGILAAAKVIDTKSEEELEDYMvEIDILASCDHPNIVKLLDAFYYENNLWILIEFCA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 S---EELLDRLYRKgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGF-AQNITPAELQF 6621
Cdd:cd06643    86 GgavDAVMLELERP--LTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDG--DIKLADFGVsAKNTRTLQRRD 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEII-----QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGR-VSWSSPmaAHLSEDAK 6695
Cdd:cd06643   162 SFIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGVTLIEMAQIEPPHHELNPMRVLLKIAKSEpPTLAQP--SRWSPEFK 239

                         250       260
                  ....*....|....*....|....*
gi 215274225 6696 DFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06643   240 DFLRKCLEKNVDARWTTSQLLQHPF 264
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
 6468-6721 4.81e-34

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 135.71  E-value: 4.81e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRaqaYRERDILAALSHPLVTGLLDQFETRKT------LILIL 6541
Cdd:cd14137     6 YTIEKVIGSGSFGVVYQAKLLETGEVVAIKKVLQDKRYK---NRELQIMRRLKHPNIVKLKYFFYSSGEkkdevyLNLVM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ElCSSEEL--LDRLYRK--GVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREDIKICDFGFAQNITPA 6617
Cdd:cd14137    83 E-YMPETLyrVIRHYSKnkQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLL-VDPETGVLKLCDFGSAKRLVPG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNPV-SEASDIWAMG-VISYLSLtcSSP-FAGESDRATL---LNVLeG------------- 6678
Cdd:cd14137   161 EPNVSYICSRYYRAPELIFGATDyTTAIDIWSAGcVLAELLL--GQPlFPGESSVDQLveiIKVL-Gtptreqikamnpn 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6679 ----------RVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14137   238 ytefkfpqikPHPWEKVFPKRTPPDAIDLLSKILVYNPSKRLTALEALAHPFF 290
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
 6468-6722 5.15e-34

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 135.23  E-value: 5.15e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP-----LRSRTRaQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd05609     2 FETIKLISNGAYGAVYLVRHRETRQRFAMKKINkqnliLRNQIQ-QVFVERDILTFAENPFVVSMYCSFETKRHLCMVME 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNIL---MVHparedIKICDFGFAQ------- 6612
Cdd:cd05609    81 YVEGGDCATLLKNIGPLPVDMARMYFAETVLALEYLHSYGIVHRDLKPDNLLitsMGH-----IKLTDFGLSKiglmslt 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 ------NITPAELQFSQ---YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWS 6683
Cdd:cd05609   156 tnlyegHIEKDTREFLDkqvCGTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFGQVISDEIEWP 235

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 215274225 6684 SPMAAhLSEDAKDFIKATLQRAPQAR---PSAAQCLSHPWFL 6722
Cdd:cd05609   236 EGDDA-LPDDAQDLITRLLQQNPLERlgtGGAEEVKQHPFFQ 276
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
 7681-7924 5.55e-34

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 134.76  E-value: 5.55e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHpKDKTA--------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd14194    16 GQFAVVKKCREKSTGLQYAAKFIKKR-RTKSSrrgvsredIEREVSILKEIQHPNVITLHEVYENKTDVILILELVAGGE 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL----LKVVDLGNAQslsqeKVLPSDKFK 7828
Cdd:cd14194    95 LFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAH-----KIDFGNEFK 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 DYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCY-AGLSGGAVAFLRST 7904
Cdd:cd14194   170 NIFgtpEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYfSNTSALAKDFIRRL 249

                         250       260
                  ....*....|....*....|
gi 215274225 7905 LCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14194   250 LVKDPKKRMTIQDSLQHPWI 269
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
 6467-6723 6.35e-34

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 133.88  E-value: 6.35e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06614     1 LYKNLEKIGEGASGEVYKATDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQF-SQY 6624
Cdd:cd06614    81 GSLTDIITQNPVrMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSK--DGSVKLADFGFAAQLTKEKSKRnSVV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVLEGrvswSSPM--AAHLSEDAKDFIKAT 6701
Cdd:cd06614   159 GTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPlRALFLITTKG----IPPLknPEKWSPEFKDFLNKC 234

                         250       260
                  ....*....|....*....|..
gi 215274225 6702 LQRAPQARPSAAQCLSHPwFLK 6723
Cdd:cd06614   235 LVKDPEKRPSAEELLQHP-FLK 255
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 7677-7924 8.43e-34

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 134.28  E-value: 8.43e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---KTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd14198    15 ELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGqdcRAEILHEIAVLELAKsNPRVVNLHEVYETTSEIILILEYAAGGE 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLP-CLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLL---KVVDLGNAQSLSQekvlpSDKF 7827
Cdd:cd14198    95 IFNlCVPDLAEmVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPLgdiKIVDFGMSRKIGH-----ACEL 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSR-CYAGLSGGAVAFLRS 7903
Cdd:cd14198   170 REIMgtpEYLAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLNISQVNVDYSEeTFSSVSQLATDFIQK 249

                         250       260
                  ....*....|....*....|.
gi 215274225 7904 TLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14198   250 LLVKNPEKRPTAEICLSHSWL 270
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
 6468-6720 9.69e-34

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 133.96  E-value: 9.69e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVkrvqHKGNK--------ILCAAKfiplrSRtRAQAYRERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd14010     2 YVLYDEIGRGKHSVV----YKGRRkgtiefvaIKCVDK-----SK-RPEVLNEVRLTHELKHPNVLKFYEWYETSNHLWL 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-------- 6611
Cdd:cd14010    72 VVEYCTGGDLETLLRQDGNLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGT--LKLSDFGLArregeilk 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 ---------QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESdRATLL-NVLEGRVS 6681
Cdd:cd14010   150 elfgqfsdeGNVNKVSKKQAKRGTPYYMAPELFQGGVHSFASDLWALGCVLYEMFTGKPPFVAES-FTELVeKILNEDPP 228

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 215274225 6682 WSSPMAAH-LSEDAKDFIKATLQRAPQARPSAAQCLSHP-W 6720
Cdd:cd14010   229 PPPPKVSSkPSPDFKSLLKGLLEKDPAKRLSWDELVKHPfW 269
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
 6468-6720 1.08e-33

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 133.41  E-value: 1.08e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14072     2 YRLLKTIGKGNFAKVKLARHVLTGREVAIKIIdktQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd14072    82 SGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLL--DADMNIKIADFGFSNEFTPGNKLDTFC 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEAS-DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRvsWSSPMaaHLSEDAKDFIKATLQ 6703
Cdd:cd14072   160 GSPPYAAPELFQGKKYDGPEvDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGK--YRIPF--YMSTDCENLLKKFLV 235

                         250
                  ....*....|....*..
gi 215274225 6704 RAPQARPSAAQCLSHPW 6720
Cdd:cd14072   236 LNPSKRGTLEQIMKDRW 252
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
 6468-6721 1.18e-33

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 134.37  E-value: 1.18e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKG-NKILCAAKFIPLRSRT--RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07833     3 YEVLGVVGEGAYGVVLKCRNKAtGEIVAIKKFKESEDDEdvKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSE--ELLDRlYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREdIKICDFGFAQNIT-PAELQF 6621
Cdd:cd07833    83 ERTllELLEA-SPGGL-PPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENIL-VSESGV-LKLCDFGFARALTaRPASPL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPE-FVSPEIIQQNP-VSEASDIWAMGVIsYLSLTCSSP-FAGESD-------RATLLNVLEGRVS--WSSP---- 6685
Cdd:cd07833   159 TDYVATRwYRAPELLVGDTnYGKPVDVWAIGCI-MAELLDGEPlFPGDSDidqlyliQKCLGPLPPSHQElfSSNPrfag 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6686 ---------------MAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07833   238 vafpepsqpeslerrYPGKVSSPALDFLKACLRMDPKERLTCDELLQHPYF 288
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
 6464-6720 1.26e-33

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 133.28  E-value: 1.26e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHK--GNKIlcAAKFIPLRS--RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd14078     1 LLKYYELHETIGSGGFAKVKLATHIltGEKV--AIKIMDKKAlgDDLPRVKTEIEALKNLSHQHICRLYHVIETDNKIFM 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA---QNITP 6616
Cdd:cd14078    79 VLEYCPGGELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLL--DEDQNLKLIDFGLCakpKGGMD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSqYGSPEFVSPEIIQQNPV--SEAsDIWAMGVISYLSLTCSSPFagESDRATLL--NVLEGRV---SWsspmaah 6689
Cdd:cd14078   157 HHLETC-CGSPAYAAPELIQGKPYigSEA-DVWSMGVLLYALLCGFLPF--DDDNVMALyrKIQSGKYeepEW------- 225

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6690 LSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14078   226 LSPSSKLLLDQMLQVDPKKRITVKELLNHPW 256
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
 6472-6720 1.78e-33

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 132.92  E-value: 1.78e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFI-PLR--SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE------ 6542
Cdd:cd14082     9 EVLGSGQFGIVYGGKHRKTGRDVAIKVIdKLRfpTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEklhgdm 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 ---LCSSEelldrlyrKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV-HPAREDIKICDFGFAQNITPAE 6618
Cdd:cd14082    89 lemILSSE--------KGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLAsAEPFPQVKLCDFGFARIIGEKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGE---SDRATLLNVLEGRVSWSspmaaHLSEDAK 6695
Cdd:cd14082   161 FRRSVVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDediNDQIQNAAFMYPPNPWK-----EISPDAI 235

                         250       260
                  ....*....|....*....|....*
gi 215274225 6696 DFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14082   236 DLINNLLQVKMRKRYSVDKSLSHPW 260
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
 7672-7926 2.01e-33

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 133.45  E-value: 2.01e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14104     2 YMIAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFISGV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAE-RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEY--NLLKVVDLGNAQSLSqekvlPSDKFK 7828
Cdd:cd14104    82 DIFERITTaRFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRrgSYIKIIEFGQSRQLK-----PGDKFR 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 -DYL--ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVAFLRST 7904
Cdd:cd14104   157 lQYTsaEFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEYAFdDEAFKNISIEALDFVDRL 236

                         250       260
                  ....*....|....*....|..
gi 215274225 7905 LCAQPWGRPCASSCLQCPWLTE 7926
Cdd:cd14104   237 LVKERKSRMTAQEALNHPWLKQ 258
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
 6468-6720 2.17e-33

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 132.66  E-value: 2.17e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFG-FVKRVQHK--GNKIlCAAKFIPLrSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14112     5 FSFGSEIFRGRFSvIVKAVDSTteTDAH-CAVKIFEV-SDEASEAVREFESLRTLQHENVQRLIAAFKPSNFAYLVMEKL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SsEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQy 6624
Cdd:cd14112    83 Q-EDVFTRFSSNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRSWQVKLVDFGRAQKVSKLGKVPVD- 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQ-QNPVSEASDIWAMGVISYLSLTCSSPFAGESDR--ATLLNVLEGRVSWSSpMAAHLSEDAKDFIKAT 6701
Cdd:cd14112   161 GDTDWASPEFHNpETPITVQSDIWGLGVLTFCLLSGFHPFTSEYDDeeETKENVIFVKCRPNL-IFVEATQEALRFATWA 239

                         250
                  ....*....|....*....
gi 215274225 6702 LQRAPQARPSAAQCLSHPW 6720
Cdd:cd14112   240 LKKSPTRRMRTDEALEHRW 258
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
 6468-6721 2.18e-33

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 133.68  E-value: 2.18e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14209     3 FDRIKTLGTGSFGRVMLVRHKETGNYYAMKILDkqkvVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFSq 6623
Cdd:cd14209    83 VPGGEMFSHLRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQ--QGYIKVTDFGFAKRVKGRTWTLC- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 yGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQ 6703
Cdd:cd14209   160 -GTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVR----FPSHFSSDLKDLLRNLLQ 234

                         250       260
                  ....*....|....*....|...
gi 215274225 6704 -----RAPQARPSAAQCLSHPWF 6721
Cdd:cd14209   235 vdltkRFGNLKNGVNDIKNHKWF 257
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
 6474-6721 2.88e-33

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 132.00  E-value: 2.88e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRV------QHKGNKILCAAKF--IPlrsRTRAQAYRERDILAALSHPLVTGLLDQF--ETRKTLILILEL 6543
Cdd:cd14119     1 LGEGSYGKVKEVldtetlCRRAVKILKKRKLrrIP---NGEANVKREIQILRRLNHRNVIKLVDVLynEEKQKLYMVMEY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 C--SSEELLDRLYRKGVVTeAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNI---TPAE 6618
Cdd:cd14119    78 CvgGLQEMLDSAPDKRLPI-WQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLT--TDGTLKISDFGVAEALdlfAEDD 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQYGSPEFVSPEIIQQNPVSE--ASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKD 6696
Cdd:cd14119   155 TCTTSQGSPAFQPPEIANGQDSFSgfKVDIWSAGVTLYNMTTGKYPFEGDNIYKLFENIGKGEYT----IPDDVDPDLQD 230

                         250       260
                  ....*....|....*....|....*
gi 215274225 6697 FIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14119   231 LLRGMLEKDPEKRFTIEQIRQHPWF 255
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
 6474-6721 3.46e-33

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 132.05  E-value: 3.46e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHK--GNKILCAAKFipLRSR---TRAQAYRER-----DILAALSHPLVTGLLDQFETRK-TLILILE 6542
Cdd:cd13994     1 IGKGATSVVRIVTKKnpRSGVLYAVKE--YRRRddeSKRKDYVKRltseyIISSKLHHPNIVKVLDLCQDLHgKWCLVME 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNI-TPAE--- 6618
Cdd:cd13994    79 YCPGGDLFTLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDE--DGVLKLTDFGTAEVFgMPAEkes 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 -LQFSQYGSPEFVSPEIIQQNPVS-EASDIWAMGVIsYLSLTCSS-PF--AGESDRATLLNVLEGRVSWSSPMAAHLS-- 6691
Cdd:cd13994   157 pMSAGLCGSEPYMAPEVFTSGSYDgRAVDVWSCGIV-LFALFTGRfPWrsAKKSDSAYKAYEKSGDFTNGPYEPIENLlp 235

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd13994   236 SECRRLIYRMLHPDPEKRITIDEALNDPWV 265
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 6474-6720 3.86e-33

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 132.04  E-value: 3.86e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAK---FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd06626     8 IGEGTFGKVYTAVNLDTGELMAMKeirFQDNDPKTIKEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTLE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNIT-------PAELQfSQ 6623
Cdd:cd06626    88 ELLRHGRILDEAVIRVYTLQLLEGLAYLHENGIVHRDIKPANIFLDS--NGLIKLGDFGSAVKLKnntttmaPGEVN-SL 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSE---ASDIWAMGVISYLSLTCSSPFAG-ESDRATLLNVLEGRVSwSSPMAAHLSEDAKDFIK 6699
Cdd:cd06626   165 VGTPAYMAPEVITGNKGEGhgrAADIWSLGCVVLEMATGKRPWSElDNEWAIMYHVGMGHKP-PIPDSLQLSPEGKDFLS 243

                         250       260
                  ....*....|....*....|.
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06626   244 RCLESDPKKRPTASELLDHPF 264
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 6468-6719 3.90e-33

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 131.78  E-value: 3.90e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT---RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd08220     2 YEKIRVVGRGAYGTVYLCRRKDDNKLVIIKQIPVEQMTkeeRQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvHPAREDIKICDFGFAQNITPAELQFS 6622
Cdd:cd08220    82 PGGTLFEYIQQRKgsLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILL-NKKRTVVKIGDFGISKILSSKSKAYT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKATL 6702
Cdd:cd08220   161 VVGTPCYISPELCEGKPYNQKSDIWALGCVLYELASLKRAFEAANLPALVLKIMRGTF---APISDRYSEELRHLILSML 237

                         250
                  ....*....|....*..
gi 215274225 6703 QRAPQARPSAAQCLSHP 6719
Cdd:cd08220   238 HLDPNKRPTLSEIMAQP 254
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 6468-6719 4.19e-33

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 131.89  E-value: 4.19e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKG-NKILCAAK--FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQF--ETRKTLILILE 6542
Cdd:cd08217     2 YEVLETIGKGSFGTVRKVRRKSdGKILVWKEidYGKMSEKEKQQLVSEVNILRELKHPNIVRYYDRIvdRANTTLYIVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEEL---LDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHG-----VLHLDIKPSNILMvhPAREDIKICDFGFAQN 6613
Cdd:cd08217    82 YCEGGDLaqlIKKCKKeNQYIPEEFIWKIFTQLLLALYECHNRSvgggkILHRDLKPANIFL--DSDNNVKLGDFGLARV 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQFSQY-GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSE 6692
Cdd:cd08217   160 LSHDSSFAKTYvGTPYYMSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAANQLELAKKIKEGKF---PRIPSRYSS 236

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd08217   237 ELNEVIKSMLNVDPDKRPSVEELLQLP 263
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
 6468-6720 4.92e-33

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 131.62  E-value: 4.92e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA----QAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14116     7 FEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEKAgvehQLRREVEIQSHLRHPNILRLYGYFHDATRVYLILEY 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNiTPAELQFSQ 6623
Cdd:cd14116    87 APLGTVYRELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLL--GSAGELKIADFGWSVH-APSSRRTTL 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVleGRVSWSSPmaAHLSEDAKDFIKATLQ 6703
Cdd:cd14116   164 CGTLDYLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRI--SRVEFTFP--DFVTEGARDLISRLLK 239

                         250
                  ....*....|....*..
gi 215274225 6704 RAPQARPSAAQCLSHPW 6720
Cdd:cd14116   240 HNPSQRPMLREVLEHPW 256
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
 6468-6721 8.96e-33

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 130.58  E-value: 8.96e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIpLRSRTRAQAY-RERD---------ILAAL---SHPLVTGLLDQFETR 6534
Cdd:cd14004     2 YTILKEMGEGAYGQVNLAIYKSKGKEVVIKFI-FKERILVDTWvRDRKlgtvpleihILDTLnkrSHPNIVKLLDFFEDD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILEL-CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQN 6613
Cdd:cd14004    81 EFYYLVMEKhGSGMDLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGT--IKLIDFGSAAY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAelQFSQ-YGSPEFVSPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFagesdratlLNVLEGRVSWSSPMAAhLS 6691
Cdd:cd14004   159 IKSG--PFDTfVGTIDYAAPEVLRGNPyGGKEQDIWALGVLLYTLVFKENPF---------YNIEEILEADLRIPYA-VS 226

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14004   227 EDLIDLISRMLNRDVGDRPTIEELLTDPWL 256
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
 6468-6721 9.59e-33

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 132.82  E-value: 9.59e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05601     3 FEVKNVIGRGHFGEVQVVKEKATGDIYAMKVLKksetLAQEEVSFFEEERDIMAKANSPWITKLQYAFQDSENLYLVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpareD----IKICDFGFAQNITPAE 6618
Cdd:cd05601    83 HPGGDLLSLLSRyDDIFEESMARFYLAELVLAIHSLHSMGYVHRDIKPENILI------DrtghIKLADFGSAAKLSSDK 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQY--GSPEFVSPEIIQQ-NPVSEAS-----DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHL 6690
Cdd:cd05601   157 TVTSKMpvGTPDYIAPEVLTSmNGGSKGTygvecDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMNFKKFLKFPEDPKV 236

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6691 SEDAKDFIKATLQRApQARPSAAQCLSHPWF 6721
Cdd:cd05601   237 SESAVDLIKGLLTDA-KERLGYEGLCCHPFF 266
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 6468-6717 1.09e-32

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 130.48  E-value: 1.09e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd08219     2 YNVLRVVGEGSFGRALLVQHVNSDQKYAMKEIrlPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDR--LYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNIT-PAELQFS 6622
Cdd:cd08219    82 GGDLMQKikLQRGKLFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGK--VKLGDFGSARLLTsPGAYACT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKATL 6702
Cdd:cd08219   160 YVGTPYYVPPEIWENMPYNNKSDIWSLGCILYELCTLKHPFQANSWKNLILKVCQGSY---KPLPSHYSYELRSLIKQMF 236

                         250
                  ....*....|....*
gi 215274225 6703 QRAPQARPSAAQCLS 6717
Cdd:cd08219   237 KRNPRSRPSATTILS 251
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
 6466-6720 2.06e-32

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 129.77  E-value: 2.06e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14075     2 GFYRIRGELGSGNFSQVKLGIHQLTKEKVAIKILdktKLDQKTQRLLSREISSMEKLHHPNIIRLYEVVETLSKLHLVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFS 6622
Cdd:cd14075    82 YASGGELYTKISTEGKLSESEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYASNNC--VKVGDFGFSTHAKRGETLNT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQ-QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKAT 6701
Cdd:cd14075   160 FCGSPPYAAPELFKdEHYIGIYVDIWALGVLLYFMVTGVMPFRAETVAKLKKCILEGTYTIPS----YVSEPCQELIRGI 235

                         250
                  ....*....|....*....
gi 215274225 6702 LQRAPQARPSAAQCLSHPW 6720
Cdd:cd14075   236 LQPVPSDRYSIDEIKNSEW 254
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
 6474-6721 2.16e-32

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 131.57  E-value: 2.16e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQ------AYRERDILA-ALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd05570     3 LGKGSFGKVMLAERKKTDELYAIKV--LKKEVIIEdddvecTMTEKRVLAlANRHPFLTGLHACFQTEDRLYFVMEYVNG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-QNITPAELQFSQYG 6625
Cdd:cd05570    81 GDLMFHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGH--IKIADFGMCkEGIWGGNTTSTFCG 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswssPMAAHLSEDAKDFIKATLQRA 6705
Cdd:cd05570   159 TPDYIAPEILREQDYGFSVDWWALGVLLYEMLAGQSPFEGDDEDELFEAILNDEV----LYPRWLSREAVSILKGLLTKD 234

                         250       260
                  ....*....|....*....|.
gi 215274225 6706 PQAR----PSAAQCL-SHPWF 6721
Cdd:cd05570   235 PARRlgcgPKGEADIkAHPFF 255
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
 6467-6720 2.75e-32

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270992 [Multi-domain]  Cd Length: 289  Bit Score: 130.23  E-value: 2.75e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAqaYRERDILAALS-HPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14090     3 YKLTGELLGEGAYASVQTCINLYTGKEYAVKIIekhPGHSRSRV--FREVETLHQCQgHPNILQLIEYFEDDERFYLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAR-EDIKICDFGFAQNI------- 6614
Cdd:cd14090    81 KMRGGPLLSHIEKRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCESMDKvSPVKICDFDLGSGIklsstsm 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPA---ELQfSQYGSPEFVSPEIIQQNpVSEAS------DIWAMGVISYLSLTCSSPFAGES------DRA----TLLNV 6675
Cdd:cd14090   161 TPVttpELL-TPVGSAEYMAPEVVDAF-VGEALsydkrcDLWSLGVILYIMLCGYPPFYGRCgedcgwDRGeacqDCQEL 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6676 L-----EGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14090   239 LfhsiqEGEYEFPEKEWSHISAEAKDLISHLLVRDASQRYTAEQVLQHPW 288
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
 7680-7925 2.92e-32

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 129.13  E-value: 2.92e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPyhpKDK-------TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd14007    10 KGKFGNVYLAREKKSGFIVALKVIS---KSQlqksgleHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILEYAPNGE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEkvLPSDKFK---- 7828
Cdd:cd14007    87 LYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFG----WSVH--APSNRRKtfcg 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 --DYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLC 7906
Cdd:cd14007   161 tlDY---LPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFP---SSVSPEAKDLISKLLQ 234

                         250
                  ....*....|....*....
gi 215274225 7907 AQPWGRPCASSCLQCPWLT 7925
Cdd:cd14007   235 KDPSKRLSLEQVLNHPWIK 253
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
 6465-6721 3.05e-32

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 128.92  E-value: 3.05e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRaQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd06612     2 EEVFDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDLQ-EIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLD--RLYRKgVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFS 6622
Cdd:cd06612    81 GAGSVSDimKITNK-TLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNE--EGQAKLADFGVSGQLTDTMAKRN 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QY-GSPEFVSPEIIQQNPVSEASDIWAMGVisylsltcsspfagesdraTLLNVLEGRVSWSS--PMAA----------- 6688
Cdd:cd06612   158 TViGTPFWMAPEVIQEIGYNNKADIWSLGI-------------------TAIEMAEGKPPYSDihPMRAifmipnkpppt 218

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 215274225 6689 -----HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd06612   219 lsdpeKWSPEFNDFVKKCLVKDPEERPSAIQLLQHPFI 256
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
 6471-6721 3.09e-32

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 129.36  E-value: 3.09e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6471 KEEIGRGVFGFVKRVQHKGNKIL-CAAKFIPLRSRTRAQAY--RERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14202     7 KDLIGHGAFAVVFKGRHKEKHDLeVAVKCINKKNLAKSQTLlgKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-------IKICDFGFAQNITPAELQ 6620
Cdd:cd14202    87 DLADYLHTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSYSGGRKsnpnnirIKIADFGFARYLQNNMMA 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRaTLLNVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14202   167 ATLCGSPMYMAPEVIMSQHYDAKADLWSIGTIIYQCLTGKAPFQASSPQ-DLRLFYEKNKSLSPNIPRETSSHLRQLLLG 245

                         250       260
                  ....*....|....*....|.
gi 215274225 6701 TLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14202   246 LLQRNQKDRMDFDEFFHHPFL 266
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
 6468-6720 3.65e-32

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 129.17  E-value: 3.65e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQH--KGNKIlcAAKFIPLRsRTRAQAY------RERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd14070     4 YLIGRKLGEGSFAKVREGLHavTGEKV--AIKVIDKK-KAKKDSYvtknlrREGRIQQMIRHPNITQLLDILETENSYYL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGF---AQNITP 6616
Cdd:cd14070    81 VMELCPGGNLMHRIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLL--DENDNIKLIDFGLsncAGILGY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGE--SDRATLLNVLEGRVswsSPMAAHLSEDA 6694
Cdd:cd14070   159 SDPFSTQCGSPAYAAPELLARKKYGPKVDVWSIGVNMYAMLTGTLPFTVEpfSLRALHQKMVDKEM---NPLPTDLSPGA 235

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6695 KDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14070   236 ISFLRSLLEPDPLKRPNIKQALANRW 261
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1630-1711 3.66e-32

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 122.35  E-value: 3.66e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1630 QPAHREVQAEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEAGGQQLSFRL 1709
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1710 QV 1711
Cdd:cd20967    81 FV 82
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 6468-6721 4.60e-32

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 128.54  E-value: 4.60e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRS---RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd08225     2 YEIIKKIGEGSFGKIYLAKAKSDSEHCVIKEIDLTKmpvKEKEASKKEVILLAKMKHPNIVTFFASFQENGRLFIVMEYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYR-KGVV-TEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREdIKICDFGFAQNITPA-ELQF 6621
Cdd:cd08225    82 DGGDLMKRINRqRGVLfSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMV-AKLGDFGIARQLNDSmELAY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKAT 6701
Cdd:cd08225   161 TCVGTPYYLSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNLHQLVLKICQGYF---APISPNFSRDLRSLISQL 237

                         250       260
                  ....*....|....*....|
gi 215274225 6702 LQRAPQARPSAAQCLSHPWF 6721
Cdd:cd08225   238 FKVSPRDRPSITSILKRPFL 257
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
 6468-6720 4.95e-32

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 128.27  E-value: 4.95e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP---LRSRT-RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14073     3 YELLETLGKGTYGKVKLAIERATGREVAIKSIKkdkIEDEQdMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14073    83 ASGGELYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILL--DQNGNAKIADFGLSNLYSKDKLLQTF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRvsWSSPmaAHLSeDAKDFIKATL 6702
Cdd:cd14073   161 CGSPLYASPEIVNGTPyQGPEVDCWSLGVLLYTLVYGTMPFDGSDFKRLVKQISSGD--YREP--TQPS-DASGLIRWML 235

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd14073   236 TVNPKRRATIEDIANHWW 253
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
 6468-6720 5.28e-32

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 128.96  E-value: 5.28e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQAY---RERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14183     8 YKVGRTIGDGNFAVVKECVERSTGREYALKIIN-KSKCRGKEHmiqNEVSILRRVKHPNIVLLIEEMDMPTELYLVMELV 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV--HPAREDIKICDFGFAqNITPAELqFS 6622
Cdd:cd14183    87 KGGDLFDAITSTNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYehQDGSKSLKLGDFGLA-TVVDGPL-YT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLL--NVLEGRVSWSSPMAAHLSEDAKDFIKA 6700
Cdd:cd14183   165 VCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRGSGDDQEVLfdQILMGQVDFPSPYWDNVSDSAKELITM 244

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14183   245 MLQVDVDQRYSALQVLEHPW 264
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
 6474-6721 5.76e-32

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 128.21  E-value: 5.76e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14188     9 LGKGGFAKCYEMTDLTTNKVYAAKIIPhsrvSKPHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNiLMVHPAREdIKICDFGFAQNITPAELQFSQY-GSPE 6628
Cdd:cd14188    89 AHILKARKVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGN-FFINENME-LKVGDFGLAARLEPLEHRRRTIcGTPN 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQRAPQA 6708
Cdd:cd14188   167 YLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYS----LPSSLLAPAKHLIASMLSKNPED 242

                         250
                  ....*....|...
gi 215274225 6709 RPSAAQCLSHPWF 6721
Cdd:cd14188   243 RPSLDEIIRHDFF 255
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 6474-6721 7.19e-32

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 128.28  E-value: 7.19e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFV----KRVQHKGNKiLCAAKF-----IPLRSRTRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05583     2 LGTGAYGKVflvrKVGGHDAGK-LYAMKVlkkatIVQKAKTAEHTMTERQVLEAVrQSPFLVTLHYAFQTDAKLHLILDY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpARE-DIKICDFGFAQNITPAELQ-- 6620
Cdd:cd05583    81 VNGGELFTHLYQREHFTESEVRIYIGEIVLALEHLHKLGIIYRDIKLENILL---DSEgHVVLTDFGLSKEFLPGENDra 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPV--SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFI 6698
Cdd:cd05583   158 YSFCGTIEYMAPEVVRGGSDghDKAVDWWSLGVLTYELLTGASPFTVDGERNSQSEISKRILKSHPPIPKTFSAEAKDFI 237

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6699 KATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05583   238 LKLLEKDPKKRlgagpRGAHEIKEHPFF 265
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
 6469-6724 8.66e-32

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 128.23  E-value: 8.66e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT--RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06605     4 EYLGELGEGNGGVVSKVRHRPSGQIMAVKVIRLEIDEalQKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELlDRLYRKGVVTEAEV--KVYIQqLVEGLHYLHS-HGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITpAELQFSQ 6623
Cdd:cd06605    84 GSL-DKILKEVGRIPERIlgKIAVA-VVKGLIYLHEkHKIIHRDVKPSNILVNS--RGQVKLCDFGVSGQLV-DSLAKTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGvISYLSLTCSS---PFAGESDRATLLNVLEGRVSWSSPM--AAHLSEDAKDFI 6698
Cdd:cd06605   159 VGTRSYMAPERISGGKYTVKSDIWSLG-LSLVELATGRfpyPPPNAKPSMMIFELLSYIVDEPPPLlpSGKFSPDFQDFV 237

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6699 KATLQRAPQARPSAAQCLSHPWFLKS 6724
Cdd:cd06605   238 SQCLQKDPTERPSYKELMEHPFIKRY 263
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
 6468-6721 1.08e-31

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 128.20  E-value: 1.08e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQH-KGNKILCAAKFIPLRSRTRAQAY--RERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14201     8 YSRKDLVGHGAFAVVFKGRHrKKTDWEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVMEYC 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-------IKICDFGFAQNITPA 6617
Cdd:cd14201    88 NGGDLADYLQAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSYASRKKssvsgirIKIADFGFARYLQSN 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRaTLLNVLEGRVSWSSPMAAHLSEDAKDF 6697
Cdd:cd14201   168 MMAATLCGSPMYMAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPFQANSPQ-DLRMFYEKNKNLQPSIPRETSPYLADL 246

                         250       260
                  ....*....|....*....|....
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14201   247 LLGLLQRNQKDRMDFEAFFSHPFL 270
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 894-975 1.33e-31

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 120.81  E-value: 1.33e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  894 QLARRKLQAEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEAGGQRLSFHL 973
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225  974 DV 975
Cdd:cd20967    81 FV 82
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
 7677-7866 1.42e-31

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 127.32  E-value: 1.42e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd14014     7 LLGRGGMGEVYRARDTLLGRPVAIKVLRPElaedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEGGS 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLE 7832
Cdd:cd14014    87 LADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLGTPA 166

                         170       180       190
                  ....*....|....*....|....*....|....
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14014   167 YMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPP 200
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 6465-6721 1.46e-31

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 128.89  E-value: 1.46e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVKEeIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT------RAQAyrERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:cd05574     1 DHFKKIKL-LGKGDVGRVYLVRLKGTGKLFAMKVLDKEEMIkrnkvkRVLT--EREILATLDHPFLPTLYASFQTSTHLC 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYR--KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFAQNI 6614
Cdd:cd05574    78 FVMDYCPGGELFRLLQKqpGKRLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILL----HESghIMLTDFDLSKQS 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQYGSP------------------------------EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFA 6664
Cdd:cd05574   154 SVTPPPVRKSLRKgsrrssvksieketfvaepsarsnsfvgteEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFK 233

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6665 GESDRATLLNVLEGRVSWssPMAAHLSEDAKDFIKATLQRAPQAR----PSAAQCLSHPWF 6721
Cdd:cd05574   234 GSNRDETFSNILKKELTF--PESPPVSSEAKDLIRKLLVKDPSKRlgskRGASEIKRHPFF 292
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
 6468-6721 1.59e-31

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 127.38  E-value: 1.59e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQ-HKGNKILCAaKFIPLRSRTRAQAYRERDILAALS-------HPLVTgLLDQFETRKTLIL 6539
Cdd:cd14133     1 YEVLEVLGKGTFGQVVKCYdLLTGEEVAL-KIIKNNKDYLDQSLDEIRLLELLNkkdkadkYHIVR-LKDVFYFKNHLCI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSS--EELLdRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPA 6617
Cdd:cd14133    79 VFELLSQnlYEFL-KQNKFQYLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSRCQIKIIDFGSSCFLTQR 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQygSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDA--- 6694
Cdd:cd14133   158 LYSYIQ--SRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGASEVDQLARIIGTIGIPPAHMLDQGKADDelf 235

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6695 KDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14133   236 VDFLKKLLEIDPKERPTASQALSHPWL 262
STKc_Mnk2 cd14173
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
 6468-6720 1.87e-31

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271075 [Multi-domain]  Cd Length: 288  Bit Score: 127.84  E-value: 1.87e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEI-GRGVFGfvkRVQHKGNKILC---AAKFIPLR-SRTRAQAYRERDIL-AALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14173     3 YQLQEEVlGEGAYA---RVQTCINLITNkeyAVKIIEKRpGHSRSRVFREVEMLyQCQGHRNVLELIEFFEEEDKFYLVF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAR-EDIKICDFGFAQNI------ 6614
Cdd:cd14173    80 EKMRGGSILSHIHRRRHFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILCEHPNQvSPVKICDFDLGSGIklnsdc 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 ----TPAELqfSQYGSPEFVSPEIIQQNPvSEAS------DIWAMGVISYLSLTCSSPFAGES------DRAT------- 6671
Cdd:cd14173   160 spisTPELL--TPCGSAEYMAPEVVEAFN-EEASiydkrcDLWSLGVILYIMLSGYPPFVGRCgsdcgwDRGEacpacqn 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6672 --LLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14173   237 mlFESIQEGKYEFPEKDWAHISCAAKDLISKLLVRDAKQRLSAAQVLQHPW 287
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
 6474-6719 1.91e-31

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 126.71  E-value: 1.91e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKIL-CAAKFIPLRSRTRAQAY--RERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14120     1 IGHGAFAVVFKGRHRKKPDLpVAIKCITKKNLSKSQNLlgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-------IKICDFGFAQNITPAELQFSQ 6623
Cdd:cd14120    81 DYLQAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSGRKpspndirLKIADFGFARFLQDGMMAATL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRAtLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd14120   161 CGSPMYMAPEVIMSLQYDAKADLWSIGTIVYQCLTGKAPFQAQTPQE-LKAFYEKNANLRPNIPSGTSPALKDLLLGLLK 239

                         250
                  ....*....|....*.
gi 215274225 6704 RAPQARPSAAQCLSHP 6719
Cdd:cd14120   240 RNPKDRIDFEDFFSHP 255
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
7677-7913 2.29e-31

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 132.44  E-value: 2.29e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKII-PYHPKDKTAV---LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:COG0515    14 LLGRGGMGVVYLARDLRLGRPVALKVLrPELAADPEARerfRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGES 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLE 7832
Cdd:COG0515    94 LADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPG 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL-QRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:COG0515   174 YMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELlRAHLREPPPPPSELRPDLPPALDAIVLRALAKDPEE 253


                  ..
gi 215274225 7912 RP 7913
Cdd:COG0515   254 RY 255
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 6468-6720 2.67e-31

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 126.42  E-value: 2.67e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14662     2 YELVKDIGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd14662    82 ELFERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPRLKICDFGYSKSSVLHSQPKSTVGTP 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVS-EASDIWAMGVISYLSLTCSSPFAGESD----RATLLNVLEgrVSWSSPMAAHLSEDAKDFIKATL 6702
Cdd:cd14662   162 AYIAPEVLSRKEYDgKVADVWSCGVTLYVMLVGAYPFEDPDDpknfRKTIQRIMS--VQYKIPDYVRVSQDCRHLLSRIF 239

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd14662   240 VANPAKRITIPEIKNHPW 257
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
 6466-6720 2.71e-31

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 126.98  E-value: 2.71e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR----TRAQayRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd06609     1 ELFTLLERIGKGSFGEVYKGIDKRTNQVVAIKVIDLEEAedeiEDIQ--QEIQFLSQCDSPYITKYYGSFLKGSKLWIIM 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAqnitpAELQF 6621
Cdd:cd06609    79 EYCGGGSVLD-LLKPGPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLS--EEGDVKLADFGVS-----GQLTS 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQ------YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAG-ESDRATLL------NVLEGRvswsspmaa 6688
Cdd:cd06609   151 TMskrntfVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDlHPMRVLFLipknnpPSLEGN--------- 221

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 6689 HLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06609   222 KFSKPFKDFVELCLNKDPKERPSAKELLKHKF 253
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
 6474-6711 3.03e-31

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 125.73  E-value: 3.03e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN----KILCAAKFiplRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd13999     1 IGSGSFGEVYKGKWRGTdvaiKKLKVEDD---NDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYI-QQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNI-TPAELQFSQYGSP 6627
Cdd:cd13999    78 YDLLHKKKIPLSWSLRLKIaLDIARGMNYLHSPPIIHRDLKSLNILLDENFT--VKIADFGLSRIKnSTTEKMTGVVGTP 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDR-ATLLNVLEGRVswsSPMAAHLSEDAKDFIKATLQRAP 6706
Cdd:cd13999   156 RWMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKELSPIqIAAAVVQKGLR---PPIPPDCPPELSKLIKRCWNEDP 232


                  ....*
gi 215274225 6707 QARPS 6711
Cdd:cd13999   233 EKRPS 237
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1446-1527 4.28e-31

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 119.27  E-value: 4.28e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1446 QPVHREVQAQAGASTTLSCEVAQAQTEVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEAGSQRLSFHL 1525
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1526 HV 1527
Cdd:cd20967    81 FV 82
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
 7681-7924 5.37e-31

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 125.80  E-value: 5.37e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYH-PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14190    15 GKFGKVHTCTEKRTGLKLAAKVINKQnSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVEGGELFERIVD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASY-SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII--TEYNLLKVVDLGNAQSLSqekvlPSDKFKDYL---ET 7833
Cdd:cd14190    95 EDYHlTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARRYN-----PREKLKVNFgtpEF 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP-VSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd14190   170 LSPEVVNYDQVSFPTDMWSMGVITYMLLSGLSPfLGDDDTETLNNVLMGNWYFDEETFEHVSDEAKDFVSNLIIKERSAR 249

                         250
                  ....*....|..
gi 215274225 7913 PCASSCLQCPWL 7924
Cdd:cd14190   250 MSATQCLKHPWL 261
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
 7677-7924 8.48e-31

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 125.50  E-value: 8.48e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKII-------PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14195    12 ELGSGQFAIVRKCREKGTGKEYAAKFIkkrrlssSRRGVSREEIEREVNILREIQHPNIITLHDIFENKTDVVLILELVS 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL----LKVVDLGNAQslsqeKVLPSD 7825
Cdd:cd14195    92 GGELFDFLAEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVpnprIKLIDFGIAH-----KIEAGN 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCY-AGLSGGAVAFL 7901
Cdd:cd14195   167 EFKNIFgtpEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYfSNTSELAKDFI 246

                         250       260
                  ....*....|....*....|...
gi 215274225 7902 RSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14195   247 RRLLVKDPKKRMTIAQSLEHSWI 269
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
 6468-6721 8.54e-31

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 125.14  E-value: 8.54e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT---RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd14069     3 WDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPgdcPENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLEYA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA---QNITPAELQF 6621
Cdd:cd14069    83 SGGELFDKIEPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLL--DENDNLKISDFGLAtvfRYKGKERLLN 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATL-LNVLEGRVS----WSSPMAAHLSedak 6695
Cdd:cd14069   161 KMCGTLPYVAPELLAKKKYrAEPVDVWSCGIVLFAMLAGELPWDQPSDSCQEySDWKENKKTyltpWKKIDTAALS---- 236

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6696 dFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14069   237 -LLRKILTENPNKRITIEDIKKHPWY 261
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
 6468-6727 1.94e-30

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 125.38  E-value: 1.94e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFV-KRVQHKGNKILcAAKFIPLRSRTRAQ------AYRERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd07841     2 YEKGKKLGEGTYAVVyKARDKETGRIV-AIKKIKLGERKEAKdginftALREIKLLQELKHPNIIGLLDVFGHKSNINLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSS--EELLDRlyRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA------- 6611
Cdd:cd07841    81 FEFMETdlEKVIKD--KSIVLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLI--ASDGVLKLADFGLArsfgspn 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 -----QNIT----PAELQF--SQYGSpefvspeiiqqnpvseASDIWAMGVIsYLSLTCSSPF-AGESD--------RA- 6670
Cdd:cd07841   157 rkmthQVVTrwyrAPELLFgaRHYGV----------------GVDMWSVGCI-FAELLLRVPFlPGDSDidqlgkifEAl 219

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6671 ------------TLLNVLEgrVSWSSPMAAH-----LSEDAKDFIKATLQRAPQARPSAAQCLSHPWFlKSMPA 6727
Cdd:cd07841   220 gtpteenwpgvtSLPDYVE--FKPFPPTPLKqifpaASDDALDLLQRLLTLNPNKRITARQALEHPYF-SNDPA 290
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1354-1435 2.19e-30

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 117.34  E-value: 2.19e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1354 QLAHRKVQAEAGAIATLSCEVAQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEAGGQRLSFSL 1433
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1434 DV 1435
Cdd:cd20967    81 FV 82
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
 6468-6720 2.30e-30

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 124.21  E-value: 2.30e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIpLRSR-----TRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14117     8 FDIGRPLGKGKFGNVYLAREKQSKFIVALKVL-FKSQiekegVEHQLRREIEIQSHLRHPNILRLYNYFHDRKRIYLILE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNiTPAELQFS 6622
Cdd:cd14117    87 YAPRGELYKELQKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGY--KGELKIADFGWSVH-APSLRRRT 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLegRVSWSSPmaAHLSEDAKDFIKATL 6702
Cdd:cd14117   164 MCGTLDYLPPEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFESASHTETYRRIV--KVDLKFP--PFLSDGSRDLISKLL 239

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd14117   240 RYHPSERLPLKGVMEHPW 257
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
 6468-6720 2.33e-30

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 123.53  E-value: 2.33e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKiLCAAKFIPlRSRTRAQA-----YRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14161     5 YEFLETLGKGTYGRVKKARDSSGR-LVAIKSIR-KDRIKDEQdllhiRREIEIMSSLNHPHIISVYEVFENSSKIVIVME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAqNITPAELQFS 6622
Cdd:cd14161    83 YASRGDLYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILL--DANGNIKIADFGLS-NLYNQDKFLQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QY-GSPEFVSPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGrvSWSSPmaAHLSeDAKDFIKA 6700
Cdd:cd14161   160 TYcGSPLYASPEIVNGRPyIGPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSG--AYREP--TKPS-DACGLIRW 234

                         250       260
                  ....*....|....*....|
gi 215274225 6701 TLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14161   235 LLMVNPERRATLEDVASHWW 254
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
 7672-7874 2.80e-30

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 123.91  E-value: 2.80e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH--PKDKTAVLR-----EYEALKGLRHPHLAQLHAAYLSPRHLVLI 7744
Cdd:cd14196     7 YDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRqsRASRRGVSReeierEVSILRQVLHPNIITLHDVYENRTDVVLI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL----LKVVDLGNAQSLsQEK 7820
Cdd:cd14196    87 LELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLAHEI-EDG 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7821 VlpsdKFKDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd14196   166 V----EFKNIFgtpEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQE 218
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
 6472-6721 3.12e-30

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 123.36  E-value: 3.12e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGN------KILCAAKFIPLRSRTRAQAyrERDILAALSH-PLVTGLLDQFETRKTLILILELC 6544
Cdd:cd05611     2 KPISKGAFGSVYLAKKRSTgdyfaiKVLKKSDMIAKNQVTNVKA--ERAIMMIQGEsPYVAKLYYSFQSKDYLYLVMEYL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd05611    80 NGGDCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLI--DQTGHLKLTDFGLSRNGLEKRHNKKFV 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd05611   158 GTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCSPEAVDLINRLLCM 237

                         250       260
                  ....*....|....*....|
gi 215274225 6705 APQARPSA---AQCLSHPWF 6721
Cdd:cd05611   238 DPAKRLGAngyQEIKSHPFF 257
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 6468-6720 3.69e-30

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 123.17  E-value: 3.69e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd14665     2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd14665    82 ELFERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPRLKICDFGYSKSSVLHSQPKSTVGTP 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEII-QQNPVSEASDIWAMGVISYLSLTCSSPFAGESD----RATLLNVLEgrVSWSSPMAAHLSEDAKDFIKATL 6702
Cdd:cd14665   162 AYIAPEVLlKKEYDGKIADVWSCGVTLYVMLVGAYPFEDPEEprnfRKTIQRILS--VQYSIPDYVHISPECRHLISRIF 239

                         250
                  ....*....|....*...
gi 215274225 6703 QRAPQARPSAAQCLSHPW 6720
Cdd:cd14665   240 VADPATRITIPEIRNHEW 257
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
 6468-6719 3.95e-30

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 122.89  E-value: 3.95e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRS---RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd08530     2 FKVLKKLGKGSYGSVYKVKRLSDNQVYALKEVNLGSlsqKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYR----KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHParEDIKICDFGFAQNITPAeLQ 6620
Cdd:cd08530    82 PFGDLSKLISKrkkkRRLFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAG--DLVKIGDLGISKVLKKN-LA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKA 6700
Cdd:cd08530   159 KTQIGTPLYAAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEARTMQELRYKVCRGKF---PPIPPVYSQDLQQIIRS 235

                         250
                  ....*....|....*....
gi 215274225 6701 TLQRAPQARPSAAQCLSHP 6719
Cdd:cd08530   236 LLQVNPKKRPSCDKLLQSP 254
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
 6468-6721 4.03e-30

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 123.98  E-value: 4.03e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR---TRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd07832     2 YKILGRIGEGAHGIVFKAKDRETGETVALKKVALRKLeggIPNQALREIKALQACqGHPYVVKLRDVFPHGTGFVLVFEY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEeLLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQ-NITPAELQF 6621
Cdd:cd07832    82 MLSS-LSEVLrDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLIS--STGVLKIADFGLARlFSEEDPRLY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 S-QYGSPEFVSPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLegRV-------SW---------- 6682
Cdd:cd07832   159 ShQVATRWYRAPELLYGSRkYDEGVDLWAVGCIFAELLNGSPLFPGENDIEQLAIVL--RTlgtpnekTWpeltslpdyn 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6683 --SSP---------MAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07832   237 kiTFPeskgirleeIFPDCSPEAIDLLKGLLVYNPKKRLSAEEALRHPYF 286
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1267-1343 4.58e-30

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 116.57  E-value: 4.58e-30
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1267 EVRTEAGASATLSCEVAQAQTEVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEAGGQRLSFHLDV 1343
Cdd:cd20967     6 AVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
 7670-7924 4.71e-30

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 123.04  E-value: 4.71e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVL---REYEALKGLRHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd14097     1 KIYTFGRKLGQGSFGVVIEATHKETQTKWAIKKINREKAGSSAVKlleREVDILKHVNHAHIIHLEEVFETPKRMYLVME 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT------EYNL-LKVVDLGNAqslSQE 7819
Cdd:cd14097    81 LCEDGELKELLLRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKssiidnNDKLnIKVTDFGLS---VQK 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7820 KVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSR-CYAGLSG 7895
Cdd:cd14097   158 YGLGEDMLQETCGTpiyMAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEEKLFEEIRKGDLTFTQsVWQSVSD 237

                         250       260
                  ....*....|....*....|....*....
gi 215274225 7896 GAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14097   238 AAKNVLQQLLKVDPAHRMTASELLDNPWI 266
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
 6466-6719 4.73e-30

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 122.49  E-value: 4.73e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVkEEIGRGVFGFVKRVQHKGNKILCAAK--FIPLR-SRTRAQAYRERDILAALS-HPLVTGLLDQFETRKTLILIL 6541
Cdd:cd13997     1 HFHEL-EQIGSGSFSEVFKVRSKVDGCLYAVKksKKPFRgPKERARALREVEAHAALGqHPNIVRYYSSWEEGGHLYIQM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELC---SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAe 6618
Cdd:cd13997    80 ELCengSLQDALEELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGT--CKIGDFGLATRLETS- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQyGSPEFVSPEIIQQNPV-SEASDIWAMGVISYlSLTCSSPFAgeSDRATLLNVLEGRVswSSPMAAHLSEDAKDF 6697
Cdd:cd13997   157 GDVEE-GDSRYLAPELLNENYThLPKADIFSLGVTVY-EAATGEPLP--RNGQQWQQLRQGKL--PLPPGLVLSQELTRL 230

                         250       260
                  ....*....|....*....|..
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd13997   231 LKVMLDPDPTRRPTADQLLAHD 252
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 6468-6721 6.59e-30

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 122.35  E-value: 6.59e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRS--RTRAQAYRERDILA---------ALSHPLVTGLLDQFETRKT 6536
Cdd:cd14005     2 YEVGDLLGKGGFGTVYSGVRIRDGLPVAVKFVP-KSrvTEWAMINGPVPVPLeialllkasKPGVPGVIRLLDWYERPDG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILELCSS-EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREDIKICDFGFAqnit 6615
Cdd:cd14005    81 FLLIMERPEPcQDLFDFITERGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLL-INLRTGEVKLIDFGCG---- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6616 pAELQFSQY----GSPEFVSPEIIQQ-----NPVSeasdIWAMGVISYLSLTCSSPFAGESDratllnVLEGRVsWSSPm 6686
Cdd:cd14005   156 -ALLKDSVYtdfdGTRVYSPPEWIRHgryhgRPAT----VWSLGILLYDMLCGDIPFENDEQ------ILRGNV-LFRP- 222

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 215274225 6687 aaHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14005   223 --RLSKECCDLISRCLQFDPSKRPSLEQILSHPWF 255
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
 7669-7924 8.41e-30

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 122.25  E-value: 8.41e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKAS--GRALAAKIIPYhPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd14112     2 TGRFSFGSEIFRGRFSVIVKAVDSTTetDAHCAVKIFEV-SDEASEAVREFESLRTLQHENVQRLIAAFKPSNFAYLVME 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGpELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN--LLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd14112    81 KLQE-DVFTRFSSNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRswQVKLVDFGRAQKVSKLGKVPV 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 DKFKDYletMAPELLEG-QGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQrglRKGLVRLSRC-----YAGLSGGAV 7898
Cdd:cd14112   160 DGDTDW---ASPEFHNPeTPITVQSDIWGLGVLTFCLLSGFHPFTSEYDDEEE---TKENVIFVKCrpnliFVEATQEAL 233

                         250       260
                  ....*....|....*....|....*.
gi 215274225 7899 AFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14112   234 RFATWALKKSPTRRMRTDEALEHRWL 259
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1170-1251 9.58e-30

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 115.42  E-value: 9.58e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1170 QSVHNEVQAEAGTTAMLSCEVAQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEAGGQRVSFQL 1249
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1250 HI 1251
Cdd:cd20967    81 FV 82
Pkinase pfam00069
Protein kinase domain;
7677-7924 1.78e-29

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 119.66  E-value: 1.78e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:pfam00069    6 KLGSGSFGTVYKAKHRDTGKIVAIKKIKKEkikKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGGSL 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7754 LPCLAERASYSESEVKDYLWQMLSAtqylhnqhilhldlrsenmiiteynllkvvdLGNAQSLSQEKVLPsdkfkDYlet 7833
Cdd:pfam00069   86 FDLLSEKGAFSEREAKFIMKQILEG-------------------------------LESGSSLTTFVGTP-----WY--- 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7834 MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGRP 7913
Cdd:pfam00069  127 MAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLKKLLKKDPSKRL 206

                          250
                   ....*....|.
gi 215274225  7914 CASSCLQCPWL 7924
Cdd:pfam00069  207 TATQALQHPWF 217
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
 6468-6720 2.37e-29

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 120.90  E-value: 2.37e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN-KILCAAKFIPLRSR-TRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd14088     3 YDLGQVIKTEEFCEIFRAKDKTTgKLYTCKKFLKRDGRkVRKAAKNEINILKMVKHPNILQLVDVFETRKEYFIFLELAT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQniTPAELQFSQY 6624
Cdd:cd14088    83 GREVFDWILDQGYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVYYNRLKNSkIVISDFHLAK--LENGLIKEPC 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES--------DRATLLNVLEGRVSWSSPMAAHLSEDAKD 6696
Cdd:cd14088   161 GTPEYLAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEAeeddyenhDKNLFRKILAGDYEFDSPYWDDISQAAKD 240

                         250       260
                  ....*....|....*....|....
gi 215274225 6697 FIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14088   241 LVTRLMEVEQDQRITAEEAISHEW 264
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
 7681-7924 2.50e-29

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 120.79  E-value: 2.50e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYH-PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP-CLA 7758
Cdd:cd14193    15 GRFGQVHKCEEKSSGLKLAAKIIKARsQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDrIID 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT--EYNLLKVVDLGNAQslsqeKVLPSDKFKDYL---ET 7833
Cdd:cd14193    95 ENYNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVsrEANQVKIIDFGLAR-----RYKPREKLRVNFgtpEF 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP-VSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd14193   170 LAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPfLGEDDNETLNNILACQWDFEDEEFADISEEAKDFISKLLIKEKSWR 249

                         250
                  ....*....|..
gi 215274225 7913 PCASSCLQCPWL 7924
Cdd:cd14193   250 MSASEALKHPWL 261
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
 6468-6720 2.95e-29

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 121.02  E-value: 2.95e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR--TRAQA--------------YRERDILAALSHPLVTGLLDQF 6531
Cdd:cd14077     3 WEFVKTIGAGSMGKVKLAKHIRTGEKCAIKIIPRASNagLKKERekrlekeisrdirtIREAALSSLLNHPHICRLRDFL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6532 ETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA 6611
Cdd:cd14077    83 RTPNHYYMLFEYVDGGQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILI--SKSGNIKIIDFGLS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 qNITPAELQFSQY-GSPEFVSPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaH 6689
Cdd:cd14077   161 -NLYDPRRLLRTFcGSLYFAAPELLQAQPyTGPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVEYPS----Y 235

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6690 LSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14077   236 LSSECKSLISRMLVVDPKKRATLEQVLNHPW 266
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
 6468-6721 3.53e-29

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 122.25  E-value: 3.53e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQ-AYRERDILAALSHPLVTGLLD-----QFETRKTLIL 6539
Cdd:cd07834     2 YELLKPIGSGAYGVVCSAYDKRTGRKVAIKKISNvfDDLIDAKrILREIKILRHLKHENIIGLLDilrppSPEEFNDVYI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEelLDR-LYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPae 6618
Cdd:cd07834    82 VTELMETD--LHKvIKSPQPLTDDHIQYFLYQILRGLKYLHSAGVIHRDLKPSNILV--NSNCDLKICDFGLARGVDP-- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 lQFSQYGSPEFV------SPEII-QQNPVSEASDIWAMGVI--------------SY---LSLTCS---SP-------FA 6664
Cdd:cd07834   156 -DEDKGFLTEYVvtrwyrAPELLlSSKKYTKAIDIWSVGCIfaelltrkplfpgrDYidqLNLIVEvlgTPseedlkfIS 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6665 GESDRATLLNVLEGR-VSWSSPMaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07834   235 SEKARNYLKSLPKKPkKPLSEVF-PGASPEAIDLLEKMLVFNPKKRITADEALAHPYL 291
I-set pfam07679
Immunoglobulin I-set domain;
10-99 4.14e-29

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 113.89  E-value: 4.14e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIG 89
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 215274225    90 EAFAAVGLQV 99
Cdd:pfam07679   81 EAEASAELTV 90
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
 6468-6719 4.29e-29

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 119.72  E-value: 4.29e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplRSRTRAQAYRERDILAALS------HPLVTGLLDQFETRKTLILIL 6541
Cdd:cd14050     3 FTILSKLGEGSFGEVFKVRSREDGKLYAVKRS--RSRFRGEKDRKRKLEEVERheklgeHPNCVRFIKAWEEKGILYIQT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSsEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQF 6621
Cdd:cd14050    81 ELCD-TSLQQYCEETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGV--CKLGDFGLVVELDKEDIHD 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPvSEASDIWAMGvISYLSLTCSspfagesdratlLNVLEGRVSWS--------SPMAAHLSED 6693
Cdd:cd14050   158 AQEGDPRYMAPELLQGSF-TKAADIFSLG-ITILELACN------------LELPSGGDGWHqlrqgylpEEFTAGLSPE 223

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd14050   224 LRSIIKLMMDPDPERRPTAEDLLALP 249
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 6468-6717 6.89e-29

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 120.09  E-value: 6.89e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDI--LAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd13996     8 FEEIELLGSGGFGSVYKVRNKVDGVTYAIKKIRLTEKSSASEKVLREVkaLAKLNHPNIVRYYTAWVEEPPLYIQMELCE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGVVTEAEVKVYI---QQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREdIKICDFGFAQNITPAE---- 6618
Cdd:cd13996    88 GGTLRDWIDRRNSSSKNDRKLALelfKQILKGVSYIHSKGIVHRDLKPSNIFLDNDDLQ-VKIGDFGLATSIGNQKreln 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 -LQFSQY----------GSPEFVSPEIIQQNPVSEASDIWAMGVIsYLSLTCssPFAGESDRATLL-NVLEGRVSWSspM 6686
Cdd:cd13996   167 nLNNNNNgntsnnsvgiGTPLYASPEQLDGENYNEKADIYSLGII-LFEMLH--PFKTAMERSTILtDLRNGILPES--F 241

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6687 AAHLSEDAkDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd13996   242 KAKHPKEA-DLIQSLLSKNPEERPSAEQLLR 271
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 7681-7936 7.61e-29

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 120.87  E-value: 7.61e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIpyhpKDKTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14092    17 GSFSVCRKCVHKKTGQEFAVKIV----SRRLDTSREVQLLRLCQgHPNIVKLHEVFQDELHTYLVMELLRGGELLERIRK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKVLPSDKFKdyLETMAP 7836
Cdd:cd14092    93 KKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDddaEIKIVDFGFARLKPENQPLKTPCFT--LPYAAP 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7837 ELLEGQGAVP----QTDIWAIGVTAFIMLSAEYP----VSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14092   171 EVLKQALSTQgydeSCDLWSLGVILYTMLSGQVPfqspSRNESAAEIMKRIKSGDFSFdGEEWKNVSSEAKSLIQGLLTV 250

                         250       260
                  ....*....|....*....|....*....
gi 215274225 7908 QPWGRPCASSCLQCPWLTeegPACSRPAP 7936
Cdd:cd14092   251 DPSKRLTMSELRNHPWLQ---GSSSPSST 276
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 6468-6720 8.30e-29

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 119.45  E-value: 8.30e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFG---FVKRVQHKGNKILCAAKFIP---LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd08222     2 YRVVRKLGSGNFGtvyLVSDLKATADEELKVLKEISvgeLQPDETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCIVT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRL--YRK--GVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDIKICDFGFAQNIT-P 6616
Cdd:cd08222    82 EYCEGGDLDDKIseYKKsgTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFL---KNNVIKVGDFGISRILMgT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKD 6696
Cdd:cd08222   159 SDLATTFTGTPYYMSPEVLKHEGYNSKSDIWSLGCILYEMCCLKHAFDGQNLLSVMYKIVEGET---PSLPDKYSKELNA 235

                         250       260
                  ....*....|....*....|....
gi 215274225 6697 FIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd08222   236 IYSRMLNKDPALRPSAAEILKIPF 259
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 6468-6720 9.68e-29

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 119.08  E-value: 9.68e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR---SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILI-LEL 6543
Cdd:cd08223     2 YQFLRVIGKGSYGEVWLVRHKRDRKQYVIKKLNLKnasKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDGFLYIvMGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLY-RKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpaREDI-KICDFGFAQNI-TPAEL 6619
Cdd:cd08223    82 CEGGDLYTRLKeQKGVlLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLT---KSNIiKVGDLGIARVLeSSSDM 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIK 6699
Cdd:cd08223   159 ATTLIGTPYYMSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDMNSLVYKILEGKL---PPMPKQYSPELGELIK 235

                         250       260
                  ....*....|....*....|.
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd08223   236 AMLHQDPEKRPSVKRILRQPY 256
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7669-7923 1.10e-28

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 119.01  E-value: 1.10e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP-KDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd14083     2 RDKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDKKAlKGKEDSLEnEIAVLRKIKHPNIVQLLDIYESKSHLYLVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDLGnaqS 7815
Cdd:cd14083    82 LVTGGELFDRIVEKGSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLyyspdedskimISDFGLSKMEDSG---V 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7816 LSQEKVLPSdkfkdYLetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCY-AGLS 7894
Cdd:cd14083   159 MSTACGTPG-----YV---APEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDSKLFAQILKAEYEFDSPYwDDIS 230

                         250       260
                  ....*....|....*....|....*....
gi 215274225 7895 GGAVAFLRSTLCAQPWGRPCASSCLQCPW 7923
Cdd:cd14083   231 DSAKDFIRHLMEKDPNKRYTCEQALEHPW 259
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 6468-6719 1.27e-28

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 118.76  E-value: 1.27e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd08218     2 YVRIKKIGEGSFGKALLVKSKEDGKQYVIKEInisKMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRL-YRKGVV-TEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNI-LMVHPAredIKICDFGFAQNI-TPAELQ 6620
Cdd:cd08218    82 DGGDLYKRInAQRGVLfPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIfLTKDGI---IKLGDFGIARVLnSTVELA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKA 6700
Cdd:cd08218   159 RTCIGTPYYLSPEICENKPYNNKSDIWALGCVLYEMCTLKHAFEAGNMKNLVLKIIRGSY---PPVPSRYSYDLRSLVSQ 235

                         250
                  ....*....|....*....
gi 215274225 6701 TLQRAPQARPSAAQCLSHP 6719
Cdd:cd08218   236 LFKRNPRDRPSINSILEKP 254
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
 6468-6721 1.58e-28

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 119.46  E-value: 1.58e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKF--IP--LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05612     3 FERIKTIGTGTFGRVHLVRDRISEHYYALKVmaIPevIRLKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpARE-DIKICDFGFAQNITpaELQFS 6622
Cdd:cd05612    83 VPGGELFSYLRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILL---DKEgHIKLTDFGFAKKLR--DRTWT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKATL 6702
Cdd:cd05612   158 LCGTPEYLAPEVIQSKGHNKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKLEFPR----HLDLYAKDLIKKLL 233

                         250       260
                  ....*....|....*....|....
gi 215274225 6703 -----QRAPQARPSAAQCLSHPWF 6721
Cdd:cd05612   234 vvdrtRRLGNMKNGADDVKNHRWF 257
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
 6511-6721 1.73e-28

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 118.23  E-value: 1.73e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6511 RERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKP 6590
Cdd:cd06625    51 CEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPGGSVKDEIKAYGALTENVTRKYTRQILEGLAYLHSNMIVHRDIKG 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6591 SNILmvHPAREDIKICDFGFA---QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES 6667
Cdd:cd06625   131 ANIL--RDSNGNVKLGDFGASkrlQTICSSTGMKSVTGTPYWMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPWAEFE 208

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6668 DRATLLNVLEGRVSWSSPmaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd06625   209 PMAAIFKIATQPTNPQLP--PHVSEDARDFLSLIFVRNKKQRPSAEELLSHSFV 260
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
 6474-6721 2.32e-28

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 118.11  E-value: 2.32e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14187    15 LGKGGFAKCYEITDADTKEVFAGKIVPksllLKPHQKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRSL 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNIT-PAELQFSQYGSPE 6628
Cdd:cd14187    95 LELHKRRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDM--EVKIGDFGLATKVEyDGERKKTLCGTPN 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQRAPQA 6708
Cdd:cd14187   173 YIAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSCLKETYLRIKKNEYS----IPKHINPVAASLIQKMLQTDPTA 248

                         250
                  ....*....|...
gi 215274225 6709 RPSAAQCLSHPWF 6721
Cdd:cd14187   249 RPTINELLNDEFF 261
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1078-1159 2.46e-28

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 111.57  E-value: 2.46e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1078 QSVHNEVQAEAGASAMLSCEVAQAQTEVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEAGGQRVSFHL 1157
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1158 HI 1159
Cdd:cd20967    81 FV 82
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
 6468-6714 2.68e-28

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 118.21  E-value: 2.68e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAK--FIPLRSRTRaQAYRERDILAALS-HPLVTGLLD----QFETRKTLILI 6540
Cdd:cd13985     2 YQVTKQLGEGGFSYVYLAHDVNTGRRYALKrmYFNDEEQLR-VAIKEIEIMKRLCgHPNIVQYYDsailSSEGRKEVLLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSE--ELLDRLYRKGVvTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPARedIKICDFGFAQNITP 6616
Cdd:cd13985    81 MEYCPGSlvDILEKSPPSPL-SEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGR--FKLCDFGSATTEHY 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 ----------AELQFSQYGSPEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFagesDRATLLNVLEGRVSWs 6683
Cdd:cd13985   158 pleraeevniIEEEIQKNTTPMYRAPEMIdlySKKPIGEKADIWALGCLLYKLCFFKLPF----DESSKLAIVAGKYSI- 232

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6684 sPMAAHLSEDAKDFIKATLQRAPQARPSAAQ 6714
Cdd:cd13985   233 -PEQPRYSPELHDLIRHMLTPDPAERPDIFQ 262
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 7678-7909 2.84e-28

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 117.23  E-value: 2.84e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVLREYEA---------LKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd05123     1 LGKGSFGKVLLVRKKDTGKLYAMKVL-----RKKEIIKRKEVehtlnerniLERVNHPFIVKLHYAFQTEEKLYLVLDYV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSqeKVLPSDKFK 7828
Cdd:cd05123    76 PGGELFSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFG----LA--KELSSDGDR 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 DY-----LETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCyagLSGGAVAFLRS 7903
Cdd:cd05123   150 TYtfcgtPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPEY---VSPEAKSLISG 226


                  ....*.
gi 215274225 7904 TLCAQP 7909
Cdd:cd05123   227 LLQKDP 232
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7672-7927 3.05e-28

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 118.77  E-value: 3.05e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPyHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14085     5 FEIESELGRGATSVVYRCRQKGTQKPYAVKKLK-KTVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDlgnaQSLSQEK 7820
Cdd:cd14085    84 ELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLyatpapdaplkIADFGLSKIVD----QQVTMKT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7821 VLPSDKFkdyletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD--LQRGLRKGLVRLSRCYAGLSGGAV 7898
Cdd:cd14085   160 VCGTPGY------CAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDERGDQymFKRILNCDYDFVSPWWDDVSLNAK 233

                         250       260
                  ....*....|....*....|....*....
gi 215274225 7899 AFLRSTLCAQPWGRPCASSCLQCPWLTEE 7927
Cdd:cd14085   234 DLVKKLIVLDPKKRLTTQQALQHPWVTGK 262
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
 7678-7924 3.25e-28

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 117.65  E-value: 3.25e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYH------------PKDKTA---VLREYEALKGLRHPHLAQLHAAYLSP--RH 7740
Cdd:cd14008     1 LGRGSFGKVKLALDTETGQLYAIKIFNKSrlrkrregkndrGKIKNAlddVRREIAIMKKLDHPNIVRLYEVIDDPesDK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7741 LVLILELCSGPEL--LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsq 7818
Cdd:cd14008    81 LYLVLEYCEGGPVmeLDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMF-- 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7819 ekvlpsDKFKDYLET-------MAPELLEGQGAV---PQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSR 7888
Cdd:cd14008   159 ------EDGNDTLQKtagtpafLAPELCDGDSKTysgKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNDEFPI 232

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 215274225 7889 CyAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14008   233 P-PELSPELKDLLRRMLEKDPEKRITLKEIKEHPWV 267
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
 6468-6720 5.87e-28

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 117.00  E-value: 5.87e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEV-KEEIGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQayRERDI-LAALSHPLVTGLLDQFET----RKTLILIL 6541
Cdd:cd14089     2 YTIsKQVLGLGINGKVLECFHKKTGEKFALKV--LRDNPKAR--REVELhWRASGCPHIVRIIDVYENtyqgRKCLLVVM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDI-KICDFGFAQNITPAE 6618
Cdd:cd14089    78 ECMEGGELFSRIQERADsaFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGPNAIlKLTDFGFAKETTTKK 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 -LQFSQYgSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF---------AGESDRatllnVLEGRVSWSSPMAA 6688
Cdd:cd14089   158 sLQTPCY-TPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFysnhglaisPGMKKR-----IRNGQYEFPNPEWS 231

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 6689 HLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14089   232 NVSEEAKDLIRGLLKTDPSERLTIEEVMNHPW 263
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
 6468-6720 7.93e-28

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 116.50  E-value: 7.93e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrSRTRAQA-------YRERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd14164     2 YTLGTTIGEGSFSKVKLATSQKYCCKVAIKIV---DRRRASPdfvqkflPRELSILRRVNHPNIVQMFECIEVANGRLYI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhPAREDIKICDFGFAQNIT-PAEL 6619
Cdd:cd14164    79 VMEAAATDLLQKIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLS-ADDRKIKIADFGFARFVEdYPEL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGesDRATLLNVLEGRVSWSSPMAahLSEDAKDFI 6698
Cdd:cd14164   158 STTFCGSRAYTPPEVILGTPYdPKKYDVWSLGVVLYVMVTGTMPFDE--TNVRRLRLQQRGVLYPSGVA--LEEPCRALI 233

                         250       260
                  ....*....|....*....|..
gi 215274225 6699 KATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14164   234 RTLLQFNPSTRPSIQQVAGNSW 255
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
 6468-6714 8.17e-28

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 116.60  E-value: 8.17e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAK----FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd08224     2 YEIEKKIGKGQFSVVYRARCLLDGRLVALKkvqiFEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELlDRLYR-----KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFG----FAQNI 6614
Cdd:cd08224    82 ADAGDL-SRLIKhfkkqKRLIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFIT--ANGVVKLGDLGlgrfFSSKT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAelqFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRatlLNVLEGRVSWS--SPM-AAHLS 6691
Cdd:cd08224   159 TAA---HSLVGTPYYMSPERIREQGYDFKSDIWSLGCLLYEMAALQSPFYGEKMN---LYSLCKKIEKCeyPPLpADLYS 232

                         250       260
                  ....*....|....*....|...
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQ 6714
Cdd:cd08224   233 QELRDLVAACIQPDPEKRPDISY 255
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 6474-6709 8.53e-28

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 117.83  E-value: 8.53e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIplRSRTRAQAYRErdiLAAL----SHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14179    15 LGEGSFSICRKCLHKKTNQEYAVKIV--SKRMEANTQRE---IAALklceGHPNIVKLHEVYHDQLHTFLVMELLKGGEL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPA-REDIKICDFGFAQnITPAELQFSQygSP- 6627
Cdd:cd14179    90 LERIKKKQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTDESdNSEIKIIDFGFAR-LKPPDNQPLK--TPc 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 ---EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-------GRVSWSSPMAAHLSEDAKDF 6697
Cdd:cd14179   167 ftlHYAAPELLNYNGYDESCDLWSLGVILYTMLSGQVPFQCHDKSLTCTSAEEimkkikqGDFSFEGEAWKNVSQEAKDL 246

                         250
                  ....*....|..
gi 215274225 6698 IKATLQRAPQAR 6709
Cdd:cd14179   247 IQGLLTVDPNKR 258
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
 6468-6720 9.29e-28

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 116.99  E-value: 9.29e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN------KILCAAKFI-----PLRSRTRA----------------QAYRERDILAALS 6520
Cdd:cd14199     4 YKLKDEIGKGSYGVVKLAYNEDDntyyamKVLSKKKLMrqagfPRRPPPRGaraapegctqprgpieRVYQEIAILKKLD 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6521 HPLVTGLLDQFE--TRKTLILILELCSSEELLDRLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhp 6598
Cdd:cd14199    84 HPNVVKLVEVLDdpSEDHLYMVFELVKQGPVMEVPTLKPL-SEDQARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLV--- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6599 aRED--IKICDFGFAQNITPAE-LQFSQYGSPEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFAGEsdRATL 6672
Cdd:cd14199   160 -GEDghIKIADFGVSNEFEGSDaLLTNTVGTPAFMAPETLsetRKIFSGKALDVWAMGVTLYCFVFGQCPFMDE--RILS 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6673 LNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14199   237 LHSKIKTQPLEFPDQPDISDDLKDLLFRMLDKNPESRISVPEIKLHPW 284
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
 6474-6721 9.56e-28

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 116.18  E-value: 9.56e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQAYRER-----DILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd14189     9 LGKGGFARCYEMTDLATNKTYAVKVIP-HSRVAKPHQREKivneiELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKS 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFSQY-GSP 6627
Cdd:cd14189    88 LAHIWKARHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINE--NMELKVGDFGLAARLEPPEQRKKTIcGTP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEgrVSWSSPmaAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd14189   166 NYLAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDLKETYRCIKQ--VKYTLP--ASLSLPARHLLAGILKRNPG 241

                         250
                  ....*....|....
gi 215274225 6708 ARPSAAQCLSHPWF 6721
Cdd:cd14189   242 DRLTLDQILEHEFF 255
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
 7680-7882 1.33e-27

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 115.81  E-value: 1.33e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14081    11 KGQTGLVKLAKHCVTGQKVAIKIVNkeklSKESVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVLEYVSGGELFD 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqSLSQEKVLpsdkfkdyLET-- 7833
Cdd:cd14081    91 YLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMA-SLQPEGSL--------LETsc 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7834 -----MAPELLEGQ---GAvpQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKG 7882
Cdd:cd14081   162 gsphyACPEVIKGEkydGR--KADIWSCGVILYALLVGALPFDDDNLRQLLEKVKRG 216
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
 6456-6721 1.34e-27

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 118.04  E-value: 1.34e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6456 EKQSHRRklhsfYEVKEEIGRGVFGFVKRVQHKGNKILCAAK--FIPLRSRTRAQ-AYRERDILAALS-HPLVTGLLDQF 6531
Cdd:cd07852     2 DKHILRR-----YEILKKLGKGAYGIVWKAIDKKTGEVVALKkiFDAFRNATDAQrTFREIMFLQELNdHPNIIKLLNVI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6532 --ETRKTLILILELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFG 6609
Cdd:cd07852    77 raENDKDIYLVFEYMETD--LHAVIRANILEDIHKQYIMYQLLKALKYLHSGGVIHRDLKPSNILLNSDCR--VKLADFG 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6610 FAQNITPAELQFSQYGSPEFV------SPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDratlLNVLE----- 6677
Cdd:cd07852   153 LARSLSQLEEDDENPVLTDYVatrwyrAPEILLGSTrYTKGVDMWSVGCILGEMLLGKPLFPGTST----LNQLEkiiev 228

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6678 -GR------VSWSSPMAAHL-------------------SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07852   229 iGRpsaediESIQSPFAATMleslppsrpksldelfpkaSPDALDLLKKLLVFNPNKRLTAEEALRHPYV 298
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
 7681-7924 1.73e-27

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 115.44  E-value: 1.73e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYH-PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14192    15 GRFGQVHKCTELSTGLTLAAKIIKVKgAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGELFDRITD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RaSYSESEVKDYLW--QMLSATQYLHNQHILHLDLRSENMIITEY--NLLKVVDLGNAQslsqeKVLPSDKFKDYL---E 7832
Cdd:cd14192    95 E-SYQLTELDAILFtrQICEGVHYLHQHYILHLDLKPENILCVNStgNQIKIIDFGLAR-----RYKPREKLKVNFgtpE 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG-ARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:cd14192   169 FLAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETdAETMNNIVNCKWDFDAEAFENLSEEAKDFISRLLVKEKSC 248

                         250
                  ....*....|...
gi 215274225 7912 RPCASSCLQCPWL 7924
Cdd:cd14192   249 RMSATQCLKHEWL 261
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 6474-6722 2.12e-27

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 116.51  E-value: 2.12e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIplrSRtRAQAYRERDIlAAL----SHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14180    14 LGEGSFSVCRKCRHRQSGQEYAVKII---SR-RMEANTQREV-AALrlcqSHPNIVALHEVLHDQYHTYLVMELLRGGEL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFAQnITPAELQFSQygSP- 6627
Cdd:cd14180    89 LDRIKKKARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYADESDGAvLKVIDFGFAR-LRPQGSRPLQ--TPc 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 ---EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRAT-------LLNVLEGRVSWSSPMAAHLSEDAKDF 6697
Cdd:cd14180   166 ftlQYAAPELFSNQGYDESCDLWSLGVILYTMLSGQVPFQSKRGKMFhnhaadiMHKIKEGDFSLEGEAWKGVSEEAKDL 245

                         250       260
                  ....*....|....*....|....*
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHPWFL 6722
Cdd:cd14180   246 VRGLLTVDPAKRLKLSELRESDWLQ 270
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 6468-6720 2.72e-27

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 115.09  E-value: 2.72e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEV-KEEIGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQAYRERDILAAlSHPLVTGLLDQFET----RKTLILILE 6542
Cdd:cd14172     5 YKLsKQVLGLGVNGKVLECFHRRTGQKCALKL--LYDSPKARREVEHHWRAS-GGPHIVHILDVYENmhhgKRCLLIIME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmvHPARED---IKICDFGFAQNITPA 6617
Cdd:cd14172    82 CMEGGELFSRIQERGdqAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLL--YTSKEKdavLKLTDFGFAKETTVQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 E-LQFSQYgSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRA----TLLNVLEGRVSWSSPMAAHLSE 6692
Cdd:cd14172   160 NaLQTPCY-TPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAispgMKRRIRMGQYGFPNPEWAEVSE 238

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14172   239 EAKQLIRHLLKTDPTERMTITQFMNHPW 266
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
 7677-7924 2.84e-27

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 114.93  E-value: 2.84e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKT---AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd06606     7 LLGKGSFGSVYLALNLDTGELMAVKEVELSGDSEEeleALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGSL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDK-FKDYLE 7832
Cdd:cd06606    87 ASLLKKFGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTKsLRGTPY 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG---ARDLQRGLRKGLVRLSRCyagLSGGAVAFLRSTLCAQP 7909
Cdd:cd06606   167 WMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGnpvAALFKIGSSGEPPPIPEH---LSEEAKDFLRKCLQRDP 243

                         250
                  ....*....|....*
gi 215274225 7910 WGRPCASSCLQCPWL 7924
Cdd:cd06606   244 KKRPTADELLQHPFL 258
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
 7678-7923 3.10e-27

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 114.73  E-value: 3.10e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA-------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14095     8 IGDGNFAVVKECRDKATDKEYALKII-----DKAKckgkehmIENEVAILRRVKHPNIVQLIEEYDTDTELYLVMELVKG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL----LKVVDLGnaqsLSQEKVLPsdk 7826
Cdd:cd14095    83 GDLFDAITSSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEDgsksLKLADFG----LATEVKEP--- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 fkdyLETM-------APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG--ARDLQRGLRKGLVR-LSRCYAGLSGG 7896
Cdd:cd14095   156 ----LFTVcgtptyvAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDrdQEELFDLILAGEFEfLSPYWDNISDS 231

                         250       260
                  ....*....|....*....|....*..
gi 215274225 7897 AVAFLRSTLCAQPWGRPCASSCLQCPW 7923
Cdd:cd14095   232 AKDLISRMLVVDPEKRYSAGQVLDHPW 258
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
 7680-7923 3.38e-27

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 114.88  E-value: 3.38e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYH-----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14098    10 SGTFAEVKKAVEVETGKMRAIKQIVKRkvagnDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGGDLM 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN--LLKVVDLGNAqslsqeKVLPSDKFkdyLE 7832
Cdd:cd14098    90 DFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLA------KVIHTGTF---LV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TM-------APELLEGQGAVPQ------TDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKG------LVRLSrcyagL 7893
Cdd:cd14098   161 TFcgtmaylAPEILMSKEQNLQggysnlVDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGrytqppLVDFN-----I 235

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 7894 SGGAVAFLRSTLCAQPWGRPCASSCLQCPW 7923
Cdd:cd14098   236 SEEAIDFILRLLDVDPEKRMTAAQALDHPW 265
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
 6468-6721 3.61e-27

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 115.32  E-value: 3.61e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07830     1 YKVIKQLGDGTFGSVYLARNKETGELVAIKKMkkKFYSWEECMNLREVKSLRKLnEHPNIVKLKEVFRENDELYFVFEYM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 ssEELLDRLYRK---GVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPaelqf 6621
Cdd:cd07830    81 --EGNLYQLMKDrkgKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVS--GPEVVKIADFGLAREIRS----- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 sqygSP---EFVS------PEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSWS--- 6683
Cdd:cd07830   152 ----RPpytDYVStrwyraPEILLRSTSySSPVDIWALGCIMAELYTLRPLFPGSSEIDQLYKICSvlgtpTKQDWPegy 227

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6684 ---------------SPMAAHL---SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07830   228 klasklgfrfpqfapTSLHQLIpnaSPEAIDLIKDMLRWDPKKRPTASQALQHPYF 283
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
 7678-7924 3.87e-27

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 114.40  E-value: 3.87e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA-------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14078    11 IGSGGFAKVKLATHILTGEKVAIKIM-----DKKAlgddlprVKTEIEALKNLSHQHICRLYHVIETDNKIFMVLEYCPG 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSlsqekvlPSDKFKDY 7830
Cdd:cd14078    86 GELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCAK-------PKGGMDHH 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 LET-------MAPELLEGQGAV-PQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGlvrlsrCYAG---LSGGAVA 7899
Cdd:cd14078   159 LETccgspayAAPELIQGKPYIgSEADVWSMGVLLYALLCGFLPFDDDNVMALYRKIQSG------KYEEpewLSPSSKL 232

                         250       260
                  ....*....|....*....|....*
gi 215274225 7900 FLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14078   233 LLDQMLQVDPKKRITVKELLNHPWV 257
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
 7680-7924 4.78e-27

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 114.19  E-value: 4.78e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14099    11 KGGFAKCYEVTDMSTGKVYAGKVVPksslTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCSNGSLME 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQekvlPSDKFKDYLET-- 7833
Cdd:cd14099    91 LLKRRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEY----DGERKKTLCGTpn 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 -MAPELLEG-QGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRcYAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:cd14099   167 yIAPEVLEKkKGHSFEVDIWSLGVILYTLLVGKPPFETSDVKETYKRIKKNEYSFPS-HLSISDEAKDLIRSMLQPDPTK 245

                         250
                  ....*....|...
gi 215274225 7912 RPCASSCLQCPWL 7924
Cdd:cd14099   246 RPSLDEILSHPFF 258
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
 7672-7866 7.65e-27

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 114.23  E-value: 7.65e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKT---------AVLREYEALKGLRHPHLAQLHAAYLSPRHLV 7742
Cdd:cd05581     3 FKFGKPLGEGSYSTVVLAKEKETGKEYAIKVL-----DKRhiikekkvkYVTIEKEVLSRLAHPGIVKLYYTFQDESKLY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVL 7822
Cdd:cd05581    78 FVLEYAPNGDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPDSSP 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7823 PSDKFK-------------------DYLetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05581   158 ESTKGDadsqiaynqaraasfvgtaEYV---SPELLNEKPAGKSSDLWALGCIIYQMLTGKPP 217
STKc_NDR2 cd05627
Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze ...
 6468-6721 8.24e-27

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270776 [Multi-domain]  Cd Length: 366  Bit Score: 116.31  E-value: 8.24e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05627     4 FESLKVIGRGAFGEVRLVQKKDTGHIYAMKILRkadmLEKEQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYLIMEF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFG------------FA 6611
Cdd:cd05627    84 LPGGDMMTLLMKKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLL--DAKGHVKLSDFGlctglkkahrteFY 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNIT---PAELQF---------------------SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES 6667
Cdd:cd05627   162 RNLThnpPSDFSFqnmnskrkaetwkknrrqlaySTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSET 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6668 DRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQ--ARPSAAQCLSHPWF 6721
Cdd:cd05627   242 PQETYRKVMNWKETLVFPPEVPISEKAKDLILRFCTDAENriGSNGVEEIKSHPFF 297
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7680-7925 9.05e-27

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 113.83  E-value: 9.05e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHP-KDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14169    13 EGAFSEVVLAQERGSQRLVALKCIPKKAlRGKEAMVEnEIAVLRRINHENIVSLEDIYESPTHLYLAMELVTGGELFDRI 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDLGnaqSLSQEKVLPSdk 7826
Cdd:cd14169    93 IERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLyatpfedskimISDFGLSKIEAQG---MLSTACGTPG-- 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 fkdyleTMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCY-AGLSGGAVAFLRSTL 7905
Cdd:cd14169   168 ------YVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAEYEFDSPYwDDISESAKDFIRHLL 241

                         250       260
                  ....*....|....*....|
gi 215274225 7906 CAQPWGRPCASSCLQCPWLT 7925
Cdd:cd14169   242 ERDPEKRFTCEQALQHPWIS 261
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
 7665-7924 1.04e-26

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 113.64  E-value: 1.04e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7665 PLPSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKII---------PYHPKDKTAVLREYEALKGLRHPHLAQLHAAY 7735
Cdd:cd14084     1 PKELRKKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIInkrkftigsRREINKPRNIETEIEILKKLSHPCIIKIEDFF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7736 LSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT---EYNLLKVVDLGn 7812
Cdd:cd14084    81 DAEDDYYIVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSsqeEECLIKITDFG- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7813 aqslsQEKVLPSDKFkdyLETM-------APELLEGQGAVPQT---DIWAIGVTAFIMLSAEYPVSSEGAR-DLQRGLRK 7881
Cdd:cd14084   160 -----LSKILGETSL---MKTLcgtptylAPEVLRSFGTEGYTravDCWSLGVILFICLSGYPPFSEEYTQmSLKEQILS 231

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7882 GLVRL-SRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14084   232 GKYTFiPKAWKNVSEEAKDLVKKMLVVDPSRRPSIEEALEHPWL 275
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
 7678-7924 1.20e-26

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 112.99  E-value: 1.20e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVL-----REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd14070    10 LGEGSFAKVREGLHAVTGEKVAIKVIDKKKAKKDSYVtknlrREGRIQQMIRHPNITQLLDILETENSYYLVMELCPGGN 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpSDKFKDYLE 7832
Cdd:cd14070    90 LMHRIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNCAGILGY--SDPFSTQCG 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 T---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE--GARDLQRGLRKGlvRLSRCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14070   168 SpayAAPELLARKKYGPKVDVWSIGVNMYAMLTGTLPFTVEpfSLRALHQKMVDK--EMNPLPTDLSPGAISFLRSLLEP 245

                         250
                  ....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWL 7924
Cdd:cd14070   246 DPLKRPNIKQALANRWL 262
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
 6468-6721 2.04e-26

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 112.39  E-value: 2.04e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAY--RERDILAALSHPLVTGLLDQFETRKTLI-LILE 6542
Cdd:cd14163     2 YQLGKTIGEGTYSKVKEAFSKKHQRKVAIKIIDKSGGPEEfiQRFlpRELQIVERLDHKNIIHVYEMLESADGKIyLVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDIKICDFGFAQNITPAELQFS 6622
Cdd:cd14163    82 LAEDGDVFDCVLHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALL---QGFTLKLTDFGFAKQLPKGGRELS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QY--GSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFaGESDRATLLNVLEGRVSWssPMAAHLSEDAKDFIK 6699
Cdd:cd14163   159 QTfcGSTAYAAPEVLQGVPHdSRKGDIWSMGVVLYVMLCAQLPF-DDTDIPKMLCQQQKGVSL--PGHLGVSRTCQDLLK 235

                         250       260
                  ....*....|....*....|..
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14163   236 RLLEPDMVLRPSIEEVSWHPWL 257
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 986-1067 2.24e-26

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 105.79  E-value: 2.24e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  986 QVAHSEVQAEAGASATLSCEVAQAQTEVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEARGQRVSFRL 1065
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 1066 HI 1067
Cdd:cd20967    81 FV 82
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 7681-7934 2.65e-26

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 113.43  E-value: 2.65e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTAvlREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14180    17 GSFSVCRKCRHRQSGQEYAVKIISRRMEANTQ--REVAALRLCQsHPNIVALHEVLHDQYHTYLVMELLRGGELLDRIKK 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII---TEYNLLKVVDLGNAQSLSQ-EKVLPSDKFKdyLETMA 7835
Cdd:cd14180    95 KARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYadeSDGAVLKVIDFGFARLRPQgSRPLQTPCFT--LQYAA 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7836 PELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG-------ARDLQRGLRKGLVRLS-RCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14180   173 PELFSNQGYDESCDLWSLGVILYTMLSGQVPFQSKRgkmfhnhAADIMHKIKEGDFSLEgEAWKGVSEEAKDLVRGLLTV 252

                         250       260
                  ....*....|....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWLTEEGPACSRP 7934
Cdd:cd14180   253 DPAKRLKLSELRESDWLQGGSALSSTP 279
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
 7678-7949 2.78e-26

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 112.73  E-value: 2.78e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPyhpKDKTAVLREYEALkgLR---HPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14091     8 IGKGSYSVCKRCIHKATGKEYAVKIID---KSKRDPSEEIEIL--LRygqHPNIITLRDVYDDGNSVYLVTELLRGGELL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIiteYNL-------LKVVDLGNAQSLSQEKVLpsdkf 7827
Cdd:cd14091    83 DRILRQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNIL---YADesgdpesLRICDFGFAKQLRAENGL----- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 kdyLET-------MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSS---EGARDLqrglrkgLVRLSRCYAGLSGG- 7896
Cdd:cd14091   155 ---LMTpcytanfVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFASgpnDTPEVI-------LARIGSGKIDLSGGn 224

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7897 -------AVAFLRSTLCAQPWGRPCASSCLQCPWLTEEGPACSRPAPVTFPTARLRVFVR 7949
Cdd:cd14091   225 wdhvsdsAKDLVRKMLHVDPSQRPTAAQVLQHPWIRNRDSLPQRQLTDPQDAALVKGAVA 284
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
 6468-6721 2.84e-26

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 112.85  E-value: 2.84e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN-KILCAAKFI-----PLrsrTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd07847     3 YEKLSKIGEGSYGVVFKCRNRETgQIVAIKKFVeseddPV---IKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEEL--LDRlYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAEL 6619
Cdd:cd07847    80 EYCDHTVLneLEK-NPRGV-PEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQ--IKLCDFGFARILTGPGD 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPE-FVSPEII----QQNPvseASDIWAMGVIsYLSLTCSSP-FAGESD-------RATL-------------- 6672
Cdd:cd07847   156 DYTDYVATRwYRAPELLvgdtQYGP---PVDVWAIGCV-FAELLTGQPlWPGKSDvdqlyliRKTLgdliprhqqifstn 231

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6673 -------LNVLEGRVSWSSPMaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07847   232 qffkglsIPEPETREPLESKF-PNISSPALSFLKGCLQMDPTERLSCEELLEHPYF 286
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 7681-7934 3.38e-26

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 113.21  E-value: 3.38e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTAvlREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14179    18 GSFSICRKCLHKKTNQEYAVKIVSKRMEANTQ--REIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKK 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQ-SLSQEKVLPSDKFKdyLETMA 7835
Cdd:cd14179    96 KQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTDESdnsEIKIIDFGFARlKPPDNQPLKTPCFT--LHYAA 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7836 PELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG-------ARDLQRGLRKGLVRLS-RCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14179   174 PELLNYNGYDESCDLWSLGVILYTMLSGQVPFQCHDksltctsAEEIMKKIKQGDFSFEgEAWKNVSQEAKDLIQGLLTV 253

                         250       260
                  ....*....|....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWLTEEGPACSRP 7934
Cdd:cd14179   254 DPNKRIKMSGLRYNEWLQDGSQLSSNP 280
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
 6468-6720 3.62e-26

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 113.94  E-value: 3.62e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI-PLRSRTRAQ-AYRERDILAALSHPLVTGLLD-----QFETRKTLILI 6540
Cdd:cd07849     7 YQNLSYIGEGAYGMVCSAVHKPTGQKVAIKKIsPFEHQTYCLrTLREIKILLRFKHENIIGILDiqrppTFESFKDVYIV 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQ 6620
Cdd:cd07849    87 QELMETD--LYKLIKTQHLSNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLL--NTNCDLKICDFGLARIADPEHDH 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYgsPEFV------SPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE---------------- 6677
Cdd:cd07849   163 TGFL--TEYVatrwyrAPEImLNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKDYLHQLNLILGilgtpsqedlnciisl 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6678 ------------GRVSWSSpMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd07849   241 karnyikslpfkPKVPWNK-LFPNADPKALDLLDKMLTFNPHKRITVEEALAHPY 294
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
 7678-7909 4.43e-26

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 111.16  E-value: 4.43e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14009     1 IGRGSFATVWKGRHKQTGEVVAIKEISRKklnKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL---LKVVDLGNAQSLSQEkvlpsdkfkDYL 7831
Cdd:cd14009    81 QYIRKRGRLPEAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSGDdpvLKIADFGFARSLQPA---------SMA 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 ET-------MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSR-CYAGLSGGAVAFLRS 7903
Cdd:cd14009   152 ETlcgsplyMAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVQLLRNIERSDAVIPFpIAAQLSPDCKDLLRR 231


                  ....*.
gi 215274225 7904 TLCAQP 7909
Cdd:cd14009   232 LLRRDP 237
STKc_Mnk1 cd14174
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
 6467-6720 4.81e-26

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271076 [Multi-domain]  Cd Length: 289  Bit Score: 112.05  E-value: 4.81e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEI-GRGVFGFVKRVQHKGNKILCAAKFIPLRS-RTRAQAYRERDIL-AALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd14174     2 LYRLTDELlGEGAYAKVQGCVSLQNGKEYAVKIIEKNAgHSRSRVFREVETLyQCQGNKNILELIEFFEDDTRFYLVFEK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAR-EDIKICDF----GFAQN----- 6613
Cdd:cd14174    82 LRGGSILAHIQKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILCESPDKvSPVKICDFdlgsGVKLNsactp 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQfSQYGSPEFVSPEIIQQNpVSEAS------DIWAMGVISYLSLTCSSPFAGES------DRATLLNVL----- 6676
Cdd:cd14174   162 ITTPELT-TPCGSAEYMAPEVVEVF-TDEATfydkrcDLWSLGVILYIMLSGYPPFVGHCgtdcgwDRGEVCRVCqnklf 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6677 ----EGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14174   240 esiqEGKYEFPDKDWSHISSEAKDLISKLLVRDAKERLSAAQVLQHPW 287
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
 7680-7861 5.87e-26

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 111.29  E-value: 5.87e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKII--------PYHPKD-KTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14093    13 RGVSSTVRRCIEKETGQEFAVKIIditgekssENEAEElREATRREIEILRQVsGHPNIIELHDVFESPTFIFLVFELCR 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFKD 7829
Cdd:cd14093    93 KGELFDYLTEVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLD-----EGEKLRE 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 215274225 7830 YLET---MAPELLEGQ------GAVPQTDIWAIGVTAFIML 7861
Cdd:cd14093   168 LCGTpgyLAPEVLKCSmydnapGYGKEVDMWACGVIMYTLL 208
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
 6474-6721 6.00e-26

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 113.05  E-value: 6.00e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDIL---AALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd05586     1 IGKGTFGQVYQVRKKDTRRIYAMKVLSkkviVAKKEVAHTIGERNILvrtALDESPFIVGLKFSFQTPTDLYLVTDYMSG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQ-NITPAELQFSQYG 6625
Cdd:cd05586    81 GELFWHLQKEGRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILL--DANGHIALCDFGLSKaDLTDNKTTNTFCG 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEI-IQQNPVSEASDIWAMGVISYlSLTCS-SPFAGESDRATLLNVLEGRVSWSSPMaahLSEDAKDFIKATLQ 6703
Cdd:cd05586   159 TTEYLAPEVlLDEKGYTKMVDFWSLGVLVF-EMCCGwSPFYAEDTQQMYRNIAFGKVRFPKDV---LSDEGRSFVKGLLN 234

                         250       260
                  ....*....|....*....|..
gi 215274225 6704 RAPQAR----PSAAQCLSHPWF 6721
Cdd:cd05586   235 RNPKHRlgahDDAVELKEHPFF 256
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
 7677-7924 6.56e-26

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 110.76  E-value: 6.56e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH-PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd05122     7 KIGKGGFGVVYKARHKKTGQIVAIKKINLEsKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSGGSLKD 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERA-SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlPSDKFKDYLETM 7834
Cdd:cd05122    87 LLKNTNkTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGK--TRNTFVGTPYWM 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7835 APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGA-RDLQRGLRKGLVRLsRCYAGLSGGAVAFLRSTLCAQPWGRP 7913
Cdd:cd05122   165 APEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPPmKALFLIATNGPPGL-RNPKKWSKEFKDFLKKCLQKDPEKRP 243

                         250
                  ....*....|.
gi 215274225 7914 CASSCLQCPWL 7924
Cdd:cd05122   244 TAEQLLKHPFI 254
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
 6452-6721 7.06e-26

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 113.25  E-value: 7.06e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6452 EPDSEKQSHRRKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGL 6527
Cdd:cd05593     1 EMDASTTHHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILKkeviIAKDEVAHTLTESRVLKNTRHPFLTSL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6528 LDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICD 6607
Cdd:cd05593    81 KYSFQTKDRLCFVMEYVNGGELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGH--IKITD 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6608 FGFA-QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPm 6686
Cdd:cd05593   159 FGLCkEGITDAATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFPRT- 237

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 6687 aahLSEDAKDFIKATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05593   238 ---LSADAKSLLSGLLIKDPNKRlgggpDDAKEIMRHSFF 274
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
 6469-6723 7.48e-26

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 111.38  E-value: 7.48e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQFETRK-TLILILEL-- 6543
Cdd:cd06620     8 ETLKDLGAGNGGSVSKVLHIPTGTIMAKKVIHIdaKSSVRKQILRELQILHECHSPYIVSFYGAFLNENnNIIICMEYmd 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSeelLDRLYRK-GVVTEAEVKVYIQQLVEGLHYLHS-HGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAeLQF 6621
Cdd:cd06620    88 CGS---LDKILKKkGPFPEEVLGKIAVAVLEGLTYLYNvHRIIHRDIKPSNILVNS--KGQIKLCDFGVSGELINS-IAD 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGvISYLSL-TCSSPFAGESDR-------ATLLNVLEGRVSWSSPM---AAHL 6690
Cdd:cd06620   162 TFVGTSTYMSPERIQGGKYSVKSDVWSLG-LSIIELaLGEFPFAGSNDDddgyngpMGILDLLQRIVNEPPPRlpkDRIF 240

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 6691 SEDAKDFIKATLQRAPQARPSAAQCLSHPWFLK 6723
Cdd:cd06620   241 PKDLRDFVDRCLLKDPRERPSPQLLLDHDPFIQ 273
STKc_NDR1 cd05628
Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze ...
 6468-6698 8.70e-26

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270777 [Multi-domain]  Cd Length: 376  Bit Score: 113.60  E-value: 8.70e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05628     3 FESLKVIGRGAFGEVRLVQKKDTGHVYAMKILRkadmLEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEF 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPA------ 6617
Cdd:cd05628    83 LPGGDMMTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLL--DSKGHVKLSDFGLCTGLKKAhrtefy 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ------------------------------ELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES 6667
Cdd:cd05628   161 rnlnhslpsdftfqnmnskrkaetwkrnrrQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSET 240

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6668 DRATLLNVLEGRVSWSSPMAAHLSEDAKDFI 6698
Cdd:cd05628   241 PQETYKKVMNWKETLIFPPEVPISEKAKDLI 271
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
 6466-6721 9.18e-26

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270844 [Multi-domain]  Cd Length: 284  Bit Score: 111.06  E-value: 9.18e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVkEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd07860     1 NFQKV-EKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEgvpSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSE--ELLDRLYRKGVVTeAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNI-TPAEL 6619
Cdd:cd07860    80 FLHQDlkKFMDASALTGIPL-PLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLI--NTEGAIKLADFGLARAFgVPVRT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSWS---------- 6683
Cdd:cd07860   157 YTHEVVTLWYRAPEILLGCKYySTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRtlgtpDEVVWPgvtsmpdykp 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6684 ----------SPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07860   237 sfpkwarqdfSKVVPPLDEDGRDLLSQMLHYDPNKRISAKAALAHPFF 284
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
 6472-6720 9.82e-26

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 110.60  E-value: 9.82e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVK-RVQHKGNkiLCAAKFIPLRSRTRAQAYR-------ERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd06631     7 NVLGKGAYGTVYcGLTSTGQ--LIAVKQVELDTSDKEKAEKeyeklqeEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNIlMVHPAREdIKICDFGFAQNI-------TP 6616
Cdd:cd06631    85 VPGGSIASILARFGALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNI-MLMPNGV-IKLIDFGCAKRLcinlssgSQ 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRvswsSPMAA---HLSED 6693
Cdd:cd06631   163 SQLLKSMRGTPYWMAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMNPMAAIFAIGSGR----KPVPRlpdKFSPE 238

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06631   239 ARDFVHACLTRDQDERPSAEQLLKHPF 265
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
 6474-6722 1.07e-25

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 112.02  E-value: 1.07e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKF----IPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05595     3 LGKGTFGKVILVREKATGRYYAMKIlrkeVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-QNITPAELQFSQYGSPE 6628
Cdd:cd05595    83 FFHLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGH--IKITDFGLCkEGITDGATMKTFCGTPE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKATLQRAPQA 6708
Cdd:cd05595   161 YLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPR----TLSPEAKSLLAGLLKKDPKQ 236

                         250
                  ....*....|....*....
gi 215274225 6709 R----PSAAQ-CLSHPWFL 6722
Cdd:cd05595   237 RlgggPSDAKeVMEHRFFL 255
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
 6468-6721 1.12e-25

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 110.53  E-value: 1.12e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL-RSRTRA-QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd06610     3 YELIEVIGSGATAVVYAAYCLPKKEKVAIKRIDLeKCQTSMdELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLD---RLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNI-TPAELQ- 6620
Cdd:cd06610    83 GGSLLDimkSSYPRGGLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILL--GEDGSVKIADFGVSASLaTGGDRTr 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 ---FSQYGSPEFVSPEIIQQ-NPVSEASDIWAMGvISYLSL-TCSSPFAGESDRATLLNVLEgrvswSSPMAAHLSEDAK 6695
Cdd:cd06610   161 kvrKTFVGTPCWMAPEVMEQvRGYDFKADIWSFG-ITAIELaTGAAPYSKYPPMKVLMLTLQ-----NDPPSLETGADYK 234

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 6696 -------DFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd06610   235 kysksfrKMISLCLQKDPSKRPTAEELLKHKFF 267
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
 6468-6721 1.64e-25

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 109.87  E-value: 1.64e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR--SRTRAQAY--RERDILAALSHPLVTGLLDQFETRKTLILI-LE 6542
Cdd:cd14165     3 YILGINLGEGSYAKVKSAYSERLKCNVAIKIIDKKkaPDDFVEKFlpRELEILARLNHKSIIKTYEIFETSDGKVYIvME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAE---- 6618
Cdd:cd14165    83 LGVQGDLLEFIKLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLL--DKDFNIKLTDFGFSKRCLRDEngri 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 -LQFSQYGSPEFVSPEIIQQNPVS-EASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAAHLSEDAKD 6696
Cdd:cd14165   161 vLSKTFCGSAAYAAPEVLQGIPYDpRIYDIWSLGVILYIMVCGSMPYDDSNVKKMLKIQKEHRVRF--PRSKNLTSECKD 238

                         250       260
                  ....*....|....*....|....*
gi 215274225 6697 FIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14165   239 LIYRLLQPDVSQRLCIDEVLSHPWL 263
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
 6474-6720 1.90e-25

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 109.93  E-value: 1.90e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPL---------RSRTRAQAY-RERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd06628     8 IGSGSFGSVYLGMNASSGELMAVKQVELpsvsaenkdRKKSMLDALqREIALLRELQHENIVQYLGSSSDANHLNIFLEY 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAEL---- 6619
Cdd:cd06628    88 VPGGSVATLLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDN--KGGIKISDFGISKKLEANSLstkn 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 ---QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAgESDRATLLNVLEGRVSWSSPmaAHLSEDAKD 6696
Cdd:cd06628   166 ngaRPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPFP-DCTQMQAIFKIGENASPTIP--SNISSEARD 242

                         250       260
                  ....*....|....*....|....
gi 215274225 6697 FIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06628   243 FLEKTFEIDHNKRPTADELLKHPF 266
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 7678-7923 2.21e-25

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 109.42  E-value: 2.21e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVL---------REYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd14663     8 LGEGTFAKVKFARNTKTGESVAIKII-----DKEQVAregmveqikREIAIMKLLRHPNIVELHEVMATKTKIFFVMELV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSqekVLPSDKFK 7828
Cdd:cd14663    83 TGGELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFG----LS---ALSEQFRQ 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 D-YLET-------MAPELLEGQGAV-PQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCyagLSGGAVA 7899
Cdd:cd14663   156 DgLLHTtcgtpnyVAPEVLARRGYDgAKADIWSCGVILFVLLAGYLPFDDENLMALYRKIMKGEFEYPRW---FSPGAKS 232

                         250       260
                  ....*....|....*....|....
gi 215274225 7900 FLRSTLCAQPWGRPCASSCLQCPW 7923
Cdd:cd14663   233 LIKRILDPNPSTRITVEQIMASPW 256
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
 6473-6720 2.44e-25

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 109.76  E-value: 2.44e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRV------QHKGNKILCAAKFI--------PLRSRTRAQA----------YRERDILAALSHP----LV 6524
Cdd:cd14118     1 EIGKGSYGIVKLAyneednTLYAMKILSKKKLLkqagffrrPPPRRKPGALgkpldpldrvYREIAILKKLDHPnvvkLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6525 TGLLDQFEtrKTLILILELCSSEELLdRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIK 6604
Cdd:cd14118    81 EVLDDPNE--DNLYMVFELVDKGAVM-EVPTDNPLSEETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLLLGDDGH--VK 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6605 ICDFGFAQNITPAELQFSQ-YGSPEFVSPEIIQQNPVS---EASDIWAMGVISYLSLTCSSPFagESDRATLLNVLEGRV 6680
Cdd:cd14118   156 IADFGVSNEFEGDDALLSStAGTPAFMAPEALSESRKKfsgKALDIWAMGVTLYCFVFGRCPF--EDDHILGLHEKIKTD 233

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 6681 SWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14118   234 PVVFPDDPVVSEQLKDLILRMLDKNPSERITLPEIKEHPW 273
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
 7680-7913 2.45e-25

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 108.95  E-value: 2.45e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPY----HPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14188    11 KGGFAKCYEMTDLTTNKVYAAKIIPHsrvsKPHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMAH 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFKDYL---- 7831
Cdd:cd14188    91 ILKARKVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLE-----PLEHRRRTIcgtp 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:cd14188   166 NYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYSLP---SSLLAPAKHLIASMLSKNPED 242


                  ..
gi 215274225 7912 RP 7913
Cdd:cd14188   243 RP 244
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
 6455-6738 2.82e-25

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 111.45  E-value: 2.82e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6455 SEKQSHRRKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFE 6532
Cdd:PLN00034   63 SGSAPSAAKSLSELERVNRIGSGAGGTVYKVIHRPTGRLYALKVIygNHEDTVRRQICREIEILRDVNHPNVVKCHDMFD 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6533 TRKTLILILELCSSEELLDRlyrkGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFG--- 6609
Cdd:PLN00034  143 HNGEIQVLLEFMDGGSLEGT----HIADEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLI--NSAKNVKIADFGvsr 216

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6610 -FAQNITPAElqfSQYGSPEFVSPEIIQQNPV-----SEASDIWAMGViSYLSLTCSS-PFA--GESDRATLLNVlegrV 6680
Cdd:PLN00034  217 iLAQTMDPCN---SSVGTIAYMSPERINTDLNhgaydGYAGDIWSLGV-SILEFYLGRfPFGvgRQGDWASLMCA----I 288

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6681 SWSSPMAA--HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKSMPAEEAHFINTKQL 6738
Cdd:PLN00034  289 CMSQPPEApaTASREFRHFISCCLQREPAKRWSAMQLLQHPFILRAQPGQGQGGPNLHQL 348
STKc_LATS cd05598
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the ...
 6466-6721 2.83e-25

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270749 [Multi-domain]  Cd Length: 333  Bit Score: 110.87  E-value: 2.83e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFipLRSRT---RAQAYR---ERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd05598     1 SMFEKIKTIGVGAFGEVSLVRKKDTNALYAMKT--LRKKDvlkRNQVAHvkaERDILAEADNEWVVKLYYSFQDKENLYF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFG------FAQN 6613
Cdd:cd05598    79 VMDYIPGGDLMSLLIKKGIFEEDLARFYIAELVCAIESVHKMGFIHRDIKPDNILI--DRDGHIKLTDFGlctgfrWTHD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 itpaelqfSQY-------GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPM 6686
Cdd:cd05598   157 --------SKYylahslvGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVINWRTTLKIPH 228

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 215274225 6687 AAHLSEDAKDFIKATLQRAPQ--ARPSAAQCLSHPWF 6721
Cdd:cd05598   229 EANLSPEAKDLILRLCCDAEDrlGRNGADEIKAHPFF 265
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
 7672-7924 2.98e-25

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 109.07  E-value: 2.98e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKG----------------LRHPHLAQLHAAY 7735
Cdd:cd14077     3 WEFVKTIGAGSMGKVKLAKHIRTGEKCAIKIIPRASNAGLKKEREKRLEKEisrdirtireaalsslLNHPHICRLRDFL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7736 LSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQS 7815
Cdd:cd14077    83 RTPNHYYMLFEYVDGGQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNL 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7816 LSQEKVLPSdkFKDYLETMAPELLEGQGAV-PQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCyagLS 7894
Cdd:cd14077   163 YDPRRLLRT--FCGSLYFAAPELLQAQPYTgPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVEYPSY---LS 237

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 7895 GGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14077   238 SECKSLISRMLVVDPKKRATLEQVLNHPWM 267
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 6468-6721 3.08e-25

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 110.78  E-value: 3.08e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQ----HKGNKiLCAAKF-----IPLRSRTRAQAYRERDILAALSH-PLVTGLLDQFETRKTL 6537
Cdd:cd05614     2 FELLKVLGTGAYGKVFLVRkvsgHDANK-LYAMKVlrkaaLVQKAKTVEHTRTERNVLEHVRQsPFLVTLHYAFQTDAKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPA 6617
Cdd:cd05614    81 HLILDYVSGGELFTHLYQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILL--DSEGHVVLTDFGLSKEFLTE 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQ--FSQYGSPEFVSPEIIQ-QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDA 6694
Cdd:cd05614   159 EKErtYSFCGTIEYMAPEIIRgKSGHGKAVDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRILKCDPPFPSFIGPVA 238

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 6695 KDFIKATLQRAPQAR----PSAAQCL-SHPWF 6721
Cdd:cd05614   239 RDLLQKLLCKDPKKRlgagPQGAQEIkEHPFF 270
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
 6509-6721 3.30e-25

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 109.28  E-value: 3.30e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6509 AYRERDIL-AALSHPLVTGLLDQFETRKTLILILELC--SSEELLD--RLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGV 6583
Cdd:cd13982    41 ADREVQLLrESDEHPNVIRYFCTEKDRQFLYIALELCaaSLQDLVEspRESKLFLRPGLEPVRLLRQIASGLAHLHSLNI 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6584 LHLDIKPSNILMVHPARED---IKICDFGFAQNITPAELQFSQY----GSPEFVSPEIIQQNP---VSEASDIWAMGVIS 6653
Cdd:cd13982   121 VHRDLKPQNILISTPNAHGnvrAMISDFGLCKKLDVGRSSFSRRsgvaGTSGWIAPEMLSGSTkrrQTRAVDIFSLGCVF 200

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6654 YLSLT-CSSPFAGESDRATllNVLEGRVSWSSPM-AAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd13982   201 YYVLSgGSHPFGDKLEREA--NILKGKYSLDKLLsLGEHGPEAQDLIERMIDFDPEKRPSAEEVLNHPFF 268
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
 7681-7924 3.44e-25

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 109.71  E-value: 3.44e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAK---IIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCsGPELLPCL 7757
Cdd:cd07833    12 GAYGVVLKCRNKATGEIVAIKkfkESEDDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYV-ERTLLELL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 -AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDkfkDYLET--- 7833
Cdd:cd07833    91 eASPGGLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPASPLT---DYVATrwy 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 MAPELLEGQGAV-PQTDIWAIGVTAFIMLSAE--YP------------------VSSEGARDLQ----RGLR----KGLV 7884
Cdd:cd07833   168 RAPELLVGDTNYgKPVDVWAIGCIMAELLDGEplFPgdsdidqlyliqkclgplPPSHQELFSSnprfAGVAfpepSQPE 247

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 215274225 7885 RLSRCYAG-LSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd07833   248 SLERRYPGkVSSPALDFLKACLRMDPKERLTCDELLQHPYF 288
STKc_MAPKAPK5 cd14171
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 6468-6720 3.60e-25

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271073 [Multi-domain]  Cd Length: 289  Bit Score: 109.47  E-value: 3.60e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEV--KEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERdilAALSHPLVTGLLD------QF----ETRK 6535
Cdd:cd14171     6 YEVnwTQKLGTGISGPVRVCVKKSTGERFALKILLDRPKARTEVRLHM---MCSGHPNIVQIYDvyansvQFpgesSPRA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 TLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARE-DIKICDFGFAQnI 6614
Cdd:cd14171    83 RLLIVMELMEGGELFDRISQHRHFTEKQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLKDNSEDaPIKLCDFGFAK-V 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQYgSPEFVSPEII--QQNPVSEAS---------------DIWAMGVISYLSLTCSSPFAGESDRATLLN--- 6674
Cdd:cd14171   162 DQGDLMTPQF-TPYYVAPQVLeaQRRHRKERSgiptsptpytydkscDMWSLGVIIYIMLCGYPPFYSEHPSRTITKdmk 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6675 --VLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14171   241 rkIMTGSYEFPEEEWSQISEMAKDIVRKLLCVDPEERMTIEEVLHHPW 288
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 6468-6710 3.92e-25

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 108.96  E-value: 3.92e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQ-HKGNKILCAAK---FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd08228     4 FQIEKKIGRGQFSEVYRATcLLDRKPVALKKvqiFEMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLEL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLY----RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFG----FAQNIT 6615
Cdd:cd08228    84 ADAGDLSQMIKyfkkQKRLIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFIT--ATGVVKLGDLGlgrfFSSKTT 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6616 PAElqfSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGesDRATLLNVLEGRVSWSSP--MAAHLSED 6693
Cdd:cd08228   162 AAH---SLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYG--DKMNLFSLCQKIEQCDYPplPTEHYSEK 236

                         250
                  ....*....|....*..
gi 215274225 6694 AKDFIKATLQRAPQARP 6710
Cdd:cd08228   237 LRELVSMCIYPDPDQRP 253
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7670-7924 6.37e-25

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 108.93  E-value: 6.37e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd14166     3 ETFIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDLGnaqSLS 7817
Cdd:cd14166    83 SGGELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLyltpdenskimITDFGLSKMEQNG---IMS 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7818 QEKVLPSdkfkdyleTMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGG 7896
Cdd:cd14166   160 TACGTPG--------YVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYYEFeSPFWDDISES 231

                         250       260
                  ....*....|....*....|....*...
gi 215274225 7897 AVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14166   232 AKDFIRHLLEKNPSKRYTCEKALSHPWI 259
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
 6474-6721 6.84e-25

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 109.58  E-value: 6.84e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP---LRSRTRA-QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05585     2 IGKGSFGKVMQVRKKDTSRIYALKTIRkahIVSRSEVtHTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFINGGEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQ-NITPAELQFSQYGSPE 6628
Cdd:cd05585    82 FHHLQREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYTGH--IALCDFGLCKlNMKDDDKTNTFCGTPE 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPmaahLSEDAKDFIKATLQRAPQA 6708
Cdd:cd05585   160 YLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRFPDG----FDRDAKDLLIGLLNRDPTK 235

                         250
                  ....*....|....*.
gi 215274225 6709 R---PSAAQCLSHPWF 6721
Cdd:cd05585   236 RlgyNGAQEIKNHPFF 251
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
 6468-6721 8.19e-25

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 108.28  E-value: 8.19e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHK-GNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07846     3 YENLGLVGEGSYGMVMKCRHKeTGQIVAIKKFLesEDDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SsEELLDRL--YRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNI-TPAELQF 6621
Cdd:cd07846    83 D-HTVLDDLekYPNGL-DESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGV--VKLCDFGFARTLaAPGEVYT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNP-VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE--GRVS-------WSSPMAA--- 6688
Cdd:cd07846   159 DYVATRWYRAPELLVGDTkYGKAVDVWAVGCLVTEMLTGEPLFPGDSDIDQLYHIIKclGNLIprhqelfQKNPLFAgvr 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6689 ---------------HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07846   239 lpevkeveplerrypKLSGVVIDLAKKCLHIDPDKRPSCSELLHHEFF 286
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
 7681-7924 9.71e-25

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 107.65  E-value: 9.71e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQC-WEKAS-GRALAAKIIPYH--PKD-KTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14080    11 GSYSKVKLAeYTKSGlKEKVACKIIDKKkaPKDfLEKFLpRELEILRKLRHPNIIQVYSIFERGSKVFIFMEYAEHGDLL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqslsqeKVLPSDKFKDYLETM 7834
Cdd:cd14080    91 EYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFA------RLCPDDDGDVLSKTF 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7835 -------APELLEGQGAVPQT-DIWAIGVTAFIMLSAEYPVS-SEGARDLQRGLRKGlVRLSRCYAGLSGGAVAFLRSTL 7905
Cdd:cd14080   165 cgsaayaAPEILQGIPYDPKKyDIWSLGVILYIMLCGSMPFDdSNIKKMLKDQQNRK-VRFPSSVKKLSPECKDLIDQLL 243

                         250
                  ....*....|....*....
gi 215274225 7906 CAQPWGRPCASSCLQCPWL 7924
Cdd:cd14080   244 EPDPTKRATIEEILNHPWL 262
I-set pfam07679
Immunoglobulin I-set domain;
5126-5216 1.01e-24

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 101.57  E-value: 1.01e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDqQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  5206 GVSSTKAELRV 5216
Cdd:pfam07679   80 GEAEASAELTV 90
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
 6509-6720 1.08e-24

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 107.79  E-value: 1.08e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6509 AYRERDILAALSHPLVTGLLDQFETRK-TLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSH--GVLH 6585
Cdd:cd13990    51 ALREYEIHKSLDHPRIVKLYDVFEIDTdSFCTVLEYCDGNDLDFYLKQHKSIPEREARSIIMQVVSALKYLNEIkpPIIH 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6586 LDIKPSNILMVHPARE-DIKICDFGFAQ-------NITPAELQFSQYGSPEFVSPEIIQQNP----VSEASDIWAMGVIS 6653
Cdd:cd13990   131 YDLKPGNILLHSGNVSgEIKITDFGLSKimddesyNSDGMELTSQGAGTYWYLPPECFVVGKtppkISSKVDVWSVGVIF 210

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6654 YLSLTCSSPFAGESDRA------TLLNVLEGrvswSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd13990   211 YQMLYGRKPFGHNQSQEaileenTILKATEV----EFPSKPVVSSEAKDFIRRCLTYRKEDRPDVLQLANDPY 279
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 6014-6104 1.18e-24

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 101.39  E-value: 1.18e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLT-GVDSGQYMCFAASA 6092
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATNQ 81

                          90
                  ....*....|..
gi 215274225 6093 AGNCSTLGKILV 6104
Cdd:cd20971    82 GGSVSGTASLEV 93
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
 6468-6668 1.38e-24

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 107.44  E-value: 1.38e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--------PLRSRTRAQAYRERDILAALS-HPLVTGLLDQFETRKTLI 6538
Cdd:cd13993     2 YQLISPIGEGAYGVVYLAVDLRTGRKYAIKCLyksgpnskDGNDFQKLPQLREIDLHRRVSrHPNIITLHDVFETEVAIY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLY-RKGVVTEAE-VKVYIQQLVEGLHYLHSHGVLHLDIKPSNIlMVHPAREDIKICDFGFA--QNI 6614
Cdd:cd13993    82 IVLEYCPNGDLFEAITeNRIYVGKTElIKNVFLQLIDAVKHCHSLGIYHRDIKPENI-LLSQDEGTVKLCDFGLAttEKI 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6615 TPaelQFSQyGSPEFVSPEIIQQNPVSEAS------DIWAMGVIsYLSLTCS-SPF--AGESD 6668
Cdd:cd13993   161 SM---DFGV-GSEFYMAPECFDEVGRSLKGypcaagDIWSLGII-LLNLTFGrNPWkiASESD 218
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
 6468-6719 1.47e-24

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 107.01  E-value: 1.47e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR-SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06613     2 YELIQRIGSGTYGDVYKARNIATGELAAVKVIKLEpGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITpAELQ--FSQY 6624
Cdd:cd06613    82 GSLQDIYQVTGPLSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTE--DGDVKLADFGVSAQLT-ATIAkrKSFI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQN---PVSEASDIWAMGvISYLSLTCSSP--FAGESDRATLL--------NVLEGRVSWSSPMaaHls 6691
Cdd:cd06613   159 GTPYWMAPEVAAVErkgGYDGKCDIWALG-ITAIELAELQPpmFDLHPMRALFLipksnfdpPKLKDKEKWSPDF--H-- 233

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6692 edakDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd06613   234 ----DFIKKCLTKNPKKRPTATKLLQHP 257
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 6472-6725 1.72e-24

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 107.51  E-value: 1.72e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRT--RAQAYRERDILAALSHPLVTGLLDQF--ETRKTLILILELCSSE 6547
Cdd:cd06621     7 SSLGEGAGGSVTKCRLRNTKTIFALKTITTDPNPdvQKQILRELEINKSCASPYIVKYYGAFldEQDSSIGIAMEYCEGG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELlDRLYRK-----GVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFA-QNITPAELQF 6621
Cdd:cd06621    87 SL-DSIYKKvkkkgGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLT--RKGQVKLCDFGVSgELVNSLAGTF 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SqyGSPEFVSPEIIQQNPVSEASDIWAMGV-ISYLSLTCsSPFAGE-SDRATLLNVLEGRVSWSSP-------MAAHLSE 6692
Cdd:cd06621   164 T--GTSYYMAPERIQGGPYSITSDVWSLGLtLLEVAQNR-FPFPPEgEPPLGPIELLSYIVNMPNPelkdepeNGIKWSE 240

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSHPWFLKSM 6725
Cdd:cd06621   241 SFKDFIEKCLEKDGTRRPGPWQMLAHPWIKAQE 273
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7672-7924 2.32e-24

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 106.65  E-value: 2.32e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKD--KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14167     5 YDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKALEgkETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVS 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDLGNAqsLSQ 7818
Cdd:cd14167    85 GGELFDRIVEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysldedskimISDFGLSKIEGSGSV--MST 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7819 EKVLPSdkfkdyleTMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCY-AGLSGGA 7897
Cdd:cd14167   163 ACGTPG--------YVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFDSPYwDDISDSA 234

                         250       260
                  ....*....|....*....|....*..
gi 215274225 7898 VAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14167   235 KDFIQHLMEKDPEKRFTCEQALQHPWI 261
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
 6467-6722 2.37e-24

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 106.53  E-value: 2.37e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKIlCAAKFIPLRSR---TRAQAYRERDILAALSH-PLVTGLLDQ--FETRKTLILI 6540
Cdd:cd14131     2 PYEILKQLGKGGSSKVYKVLNPKKKI-YALKRVDLEGAdeqTLQSYKNEIELLKKLKGsDRIIQLYDYevTDEDDYLYMV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LEL--CSSEELLdRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpaREDIKICDFGFAQNITPAE 6618
Cdd:cd14131    81 MECgeIDLATIL-KKKRPKPIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANFLLV---KGRLKLIDFGIAKAIQNDT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 ---LQFSQYGSPEFVSPEIIQQN----------PVSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVLEGRVSWSS 6684
Cdd:cd14131   157 tsiVRDSQVGTLNYMSPEAIKDTsasgegkpksKIGRPSDVWSLGCILYQMVYGKTPFQHITNpIAKLQAIIDPNHEIEF 236

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 215274225 6685 PmaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPwFL 6722
Cdd:cd14131   237 P--DIPNPDLIDVMKRCLQRDPKKRPSIPELLNHP-FL 271
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 6417-6723 2.99e-24

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 110.88  E-value: 2.99e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6417 RHVASKDAGVY-TCLAQNTGGQVLckaellvlgGDNEPdsekQSHrrklhsFYEVKEEIGRG--VFGFVK-RVQHKGNKI 6492
Cdd:PTZ00267   36 KYCADLDPEAYkKCVDLPEGEEVP---------ESNNP----REH------MYVLTTLVGRNptTAAFVAtRGSDPKEKV 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6493 LcaAKFIPLR-SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS----SEELLDRLYRKGVVTEAEVKVY 6567
Cdd:PTZ00267   97 V--AKFVMLNdERQAAYARSELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSggdlNKQIKQRLKEHLPFQEYEVGLL 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6568 IQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPA---ELQFSQYGSPEFVSPEIIQQNPVSEAS 6644
Cdd:PTZ00267  175 FYQIVLALDEVHSRKMMHRDLKSANIFLMPTGI--IKLGDFGFSKQYSDSvslDVASSFCGTPYYLAPELWERKRYSKKA 252

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6645 DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLsHPWFLK 6723
Cdd:PTZ00267  253 DMWSLGVILYELLTLHRPFKGPSQREIMQQVLYGKY---DPFPCPVSSGMKALLDPLLSKNPALRPTTQQLL-HTEFLK 327
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
 6472-6724 3.00e-24

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 106.70  E-value: 3.00e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFV-KRVQHKGNKILcAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd06641    10 EKIGKGSFGEVfKGIDNRTQKVV-AIKIIDLEEAEDEieDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGS 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFSQY-GSP 6627
Cdd:cd06641    89 ALD-LLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHG--EVKLADFGVAGQLTDTQIKRN*FvGTP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGvISYLSLTCSSPFAGESDRATLLNVLEGrvswSSP--MAAHLSEDAKDFIKATLQRA 6705
Cdd:cd06641   166 FWMAPEVIKQSAYDSKADIWSLG-ITAIELARGEPPHSELHPMKVLFLIPK----NNPptLEGNYSKPLKEFVEACLNKE 240

                         250
                  ....*....|....*....
gi 215274225 6706 PQARPSAAQCLSHPWFLKS 6724
Cdd:cd06641   241 PSFRPTAKELLKHKFILRN 259
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
 7680-7913 3.04e-24

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 105.78  E-value: 3.04e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPY----HPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14189    11 KGGFARCYEMTDLATNKTYAVKVIPHsrvaKPHQREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSLAH 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFKDYL---- 7831
Cdd:cd14189    91 IWKARHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLE-----PPEQRKKTIcgtp 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCyagLSGGAVAFLRSTLCAQPWG 7911
Cdd:cd14189   166 NYLAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDLKETYRCIKQVKYTLPAS---LSLPARHLLAGILKRNPGD 242


                  ..
gi 215274225 7912 RP 7913
Cdd:cd14189   243 RL 244
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
 6468-6720 3.56e-24

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 106.03  E-value: 3.56e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAK--FIPLRSRTR-------AQAYRERDILAALSHPLVTGLLDQFETRKTLI 6538
Cdd:cd14076     3 YILGRTLGEGEFGKVKLGWPLPKANHRSGVqvAIKLIRRDTqqencqtSKIMREINILKGLTHPNIVRLLDVLKTKKYIG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITP-- 6616
Cdd:cd14076    83 IVLEFVSGGELFDYILARRRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLL--DKNRNLVITDFGFANTFDHfn 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQQNPVSEAS--DIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-GRVSWSSPM--AAHLS 6691
Cdd:cd14076   161 GDLMSTSCGSPCYAAPELVVSDSMYAGRkaDIWSCGVILYAMLAGYLPFDDDPHNPNGDNVPRlYRYICNTPLifPEYVT 240

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14076   241 PKARDLLRRILVPNPRKRIRLSAIMRHAW 269
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
 6472-6712 3.81e-24

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 105.93  E-value: 3.81e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKIlcAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLdQFETRKTL----ILILELCS 6545
Cdd:cd13979     9 EPLGSGGFGSVYKATYKGETV--AVKIVRRRRKNRAsrQSFWAELNAARLRHENIVRVL-AAETGTDFaslgLIIMEYCG 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDI-KICDFGFAQNI-TPAELQFS 6622
Cdd:cd13979    86 NGTLQQLIYEgSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILI---SEQGVcKLCDFGCSVKLgEGNEVGTP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 ---QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESdRATLLNVLEGRVswsSPMAAHLSEDA----- 6694
Cdd:cd13979   163 rshIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYAGLR-QHVLYAVVAKDL---RPDLSGLEDSEfgqrl 238

                         250
                  ....*....|....*...
gi 215274225 6695 KDFIKATLQRAPQARPSA 6712
Cdd:cd13979   239 RSLISRCWSAQPAERPNA 256
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 6531-6739 5.28e-24

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 106.66  E-value: 5.28e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6531 FETRKTLILILELCSSEELLDRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDI-KICD 6607
Cdd:cd14170    68 YAGRKCLLIVMECLDGGELFSRIQDRGdqAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAIlKLTD 147

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6608 FGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE----GRVSWS 6683
Cdd:cd14170   148 FGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTrirmGQYEFP 227

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6684 SPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKSMPAEEAHFINTKQLK 6739
Cdd:cd14170   228 NPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKVPQTPLHTSRVLK 283
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
 7678-7866 5.63e-24

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 105.17  E-value: 5.63e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKT--------AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14071     8 IGKGNFAVVKLARHRITKTEVAIKII-----DKSqldeenlkKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEYAS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpsdkfkD 7829
Cdd:cd14071    83 NGEIFDYLAQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPG---------E 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 7830 YLET-------MAPELLEGQGAV-PQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14071   154 LLKTwcgsppyAAPEVFEGKEYEgPQLDIWSLGVVLYVLVCGALP 198
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
 6468-6720 6.55e-24

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 105.80  E-value: 6.55e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRV------QHKGNKILCAAKFI---------PLRSRTRAQA------------YRERDILAALS 6520
Cdd:cd14200     2 YKLQSEIGKGSYGVVKLAynesddKYYAMKVLSKKKLLkqygfprrpPPRGSKAAQGeqakplaplervYQEIAILKKLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6521 HPLVTGLLDQFE--TRKTLILILELcsseelldrlYRKGVV---------TEAEVKVYIQQLVEGLHYLHSHGVLHLDIK 6589
Cdd:cd14200    82 HVNIVKLIEVLDdpAEDNLYMVFDL----------LRKGPVmevpsdkpfSEDQARLYFRDIVLGIEYLHYQKIVHRDIK 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6590 PSNILMVHPARedIKICDFGFAQNITPAELQFSQY-GSPEFVSPEIIQQNPVS---EASDIWAMGVISYLSLTCSSPFAG 6665
Cdd:cd14200   152 PSNLLLGDDGH--VKIADFGVSNQFEGNDALLSSTaGTPAFMAPETLSDSGQSfsgKALDVWAMGVTLYCFVYGKCPFID 229

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6666 ESDRAtLLNVLEGRVSwSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14200   230 EFILA-LHNKIKNKPV-EFPEEPEISEELKDLILKMLDKNPETRITVPEIKVHPW 282
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
 7671-7866 7.05e-24

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 104.61  E-value: 7.05e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK---TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd06627     1 NYQLGDLIGRGAFGSVYKGLNLNTGEFVAIKQISLEKIPKsdlKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSdkf 7827
Cdd:cd06627    81 VENGSLASIIKKFGKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKDEN--- 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7828 kDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06627   158 -SVVGTpywMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPP 198
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
 6468-6720 8.06e-24

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 105.08  E-value: 8.06e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALS-HPLVTGLLDQFETRKTLI------LI 6540
Cdd:cd06608     8 FELVEVIGEGTYGKVYKARHKKTGQLAAIKIMDIIEDEEEEIKLEINILRKFSnHPNIATFYGAFIKKDPPGgddqlwLV 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELC---SSEELLDRLYRKGVVTEAEVKVYI-QQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAqnitp 6616
Cdd:cd06608    88 MEYCgggSVTDLVKGLRKKGKRLKEEWIAYIlRETLRGLAYLHENKVIHRDIKGQNILLTEEAE--VKLVDFGVS----- 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQ------YGSPEFVSPEII--QQNPVSE---ASDIWAMGvISYLSLTCSSPFAGE--SDRATLLNVLEGRVSWS 6683
Cdd:cd06608   161 AQLDSTLgrrntfIGTPYWMAPEVIacDQQPDASydaRCDVWSLG-ITAIELADGKPPLCDmhPMRALFKIPRNPPPTLK 239

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 215274225 6684 SPmaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06608   240 SP--EKWSKEFNDFISECLIKNYEQRPFTEELLEHPF 274
pk1 PHA03390
serine/threonine-protein kinase 1; Provisional
 6531-6703 8.15e-24

serine/threonine-protein kinase 1; Provisional


Pssm-ID: 223069 [Multi-domain]  Cd Length: 267  Bit Score: 104.94  E-value: 8.15e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6531 FETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvHPAREDIKICDFGF 6610
Cdd:PHA03390   78 VTTLKGHVLIMDYIKDGDLFDLLKKEGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLY-DRAKDRIYLCDYGL 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 AQNI-TPaelqfSQY-GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAA 6688
Cdd:PHA03390  157 CKIIgTP-----SCYdGTLDYFSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHPFKEDEDEELDLESLLKRQQKKLPFIK 231

                         170
                  ....*....|....*
gi 215274225 6689 HLSEDAKDFIKATLQ 6703
Cdd:PHA03390  232 NVSKNANDFVQSMLK 246
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
 7691-7924 1.00e-23

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 104.52  E-value: 1.00e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7691 EKASGRALAAKIIPYHPkdktAVLREYEALKGLRHPHLAQLHAAY-LSPRHLVLILELCSGPELLPCLAERAS--YSESE 7767
Cdd:cd14109    25 ERSTGRNFLAQLRYGDP----FLMREVDIHNSLDHPNIVQMHDAYdDEKLAVTVIDNLASTIELVRDNLLPGKdyYTERQ 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7768 VKDYLWQMLSATQYLHNQHILHLDLRSENMIItEYNLLKVVDLGNAQSLSQEKVLPSDKFKDylETMAPELLEGQGAVPQ 7847
Cdd:cd14109   101 VAVFVRQLLLALKHMHDLGIAHLDLRPEDILL-QDDKLKLADFGQSRRLLRGKLTTLIYGSP--EFVSPEIVNSYPVTLA 177

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 7848 TDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14109   178 TDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWSFdSSPLGNISDDARDFIKKLLVYIPESRLTVDEALNHPWF 255
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
 6511-6718 1.08e-23

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 103.73  E-value: 1.08e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6511 RERDI--LAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDI 6588
Cdd:cd14059    28 KETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEVLRAGREITPSLLVDWSKQIASGMNYLHLHKIIHRDL 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6589 KPSNILMVHpaREDIKICDFGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD 6668
Cdd:cd14059   108 KSPNVLVTY--NDVLKISDFGTSKELSEKSTKMSFAGTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTGEIPYKDVDS 185

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6669 RATLLNVleGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14059   186 SAIIWGV--GSNSLQLPVPSTCPDGFKLLMKQCWNSKPRNRPSFRQILMH 233
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
 7678-7866 1.22e-23

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 105.05  E-value: 1.22e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---------KTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14181    18 IGRGVSSVVRRCVHRHTGQEFAVKIIEVTAERlspeqleevRSSTLKEIHILRQVSgHPSIITLIDSYESSTFIFLVFDL 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKF 7827
Cdd:cd14181    98 MRRGELFDYLTEKVTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLE-----PGEKL 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYLET---MAPELL--------EGQGAvpQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14181   173 RELCGTpgyLAPEILkcsmdethPGYGK--EVDLWACGVILFTLLAGSPP 220
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 6468-6721 1.23e-23

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 107.39  E-value: 1.23e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCA----AKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05621    54 YDVVKVIGRGAFGEVQLVRHKASQKVYAmkllSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEY 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQF-- 6621
Cdd:cd05621   134 MPGGDLVN-LMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKYGH--LKLADFGTCMKMDETGMVHcd 210

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNP----VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDF 6697
Cdd:cd05621   211 TAVGTPDYISPEVLKSQGgdgyYGRECDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIMDHKNSLNFPDDVEISKHAKNL 290

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6698 IKATL--QRAPQARPSAAQCLSHPWF 6721
Cdd:cd05621   291 ICAFLtdREVRLGRNGVEEIKQHPFF 316
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 7677-7864 1.35e-23

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 103.85  E-value: 1.35e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLR----HPHLAQLHAAYLSP--RHLVLILELCsG 7750
Cdd:cd05118     6 KIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLNdvegHPNIVKLLDVFEHRggNHLCLVFELM-G 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSEN-MIITEYNLLKVVDLGNAQSLSQEkvlPSDKFK 7828
Cdd:cd05118    85 MNLYELIKDYPRgLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENiLINLELGQLKLADFGLARSFTSP---PYTPYV 161

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7829 DYLETMAPELLEGQGAVPQT-DIWAIGVTAFIMLSAE 7864
Cdd:cd05118   162 ATRWYRAPEVLLGAKPYGSSiDIWSLGCILAELLTGR 198
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
 7678-7933 1.45e-23

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 105.32  E-value: 1.45e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPY-----HPKDKTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14094    11 IGKGPFSVVRRCIHRETGQQFAVKIVDVakftsSPGLSTEDLkREASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGA 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERAS----YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL---LKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd14094    91 DLCFEIVKRADagfvYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLLASKENsapVKLGGFGVAIQLGESGLVAG 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 DKFkDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARdLQRGLRKGLVRLS-RCYAGLSGGAVAFLRS 7903
Cdd:cd14094   171 GRV-GTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNpRQWSHISESAKDLVRR 248

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 7904 TLCAQPWGRPCASSCLQCPWLTEEGPACSR 7933
Cdd:cd14094   249 MLMLDPAERITVYEALNHPWIKERDRYAYR 278
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 6474-6721 2.11e-23

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 103.66  E-value: 2.11e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRS---RTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd08221     8 LGRGAFGEAVLYRKTEDNSLVVWKEVNLSRlseKERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCNGGNLH 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYR-KGVVTEAEVKV-YIQQLVEGLHYLHSHGVLHLDIKPSNILMVHParEDIKICDFGFAQNI-TPAELQFSQYGSP 6627
Cdd:cd08221    88 DKIAQqKNQLFPEEVVLwYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKA--DLVKLGDFGISKVLdSESSMAESIVGTP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMaahLSEDAKDFIKATLQRAPQ 6707
Cdd:cd08221   166 YYMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTFDATNPLRLAVKIVQGEYEDIDEQ---YSEEIIQLVHDCLHQDPE 242

                         250
                  ....*....|....
gi 215274225 6708 ARPSAAQCLSHPWF 6721
Cdd:cd08221   243 DRPTAEELLERPLL 256
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 6451-6721 2.78e-23

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270747 [Multi-domain]  Cd Length: 352  Bit Score: 105.54  E-value: 2.78e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6451 NEPDSEKQSHRRKLHSFYEVKEeIGRGVFGFVKRVQHKGNKILCA----AKFIPLRSRTRAQAYRERDILAALSHPLVTG 6526
Cdd:cd05596    12 EKPVNEITKLRMNAEDFDVIKV-IGRGAFGEVQLVRHKSTKKVYAmkllSKFEMIKRSDSAFFWEERDIMAHANSEWIVQ 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6527 LLDQFETRKTLILILELCSSEELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKIC 6606
Cdd:cd05596    91 LHYAFQDDKYLYMVMDYMPGGDLVN-LMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLL--DASGHLKLA 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6607 DFGFAQNITPAELQFSQ--YGSPEFVSPEIIQ----QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRV 6680
Cdd:cd05596   168 DFGTCMKMDKDGLVRSDtaVGTPDYISPEVLKsqggDGVYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYGKIMNHKN 247

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 215274225 6681 SWSSPMAAHLSEDAKDFIKATLQRAPQ--ARPSAAQCLSHPWF 6721
Cdd:cd05596   248 SLQFPDDVEISKDAKSLICAFLTDREVrlGRNGIEEIKAHPFF 290
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
 7672-7878 2.96e-23

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 102.85  E-value: 2.96e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAK--IIP-YHPKDKTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd13997     2 FHELEQIGSGSFSEVFKVRSKVDGCLYAVKksKKPfRGPKERARALREVEAHAALgQHPNIVRYYSSWEEGGHLYIQMEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAE---RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsqekvlps 7824
Cdd:cd13997    82 CENGSLQDALEElspISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRL-------- 153

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 DKFKDYLET----MAPELLEGQGA-VPQTDIWAIGVTAFIMLSA-EYPVSSEGARDLQRG 7878
Cdd:cd13997   154 ETSGDVEEGdsryLAPELLNENYThLPKADIFSLGVTVYEAATGePLPRNGQQWQQLRQG 213
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
 7678-7924 3.14e-23

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 103.00  E-value: 3.14e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14087     9 IGRGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDRI 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII----TEYNLLkVVDLGNAqslSQEKVLPSDKFKDYL-- 7831
Cdd:cd14087    89 IAKGSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYyhpgPDSKIM-ITDFGLA---STRKKGPNCLMKTTCgt 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 -ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLS-RCYAGLSGGAVAFLRSTLCAQP 7909
Cdd:cd14087   165 pEYIAPEILLRKPYTQSVDMWAVGVIAYILLSGTMPFDDDNRTRLYRQILRAKYSYSgEPWPSVSNLAKDFIDRLLTVNP 244

                         250
                  ....*....|....*
gi 215274225 7910 WGRPCASSCLQCPWL 7924
Cdd:cd14087   245 GERLSATQALKHPWI 259
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 6469-6723 3.24e-23

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 103.78  E-value: 3.24e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06622     4 EVLDELGKGNYGSVYKVLHRPTGVTMAMKEIrlELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELlDRLYRKGVVT----EAEVKVYIQQLVEGLHYL-HSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITpAELQF 6621
Cdd:cd06622    84 GSL-DKLYAGGVATegipEDVLRRITYAVVKGLKFLkEEHNIIHRDVKPTNVLV--NGNGQVKLCDFGVSGNLV-ASLAK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQ-----QNPV-SEASDIWAMGV-ISYLSLTCSsPFAGESdRATLLNVLEGRVSWSSP-MAAHLSED 6693
Cdd:cd06622   160 TNIGCQSYMAPERIKsggpnQNPTyTVQSDVWSLGLsILEMALGRY-PYPPET-YANIFAQLSAIVDGDPPtLPSGYSDD 237

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPWFLK 6723
Cdd:cd06622   238 AQDFVAKCLNKIPNRRPTYAQLLEHPWLVK 267
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
 6474-6709 3.25e-23

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 105.10  E-value: 3.25e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAA-LSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05602    15 IGKGSFGKVLLARHKSDEKFYAVKVLQkkaiLKKKEEKHIMSERNVLLKnVKHPFLVGLHFSFQTTDKLYFVLDYINGGE 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05602    95 LFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILL--DSQGHIVLTDFGLCkENIEPNGTTSTFCGTP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05602   173 EYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQ----LKPNITNSARHLLEGLLQKDRT 248


                  ..
gi 215274225 6708 AR 6709
Cdd:cd05602   249 KR 250
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
 6474-6721 4.44e-23

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 104.39  E-value: 4.44e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNK----ILCAAKFIPLRSRTRAQAYRERDILA-ALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05592     3 LGKGSFGKVMLAELKGTNqyfaIKALKKDVVLEDDDVECTMIERRVLAlASQHPFLTHLFCTFQTESHLFFVMEYLNGGD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05592    83 LMFHIQQSGRFDEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGH--IKIADFGMCkENIYGENKASTFCGTP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05592   161 DYIAPEILKGQKYNQSVDWWSFGVLLYEMLIGQSPFHGEDEDELFWSICNDTPHYPR----WLTKEAASCLSLLLERNPE 236

                         250
                  ....*....|....*....
gi 215274225 6708 ARPSAAQCL-----SHPWF 6721
Cdd:cd05592   237 KRLGVPECPagdirDHPFF 255
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 6468-6723 4.46e-23

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 103.54  E-value: 4.46e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFG---FVKRVQHKGNKILCAAKF-----IPLRSRTRAQAYRERDILAALSH-PLVTGLLDQFETRKTLI 6538
Cdd:cd05613     2 FELLKVLGTGAYGkvfLVRKVSGHDAGKLYAMKVlkkatIVQKAKTAEHTRTERQVLEHIRQsPFLVTLHYAFQTDTKLH 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAE 6618
Cdd:cd05613    82 LILDYINGGELFTHLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILL--DSSGHVVLTDFGLSKEFLLDE 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQ--FSQYGSPEFVSPEIIQ--QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDA 6694
Cdd:cd05613   160 NEraYSFCGTIEYMAPEIVRggDSGHDKAVDWWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYPQEMSALA 239

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 6695 KDFIKATLQRAPQAR----PSAAQCL-SHPWFLK 6723
Cdd:cd05613   240 KDIIQRLLMKDPKKRlgcgPNGADEIkKHPFFQK 273
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
 7677-7858 5.10e-23

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 102.33  E-value: 5.10e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGpEL 7753
Cdd:cd14002     8 LIGEGSFGKVYKGRRKYTGQVVALKFIPKRgksEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYAQG-EL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEK-VLPSDKfkdylE 7832
Cdd:cd14002    87 FQILEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNTlVLTSIK-----G 161

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7833 T---MAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd14002   162 TplyMAPELVQEQPYDHTADLWSLGCILY 190
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
 7678-7886 5.58e-23

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 102.21  E-value: 5.58e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14072     8 IGKGNFAKVKLARHVLTGREVAIKIIdktQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVF 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLpsDKFKDYLETM 7834
Cdd:cd14072    88 DYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPGNKL--DTFCGSPPYA 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7835 APELLEGQ---GavPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL 7886
Cdd:cd14072   166 APELFQGKkydG--PEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRI 218
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
 6474-6721 5.73e-23

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 104.22  E-value: 5.73e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILA-ALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05590     3 LGKGSFGKVMLARLKESGRLYAVKVLKkdviLQDDDVECTMTEKRILSlARNHPFLTQLYCCFQTPDRLFFVMEFVNGGD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05590    83 LMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGH--CKLADFGMCkEGIFNGKTTSTFCGTP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05590   161 DYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPT----WLSQDAVDILKAFMTKNPT 236

                         250       260
                  ....*....|....*....|
gi 215274225 6708 ARPSA------AQCLSHPWF 6721
Cdd:cd05590   237 MRLGSltlggeEAILRHPFF 256
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
 6474-6721 6.74e-23

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270739 [Multi-domain]  Cd Length: 320  Bit Score: 103.63  E-value: 6.74e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQ------AYRERDILAALSHP-LVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd05587     4 LGKGSFGKVMLAERKGTDELYAIKI--LKKDVIIQdddvecTMVEKRVLALSGKPpFLTQLHSCFQTMDRLYFVMEYVNG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYG 6625
Cdd:cd05587    82 GDLMYHIQQVGKFKEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVML--DAEGHIKIADFGMCkEGIFGGKTTRTFCG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAahLSEDAKDFIKATLQRA 6705
Cdd:cd05587   160 TPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSY--PKS--LSKEAVSICKGLLTKH 235

                         250       260
                  ....*....|....*....|.
gi 215274225 6706 PQAR----PSAAQCL-SHPWF 6721
Cdd:cd05587   236 PAKRlgcgPTGERDIkEHPFF 256
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 6468-6718 9.17e-23

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 102.26  E-value: 9.17e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKT--------- 6536
Cdd:cd14048     8 FEPIQCLGRGGFGVVFEAKNKVDDCNYAVKRIrlPNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPPegwqekmde 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 --LILILELCSSEELLDRLYRKGVVTEAEVKV---YIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFA 6611
Cdd:cd14048    88 vyLYIQMQLCRKENLKDWMNRRCTMESRELFVclnIFKQIASAVEYLHSKGLIHRDLKPSNVFFS--LDDVVKVGDFGLV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAELQFS-------------QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTcssPFAGESDRA-TLLNVLE 6677
Cdd:cd14048   166 TAMDQGEPEQTvltpmpayakhtgQVGTRLYMSPEQIHGNQYSEKVDIFALGLILFELIY---SFSTQMERIrTLTDVRK 242

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 215274225 6678 GRVswsSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14048   243 LKF---PALFTNKYPEERDMVQQMLSPSPSERPEAHEVIEH 280
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
 7677-7855 1.05e-22

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 101.39  E-value: 1.05e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd08215     7 VIGKGSFGSAYLVRRKSDGKLYVLKEIDLSnmsEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYADGGDL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERAS----YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqslsqeKVLPSDkfKD 7829
Cdd:cd08215    87 AQKIKKQKKkgqpFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGIS------KVLEST--TD 158

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 215274225 7830 YLET-------MAPELLEGQgavP---QTDIWAIGV 7855
Cdd:cd08215   159 LAKTvvgtpyyLSPELCENK---PynyKSDIWALGC 191
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 6468-6721 1.09e-22

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270772 [Multi-domain]  Cd Length: 405  Bit Score: 105.09  E-value: 1.09e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCA----AKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05622    75 YEVVKVIGRGAFGEVQLVRHKSTRKVYAmkllSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEY 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQF-- 6621
Cdd:cd05622   155 MPGGDLVN-LMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGH--LKLADFGTCMKMNKEGMVRcd 231

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNP----VSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDF 6697
Cdd:cd05622   232 TAVGTPDYISPEVLKSQGgdgyYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFPDDNDISKEAKNL 311

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6698 IKATL--QRAPQARPSAAQCLSHPWF 6721
Cdd:cd05622   312 ICAFLtdREVRLGRNGVEEIKRHLFF 337
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 7672-7886 1.26e-22

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 101.22  E-value: 1.26e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14665     2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII--TEYNLLKVVDLGNAQSlsqeKVLPSDKfKD 7829
Cdd:cd14665    82 ELFERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKS----SVLHSQP-KS 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7830 YLET---MAPELL---EGQGAVpqTDIWAIGVTAFIMLSAEYPVSSEgarDLQRGLRKGLVRL 7886
Cdd:cd14665   157 TVGTpayIAPEVLlkkEYDGKI--ADVWSCGVTLYVMLVGAYPFEDP---EEPRNFRKTIQRI 214
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
 6472-6723 1.26e-22

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 101.67  E-value: 1.26e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd06642    10 ERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGSA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQY-GSPE 6628
Cdd:cd06642    90 LD-LLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLL--SEQGDVKLADFGVAGQLTDTQIKRNTFvGTPF 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEgrvswSSP--MAAHLSEDAKDFIKATLQRAP 6706
Cdd:cd06642   167 WMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPK-----NSPptLEGQHSKPFKEFVEACLNKDP 241

                         250
                  ....*....|....*..
gi 215274225 6707 QARPSAAQCLSHPWFLK 6723
Cdd:cd06642   242 RFRPTAKELLKHKFITR 258
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
 7672-7924 1.32e-22

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 101.23  E-value: 1.32e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKII-PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14191     4 YDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFkAYSAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLP-CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEY--NLLKVVDLGNAQSLSQE---KVLPS 7824
Cdd:cd14191    84 GELFErIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKtgTKIKLIDFGLARRLENAgslKVLFG 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 DKfkdylETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLS-RCYAGLSGGAVAFLRS 7903
Cdd:cd14191   164 TP-----EFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDdEAFDEISDDAKDFISN 238

                         250       260
                  ....*....|....*....|.
gi 215274225 7904 TLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14191   239 LLKKDMKARLTCTQCLQHPWL 259
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
 7678-7866 1.39e-22

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 101.23  E-value: 1.39e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQC--WEKASGRALAAKIipYHPKDKTA--------VLREYEALKGLRHPHLAQLHAAYLSP-RHLVLILE 7746
Cdd:cd13994     1 IGKGATSVVRIVtkKNPRSGVLYAVKE--YRRRDDESkrkdyvkrLTSEYIISSKLHHPNIVKVLDLCQDLhGKWCLVME 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL--SQEKVLP- 7823
Cdd:cd13994    79 YCPGGDLFTLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEVFgmPAEKESPm 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7824 SDKFKDYLETMAPELLEGQGAVPQ-TDIWAIGVTAFIMLSAEYP 7866
Cdd:cd13994   159 SAGLCGSEPYMAPEVFTSGSYDGRaVDVWSCGIVLFALFTGRFP 202
STKc_NDR_like_fungal cd05629
Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs ...
 6467-6721 1.42e-22

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270778 [Multi-domain]  Cd Length: 377  Bit Score: 104.16  E-value: 1.42e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEeIGRGVFGFVKRVQHKGNKILCAAKFIpLRSRT-----RAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd05629     3 FHTVKV-IGKGAFGEVRLVQKKDTGKIYAMKTL-LKSEMfkkdqLAHVKAERDVLAESDSPWVVSLYYSFQDAQYLYLIM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQ--------- 6612
Cdd:cd05629    81 EFLPGGDLMTMLIKYDTFSEDVTRFYMAECVLAIEAVHKLGFIHRDIKPDNILI--DRGGHIKLSDFGLSTgfhkqhdsa 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 --------------------------NITPAE-------------LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVIS 6653
Cdd:cd05629   159 yyqkllqgksnknridnrnsvavdsiNLTMSSkdqiatwkknrrlMAYSTVGTPDYIAPEIFLQQGYGQECDWWSLGAIM 238

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6654 YLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQ--ARPSAAQCLSHPWF 6721
Cdd:cd05629   239 FECLIGWPPFCSENSHETYRKIINWRETLYFPDDIHLSVEAEDLIRRLITNAENrlGRGGAHEIKSHPFF 308
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 6466-6720 1.58e-22

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 101.40  E-value: 1.58e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR--AQAYRERDILAALSH---PLVTGLLDQFETRKTLILI 6540
Cdd:cd06917     1 SLYRRLELVGRGSYGAVYRGYHVKTGRVVALKVLNLDTDDDdvSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWII 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELlDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQ 6620
Cdd:cd06917    81 MDYCEGGSI-RTLMRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTGN--VKLCDFGVAASLNQNSSK 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQY-GSPEFVSPEIIQQNPVSEA-SDIWAMGVISYLSLTCSSPFAG-ESDRATLLNV------LEGRvSWSSPMaahls 6691
Cdd:cd06917   158 RSTFvGTPYWMAPEVITEGKYYDTkADIWSLGITTYEMATGNPPYSDvDALRAVMLIPkskpprLEGN-GYSPLL----- 231

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6692 edaKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06917   232 ---KEFVAACLDEEPKDRLSADELLKSKW 257
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7677-7935 1.79e-22

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 101.73  E-value: 1.79e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd14086     8 ELGKGAFSVVRRCVQKSTGQEFAAKIIntkKLSARDHQKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTGGEL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKvlpsDKFKDY 7830
Cdd:cd14086    88 FEDIVAREFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASKSkgaAVKLADFGLAIEVQGDQ----QAWFGF 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 LET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL-SRCYAGLSGGAVAFLRSTLC 7906
Cdd:cd14086   164 AGTpgyLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYDYpSPEWDTVTPEAKDLINQMLT 243

                         250       260
                  ....*....|....*....|....*....
gi 215274225 7907 AQPWGRPCASSCLQCPWLTEegpaCSRPA 7935
Cdd:cd14086   244 VNPAKRITAAEALKHPWICQ----RDRVA 268
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
 6472-6748 1.97e-22

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 101.28  E-value: 1.97e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd06640    10 ERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGSA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFSQY-GSPE 6628
Cdd:cd06640    90 LD-LLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQG--DVKLADFGVAGQLTDTQIKRNTFvGTPF 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGvISYLSLTCSSPfaGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQA 6708
Cdd:cd06640   167 WMAPEVIQQSAYDSKADIWSLG-ITAIELAKGEP--PNSDMHPMRVLFLIPKNNPPTLVGDFSKPFKEFIDACLNKDPSF 243

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 215274225 6709 RPSAAQCLSHPWFLKsmpaeeaHFINTKQLKFLLAR-SRWQ 6748
Cdd:cd06640   244 RPTAKELLKHKFIVK-------NAKKTSYLTELIDRfKRWK 277
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
 7672-7884 2.53e-22

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 100.45  E-value: 2.53e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH--PKD-KTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14162     2 YIVGKTLGHGSYAVVKKAYSTKHKCKVAIKIVSKKkaPEDyLQKFLpREIEVIKGLKHPNLICFYEAIETTSRVYIIMEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSlsqeKVLPSDKF 7827
Cdd:cd14162    82 AENGDLLDYIRKNGALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFARG----VMKTKDGK 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7828 KDYLETM-------APELLEGQGAVPQ-TDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLV 7884
Cdd:cd14162   158 PKLSETYcgsyayaSPEILRGIPYDPFlSDIWSMGVVLYTMVYGRLPFDDSNLKVLLKQVQRRVV 222
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
 6468-6721 2.98e-22

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 100.81  E-value: 2.98e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKfiplrsRTRAQAYRE-------RDI-----LAALSHPLVTGLLDQFET-- 6533
Cdd:cd07838     1 YEEVAEIGEGAYGTVYKARDLQDGRFVALK------KVRVPLSEEgiplstiREIallkqLESFEHPNVVRLLDVCHGpr 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 --RKTLI-LILELCSSE--ELLDRLYRKGVVTEAeVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDF 6608
Cdd:cd07838    75 tdRELKLtLVFEHVDQDlaTYLDKCPKPGLPPET-IKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVT--SDGQVKLADF 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6609 GFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYlSLTCSSP-FAGESDRATLLNVLE--GR------ 6679
Cdd:cd07838   152 GLARIYSFEMALTSVVVTLWYRAPEVLLQSSYATPVDMWSVGCIFA-ELFNRRPlFRGSSEADQLGKIFDviGLpseeew 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6680 -----VSWSS-------PMAA---HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07838   231 prnsaLPRSSfpsytprPFKSfvpEIDEEGLDLLKKMLTFNPHKRISAFEALQHPYF 287
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 7670-7931 3.01e-22

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 101.28  E-value: 3.01e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP--KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14168    10 KIFEFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKAlkGKESSIENEIAVLRKIKHENIVALEDIYESPNHLYLVMQL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDLGNAQSL 7816
Cdd:cd14168    90 VSGGELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLyfsqdeeskimISDFGLSKMEGKGDVMST 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7817 SQEKvlPSdkfkdyleTMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCY-AGLSG 7895
Cdd:cd14168   170 ACGT--PG--------YVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKADYEFDSPYwDDISD 239

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 215274225 7896 GAVAFLRSTLCAQPWGRPCASSCLQCPWLTEEGPAC 7931
Cdd:cd14168   240 SAKDFIRNLMEKDPNKRYTCEQALRHPWIAGDTALC 275
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
 6468-6721 3.18e-22

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 101.10  E-value: 3.18e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRS------RTraqAYRERDILAALSHPLVTGLLD------QFETRK 6535
Cdd:cd07840     1 YEKIAQIGEGTYGQVYKARNKKTGELVALKKIRMENekegfpIT---AIREIKLLQKLDHPNVVRLKEivtskgSAKYKG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 TLILILELCSsEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNI 6614
Cdd:cd07840    78 SIYMVFEYMD-HDLTGLLDNPEVkFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINN--DGVLKLADFGLARPY 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQ-FSQ------YGSPEFV------SPEIiqqnpvseasDIWAMGVISYLSLTCSSPFAGESDratlLNVLE---- 6677
Cdd:cd07840   155 TKENNAdYTNrvitlwYRPPELLlgatryGPEV----------DMWSVGCILAELFTGKPIFQGKTE----LEQLEkife 220

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6678 --GRV---SWSS----PMAAHL------------------SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07840   221 lcGSPteeNWPGvsdlPWFENLkpkkpykrrlrevfknviDPSALDLLDKLLTLDPKKRISADQALQHEYF 291
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
 6468-6721 3.35e-22

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 100.81  E-value: 3.35e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILA--ALS-HPLVTGLLDQFETRKT--LILILE 6542
Cdd:cd07831     1 YKILGKIGEGTFSEVLKAQSRKTGKYYAIKCMKKHFKSLEQVNNLREIQAlrRLSpHPNILRLIEVLFDRKTgrLALVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LcsseelLD-RLY-----RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDIKICDFGFAQNITp 6616
Cdd:cd07831    81 L------MDmNLYelikgRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILI---KDDILKLADFGSCRGIY- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPE-FVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGES---------------DRATLLNVLEGR 6679
Cdd:cd07831   151 SKPPYTEYISTRwYRAPECLLTDGYyGPKMDIWAVGCVFFEILSLFPLFPGTNeldqiakihdvlgtpDAEVLKKFRKSR 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6680 V----------SWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07831   231 HmnynfpskkgTGLRKLLPNASAEGLDLLKKLLAYDPDERITAKQALRHPYF 282
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
 7678-7879 3.98e-22

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 99.72  E-value: 3.98e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA-------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14184     9 IGDGNFAVVKECVERSTGKEFALKII-----DKAKccgkehlIENEVSILRRVKHPNIIMLIEEMDTPAELYLVMELVKG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEY----NLLKVVDLGNAQSLSQekvlPSDK 7826
Cdd:cd14184    84 GDLFDAITSSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCEYpdgtKSLKLGDFGLATVVEG----PLYT 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7827 FKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGarDLQRGL 7879
Cdd:cd14184   160 VCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSEN--NLQEDL 210
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
 7675-7924 4.15e-22

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 99.71  E-value: 4.15e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7675 QTqIQRGRFSVVRQCWEKASGRALAAKII--PYHPKD-KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14069     7 QT-LGEGAFGEVFLAVNRNTEEAVAVKFVdmKRAPGDcPENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLEYASGG 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLS---QEKVLpsDKFK 7828
Cdd:cd14069    86 ELFDKIEPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFRykgKERLL--NKMC 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 DYLETMAPELLEGQG-AVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRC-YAGLSGGAVAFLRSTLC 7906
Cdd:cd14069   164 GTLPYVAPELLAKKKyRAEPVDVWSCGIVLFAMLAGELPWDQPSDSCQEYSDWKENKKTYLTpWKKIDTAALSLLRKILT 243

                         250
                  ....*....|....*...
gi 215274225 7907 AQPWGRPCASSCLQCPWL 7924
Cdd:cd14069   244 ENPNKRITIEDIKKHPWY 261
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
 6474-6709 4.64e-22

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 101.23  E-value: 4.64e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHP-LVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05616     8 LGKGSFGKVMLAERKGTDELYAVKILKkdvvIQDDDVECTMVEKRVLALSGKPpFLTQLHSCFQTMDRLYFVMEYVNGGD 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05616    88 LMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVML--DSEGHIKIADFGMCkENIWDGVTTKTFCGTP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMaahlSEDAKDFIKATLQRAPQ 6707
Cdd:cd05616   166 DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSM----SKEAVAICKGLMTKHPG 241


                  ..
gi 215274225 6708 AR 6709
Cdd:cd05616   242 KR 243
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
 6474-6720 4.73e-22

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 99.71  E-value: 4.73e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQA-YRERDILAALS-HPLVTGLLD-QFETRKTLILILELCSSEELL 6550
Cdd:cd13987     1 LGEGTYGKVLLAVHKGSGTKMALKFVP-KPSTKLKDfLREYNISLELSvHPHIIKTYDvAFETEDYYVFAQEYAPYGDLF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQnITPAELQFSQYGSPeFV 6630
Cdd:cd13987    80 SIIPPQVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLFDKDCRRVKLCDFGLTR-RVGSTVKRVSGTIP-YT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6631 SPEIIQQNP-----VSEASDIWAMGVISYLSLTCSSPF--AGESDR--ATLLNVLEGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:cd13987   158 APEVCEAKKnegfvVDPSIDVWAFGVLLFCCLTGNFPWekADSDDQfyEEFVRWQKRKNTAVPSQWRRFTPKALRMFKKL 237

                         250       260
                  ....*....|....*....|..
gi 215274225 6702 LQRAPQARPSAAQ---CLSHPW 6720
Cdd:cd13987   238 LAPEPERRCSIKEvfkYLGDRW 259
PKc_DYRK cd14210
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
 6468-6721 5.52e-22

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.


Pssm-ID: 271112 [Multi-domain]  Cd Length: 311  Bit Score: 100.70  E-value: 5.52e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRV-QHKGNKiLCAAKFIPLRSRTRAQAYRERDILAAL-------SHPLVTgLLDQFETRKTLIL 6539
Cdd:cd14210    15 YEVLSVLGKGSFGQVVKClDHKTGQ-LVAIKIIRNKKRFHQQALVEVKILKHLndndpddKHNIVR-YKDSFIFRGHLCI 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSE--ELLDRLYRKGVVTEAeVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFG---FAQNI 6614
Cdd:cd14210    93 VFELLSINlyELLKSNNFQGLSLSL-IRKFAKQILQALQFLHKLNIIHCDLKPENILLKQPSKSSIKVIDFGsscFEGEK 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQfSQYgspeFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES--------------------DRATLLN 6674
Cdd:cd14210   172 VYTYIQ-SRF----YRAPEVILGLPYDTAIDMWSLGCILAELYTGYPLFPGENeeeqlacimevlgvppksliDKASRRK 246

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6675 VL----------------EGRVSWSSPMAAHLSEDAK--DFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14210   247 KFfdsngkprpttnskgkKRRPGSKSLAQVLKCDDPSflDFLKKCLRWDPSERMTPEEALQHPWI 311
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
 6468-6721 6.79e-22

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 99.67  E-value: 6.79e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07835     1 YQKLEKIGEGTYGVVYKARDKLTGEIVALKKIRLETEDEgvpSTAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEFL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSE--ELLDRLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQnitpaelqfs 6622
Cdd:cd07835    81 DLDlkKYMDSSPLTGL-DPPLIKSYLYQLLQGIAFCHSHRVLHRDLKPQNLLI--DTEGALKLADFGLAR---------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSP------EFV-----SPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSW--- 6682
Cdd:cd07835   148 AFGVPvrtythEVVtlwyrAPEIlLGSKHYSTPVDIWSVGCIFAEMVTRRPLFPGDSEIDQLFRIFRtlgtpDEDVWpgv 227

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6683 --------------SSPMAAH---LSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07835   228 tslpdykptfpkwaRQDLSKVvpsLDEDGLDLLSQMLVYDPAKRISAKAALQHPYF 283
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
 6472-6721 1.13e-21

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 98.45  E-value: 1.13e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRV--QHKGNKIL-CAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFET--RKTLILILELCSS 6546
Cdd:cd13983     7 EVLGRGSFKTVYRAfdTEEGIEVAwNEIKLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDSWESksKKEVIFITELMTS 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILmVHPAREDIKICDFGFAqnitpAELQFSQ- 6623
Cdd:cd13983    87 GTLKQYLKRFKRLKLKVIKSWCRQILEGLNYLHTRDppIIHRDLKCDNIF-INGNTGEVKIGDLGLA-----TLLRQSFa 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 ---YGSPEFVSPEIIQQNpVSEASDIWAMGVI-------SYLSLTCSSPfagesdRATLLNVLEGRVSWSspMAAHLSED 6693
Cdd:cd13983   161 ksvIGTPEFMAPEMYEEH-YDEKVDIYAFGMCllematgEYPYSECTNA------AQIYKKVTSGIKPES--LSKVKDPE 231

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6694 AKDFIKATLqRAPQARPSAAQCLSHPWF 6721
Cdd:cd13983   232 LKDFIEKCL-KPPDERPSARELLEHPFF 258
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
 6468-6721 1.37e-21

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 98.91  E-value: 1.37e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP---LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07848     3 FEVLGVVGEGAYGVVLKCRHKETKEIVAIKKFKdseENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSE--ELLDRLyRKGVVTEaEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPA-ELQF 6621
Cdd:cd07848    83 EKNmlELLEEM-PNGVPPE-KVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISH--NDVLKLCDFGFARNLSEGsNANY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPE-FVSPEIIQQNPVSEASDIWAMGVIsYLSLTCSSP-FAGESDRATLLNVL---------EGRVSWSSPMAAHL 6690
Cdd:cd07848   159 TEYVATRwYRSPELLLGAPYGKAVDMWSVGCI-LGELSDGQPlFPGESEIDQLFTIQkvlgplpaeQMKLFYSNPRFHGL 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6691 SEDAK-------------------DFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07848   238 RFPAVnhpqslerrylgilsgvllDLMKNLLKLNPTDRYLTEQCLNHPAF 287
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 7678-7886 1.78e-21

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 97.92  E-value: 1.78e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14662     8 IGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGGELFERI 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII--TEYNLLKVVDLGNAQSlsqeKVLPSdKFKDYLET-- 7833
Cdd:cd14662    88 CNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKS----SVLHS-QPKSTVGTpa 162

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7834 -MAPELL---EGQGAVpqTDIWAIGVTAFIMLSAEYPVSSEgarDLQRGLRKGLVRL 7886
Cdd:cd14662   163 yIAPEVLsrkEYDGKV--ADVWSCGVTLYVMLVGAYPFEDP---DDPKNFRKTIQRI 214
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
 6469-6741 1.87e-21

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 98.65  E-value: 1.87e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP--LRSRTRAQAYRERDILAALSHPLVT----GLLDQfetRKTLILILE 6542
Cdd:cd06617     4 EVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRatVNSQEQKRLLMDLDISMRSVDCPYTvtfyGALFR---EGDVWICME 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEelLDRLYRK----GVVTEAEVKVYIQ-QLVEGLHYLHSH-GVLHLDIKPSNILMVHpaREDIKICDFGFAQNITP 6616
Cdd:cd06617    81 VMDTS--LDKFYKKvydkGLTIPEDILGKIAvSIVKALEYLHSKlSVIHRDVKPSNVLINR--NGQVKLCDFGISGYLVD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIqqNPVSEA------SDIWAMGvISYLSL--------TCSSPFAgesdraTLLNVLEGrvsw 6682
Cdd:cd06617   157 SVAKTIDAGCKPYMAPERI--NPELNQkgydvkSDVWSLG-ITMIELatgrfpydSWKTPFQ------QLKQVVEE---- 223

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6683 SSPM--AAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFlksmpaEEAHFINTKQLKFL 6741
Cdd:cd06617   224 PSPQlpAEKFSPEFQDFVNKCLKKNYKERPNYPELLQHPFF------ELHLSKNTDVASFV 278
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
 6473-6723 2.28e-21

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 97.52  E-value: 2.28e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETRKTLILILELC--SS 6546
Cdd:cd06607     8 EIGHGSFGAVYYARNKRTSEVVAIKKMSYSGKQSTEKWqdiiKEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEYClgSA 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAElqfSQYGS 6626
Cdd:cd06607    88 SDIVE-VHKKPL-QEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGT--VKLADFGSASLVCPAN---SFVGT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEII---QQNPVSEASDIWAMGVisylslTC------SSPFAGESDRATLLNVLEGrvswSSPM--AAHLSEDAK 6695
Cdd:cd06607   161 PYWMAPEVIlamDEGQYDGKVDVWSLGI------TCielaerKPPLFNMNAMSALYHIAQN----DSPTlsSGEWSDDFR 230

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6696 DFIKATLQRAPQARPSAAQCLSHPWFLK 6723
Cdd:cd06607   231 NFVDSCLQKIPQDRPSAEDLLKHPFVTR 258
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
 7681-7869 2.29e-21

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 97.36  E-value: 2.29e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGR-ALAAKIIPYHPKDKTAV---LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd14121     6 GTYATVYKAYRKSGAReVVAVKCVSKSSLNKASTenlLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRF 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN--LLKVVDLGNAQSLSQEKVLPSdkFKDYLETM 7834
Cdd:cd14121    86 IRSRRTLPESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSRYnpVLKLADFGFAQHLKPNDEAHS--LRGSPLYM 163

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 215274225 7835 APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSS 7869
Cdd:cd14121   164 APEMILKKKYDARVDLWSVGVILYECLFGRAPFAS 198
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
 6473-6727 2.77e-21

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 98.96  E-value: 2.77e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETRKTLILILELC--SS 6546
Cdd:cd06633    28 EIGHGSFGAVYFATNSHTNEVVAIKKMSYSGKQTNEKWqdiiKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEYClgSA 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrlYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAElqfSQYGS 6626
Cdd:cd06633   108 SDLLE--VHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQ--VKLADFGSASIASPAN---SFVGT 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGrvswSSP--MAAHLSEDAKDFIKAT 6701
Cdd:cd06633   181 PYWMAPEVIlamDEGQYDGKVDIWSLGITCIELAERKPPLFNMNAMSALYHIAQN----DSPtlQSNEWTDSFRGFVDYC 256

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6702 LQRAPQARPSAAQCLSHPWFLKSMPA 6727
Cdd:cd06633   257 LQKIPQERPSSAELLRHDFVRRERPP 282
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
 6474-6722 3.19e-21

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 98.97  E-value: 3.19e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN------KILcaAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd05571     3 LGKGTFGKVILCREKATgelyaiKIL--KKEVIIAKDEVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGS 6626
Cdd:cd05571    81 ELFFHLSRERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLL--DKDGHIKITDFGLCkEEISYGATTKTFCGT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGEsDRATLLN-VLEGRVSWSSpmaaHLSEDAKDFIKATLQRA 6705
Cdd:cd05571   159 PEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNR-DHEVLFElILMEEVRFPS----TLSPEAKSLLAGLLKKD 233

                         250       260
                  ....*....|....*....|..
gi 215274225 6706 PQAR----PS-AAQCLSHPWFL 6722
Cdd:cd05571   234 PKKRlgggPRdAKEIMEHPFFA 255
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
 7680-7924 3.48e-21

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 96.95  E-value: 3.48e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPY----HPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14079    12 VGSFGKVKLAEHELTGHKVAVKILNRqkikSLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVMEYVSGGELFD 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQekvLPSDkfKDYLET-- 7833
Cdd:cd14079    92 YIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFG----LSN---IMRD--GEFLKTsc 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 -----MAPELLEGQG-AVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCA 7907
Cdd:cd14079   163 gspnyAAPEVISGKLyAGPEVDVWSCGVILYALLCGSLPFDDEHIPNLFKKIKSGIYTIP---SHLSPGARDLIKRMLVV 239

                         250
                  ....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWL 7924
Cdd:cd14079   240 DPLKRITIPEIRQHPWF 256
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
 6463-6718 3.49e-21

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 97.44  E-value: 3.49e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd14046     3 RYLTDFEELQVLGKGAFGQVVKVRNKLDGRYYAIKKIKLRSESKNnsRILREVMLLSRLNHQHVVRYYQAWIERANLYIQ 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQN------- 6613
Cdd:cd14046    83 MEYCEKSTLRDLIDSGLFQDTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFL--DSNGNVKIGDFGLATSnklnvel 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 -------ITPAELQF-----SQYGSPEFVSPEiIQQNPVS---EASDIWAMGVISYlslTCSSPFAGESDRATLLNVLEG 6678
Cdd:cd14046   161 atqdinkSTSAALGSsgdltGNVGTALYVAPE-VQSGTKStynEKVDMYSLGIIFF---EMCYPFSTGMERVQILTALRS 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 215274225 6679 rVSWSSPMAAHLSEDAKDF--IKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14046   237 -VSIEFPPDFDDNKHSKQAklIRWLLNHDPAKRPSAQELLKS 277
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
 6461-6718 3.80e-21

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 97.41  E-value: 3.80e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6461 RRKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR-AQAYRERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd06646     4 RRNPQHDYELIQRVGSGTYGDVYKARNLHTGELAAVKIIKLEPGDDfSLIQQEIFMVKECKHCNIVAYFGSYLSREKLWI 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAEL 6619
Cdd:cd06646    84 CMEYCGGGSLQDIYHVTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNG--DVKLADFGVAAKITATIA 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQY-GSPEFVSPEI--IQQN-PVSEASDIWAMGVISYLSLTCSSP-FAGESDRATLLNV--------LEGRVSWSSPM 6686
Cdd:cd06646   162 KRKSFiGTPYWMAPEVaaVEKNgGYNQLCDIWAVGITAIELAELQPPmFDLHPMRALFLMSksnfqppkLKDKTKWSSTF 241

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 6687 aahlsedaKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd06646   242 --------HNFVKISLTKNPKKRPTAERLLTH 265
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
 6474-6709 4.00e-21

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 98.92  E-value: 4.00e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHP-LVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05615    18 LGKGSFGKVMLAERKGSDELYAIKILKkdvvIQDDDVECTMVEKRVLALQDKPpFLTQLHSCFQTVDRLYFVMEYVNGGD 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05615    98 LMYHIQQVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVML--DSEGHIKIADFGMCkEHMVEGVTTRTFCGTP 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMaahlSEDAKDFIKATLQRAPQ 6707
Cdd:cd05615   176 DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSL----SKEAVSICKGLMTKHPA 251


                  ..
gi 215274225 6708 AR 6709
Cdd:cd05615   252 KR 253
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
 7676-7870 4.34e-21

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 97.44  E-value: 4.34e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd07847     7 SKIGEGSYGVVFKCRNRETGQIVAIKKFVESEDDpviKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEYCDHTV 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQekvlPSDKFKDYLE 7832
Cdd:cd07847    87 LNELEKNPRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILTG----PGDDYTDYVA 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7833 T---MAPELLEGQGAV-PQTDIWAIGVTAFIMLSAE--YPVSSE 7870
Cdd:cd07847   163 TrwyRAPELLVGDTQYgPPVDVWAIGCVFAELLTGQplWPGKSD 206
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
 6474-6721 4.42e-21

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 98.33  E-value: 4.42e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFipLRSRTRAQ------AYRERDILA-ALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd05591     3 LGKGSFGKVMLAERKGTDEVYAIKV--LKKDVILQdddvdcTMTEKRILAlAAKHPFLTALHSCFQTKDRLFFVMEYVNG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYG 6625
Cdd:cd05591    81 GDLMFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILL--DAEGHCKLADFGMCkEGILNGKTTTTFCG 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWsspmAAHLSEDAKDFIKATLQRA 6705
Cdd:cd05591   159 TPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLY----PVWLSKEAVSILKAFMTKN 234

                         250       260
                  ....*....|....*....|...
gi 215274225 6706 PQARPS--AAQC-----LSHPWF 6721
Cdd:cd05591   235 PAKRLGcvASQGgedaiRQHPFF 257
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
 6473-6726 5.34e-21

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 97.79  E-value: 5.34e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETRKTLILILELC--SS 6546
Cdd:cd06634    22 EIGHGSFGAVYFARDVRNNEVVAIKKMSYSGKQSNEKWqdiiKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEYClgSA 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrlYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAElqfSQYGS 6626
Cdd:cd06634   102 SDLLE--VHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGL--VKLGDFGSASIMAPAN---SFVGT 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRvswsSPM--AAHLSEDAKDFIKAT 6701
Cdd:cd06634   175 PYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNE----SPAlqSGHWSEYFRNFVDSC 250

                         250       260
                  ....*....|....*....|....*
gi 215274225 6702 LQRAPQARPSAAQCLSHPWFLKSMP 6726
Cdd:cd06634   251 LQKIPQDRPTSDVLLKHRFLLRERP 275
PKc_CLK cd14134
Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity ...
 6463-6721 5.42e-21

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271036 [Multi-domain]  Cd Length: 332  Bit Score: 98.41  E-value: 5.42e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSH------PLVTGLLDQFETRKT 6536
Cdd:cd14134     9 LLTNRYKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEkdpngkSHCVQLRDWFDYRGH 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILELC-SSeeLLDRL--YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV----------------- 6596
Cdd:cd14134    89 MCIVFELLgPS--LYDFLkkNNYGPFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILLVdsdyvkvynpkkkrqir 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6597 HPAREDIKICDFGFAQnitpaelqF-SQYGSPeFVS------PEIIQQNPVSEASDIWAMGVI----------------- 6652
Cdd:cd14134   167 VPKSTDIKLIDFGSAT--------FdDEYHSS-IVStrhyraPEVILGLGWSYPCDVWSIGCIlvelytgellfqthdnl 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6653 -----------------SYLSLTCSSPF----------AGESDRATLLNVLEGRVSWsspMAAHLSEDAK--DFIKATLQ 6703
Cdd:cd14134   238 ehlammerilgplpkrmIRRAKKGAKYFyfyhgrldwpEGSSSGRSIKRVCKPLKRL---MLLVDPEHRLlfDLIRKMLE 314

                         330
                  ....*....|....*...
gi 215274225 6704 RAPQARPSAAQCLSHPWF 6721
Cdd:cd14134   315 YDPSKRITAKEALKHPFF 332
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
 6472-6721 5.86e-21

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 97.17  E-value: 5.86e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR--TRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE-- 6547
Cdd:cd07836     6 EKLGEGTYATVYKGRNRTTGEIVALKEIHLDAEegTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKDlk 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQygsp 6627
Cdd:cd07836    86 KYMDTHGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLI--NKRGELKLADFGLARAFGIPVNTFSN---- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVS-----PEIIQQNPVSEAS-DIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSW-----------SSP 6685
Cdd:cd07836   160 EVVTlwyraPDVLLGSRTYSTSiDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRimgtpTESTWpgisqlpeykpTFP 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 6686 MAA---------HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07836   240 RYPpqdlqqlfpHADPLGIDLLHRLLQLNPELRISAHDALQHPWF 284
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
 6457-6721 6.16e-21

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 98.56  E-value: 6.16e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6457 KQSHRRKLHSFyEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFE 6532
Cdd:cd05594    17 KPKHKVTMNDF-EYLKLLGKGTFGKVILVKEKATGRYYAMKILKkeviVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQ 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6533 TRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSH-GVLHLDIKPSNILMVHPARedIKICDFGFA 6611
Cdd:cd05594    96 THDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEkNVVYRDLKLENLMLDKDGH--IKITDFGLC 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 -QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPmaahL 6690
Cdd:cd05594   174 kEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRT----L 249

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 215274225 6691 SEDAKDFIKATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05594   250 SPEAKSLLSGLLKKDPKQRlgggpDDAKEIMQHKFF 285
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
 7678-7854 6.43e-21

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 96.78  E-value: 6.43e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKD----KTAvLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgPEL 7753
Cdd:cd07829     7 LGEGTYGVVYKAKDKKTGEIVALKKIRLDNEEegipSTA-LREISLLKELKHPNIVKLLDVIHTENKLYLVFEYCD-QDL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLE 7832
Cdd:cd07829    85 KKYLDKRPGpLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFG----LARAFGIPLRTYTHEVV 160

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7833 TM---APELLEGQ----GAVpqtDIWAIG 7854
Cdd:cd07829   161 TLwyrAPEILLGSkhysTAV---DIWSVG 186
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
 7680-7870 6.45e-21

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 96.53  E-value: 6.45e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd05572     3 VGGFGRVELVQLKSKGRTFALKCVKKRhivqTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGELWT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsqekvlpSDKFKDY----- 7830
Cdd:cd05572    83 ILRDRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKL-------GSGRKTWtfcgt 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 215274225 7831 LETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd05572   156 PEYVAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGD 195
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
 7672-7927 6.89e-21

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 97.02  E-value: 6.89e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLREYEalkglRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd14175     3 YVVKETIGVGSYSVCKRCVHKATNMEYAVKVIdksKRDPSEEIEILLRYG-----QHPNIITLKDVYDDGKHVYLVTELM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN----LLKVVDLGNAQSLSQEKVLps 7824
Cdd:cd14175    78 RGGELLDKILRQKFFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVDESgnpeSLRICDFGFAKQLRAENGL-- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 dkfkdyLET-------MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSeGARDLQRGLrkgLVRLSRCYAGLSGG- 7896
Cdd:cd14175   156 ------LMTpcytanfVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFAN-GPSDTPEEI---LTRIGSGKFTLSGGn 225

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 215274225 7897 -------AVAFLRSTLCAQPWGRPCASSCLQCPWLTEE 7927
Cdd:cd14175   226 wntvsdaAKDLVSKMLHVDPHQRLTAKQVLQHPWITQK 263
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
 6474-6721 7.06e-21

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 96.83  E-value: 7.06e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR----ERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05577     1 LGRGGFGEVCACQVKATGKMYACKKLDKKRIKKKKGETmalnEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGGDL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd05577    81 KYHIYNVGtrGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHG--HVRISDLGLAVEFKGGKKIKGRVGTH 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEAS-DIWAMGVISYLSLTCSSPFageSDRATLLN-------VLEGRVSWSSpmaaHLSEDAKDFIK 6699
Cdd:cd05577   159 GYMAPEVLQKEVAYDFSvDWFALGCMLYEMIAGRSPF---RQRKEKVDkeelkrrTLEMAVEYPD----SFSPEARSLCE 231

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6700 ATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05577   232 GLLQKDPERRlgcrgGSADEVKEHPFF 258
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
 6474-6663 7.57e-21

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 97.73  E-value: 7.57e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDIL-AALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05603     3 IGKGSFGKVLLAKRKCDGKFYAVKVLQkktiLKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDYVNGGE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05603    83 LFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILL--DCQGHVVLTDFGLCkEGMEPEETTSTFCGTP 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF 6663
Cdd:cd05603   161 EYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPF 196
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 6468-6710 8.00e-21

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 97.02  E-value: 8.00e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAK----FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd08229    26 FRIEKKIGRGQFSEVYRATCLLDGVPVALKkvqiFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLEL 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELlDRLYR-----KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFG----FAQNI 6614
Cdd:cd08229   106 ADAGDL-SRMIKhfkkqKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFIT--ATGVVKLGDLGlgrfFSSKT 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAElqfSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGesDRATLLNVLEGRVSWSSP--MAAHLSE 6692
Cdd:cd08229   183 TAAH---SLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYG--DKMNLYSLCKKIEQCDYPplPSDHYSE 257

                         250
                  ....*....|....*...
gi 215274225 6693 DAKDFIKATLQRAPQARP 6710
Cdd:cd08229   258 ELRQLVNMCINPDPEKRP 275
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
 6468-6718 9.45e-21

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 102.12  E-value: 9.45e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHK-GNKILC--AAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQF--ETRKTLILILE 6542
Cdd:PTZ00266   15 YEVIKKIGNGRFGEVFLVKHKrTQEFFCwkAISYRGLKEREKSQLVIEVNVMRELKHKNIVRYIDRFlnKANQKLYILME 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEEL---LDRLYRK-GVVTEAEVKVYIQQLVEGLHYLHS-------HGVLHLDIKPSNILMVH-------------- 6597
Cdd:PTZ00266   95 FCDAGDLsrnIQKCYKMfGKIEEHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIFLSTgirhigkitaqann 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6598 -PAREDIKICDFGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVS--EASDIWAMGVISYLSLTCSSPFAGESDRATLLN 6674
Cdd:PTZ00266  175 lNGRPIAKIGDFGLSKNIGIESMAHSCVGTPYYWSPELLLHETKSydDKSDMWALGCIIYELCSGKTPFHKANNFSQLIS 254

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 215274225 6675 VLegRVSWSSPMAAHlSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:PTZ00266  255 EL--KRGPDLPIKGK-SKELNILIKNLLNLSAKERPSALQCLGY 295
I-set pfam07679
Immunoglobulin I-set domain;
6357-6446 9.66e-21

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 90.01  E-value: 9.66e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6357 PSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 215274225  6437 QVLCKAELLV 6446
Cdd:pfam07679   81 EAEASAELTV 90
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
 6535-6718 9.89e-21

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 95.88  E-value: 9.89e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmvHPAREDIKICDFGFAQNI 6614
Cdd:cd06652    79 RTLSIFMEYMPGGSIKDQLKSYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANIL--RDSVGNVKLGDFGASKRL 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQ----FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPmaAHL 6690
Cdd:cd06652   157 QTICLSgtgmKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNPQLP--AHV 234

                         170       180
                  ....*....|....*....|....*...
gi 215274225 6691 SEDAKDFIKATLQRAPQaRPSAAQCLSH 6718
Cdd:cd06652   235 SDHCRDFLKRIFVEAKL-RPSADELLRH 261
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
 7672-7888 1.01e-20

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 96.49  E-value: 1.01e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP----KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd05580     3 FEFLKTLGTGSFGRVRLVKHKDSGKYYALKILKKAKiiklKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqslsqeKVLPSDKF 7827
Cdd:cd05580    83 VPGGELFSLLRRSGRFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFA------KRVKDRTY 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7828 K-----DYLetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSR 7888
Cdd:cd05580   157 TlcgtpEYL---APEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFPS 219
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
 7672-7885 1.15e-20

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 95.41  E-value: 1.15e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKaSGRALAAKIIPYH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14161     5 YEFLETLGKGTYGRVKKARDS-SGRLVAIKSIRKDrikdEQDLLHIRREIEIMSSLNHPHIISVYEVFENSSKIVIVMEY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsdkf 7827
Cdd:cd14161    84 ASRGDLYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDK------- 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7828 kdYLETM-------APELLEGQGAV-PQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVR 7885
Cdd:cd14161   157 --FLQTYcgsplyaSPEIVNGRPYIgPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSGAYR 220
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
 6461-6720 2.01e-20

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 95.11  E-value: 2.01e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6461 RRKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLR-SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd06645     6 RRNPQEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEpGEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWI 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAEL 6619
Cdd:cd06645    86 CMEFCGGGSLQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGH--VKLADFGVSAQITATIA 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQY-GSPEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSP-FAGESDRATLLNV--------LEGRVSWSSPM 6686
Cdd:cd06645   164 KRKSFiGTPYWMAPEVAaveRKGGYNQLCDIWAVGITAIELAELQPPmFDLHPMRALFLMTksnfqppkLKDKMKWSNSF 243

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 6687 aahlsedaKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06645   244 --------HHFVKMALTKNPKKRPTAEKLLQHPF 269
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
 6468-6726 2.10e-20

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 95.95  E-value: 2.10e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06655    21 YTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKElIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEYLAG 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFS-QYG 6625
Cdd:cd06655   101 GSLTD-VVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLL--GMDGSVKLTDFGFCAQITPEQSKRStMVG 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVLEGRVSWSSPmaAHLSEDAKDFIKATLQR 6704
Cdd:cd06655   178 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlRALYLIATNGTPELQNP--EKLSPIFRDFLNRCLEM 255

                         250       260
                  ....*....|....*....|..
gi 215274225 6705 APQARPSAAQCLSHPWFLKSMP 6726
Cdd:cd06655   256 DVEKRGSAKELLQHPFLKLAKP 277
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
 7669-7924 2.38e-20

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 96.63  E-value: 2.38e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTavlREYEALkgLR---HPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd14176    18 TDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPT---EEIEIL--LRygqHPNIITLKDVYDDGKYVYVVT 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN----LLKVVDLGNAQSLSQEK- 7820
Cdd:cd14176    93 ELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESgnpeSIRICDFGFAKQLRAENg 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7821 VLPSDKFKDYLetMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSeGARDLQRGLrkgLVRLSRCYAGLSGG---- 7896
Cdd:cd14176   173 LLMTPCYTANF--VAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFAN-GPDDTPEEI---LARIGSGKFSLSGGywns 246

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 7897 ----AVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14176   247 vsdtAKDLVSKMLHVDPHQRLTAALVLRHPWI 278
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
 6468-6721 2.47e-20

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 95.37  E-value: 2.47e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSHP-------LVTGL-LDQFetrkt 6536
Cdd:cd07843     7 YEKLNRIEEGTYGVVYRARDKKTGEIVALKKLKMEKEKEGfpiTSLREINILLKLQHPnivtvkeVVVGSnLDKI----- 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 lILILELCSSE--ELLDRLyrKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQni 6614
Cdd:cd07843    82 -YMVMEYVEHDlkSLMETM--KQPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNN--RGILKICDFGLAR-- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 tpaelqfsQYGSPE-----------FVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE----- 6677
Cdd:cd07843   155 --------EYGSPLkpytqlvvtlwYRAPELLLGAKEySTAIDMWSVGCIFAELLTKKPLFPGKSEIDQLNKIFKllgtp 226

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6678 --------------GRVSWSSPM---------AAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07843   227 tekiwpgfselpgaKKKTFTKYPynqlrkkfpALSLSDNGFDLLNRLLTYDPAKRISAEDALKHPYF 293
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
 6468-6719 2.67e-20

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 95.18  E-value: 2.67e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRV---QHKGNK-ILCAAKFIPLRSRTRAQAYRERDILAALS---HPLVTGLLDQFETRKTLILI 6540
Cdd:cd14052     2 FANVELIGSGEFSQVYKVserVPTGKVyAVKKLKPNYAGAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEEL---LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNItPA 6617
Cdd:cd14052    82 TELCENGSLdvfLSELGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEG--TLKIGDFGMATVW-PL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISY-LSLTCSSPFAGE----------SDRATLLNVLEGRVS----- 6681
Cdd:cd14052   159 IRGIEREGDREYIAPEILSEHMYDKPADIFSLGLILLeAAANVVLPDNGDawqklrsgdlSDAPRLSSTDLHSASspssn 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 6682 --WSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd14052   239 ppPDPPNMPILSGSLDRVVRWMLSPEPDRRPTADDVLATP 278
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 6521-6720 3.16e-20

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 94.15  E-value: 3.16e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6521 HPLVTGLLDQFETRKTLILILEL-CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPA 6599
Cdd:cd14101    66 HRGVIRLLDWFEIPEGFLLVLERpQHCQDLFDYITERGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENIL-VDLR 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6600 REDIKICDFGfaqniTPAELQFSQY----GSPEFVSPE-IIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDratlln 6674
Cdd:cd14101   145 TGDIKLIDFG-----SGATLKDSMYtdfdGTRVYSPPEwILYHQYHALPATVWSLGILLYDMVCGDIPFERDTD------ 213

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 6675 VLEGRVSWSspmaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14101   214 ILKAKPSFN----KRVSNDCRSLIRSCLAYNPSDRPSLEQILLHPW 255
STKc_CK2_alpha cd14132
Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the ...
 6466-6721 3.24e-20

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271034 [Multi-domain]  Cd Length: 306  Bit Score: 95.30  E-value: 3.24e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI-PLRSRtraQAYRERDILAAL-SHPLVTGLLD--QFETRKTLILIL 6541
Cdd:cd14132    18 DDYEIIRKIGRGKYSEVFEGINIGNNEKVVIKVLkPVKKK---KIKREIKILQNLrGGPNIVKLLDvvKDPQSKTPSLIF 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELlDRLYRKgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNIlMVHPAREDIKICDFGFAQNITPAElqf 6621
Cdd:cd14132    95 EYVNNTDF-KTLYPT--LTDYDIRYYMYELLKALDYCHSKGIMHRDVKPHNI-MIDHEKRKLRLIDWGLAEFYHPGQ--- 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 sQY----GSPEFVSPEIIQQNPVSEAS-DIWAMGVISYLSLTCSSP-FAGESDRATLL---NVLEG-------------- 6678
Cdd:cd14132   168 -EYnvrvASRYYKGPELLVDYQYYDYSlDMWSLGCMLASMIFRKEPfFHGHDNYDQLVkiaKVLGTddlyayldkygiel 246

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6679 ------------RVSWSS---PMAAHL-SEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14132   247 pprlndilgrhsKKPWERfvnSENQHLvTPEALDLLDKLLRYDHQERITAKEAMQHPYF 305
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
 6471-6717 3.37e-20

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 94.13  E-value: 3.37e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6471 KEEIGRGVFGFVKR----VQHKGNKILCAAKFIPLRSRTRAQA--YRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:smart00219    4 GKKLGEGAFGEVYKgklkGKGGKKKVEVAVKTLKEDASEQQIEefLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYM 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6545 SSEELLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQ 6623
Cdd:smart00219   84 EGGDLLSYLrKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLV--VKISDFGLSRDLYDDDYYRKR 161

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6624 YG-SPefV---SPEIIQQNPVSEASDIWAMGVISY--LSLtCSSPFAGESDRATLLNVLEGRvswSSPMAAHLSEDAKDF 6697
Cdd:smart00219  162 GGkLP--IrwmAPESLKEGKFTSKSDVWSFGVLLWeiFTL-GEQPYPGMSNEEVLEYLKNGY---RLPQPPNCPPELYDL 235

                           250       260
                    ....*....|....*....|
gi 215274225   6698 IKATLQRAPQARPSAAQCLS 6717
Cdd:smart00219  236 MLQCWAEDPEDRPTFSELVE 255
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 6468-6710 3.43e-20

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 94.49  E-value: 3.43e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTRAQAYRERD------------ILAALSHPLVTGLLDQFETR 6534
Cdd:cd08528     2 YAVLELLGSGAFGCVYKVRKKSNgQTLLALKEINMTNPAFGRTEQERDksvgdiisevniIKEQLRHPNIVRYYKTFLEN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILEL---CSSEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSH-GVLHLDIKPSNILMvhPAREDIKICDFG 6609
Cdd:cd08528    82 DRLYIVMELiegAPLGEHFSSLKEKNEhFTEDRIWNIFVQMVLALRYLHKEkQIVHRDLKPNNIML--GEDDKVTITDFG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6610 FAQNITPAELQF-SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAA 6688
Cdd:cd08528   160 LAKQKGPESSKMtSVVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMLTLATKIVEAEY---EPLPE 236

                         250       260
                  ....*....|....*....|...
gi 215274225 6689 HL-SEDAKDFIKATLQRAPQARP 6710
Cdd:cd08528   237 GMySDDITFVIRSCLTPDPEARP 259
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
 6474-6721 3.69e-20

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 95.80  E-value: 3.69e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKF----IPLRSRTRAQAYRERDILAA-LSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05604     4 IGKGSFGKVLLAKRKRDGKYYAVKVlqkkVILNRKEQKHIMAERNVLLKnVKHPFLVGLHYSFQTTDKLYFVLDFVNGGE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05604    84 LFFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILL--DSQGHIVLTDFGLCkEGISNSDTTTTFCGTP 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05604   162 EYLAPEVIRKQPYDNTVDWWCLGSVLYEMLYGLPPFYCRDTAEMYENILHKPLV----LRPGISLTAWSILEELLEKDRQ 237

                         250
                  ....*....|....*...
gi 215274225 6708 ARPSAA----QCLSHPWF 6721
Cdd:cd05604   238 LRLGAKedflEIKNHPFF 255
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
 6473-6724 3.72e-20

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 95.05  E-value: 3.72e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFV--KRVQHKGNKIlcAAKFIPLRSRTRAQA-YRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd06659    28 KIGEGSTGVVciAREKHSGRQV--AVKMMDLRKQQRRELlFNEVVIMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGAL 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITP-AELQFSQYGSPE 6628
Cdd:cd06659   106 TD-IVSQTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGR--VKLSDFGFCAQISKdVPKRKSLVGTPY 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLlnvleGRVSWSSPMAAHLSEDA----KDFIKATLQR 6704
Cdd:cd06659   183 WMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAM-----KRLRDSPPPKLKNSHKAspvlRDFLERMLVR 257

                         250       260
                  ....*....|....*....|
gi 215274225 6705 APQARPSAAQCLSHPWFLKS 6724
Cdd:cd06659   258 DPQERATAQELLDHPFLLQT 277
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
 6472-6720 3.77e-20

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 94.37  E-value: 3.77e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGfvkRVQHKGNKI---LCAAKFIPL----------RSRTRAQAYR-ERDILAALSHPLVTGLLDQFETRKTL 6537
Cdd:cd06629     7 ELIGKGTYG---RVYLAMNATtgeMLAVKQVELpktssdradsRQKTVVDALKsEIDTLKDLDHPNIVQYLGFEETEDYF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHparEDI-KICDFGF---AQN 6613
Cdd:cd06629    84 SIFLEYVPGGSIGSCLRKYGKFEEDLVRFFTRQILDGLAYLHSKGILHRDLKADNILVDL---EGIcKISDFGIskkSDD 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQFSQYGSPEFVSPEII--QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLS 6691
Cdd:cd06629   161 IYGNNGATSMQGSVFWMAPEVIhsQGQGYSAKVDIWSLGCVVLEMLAGRRPWSDDEAIAAMFKLGNKRSAPPVPEDVNLS 240

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06629   241 PEALDFLNACFAIDPRDRPTAAELLSHPF 269
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 6469-6728 3.88e-20

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 95.13  E-value: 3.88e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQAYRerdILAAL-----SH--PLVTGLLDQFETRKTLILIL 6541
Cdd:cd06618    18 ENLGEIGSGTCGQVYKMRHKKTGHVMAVKQMR-RSGNKEENKR---ILMDLdvvlkSHdcPYIVKCYGYFITDSDVFICM 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSS--EELLDRLYrkGVVTEAEVKVYIQQLVEGLHYL-HSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAE 6618
Cdd:cd06618    94 ELMSTclDKLLKRIQ--GPIPEDILGKMTVSIVKALHYLkEKHGVIHRDVKPSNILL--DESGNVKLCDFGISGRLVDSK 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQYGSPEFVSPEIIQQNPVSE---ASDIWAMGVISYLSLTCSSPFAG-ESDRATLLNVLEGRVSwSSPMAAHLSEDA 6694
Cdd:cd06618   170 AKTRSAGCAAYMAPERIDPPDNPKydiRADVWSLGISLVELATGQFPYRNcKTEFEVLTKILNEEPP-SLPPNEGFSPDF 248

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 6695 KDFIKATLQRAPQARPSAAQCLSHPWFLKSMPAE 6728
Cdd:cd06618   249 CSFVDLCLTKDHRYRPKYRELLQHPFIRRYETAE 282
STKc_Cdc7 cd14019
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze ...
 6468-6721 4.40e-20

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270921 [Multi-domain]  Cd Length: 252  Bit Score: 93.83  E-value: 4.40e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFV---KRVQHKGNKILCAAKF-----IPLRSRTRAqaYRERDILAALS-HPLVTGLLDQFETRKTLI 6538
Cdd:cd14019     3 YRIIEKIGEGTFSSVykaEDKLHDLYDRNKGRLValkhiYPTSSPSRI--LNELECLERLGgSNNVSGLITAFRNEDQVV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDrLYRKGVVTEaeVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvHPAREDIKICDFGFAQNI-TPA 6617
Cdd:cd14019    81 AVLPYIEHDDFRD-FYRKMSLTD--IRIYLRNLFKALKHVHSFGIIHRDVKPGNFLY-NRETGKGVLVDFGLAQREeDRP 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNP-VSEASDIWAMGVI--SYLSlTCSSPFAGESDRATLLNVlegrvswsspmaAHL--SE 6692
Cdd:cd14019   157 EQRAPRAGTRGFRAPEVLFKCPhQTTAIDIWSAGVIllSILS-GRFPFFFSSDDIDALAEI------------ATIfgSD 223

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14019   224 EAYDLLDKLLELDPSKRITAEEALKHPFF 252
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
 6468-6718 4.51e-20

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 94.28  E-value: 4.51e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR-TRAQAYRERDILAALSHPLVTGLLD----QFETRKTLILIL- 6541
Cdd:cd13986     2 YRIQRLLGEGGFSFVYLVEDLSTGRLYALKKILCHSKeDVKEAMREIENYRLFNHPNILRLLDsqivKEAGGKKEVYLLl 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ---ELCSSEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSH---GVLHLDIKPSNIlMVHPAREDIkICDFGfaqNI 6614
Cdd:cd13986    82 pyyKRGSLQDEIERRLVKGTfFPEDRILHIFLGICRGLKAMHEPelvPYAHRDIKPGNV-LLSEDDEPI-LMDLG---SM 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQF-------------SQYGSPEFVSPEIIQ---QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRAT--LLNVL 6676
Cdd:cd13986   157 NPARIEIegrrealalqdwaAEHCTMPYRAPELFDvksHCTIDEKTDIWSLGCTLYALMYGESPFERIFQKGDslALAVL 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 215274225 6677 EGRVSWssPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd13986   237 SGNYSF--PDNSRYSEELHQLVKSMLVVNPAERPSIDDLLSR 276
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 6462-6716 4.67e-20

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 94.50  E-value: 4.67e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6462 RKLHSFYEVkEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSHPLVTGLLDQF--ETRKT 6536
Cdd:cd14049     3 RYLNEFEEI-ARLGKGGYGKVYKVRNKLDGQYYAIKKILIKKVTKRdcmKVLREVKVLAGLQHPNIVGYHTAWmeHVQLM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILELC--SSEELLDRLYRKG------------VVTEAEVKVyIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPARED 6602
Cdd:cd14049    82 LYIQMQLCelSLWDWIVERNKRPceeefksapytpVDVDVTTKI-LQQLLEGVTYIHSMGIVHRDLKPRNIF-LHGSDIH 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 IKICDFGFA-------------QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVIsylSLTCSSPFAGESDR 6669
Cdd:cd14049   160 VRIGDFGLAcpdilqdgndsttMSRLNGLTHTSGVGTCLYAAPEQLEGSHYDFKSDMYSIGVI---LLELFQPFGTEMER 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6670 ATLL-NVLEGRVSWSspMAAHLSEDAKdFIKATLQRAPQARPSAAQCL 6716
Cdd:cd14049   237 AEVLtQLRNGQIPKS--LCKRWPVQAK-YIKLLTSTEPSERPSASQLL 281
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
 6463-6729 4.90e-20

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 95.51  E-value: 4.90e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVKEEIGRGVFGFV---------KRVQHKgnKILCAAKFIPLRSRTraqaYRERDILAALSHPLVTGLLDQFET 6533
Cdd:cd07855     2 DVGDRYEPIETIGSGAYGVVcsaidtksgQKVAIK--KIPNAFDVVTTAKRT----LRELKILRHFKHDNIIAIRDILRP 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKTL------ILILELCSSEelLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IK 6604
Cdd:cd07855    76 KVPYadfkdvYVVLDLMESD--LHHIiHSDQPLTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLV----NENceLK 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6605 ICDFGFAQNI--TPAELQFSQ--------YGSPE--FVSPEiiqqnpVSEASDIWAMGVI--------------SY---L 6655
Cdd:cd07855   150 IGDFGMARGLctSPEEHKYFMteyvatrwYRAPElmLSLPE------YTQAIDMWSVGCIfaemlgrrqlfpgkNYvhqL 223

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6656 SL------TCSSPFAGE--SDRA-TLLNVLEGR--VSWSS--PMAahlSEDAKDFIKATLQRAPQARPSAAQCLSHPwFL 6722
Cdd:cd07855   224 QLiltvlgTPSQAVINAigADRVrRYIQNLPNKqpVPWETlyPKA---DQQALDLLSQMLRFDPSERITVAEALQHP-FL 299


                  ....*..
gi 215274225 6723 KSMPAEE 6729
Cdd:cd07855   300 AKYHDPD 306
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
 7669-7924 5.62e-20

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 94.31  E-value: 5.62e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTavlREYEALkgLR---HPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd14178     2 TDGYEIKEDIGIGSYSVCKRCVHKATSTEYAVKIIDKSKRDPS---EEIEIL--LRygqHPNIITLKDVYDDGKFVYLVM 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN----LLKVVDLGNAQSLSQEKV 7821
Cdd:cd14178    77 ELMRGGELLDRILRQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYMDESgnpeSIRICDFGFAKQLRAENG 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7822 LpsdkfkdyLET-------MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSeGARDLQRGLrkgLVRLSRCYAGLS 7894
Cdd:cd14178   157 L--------LMTpcytanfVAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFAN-GPDDTPEEI---LARIGSGKYALS 224

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 215274225 7895 GG--------AVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14178   225 GGnwdsisdaAKDIVSKMLHVDPHQRLTAPQVLRHPWI 262
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
 6468-6732 6.18e-20

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 95.12  E-value: 6.18e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd06650     7 FEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLeiKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMD 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGVVTEAEV-KVYIQqLVEGLHYL-HSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAeLQFSQ 6623
Cdd:cd06650    87 GGSLDQVLKKAGRIPEQILgKVSIA-VIKGLTYLrEKHKIMHRDVKPSNILV--NSRGEIKLCDFGVSGQLIDS-MANSF 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGV----------------ISYLSLTCSSPFAGESDRATLLNVLEGRVSWS---- 6683
Cdd:cd06650   163 VGTRSYMSPERLQGTHYSVQSDIWSMGLslvemavgrypipppdAKELELMFGCQVEGDAAETPPRPRTPGRPLSSygmd 242

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6684 --SPMA------------------AHLSEDAKDFIKATLQRAPQARPSAAQCLSHPwFLKSMPAEEAHF 6732
Cdd:cd06650   243 srPPMAifelldyivnepppklpsGVFSLEFQDFVNKCLIKNPAERADLKQLMVHA-FIKRSDAEEVDF 310
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
 6468-6721 6.55e-20

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 94.69  E-value: 6.55e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSHPLVTGLLDQF--------ETRKT 6536
Cdd:cd07866    10 YEILGKLGEGTFGEVYKARQIKTGRVVALKKILMHNEKDGfpiTALREIKILKKLKHPNVVPLIDMAverpdkskRKRGS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILIL-----ELCSseeLLDRLYRKgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA 6611
Cdd:cd07866    90 VYMVTpymdhDLSG---LLENPSVK--LTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGI--LKIADFGLA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAELQFsQYGSPE-------------FVSPEII-QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDR--ATLLNV 6675
Cdd:cd07866   163 RPYDGPPPNP-KGGGGGgtrkytnlvvtrwYRPPELLlGERRYTTAVDIWGIGCVFAEMFTRRPILQGKSDIdqLHLIFK 241

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6676 LEGRVS------WSS-PMA-----------------AHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07866   242 LCGTPTeetwpgWRSlPGCegvhsftnyprtleerfGKLGPEGLDLLSKLLSLDPYKRLTASDALEHPYF 311
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
 6448-6726 6.96e-20

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 94.73  E-value: 6.96e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6448 GGDNEPDSEKQSHRRKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY----RERDILAALSHPL 6523
Cdd:cd06635     7 GSLKDPDIAELFFKEDPEKLFSDLREIGHGSFGAVYFARDVRTSEVVAIKKMSYSGKQSNEKWqdiiKEVKFLQRIKHPN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6524 VTGLLDQFETRKTLILILELC--SSEELLDrlYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARe 6601
Cdd:cd06635    87 SIEYKGCYLREHTAWLVMEYClgSASDLLE--VHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQ- 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6602 dIKICDFGFAQNITPAElqfSQYGSPEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEG 6678
Cdd:cd06635   164 -VKLADFGSASIASPAN---SFVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQN 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6679 RvswsSP--MAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKSMP 6726
Cdd:cd06635   240 E----SPtlQSNEWSDYFRNFVDSCLQKIPQDRPTSEELLKHMFVLRERP 285
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
 6468-6723 7.86e-20

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 93.07  E-value: 7.86e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06647     9 YTRFEKIGQGASGTVYTAIDVATGQEVAIKQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrlyrkgVVTE-----AEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQF 6621
Cdd:cd06647    89 GSLTD------VVTEtcmdeGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDG--SVKLTDFGFCAQITPEQSKR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 S-QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVLEGRVSWSSPmaAHLSEDAKDFIK 6699
Cdd:cd06647   161 StMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlRALYLIATNGTPELQNP--EKLSAIFRDFLN 238

                         250       260
                  ....*....|....*....|....
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPwFLK 6723
Cdd:cd06647   239 RCLEMDVEKRGSAKELLQHP-FLK 261
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
 7678-7923 7.92e-20

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 93.09  E-value: 7.92e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA-------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd14185     8 IGDGNFAVVKECRHWNENQEYAMKII-----DKSKlkgkedmIESEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIItEYN-----LLKVVDLGnaqsLSQEKVLPSD 7825
Cdd:cd14185    83 GDLFDAIIESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLV-QHNpdkstTLKLADFG----LAKYVTGPIF 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE--GARDLQRGLRKGLVR-LSRCYAGLSGGAVAFLR 7902
Cdd:cd14185   158 TVCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSPerDQEELFQIIQLGHYEfLPPYWDNISEAAKDLIS 237

                         250       260
                  ....*....|....*....|.
gi 215274225 7903 STLCAQPWGRPCASSCLQCPW 7923
Cdd:cd14185   238 RLLVVDPEKRYTAKQVLQHPW 258
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
 7672-7924 1.01e-19

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 92.70  E-value: 1.01e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd05578     2 FQILRVIGKGSFGKVCIVQKKDTKKMFAMKYMNKQkciEKDSVRnVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS-DK 7826
Cdd:cd05578    82 LLGGDLRYHLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDGTLATStSG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAE--YPVSSEGARDLQRGLRKGLVRLSRcyAGLSGGAVAFLRST 7904
Cdd:cd05578   162 TKPY---MAPEVFMRAGYSFAVDWWSLGVTAYEMLRGKrpYEIHSRTSIEEIRAKFETASVLYP--AGWSEEAIDLINKL 236

                         250       260
                  ....*....|....*....|.
gi 215274225 7905 LCAQPWGRPCASSCLQ-CPWL 7924
Cdd:cd05578   237 LERDPQKRLGDLSDLKnHPYF 257
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
 7672-7922 1.05e-19

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 92.37  E-value: 1.05e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIP------YHPKDKTAVLREYEALKglRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd14050     3 FTILSKLGEGSFGEVFKVRSREDGKLYAVKRSRsrfrgeKDRKRKLEEVERHEKLG--EHPNCVRFIKAWEEKGILYIQT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSgPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLK------VVDLGNAQSLSQE 7819
Cdd:cd14050    81 ELCD-TSLQQYCEETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKlgdfglVVELDKEDIHDAQ 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7820 KVLPSdkfkdYletMAPELLEGQGAvPQTDIWAIGVTafiMLSA----EYPvsSEGarDLQRGLRKGLVRlSRCYAGLSG 7895
Cdd:cd14050   160 EGDPR-----Y---MAPELLQGSFT-KAADIFSLGIT---ILELacnlELP--SGG--DGWHQLRQGYLP-EEFTAGLSP 222

                         250       260
                  ....*....|....*....|....*..
gi 215274225 7896 GAVAFLRSTLCAQPWGRPCASSCLQCP 7922
Cdd:cd14050   223 ELRSIIKLMMDPDPERRPTAEDLLALP 249
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
 6468-6721 1.06e-19

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 93.25  E-value: 1.06e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07861     2 YTKIEKIGEGTYGVVYKGRNKKTGQIVAMKKIRLESEEEgvpSTAIREISLLKELQHPNIVCLEDVLMQENRLYLVFEFL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSE--ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNI-TPAELQF 6621
Cdd:cd07861    82 SMDlkKYLDSLPKGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLI--DNKGVIKLADFGLARAFgIPVRVYT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNP-VSEASDIWAMGVIsYLSLTCSSP-FAGESDRATLLNVLE-----------GRVS------- 6681
Cdd:cd07861   160 HEVVTLWYRAPEVLLGSPrYSTPVDIWSIGTI-FAEMATKKPlFHGDSEIDQLFRIFRilgtptediwpGVTSlpdyknt 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 6682 ---WSSPMAA----HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07861   239 fpkWKKGSLRtavkNLDEDGLDLLEKMLIYDPAKRISAKKALVHPYF 285
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
 6468-6724 1.17e-19

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 94.04  E-value: 1.17e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd06615     3 FEKLGELGAGNGGVVTKVLHRPSGLIMARKLIHLeiKPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYRKGVVTE---AEVKVYIqqlVEGLHYLHS-HGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAeLQF 6621
Cdd:cd06615    83 GGSLDQVLKKAGRIPEnilGKISIAV---LRGLTYLREkHKIMHRDVKPSNILV--NSRGEIKLCDFGVSGQLIDS-MAN 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGvisyLSL-------------------TCSSPFAGESDRATLLNVLEGRVSW 6682
Cdd:cd06615   157 SFVGTRSYMSPERLQGTHYTVQSDIWSLG----LSLvemaigrypipppdakeleAMFGRPVSEGEAKESHRPVSGHPPD 232

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6683 SS-PMA------------------AHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKS 6724
Cdd:cd06615   233 SPrPMAifelldyivnepppklpsGAFSDEFQDFVDKCLKKNPKERADLKELTKHPFIKRA 293
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
 7672-7866 1.22e-19

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 92.45  E-value: 1.22e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14073     3 YELLETLGKGTYGKVKLAIERATGREVAIKSIKKDkiedEQDMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSdkF 7827
Cdd:cd14073    83 ASGGELYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLLQT--F 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7828 KDYLETMAPELLEG---QGavPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14073   161 CGSPLYASPEIVNGtpyQG--PEVDCWSLGVLLYTLVYGTMP 200
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
 6474-6718 1.26e-19

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 92.38  E-value: 1.26e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAyrerDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd13995    12 IPRGAFGKVYLAQDTKTKKRMACKLIPVEQFKPSDV----EIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVLEKL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpaREDIKICDFGFAQNIT-----PAELQfsqyGSPE 6628
Cdd:cd13995    88 ESCGPMREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFM---STKAVLVDFGLSVQMTedvyvPKDLR----GTEI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRA---TLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRA 6705
Cdd:cd13995   161 YMSPEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRSaypSYLYIIHKQAPPLEDIAQDCSPAMRELLEAALERN 240

                         250
                  ....*....|...
gi 215274225 6706 PQARPSAAQCLSH 6718
Cdd:cd13995   241 PNHRSSAAELLKH 253
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
 7680-7912 1.38e-19

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 93.92  E-value: 1.38e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd05595     5 KGTFGKVILVREKATGRYYAMKILRKEviiAKDEVAhTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYL---E 7832
Cdd:cd05595    85 HLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFG----LCKEGITDGATMKTFCgtpE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEgarDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd05595   161 YLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQ---DHERLFELILMEEIRFPRTLSPEAKSLLAGLLKKDPKQR 237
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
 6474-6721 1.52e-19

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 93.50  E-value: 1.52e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05632    10 LGKGGFGEVCACQVRATgKMYACKRLEKKRIKKRkgeSMALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd05632    90 KFHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGH--IRISDLGLAVKIPEGESIRGRVGTV 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05632   168 GYMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSAKFSEEAKSICKMLLTKDPK 247

                         250
                  ....*....|....*....
gi 215274225 6708 AR-----PSAAQCLSHPWF 6721
Cdd:cd05632   248 QRlgcqeEGAGEVKRHPFF 266
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 7678-7854 1.56e-19

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 92.37  E-value: 1.56e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLR---EYEALKGLRHPHLAQLHAAYLSpRHLVLI-LELCSGPEL 7753
Cdd:cd06626     8 IGEGTFGKVYTAVNLDTGELMAMKEIRFQDNDPKTIKEiadEMKVLEGLDHPNLVRYYGVEVH-REEVYIfMEYCQEGTL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL-SQEKVLPSDKFKDYLE 7832
Cdd:cd06626    87 EELLRHGRILDEAVIRVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLkNNTTTMAPGEVNSLVG 166

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 7833 T---MAPELLEGQ------GAVpqtDIWAIG 7854
Cdd:cd06626   167 TpayMAPEVITGNkgeghgRAA---DIWSLG 194
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
 6474-6716 1.79e-19

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 92.07  E-value: 1.79e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKI-LCAAKFIPLR--SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14061     2 IGVGGFGKVYRGIWRGEEVaVKAARQDPDEdiSVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGALN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKVYIQqLVEGLHYLHSHG---VLHLDIKPSNILMVHPARED------IKICDFGFAQNITPAElQF 6621
Cdd:cd14061    82 RVLAGRKIPPHVLVDWAIQ-IARGMNYLHNEApvpIIHRDLKSSNILILEAIENEdlenktLKITDFGLAREWHKTT-RM 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVleGRVSWSSPMAAHLSEDAKDFIKAT 6701
Cdd:cd14061   160 SAAGTYAWMAPEVIKSSTFSKASDVWSYGVLLWELLTGEVPYKGIDGLAVAYGV--AVNKLTLPIPSTCPEPFAQLMKDC 237

                         250
                  ....*....|....*
gi 215274225 6702 LQRAPQARPSAAQCL 6716
Cdd:cd14061   238 WQPDPHDRPSFADIL 252
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
 6471-6716 2.64e-19

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 91.46  E-value: 2.64e-19
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6471 KEEIGRGVFGFVKR---VQHKGNK-ILCAAKFIPLRSRTRAQA--YRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:smart00221    4 GKKLGEGAFGEVYKgtlKGKGDGKeVEVAVKTLKEDASEQQIEefLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYM 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6545 SSEELLDRL--YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAELQFS 6622
Cdd:smart00221   84 PGGDLLDYLrkNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGE--NLVVKISDFGLSRDLYDDDYYKV 161

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6623 QYG-SPefV---SPEIIQQNPVSEASDIWAMGVISY--LSLtCSSPFAGESDRATLLNVLEGRVSWSSPmaaHLSEDAKD 6696
Cdd:smart00221  162 KGGkLP--IrwmAPESLKEGKFTSKSDVWSFGVLLWeiFTL-GEEPYPGMSNAEVLEYLKKGYRLPKPP---NCPPELYK 235

                           250       260
                    ....*....|....*....|
gi 215274225   6697 FIKATLQRAPQARPSAAQCL 6716
Cdd:smart00221  236 LMLQCWAEDPEDRPTFSELV 255
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
 7665-7927 2.75e-19

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 91.98  E-value: 2.75e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7665 PLPSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP-KDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLV 7742
Cdd:cd14183     1 PASISERYKVGRTIGDGNFAVVKECVERSTGREYALKIINKSKcRGKEHMIQnEVSILRRVKHPNIVLLIEEMDMPTELY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN----LLKVVDLGNAQSLSQ 7818
Cdd:cd14183    81 LVMELVKGGDLFDAITSTNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQdgskSLKLGDFGLATVVDG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7819 ekvlPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPV--SSEGARDLQRGLRKGLVRLSRCY-AGLSG 7895
Cdd:cd14183   161 ----PLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFrgSGDDQEVLFDQILMGQVDFPSPYwDNVSD 236

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 7896 GAVAFLRSTLCAQPWGRPCASSCLQCPWLTEE 7927
Cdd:cd14183   237 SAKELITMMLQVDVDQRYSALQVLEHPWVNDD 268
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
 7670-7908 3.61e-19

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270725 [Multi-domain]  Cd Length: 350  Bit Score: 93.12  E-value: 3.61e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVLR---------EYEALKGLRHPHLAQLHAAYLSPRH 7740
Cdd:cd05573     1 DDFEVIKVIGRGAFGEVWLVRDKDTGQVYAMKIL-----RKSDMLKreqiahvraERDILADADSPWIVRLHYAFQDEDH 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7741 LVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNA------- 7813
Cdd:cd05573    76 LYLVMEYMPGGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCtkmnksg 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7814 ----------QSLSQEKVLPSDKFK--------------DYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSS 7869
Cdd:cd05573   156 dresylndsvNTLFQDNVLARRRPHkqrrvraysavgtpDY---IAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYS 232

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7870 EGARDLQRGL---RKGLVRLSrcYAGLSGGAVAFLRSTLCAQ 7908
Cdd:cd05573   233 DSLVETYSKImnwKESLVFPD--DPDVSPEAIDLIRRLLCDP 272
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
 6474-6721 4.07e-19

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 91.87  E-value: 4.07e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR----ERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05608     9 LGKGGFGEVSACQMRATGKLYACKKLNKKRLKKRKGYEgamvEKRILAKVHSRFIVSLAYAFQTKTDLCLVMTIMNGGDL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYR----KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFSQY- 6624
Cdd:cd05608    89 RYHIYNvdeeNPGFQEPRACFYTAQIISGLEHLHQRRIIYRDLKPENVLLDDDG--NVRISDLGLAVELKDGQTKTKGYa 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF--AGE--SDRATLLNVLEGRVSWSSpmaaHLSEDAKDFIKA 6700
Cdd:cd05608   167 GTPGFMAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPFraRGEkvENKELKQRILNDSVTYSE----KFSPASKSICEA 242

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6701 TLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05608   243 LLAKDPEKRlgfrdGNCDGLRTHPFF 268
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
 7680-7866 4.15e-19

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 91.52  E-value: 4.15e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDKT----------AVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd14182    13 RGVSSVVRRCIHKPTRQEYAVKIIDITGGGSFspeevqelreATLKEIDILRKVSgHPNIIQLKDTYETNTFFFLVFDLM 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFK 7828
Cdd:cd14182    93 KKGELFDYLTEKVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDMNIKLTDFGFSCQLD-----PGEKLR 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7829 DYLET---MAPELLE------GQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14182   168 EVCGTpgyLAPEIIEcsmddnHPGYGKEVDMWSTGVIMYTLLAGSPP 214
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
 7670-7868 4.36e-19

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 90.79  E-value: 4.36e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPkDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd06612     3 EVFDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEE-DLQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFK 7828
Cdd:cd06612    82 AGSVSDIMkITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDT----MAKRN 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7829 DYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06612   158 TVIGTpfwMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYS 200
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
 6474-6716 4.71e-19

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 91.18  E-value: 4.71e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILcAAKFipLRSRTRA----QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14066     1 IGSGGFGTVYKGVLENGTVV-AVKR--LNEMNCAaskkEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVT----EAEVKVyIQQLVEGLHYLHSHG---VLHLDIKPSNILMVH---ParediKICDFGFAQNITPAEL 6619
Cdd:cd14066    78 EDRLHCHKGSPplpwPQRLKI-AKGIARGLEYLHEECpppIIHGDIKSSNILLDEdfeP-----KLTDFGLARLIPPSES 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQ---YGSPEFVSPEIIQQNPVSEASDIWAMGVIsYLSLTCSSPFAGESDRATLLNVLegrVSWsspMAAHLSEDAKD 6696
Cdd:cd14066   152 VSKTsavKGTIGYLAPEYIRTGRVSTKSDVYSFGVV-LLELLTGKPAVDENRENASRKDL---VEW---VESKGKEELED 224

                         250       260
                  ....*....|....*....|
gi 215274225 6697 FIKATLQRAPQARPSAAQCL 6716
Cdd:cd14066   225 ILDKRLVDDDGVEEEEVEAL 244
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 5126-5216 4.97e-19

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 85.24  E-value: 4.97e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 215274225 5206 GVSSTKAELRV 5216
Cdd:cd05744    81 GENSFNAELVV 91
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
 6535-6720 5.37e-19

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 90.91  E-value: 5.37e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmvHPAREDIKICDFGFAQNI 6614
Cdd:cd06651    84 KTLTIFMEYMPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANIL--RDSAGNVKLGDFGASKRL 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQ----FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswSSPMAAHL 6690
Cdd:cd06651   162 QTICMSgtgiRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPT--NPQLPSHI 239

                         170       180       190
                  ....*....|....*....|....*....|
gi 215274225 6691 SEDAKDFIKATLQRAPQaRPSAAQCLSHPW 6720
Cdd:cd06651   240 SEHARDFLGCIFVEARH-RPSAEELLRHPF 268
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
 7669-7925 5.98e-19

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 91.62  E-value: 5.98e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLREYEalkglRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd14177     3 TDVYELKEDIGVGSYSVCKRCIHRATNMEFAVKIIdksKRDPSEEIEILMRYG-----QHPNIITLKDVYDDGRYVYLVT 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE----YNLLKVVDLGNAQSLSQEK- 7820
Cdd:cd14177    78 ELMKGGELLDRILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYMDdsanADSIRICDFGFAKQLRGENg 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7821 VLPSDKFKDYLetMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSeGARDLQRGLrkgLVRLSRCYAGLSGG---- 7896
Cdd:cd14177   158 LLLTPCYTANF--VAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFAN-GPNDTPEEI---LLRIGSGKFSLSGGnwdt 231

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 7897 ----AVAFLRSTLCAQPWGRPCASSCLQCPWLT 7925
Cdd:cd14177   232 vsdaAKDLLSHMLHVDPHQRYTAEQVLKHSWIA 264
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 5697-5875 6.08e-19

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 88.13  E-value: 6.08e-19
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCphVPIAVAGQKAVIFRNVRDIGRFHSSFLQELQQC--DTDDDVAM---CF 5771
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKE--LKLLSPNELETLFGNIEEIYEFHRDFLDELEERieEWDDSVERigdVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5772 IKNQAAFEQYLEFLVGRVQAESVVVSTAIQEFYKKYAEEALLAgdpSQPPPPPLQHYLEQPVERVQRYQALLKELIRNKA 5851
Cdd:smart00325   79 LKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESS---PQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155

                           170       180
                    ....*....|....*....|....
gi 215274225   5852 RNRQNCALLEQAYAVVSALPQRAE 5875
Cdd:smart00325  156 EDHEDREDLKKALKAIKELANQVN 179
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
 7681-7894 6.23e-19

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 91.33  E-value: 6.23e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTA---VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd07846    12 GSYGMVMKCRHKETGQIVAIKKFLESEDDKMVkkiAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVDHTVLDDLE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQekvlPSDKFKDYLET---M 7834
Cdd:cd07846    92 KYPNGLDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAA----PGEVYTDYVATrwyR 167

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7835 APELLEGQGAVPQ-TDIWAIGVTAFIMLSAE--YPVSSegarDLQRglrkgLVRLSRCYAGLS 7894
Cdd:cd07846   168 APELLVGDTKYGKaVDVWAVGCLVTEMLTGEplFPGDS----DIDQ-----LYHIIKCLGNLI 221
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
 7674-7870 6.42e-19

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 90.52  E-value: 6.42e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQCWEKasGRALAAKIIPYHpKDKTAVLR----EYEALKgLRHPHLAQLHAA---YLSPRHLVLILE 7746
Cdd:cd13979     7 LQEPLGSGGFGSVYKATYK--GETVAVKIVRRR-RKNRASRQsfwaELNAAR-LRHENIVRVLAAetgTDFASLGLIIME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERAS--YSESEVKdYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQ--EKVL 7822
Cdd:cd13979    83 YCGNGTLQQLIYEGSEplPLAHRIL-ISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEgnEVGT 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7823 PSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd13979   162 PRSHIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYAGL 209
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
 6474-6721 6.46e-19

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270756 [Multi-domain]  Cd Length: 285  Bit Score: 91.26  E-value: 6.46e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05605     8 LGKGGFGEVCACQVRATgKMYACKKLEKKRIKKRkgeAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhparED---IKICDFGFAQNITPAELQFSQY 6624
Cdd:cd05605    88 KFHIYNMGNpgFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILL-----DDhghVRISDLGLAVEIPEGETIRGRV 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAG--------ESDRatllNVLEGRVSWSSpmaaHLSEDAKD 6696
Cdd:cd05605   163 GTVGYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAPFRArkekvkreEVDR----RVKEDQEEYSE----KFSEEAKS 234

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6697 FIKATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05605   235 ICSQLLQKDPKTRlgcrgEGAEDVKSHPFF 264
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
 7672-7912 6.65e-19

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 92.45  E-value: 6.65e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd05593    17 FDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEviiAKDEVAhTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEY 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKF 7827
Cdd:cd05593    97 VNGGELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFG----LCKEGITDAATM 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCyagLSGGAVAFLRST 7904
Cdd:cd05593   173 KTFCgtpEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFPRT---LSADAKSLLSGL 249


                  ....*...
gi 215274225 7905 LCAQPWGR 7912
Cdd:cd05593   250 LIKDPNKR 257
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
 6514-6730 6.71e-19

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 92.15  E-value: 6.71e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6514 DILAALSHPLVTGLLDQFETRkTLILILELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNI 6593
Cdd:cd07854    69 EVLGPSGSDLTEDVGSLTELN-SVYIVQEYMETD--LANVLEQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANV 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6594 LMvhpARED--IKICDFGFAQNITPaELQFSQYGSPEFV-----SPEII-QQNPVSEASDIWAMGVISYLSLTCSSPFAG 6665
Cdd:cd07854   146 FI---NTEDlvLKIGDFGLARIVDP-HYSHKGYLSEGLVtkwyrSPRLLlSPNNYTKAIDMWAAGCIFAEMLTGKPLFAG 221

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6666 ------------------ESDRATLLNVLEGRVSWSSPMAAH--------LSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd07854   222 aheleqmqlilesvpvvrEEDRNELLNVIPSFVRNDGGEPRRplrdllpgVNPEALDFLEQILTFNPMDRLTAEEALMHP 301

                         250
                  ....*....|..
gi 215274225 6720 WF-LKSMPAEEA 6730
Cdd:cd07854   302 YMsCYSCPFDEP 313
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 6474-6721 7.69e-19

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 90.57  E-value: 7.69e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPL-RSRTRAQA------YRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06630     8 LGTGAFSSCYQARDVKTGTLMAVKQVSFcRNSSSEQEevveaiREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAG 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREDIKICDFG----FAQNITPA-ELQF 6621
Cdd:cd06630    88 GSVASLLSKYGAFSENVIINYTLQILRGLAYLHDNQIIHRDLKGANLL-VDSTGQRLRIADFGaaarLASKGTGAgEFQG 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVIsYLSLTCSSPFAGESDRATLLNVLEGRVSWSSP--MAAHLSEDAKDFIK 6699
Cdd:cd06630   167 QLLGTIAFMAPEVLRGEQYGRSCDVWSVGCV-IIEMATAKPPWNAEKISNHLALIFKIASATTPppIPEHLSPGLRDVTL 245

                         250       260
                  ....*....|....*....|..
gi 215274225 6700 ATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd06630   246 RCLELQPEDRPPARELLKHPVF 267
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
 6474-6721 7.80e-19

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 91.54  E-value: 7.80e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAK-----FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05620     3 LGKGSFGKVLLAELKGKGEYFAVKalkkdVVLIDDDVECTMVEKRVLALAWENPFLTHLYCTFQTKEHLFFVMEFLNGGD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQY-GSP 6627
Cdd:cd05620    83 LMFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGH--IKIADFGMCKENVFGDNRASTFcGTP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDratllNVLEGRVSWSSPMAAH-LSEDAKDFIKATLQRAP 6706
Cdd:cd05620   161 DYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDE-----DELFESIRVDTPHYPRwITKESKDILEKLFERDP 235

                         250
                  ....*....|....*.
gi 215274225 6707 QARPSAAQCLS-HPWF 6721
Cdd:cd05620   236 TRRLGVVGNIRgHPFF 251
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 7677-7922 7.89e-19

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 90.29  E-value: 7.89e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPY---HPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRH--LVLILELCSGP 7751
Cdd:cd08217     7 TIGKGSFGTVRKVRRKSDGKILVWKEIDYgkmSEKEKQQLVSEVNILRELKHPNIVRYYDRIVDRANttLYIVMEYCEGG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLP----CLAERASYSESEVKDYLWQMLSATQYLHN-----QHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvl 7822
Cdd:cd08217    87 DLAQlikkCKKENQYIPEEFIWKIFTQLLLALYECHNrsvggGKILHRDLKPANIFLDSDNNVKLGDFGLARVLSHD--- 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7823 pSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLV-RLSRCYaglSGGAV 7898
Cdd:cd08217   164 -SSFAKTYVGTpyyMSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAANQLELAKKIKEGKFpRIPSRY---SSELN 239

                         250       260
                  ....*....|....*....|....
gi 215274225 7899 AFLRSTLCAQPWGRPCASSCLQCP 7922
Cdd:cd08217   240 EVIKSMLNVDPDKRPSVEELLQLP 263
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
 6468-6723 1.02e-18

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 90.82  E-value: 1.02e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALS-HPLVTGLLDQFETRKTLI-----LIL 6541
Cdd:cd06639    24 WDIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLPnHPNVVKFYGMFYKADQYVggqlwLVL 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELC---SSEELLDRLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPA 6617
Cdd:cd06639   104 ELCnggSVTELVKGLLKCGQrLDEAMISYILYGALLGLQHLHNNRIIHRDVKGNNILLT--TEGGVKLVDFGVSAQLTSA 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQF-SQYGSPEFVSPEII---QQNPVSEAS--DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGrvswSSPMAAH-- 6689
Cdd:cd06639   182 RLRRnTSVGTPFWMAPEVIaceQQYDYSYDArcDVWSLGITAIELADGDPPLFDMHPVKALFKIPRN----PPPTLLNpe 257

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 215274225 6690 -LSEDAKDFIKATLQRAPQARPSAAQCLSHPwFLK 6723
Cdd:cd06639   258 kWCRGFSHFISQCLIKDFEKRPSVTHLLEHP-FIK 291
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
 7678-7924 1.05e-18

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 89.77  E-value: 1.05e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd06632     8 LGSGSFGSVYEGFNGDTGDFFAVKEVSLVDDDKKSresvkqLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGG 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYL 7831
Cdd:cd06632    88 SIHKLLQRYGAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFSFAKSFKGSPYW 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7832 etMAPELLEGQGAV--PQTDIWAIGVTAFIMLSAEYPVSS-EGARDLQRGLRKGlvRLSRCYAGLSGGAVAFLRSTLCAQ 7908
Cdd:cd06632   168 --MAPEVIMQKNSGygLAVDIWSLGCTVLEMATGKPPWSQyEGVAAIFKIGNSG--ELPPIPDHLSPDAKDFIRLCLQRD 243

                         250
                  ....*....|....*.
gi 215274225 7909 PWGRPCASSCLQCPWL 7924
Cdd:cd06632   244 PEDRPTASQLLEHPFV 259
STKc_DMPK_like cd05597
Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; ...
 6468-6721 1.19e-18

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270748 [Multi-domain]  Cd Length: 331  Bit Score: 91.25  E-value: 1.19e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN------KILcaAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd05597     3 FEILKVIGRGAFGEVAVVKLKSTekvyamKIL--NKWEMLKRAETACFREERDVLVNGDRRWITKLHYAFQDENYLYLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELL-------DRLyrkgvvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNI 6614
Cdd:cd05597    81 DYYCGGDLLtllskfeDRL------PEEMARFYLAEMVLAIDSIHQLGYVHRDIKPDNVLL--DRNGHIRLADFGSCLKL 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQ--YGSPEFVSPEIIQQNPVSEAS-----DIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPM- 6686
Cdd:cd05597   153 REDGTVQSSvaVGTPDYISPEILQAMEDGKGRygpecDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKEHFSFPDd 232

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 215274225 6687 AAHLSEDAKDFIKATLQRAPQ--ARPSAAQCLSHPWF 6721
Cdd:cd05597   233 EDDVSEEAKDLIRRLICSRERrlGQNGIDDFKKHPFF 269
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
 6456-6699 1.26e-18

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270774 [Multi-domain]  Cd Length: 409  Bit Score: 92.76  E-value: 1.26e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6456 EKQSHRRKlhsfYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRE-RDILAALSHPLVTGLLDQF 6531
Cdd:cd05624    66 EMQLHRDD----FEIIKVIGRGAFGEVAVVKMKNTERIYAMKILnkwEMLKRAETACFREeRNVLVNGDCQWITTLHYAF 141

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6532 ETRKTLILILELCSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGF 6610
Cdd:cd05624   142 QDENYLYLVMDYYVGGDLLTLLSKfEDKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLL--DMNGHIRLADFGS 219

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 AQNITP-AELQFS-QYGSPEFVSPEIIQ-----QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVL--EGRVS 6681
Cdd:cd05624   220 CLKMNDdGTVQSSvAVGTPDYISPEILQamedgMGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMnhEERFQ 299

                         250
                  ....*....|....*...
gi 215274225 6682 WSSPMaAHLSEDAKDFIK 6699
Cdd:cd05624   300 FPSHV-TDVSEEAKDLIQ 316
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
 7678-7870 1.33e-18

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 89.66  E-value: 1.33e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKtaVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14010     8 IGRGKHSVVYKGRRKGTIEFVAIKCVDKSKRPE--VLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTGGDLETLL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLET---- 7833
Cdd:cd14010    86 RQDGNLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREGEILKELFGQFSDEGNVnkvs 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7834 -----------MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd14010   166 kkqakrgtpyyMAPELFQGGVHSFASDLWALGCVLYEMFTGKPPFVAE 213
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 7686-7924 1.36e-18

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 89.66  E-value: 1.36e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7686 VRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGlrhPHLAQLHAAY----LSPRHLVLILELCSGPELLPCLAERA 7761
Cdd:cd14172    20 VLECFHRRTGQKCALKLLYDSPKARREVEHHWRASGG---PHIVHILDVYenmhHGKRCLLIIMECMEGGELFSRIQERG 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7762 --SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKVLPSDKFKDYLetMAP 7836
Cdd:cd14172    97 dqAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSKEkdaVLKLTDFGFAKETTVQNALQTPCYTPYY--VAP 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7837 ELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKgLVRLSRC------YAGLSGGAVAFLRSTLCAQPW 7910
Cdd:cd14172   175 EVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAISPGMKR-RIRMGQYgfpnpeWAEVSEEAKQLIRHLLKTDPT 253

                         250
                  ....*....|....
gi 215274225 7911 GRPCASSCLQCPWL 7924
Cdd:cd14172   254 ERMTITQFMNHPWI 267
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 6468-6718 1.49e-18

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 89.47  E-value: 1.49e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRtraQAYRERDILAALSHPLVT----------GLLDQFET---- 6533
Cdd:cd14047     8 FKEIELIGSGGFGQVFKAKHRIDGKTYAIKRVKLNNE---KAEREVKALAKLDHPNIVryngcwdgfdYDPETSSSnssr 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 --RKTLILILELCSS---EELLDRLyRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDF 6608
Cdd:cd14047    85 skTKCLFIQMEFCEKgtlESWIEKR-NGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGK--VKIGDF 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6609 GFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISY-LSLTCSSPFAGESDRATLLNvleGRVswsSPMA 6687
Cdd:cd14047   162 GLVTSLKNDGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFeLLHVCDSAFEKSKFWTDLRN---GIL---PDIF 235

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6688 AHLSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14047   236 DKRYKIEKTIIKKMLSKKPEDRPNASEILRT 266
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
 6474-6721 1.71e-18

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270761 [Multi-domain]  Cd Length: 349  Bit Score: 91.09  E-value: 1.71e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05610    12 ISRGAFGKVYLGRKKNNSKLYAVKVVKkadmINKNMVHQVQAERDALALSKSPFIVHLYYSLQSANNVYLVMEYLIGGDV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQ-------NI-------- 6614
Cdd:cd05610    92 KSLLHIYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGH--IKLTDFGLSKvtlnrelNMmdilttps 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 ----------TPAE-------LQFSQ----------------------YGSPEFVSPEIIQQNPVSEASDIWAMGVISYL 6655
Cdd:cd05610   170 makpkndysrTPGQvlslissLGFNTptpyrtpksvrrgaarvegeriLGTPDYLAPELLLGKPHGPAVDWWALGVCLFE 249

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6656 SLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAhLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd05610   250 FLTGIPPFNDETPQQVFQNILNRDIPWPEGEEE-LSVNAQNAIEILLTMDPTKRAGLKELKQHPLF 314
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
 6474-6709 1.75e-18

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 90.84  E-value: 1.75e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKF----IPLRSRTRAQAYRERDILAA-LSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05575     3 IGKGSFGKVLLARHKAEGKLYAVKVlqkkAILKRNEVKHIMAERNVLLKnVKHPFLVGLHYSFQTKDKLYFVLDYVNGGE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITPAELQFSQYGSP 6627
Cdd:cd05575    83 LFFHLQRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILL--DSQGHVVLTDFGLCkEGIEPSDTTSTFCGTP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGEsDRATLL-NVLEgrvswsSPMA--AHLSEDAKDFIKATLQR 6704
Cdd:cd05575   161 EYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSR-DTAEMYdNILH------KPLRlrTNVSPSARDLLEGLLQK 233


                  ....*
gi 215274225 6705 APQAR 6709
Cdd:cd05575   234 DRTKR 238
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
 6511-6719 1.89e-18

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 88.96  E-value: 1.89e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6511 RERDILAALSHPLVTGLLDQFETRKT------LILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVL 6584
Cdd:cd14012    47 KELESLKKLRHPNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELLDSVGSVPLDTARRWTLQLLEALEYLHRNGVV 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6585 HLDIKPSNILMVHPAREDI-KICDFGFAQniTPAELQFSQ----YGSPEFVSPEIIQQN-PVSEASDIWAMGVIsYLSLT 6658
Cdd:cd14012   127 HKSLHAGNVLLDRDAGTGIvKLTDYSLGK--TLLDMCSRGsldeFKQTYWLPPELAQGSkSPTRKTDVWDLGLL-FLQML 203

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6659 CSSPfAGEsdRATLLNVLEGRVSwsspmaahLSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd14012   204 FGLD-VLE--KYTSPNPVLVSLD--------LSASLQDFLSKCLSLDPKKRPTALELLPHE 253
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
 6468-6735 1.97e-18

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 90.12  E-value: 1.97e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKF---------IPLRSrtraqaYRERDILAALSHPLVTGLLDQFETRK--T 6536
Cdd:cd07845     9 FEKLNRIGEGTYGIVYRARDTTSGEIVALKKvrmdnerdgIPISS------LREITLLLNLRHPNIVELKEVVVGKHldS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILELCSSE--ELLDRLYRKgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNI 6614
Cdd:cd07845    83 IFLVMEYCEQDlaSLLDNMPTP--FSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTD--KGCLKIADFGLARTY 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQ------YGSPEFVSPEIIQqnpvSEASDIWAMGVISYLSLTCSSPFAGESDRATL---------------- 6672
Cdd:cd07845   159 GLPAKPMTPkvvtlwYRAPELLLGCTTY----TTAIDMWAVGCILAELLAHKPLLPGKSEIEQLdliiqllgtpnesiwp 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6673 -----------------LNVLEGRVSWsspmaahLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKSMPAEEAHFINT 6735
Cdd:cd07845   235 gfsdlplvgkftlpkqpYNNLKHKFPW-------LSEAGLRLLNFLLMYDPKKRATAEEALESSYFKEKPLPCEPEMMPT 307
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
 7680-7866 2.26e-18

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 88.93  E-value: 2.26e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHP------KDKTAVLREYEALKGLRHPHLAQLHAAYLSP--RHLVLILELCSGP 7751
Cdd:cd06653    12 RGAFGEVYLCYDADTGRELAVKQVPFDPdsqetsKEVNALECEIQLLKNLRHDRIVQYYGCLRDPeeKKLSIFVEYMPGG 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsQEKVLPSDKFKDYL 7831
Cdd:cd06653    92 SVKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRI-QTICMSGTGIKSVT 170

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 215274225 7832 ET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06653   171 GTpywMSPEVISGEGYGRKADVWSVACTVVEMLTEKPP 208
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
 7680-7925 2.78e-18

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 88.84  E-value: 2.78e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRF---SVVRQCWEKA---SGRALAAKIIPY------HPKDKTAVlrEYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14187    11 RGRFlgkGGFAKCYEITdadTKEVFAGKIVPKslllkpHQKEKMSM--EIAIHRSLAHQHVVGFHGFFEDNDFVYVVLEL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKF 7827
Cdd:cd14187    89 CRRRSLLELHKRRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYD----GERK 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRcyaGLSGGAVAFLRST 7904
Cdd:cd14187   165 KTLCGTpnyIAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSCLKETYLRIKKNEYSIPK---HINPVAASLIQKM 241

                         250       260
                  ....*....|....*....|.
gi 215274225 7905 LCAQPWGRPCASSCLQCPWLT 7925
Cdd:cd14187   242 LQTDPTARPTINELLNDEFFT 262
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
 7670-7924 2.94e-18

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 88.68  E-value: 2.94e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH--PKD--KTAVLREYEALKGLRHPHLAQLHAAY-LSPRHLVLI 7744
Cdd:cd14165     1 RGYILGINLGEGSYAKVKSAYSERLKCNVAIKIIDKKkaPDDfvEKFLPRELEILARLNHKSIIKTYEIFeTSDGKVYIV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQE---KV 7821
Cdd:cd14165    81 MELGVQGDLLEFIKLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDengRI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7822 LPSDKFKDYLETMAPELLEGQGAVPQT-DIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAgLSGGAVAF 7900
Cdd:cd14165   161 VLSKTFCGSAAYAAPEVLQGIPYDPRIyDIWSLGVILYIMVCGSMPYDDSNVKKMLKIQKEHRVRFPRSKN-LTSECKDL 239

                         250       260
                  ....*....|....*....|....
gi 215274225 7901 LRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14165   240 IYRLLQPDVSQRLCIDEVLSHPWL 263
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
 6474-6721 3.24e-18

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 89.28  E-value: 3.24e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05631     8 LGKGGFGEVCACQVRATgKMYACKKLEKKRIKKRkgeAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd05631    88 KFHIYNMGNpgFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILL--DDRGHIRISDLGLAVQIPEGETVRGRVGTV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05631   166 GYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERVKREEVDRRVKEDQEEYSEKFSEDAKSICRMLLTKNPK 245

                         250
                  ....*....|....*....
gi 215274225 6708 AR-----PSAAQCLSHPWF 6721
Cdd:cd05631   246 ERlgcrgNGAAGVKQHPIF 264
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 5125-5216 3.41e-18

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 83.02  E-value: 3.41e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5125 APVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINedQQGG-HQLIITAVVPADMGVYRCLAEN 5203
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIH--QEGDlHSLIIAEAFEEDTGRYSCLATN 78

                          90
                  ....*....|...
gi 215274225 5204 SMGVSSTKAELRV 5216
Cdd:cd20972    79 SVGSDTTSAEIFV 91
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
 6467-6721 3.63e-18

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 89.65  E-value: 3.63e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFV---KRVQHKGNKILCAAKFIPLRSRT---RAQAYRERDILAALSHPLVTGLLDQF--ETRKTLI 6538
Cdd:cd07842     1 KYEIEGCIGRGTYGRVykaKRKNGKDGKEYAIKKFKGDKEQYtgiSQSACREIALLRELKHENVVSLVEVFleHADKSVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSsEELLD-----RLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED--IKICDFGFA 6611
Cdd:cd07842    81 LLFDYAE-HDLWQiikfhRQAKRVSIPPSMVKSLLWQILNGIHYLHSNWVLHRDLKPANILVMGEGPERgvVKIGDLGLA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAeLQFSQYGSPEFV-----SPEII----QQNPvseASDIWAMGVISYLSLTCSSPFAGESD---------RATLL 6673
Cdd:cd07842   160 RLFNAP-LKPLADLDPVVVtiwyrAPELLlgarHYTK---AIDIWAIGCIFAELLTLEPIFKGREAkikksnpfqRDQLE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6674 NVLE-------------------------------GRVSWSSPMAAHLSEDAK--DFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd07842   236 RIFEvlgtptekdwpdikkmpeydtlksdtkastyPNSLLAKWMHKHKKPDSQgfDLLRKLLEYDPTKRITAEEALEHPY 315


                  .
gi 215274225 6721 F 6721
Cdd:cd07842   316 F 316
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
 6468-6721 4.26e-18

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 90.05  E-value: 4.26e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQ-AYRERDILAALSHPLVTGLLDQF------ETRKTLI 6538
Cdd:cd07851    17 YQNLSPVGSGAYGQVCSAFDTKTGRKVAIKKLsrPFQSAIHAKrTYRELRLLKHMKHENVIGLLDVFtpasslEDFQDVY 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFAQnitP 6616
Cdd:cd07851    97 LVTHLMGAD--LNNIVKCQKLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAV----NEDceLKILDFGLAR---H 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQY-GSPEFVSPEII----QQNpvsEASDIWAMGVISYLSLTCSSPFAGES--DRATLLNVLEGrvswsSPMAAH 6689
Cdd:cd07851   168 TDDEMTGYvATRWYRAPEIMlnwmHYN---QTVDIWSVGCIMAELLTGKTLFPGSDhiDQLKRIMNLVG-----TPDEEL 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6690 L----SEDAKDFIKA--TLQR----------APQA--------------RPSAAQCLSHPWF 6721
Cdd:cd07851   240 LkkisSESARNYIQSlpQMPKkdfkevfsgaNPLAidllekmlvldpdkRITAAEALAHPYL 301
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 6472-6718 4.35e-18

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 87.98  E-value: 4.35e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKR---VQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd00192     1 KKLGEGAFGEVYKgklKGGDGKTVDVAVKTLKEdaSESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRL---------YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPA 6617
Cdd:cd00192    81 GDLLDFLrksrpvfpsPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLV--VKISDFGLSRDIYDD 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFV---SPEIIQQNPVSEASDIWAMGVISY--LSLtCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSE 6692
Cdd:cd00192   159 DYYRKKTGGKLPIrwmAPESLKDGIFTSKSDVWSFGVLLWeiFTL-GATPYPGLSNEEVLEYLRKGYR---LPKPENCPD 234

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd00192   235 ELYELMLSCWQLDPEDRPTFSELVER 260
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
 6468-6726 4.35e-18

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 89.01  E-value: 4.35e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06656    21 YTRFEKIGQGASGTVYTAIDIATGQEVAIKQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAG 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFS-QYG 6625
Cdd:cd06656   101 GSLTD-VVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDG--SVKLTDFGFCAQITPEQSKRStMVG 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVLEGRVSWSSPmaAHLSEDAKDFIKATLQR 6704
Cdd:cd06656   178 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlRALYLIATNGTPELQNP--ERLSAVFRDFLNRCLEM 255

                         250       260
                  ....*....|....*....|..
gi 215274225 6705 APQARPSAAQCLSHPWFLKSMP 6726
Cdd:cd06656   256 DVDRRGSAKELLQHPFLKLAKP 277
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 5697-5873 4.37e-18

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 85.81  E-value: 4.37e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCphVPIAVAGQKAVIFRNVRDIGRFHSSFLQELQQC-----DTDDDVAMCF 5771
Cdd:cd00160     4 VIKELLQTERNYVRDLKLLVEVFLKPLDKE--LLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERveewdKSGPRIGDVF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5772 IKNQAAFEQYLEFLVGRVQAESVV-----VSTAIQEFYKKYaeeallagdPSQPPPPPLQHYLEQPVERVQRYQALLKEL 5846
Cdd:cd00160    82 LKLAPFFKIYSEYCSNHPDALELLkklkkFNKFFQEFLEKA---------ESECGRLKLESLLLKPVQRLTKYPLLLKEL 152

                         170       180
                  ....*....|....*....|....*..
gi 215274225 5847 IRNKARNRQNCALLEQAYAVVSALPQR 5873
Cdd:cd00160   153 LKHTPDGHEDREDLKKALEAIKEVASQ 179
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
 6468-6654 4.42e-18

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 89.20  E-value: 4.42e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTRAQAYRERDILAALS--------HPLvtGLLDQFETRKTLI 6538
Cdd:cd14135     2 YRVYGYLGKGVFSNVVRARDLARgNQEVAIKIIRNNELMHKAGLKELEILKKLNdadpddkkHCI--RLLRHFEHKNHLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSS--EELLDRlYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREDIKICDFGFAQNIT 6615
Cdd:cd14135    80 LVFESLSMnlREVLKK-YGKNVgLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNIL-VNEKKNTLKLCDFGSASDIG 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 6616 PAELqfsqygSPEFVS-----PEIIQQNPVSEASDIWAMGVISY 6654
Cdd:cd14135   158 ENEI------TPYLVSrfyraPEIILGLPYDYPIDMWSVGCTLY 195
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
 6474-6721 4.57e-18

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 89.60  E-value: 4.57e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAK-----FIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05619    13 LGKGSFGKVFLAELKGTNQFFAIKalkkdVVLMDDDVECTMVEKRVLSLAWEHPFLTHLFCTFQTKENLFFVMEYLNGGD 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQY-GSP 6627
Cdd:cd05619    93 LMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGH--IKIADFGMCKENMLGDAKTSTFcGTP 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRAtllnvLEGRVSWSSPMAAH-LSEDAKDFIKATLQRAP 6706
Cdd:cd05619   171 DYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEEE-----LFQSIRMDNPFYPRwLEKEAKDILVKLFVREP 245

                         250
                  ....*....|....*.
gi 215274225 6707 QARPSA-AQCLSHPWF 6721
Cdd:cd05619   246 ERRLGVrGDIRQHPFF 261
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
 7672-7925 4.96e-18

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 87.65  E-value: 4.96e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd06614     2 YKNLEKIGEGASGEVYKATDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ellpCLAE-----RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsDK 7826
Cdd:cd06614    82 ----SLTDiitqnPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEK----SK 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE-GARDLQRGLRKGLVRLsRCYAGLSGGAVAFLR 7902
Cdd:cd06614   154 RNSVVGTpywMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEpPLRALFLITTKGIPPL-KNPEKWSPEFKDFLN 232

                         250       260
                  ....*....|....*....|...
gi 215274225 7903 STLCAQPWGRPCASSCLQCPWLT 7925
Cdd:cd06614   233 KCLVKDPEKRPSAEELLQHPFLK 255
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 7681-7912 5.05e-18

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 89.59  E-value: 5.05e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHP---KDKTA--VLREYEALKGLRH-PHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd05614    14 GKVFLVRKVSGHDANKLYAMKVLRKAAlvqKAKTVehTRTERNVLEHVRQsPFLVTLHYAFQTDAKLHLILDYVSGGELF 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETM 7834
Cdd:cd05614    94 THLYQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTEEKERTYSFCGTIEYM 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7835 APELLEGQGAVPQT-DIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGG-AVAFLRSTLCAQPWGR 7912
Cdd:cd05614   174 APEIIRGKSGHGKAvDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRILKCDPPFPSFIGPvARDLLQKLLCKDPKKR 253
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
 7672-7854 5.38e-18

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 87.71  E-value: 5.38e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd08224     2 YEIEKKIGKGQFSVVYRARCLLDGRLVALKKVQifemMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERAS----YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLP 7823
Cdd:cd08224    82 ADAGDLSRLIKHFKKqkrlIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTTAA 161

                         170       180       190
                  ....*....|....*....|....*....|...
gi 215274225 7824 SDKFKD--YletMAPELLEGQGAVPQTDIWAIG 7854
Cdd:cd08224   162 HSLVGTpyY---MSPERIREQGYDFKSDIWSLG 191
I-set pfam07679
Immunoglobulin I-set domain;
110-201 5.40e-18

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 82.31  E-value: 5.40e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEpdGPRVRVEELGEASALRIRAARPRDGGTYEVRAENP 189
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS--SDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 215274225   190 LGAASAAAALVV 201
Cdd:pfam07679   79 AGEAEASAELTV 90
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
 6468-6718 5.83e-18

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 88.53  E-value: 5.83e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALS-HPLVTGLLDQF-----ETRKTLILIL 6541
Cdd:cd06638    20 WEIIETIGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGMYykkdvKNGDQLWLVL 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELC---SSEELLDRLYRKGVVTEAEVKVYI-QQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPA 6617
Cdd:cd06638   100 ELCnggSVTDLVKGFLKRGERMEEPIIAYIlHEALMGLQHLHVNKTIHRDVKGNNILLT--TEGGVKLVDFGVSAQLTST 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQF-SQYGSPEFVSPEII---QQ--NPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLnvlegRVSWSSPMAAHLS 6691
Cdd:cd06638   178 RLRRnTSVGTPFWMAPEVIaceQQldSTYDARCDVWSLGITAIELGDGDPPLADLHPMRALF-----KIPRNPPPTLHQP 252

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 6692 E----DAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd06638   253 ElwsnEFNDFIRKCLTKDYEKRPTVSDLLQH 283
STKc_Sid2p_like cd05600
Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the ...
 6461-6721 5.91e-18

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270751 [Multi-domain]  Cd Length: 386  Bit Score: 90.09  E-value: 5.91e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6461 RRKL-HSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFipLRSRT------RAQAYRERDILAALSHPLVTGLLDQFET 6533
Cdd:cd05600     5 RTRLkLSDFQILTQVGQGGYGSVFLARKKDTGEICALKI--MKKKVlfklneVNHVLTERDILTTTNSPWLVKLLYAFQD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQN 6613
Cdd:cd05600    83 PENVYLAMEYVPGGDFRTLLNNSGILSEEHARFYIAEMFAAISSLHQLGYIHRDLKPENFLI--DSSGHIKLTDFGLASG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITP--------AELQ------------------------------FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYL 6655
Cdd:cd05600   161 TLSpkkiesmkIRLEevkntafleltakerrniyramrkedqnyaNSVVGSPDYMAPEVLRGEGYDLTVDYWSLGCILFE 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6656 SLTCSSPFAGESDRATLLN------VLEGRVSWSSPMAAHLSEDAKDFIKaTLQRAPQAR-PSAAQCLSHPWF 6721
Cdd:cd05600   241 CLVGFPPFSGSTPNETWANlyhwkkTLQRPVYTDPDLEFNLSDEAWDLIT-KLITDPQDRlQSPEQIKNHPFF 312
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
 6467-6709 5.99e-18

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 88.42  E-value: 5.99e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEeIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQ-----AYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd05607     4 FYEFRV-LGKGGFGEVCAVQVKNTGQMYACKKLD-KKRLKKKsgekmALLEKEILEKVNSPFIVSLAYAFETKTHLCLVM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAEL 6619
Cdd:cd05607    82 SLMNGGDLKYHIYNVGErgIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLL--DDNGNCRLSDLGLAVEVKEGKP 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRAT----LLNVLEGRVSWSSPmaaHLSEDAK 6695
Cdd:cd05607   160 ITQRAGTNGYMAPEILKEESYSYPVDWFAMGCSIYEMVAGRTPFRDHKEKVSkeelKRRTLEDEVKFEHQ---NFTEEAK 236

                         250
                  ....*....|....
gi 215274225 6696 DFIKATLQRAPQAR 6709
Cdd:cd05607   237 DICRLFLAKKPENR 250
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
 7712-7924 6.08e-18

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 87.97  E-value: 6.08e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7712 AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLD 7791
Cdd:cd06628    52 ALQREIALLRELQHENIVQYLGSSSDANHLNIFLEYVPGGSVATLLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRD 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7792 LRSENMIITEYNLLKVVDLG-------NAQSLSQEKVLPSdkFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAE 7864
Cdd:cd06628   132 IKGANILVDNKGGIKISDFGiskkleaNSLSTKNNGARPS--LQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGT 209

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7865 YPVSSegARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd06628   210 HPFPD--CTQMQAIFKIGENASPTIPSNISSEARDFLEKTFEIDHNKRPTADELLKHPFL 267
STKc_LATS1 cd05625
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the ...
 6467-6721 6.33e-18

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270775 [Multi-domain]  Cd Length: 382  Bit Score: 90.11  E-value: 6.33e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEeIGRGVFGFVKRVQHKGNKILCAAKF-----IPLRSRTrAQAYRERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd05625     3 FVKIKT-LGIGAFGEVCLARKVDTKALYATKTlrkkdVLLRNQV-AHVKAERDILAEADNEWVVRLYYSFQDKDNLYFVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGF----------- 6610
Cdd:cd05625    81 DYIPGGDMMSLLIRMGVFPEDLARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRDGH--IKLTDFGLctgfrwthdsk 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 ---------------------------AQNITPAE----------LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVIS 6653
Cdd:cd05625   159 yyqsgdhlrqdsmdfsnewgdpencrcGDRLKPLErraarqhqrcLAHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVIL 238

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6654 YLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIkATLQRAPQAR---PSAAQCLSHPWF 6721
Cdd:cd05625   239 FEMLVGQPPFLAQTPLETQMKVINWQTSLHIPPQAKLSPEASDLI-IKLCRGPEDRlgkNGADEIKAHPFF 308
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
 6473-6722 6.33e-18

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 87.50  E-value: 6.33e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQA-YRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLD 6551
Cdd:cd06648    14 KIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELlFNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALTD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6552 rLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGF-AQNITPAELQFSQYGSPEFV 6630
Cdd:cd06648    94 -IVTHTRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGR--VKLSDFGFcAQVSKEVPRRKSLVGTPYWM 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6631 SPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRvswsSPMAAHL---SEDAKDFIKATLQRAPQ 6707
Cdd:cd06648   171 APEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNE----PPKLKNLhkvSPRLRSFLDRMLVRDPA 246

                         250
                  ....*....|....*
gi 215274225 6708 ARPSAAQCLSHPWFL 6722
Cdd:cd06648   247 QRATAAELLNHPFLA 261
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
 6566-6719 6.53e-18

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 91.47  E-value: 6.53e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6566 VYIQQLVeGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQ---NITPAELQFSQYGSPEFVSPEIIQQNPVSE 6642
Cdd:PTZ00283  148 LFIQVLL-AVHHVHSKHMIHRDIKSANILLCSNGL--VKLGDFGFSKmyaATVSDDVGRTFCGTPYYVAPEIWRRKPYSK 224

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6643 ASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:PTZ00283  225 KADMFSLGVLLYELLTLKRPFDGENMEEVMHKTLAGRY---DPLPPSISPEMQEIVTALLSSDPKRRPSSSKLLNMP 298
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
 7672-7924 6.55e-18

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 87.47  E-value: 6.55e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAK---IIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd08529     2 FEILNKLGKGSFGVVYKVVRKVDGRVYALKqidISRMSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCL-AERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPsdk 7826
Cdd:cd08529    82 ENGDLHSLIkSQRGRpLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTNFA--- 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 fKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP--VSSEGArdLQRGLRKGlvRLSRCYAGLSGGAVAFL 7901
Cdd:cd08529   159 -QTIVGTpyyLSPELCEDKPYNEKSDVWALGCVLYELCTGKHPfeAQNQGA--LILKIVRG--KYPPISASYSQDLSQLI 233

                         250       260
                  ....*....|....*....|...
gi 215274225 7902 RSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd08529   234 DSCLTKDYRQRPDTTELLRNPSL 256
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
 7677-7866 7.96e-18

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 87.41  E-value: 7.96e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK------TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd06625     7 LLGQGAFGQVYLCYDADTGRELAVKQVEIDPINTeaskevKALECEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsqEKVLPSDKFKDY 7830
Cdd:cd06625    87 GSVKDEIKAYGALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRL--QTICSSTGMKSV 164

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7831 LET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06625   165 TGTpywMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPP 203
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
 6472-6718 8.64e-18

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 87.17  E-value: 8.64e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6472 EEIGRGVFGFVKR----VQHKGNKILCAAKFipLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:pfam07714    5 EKLGEGAFGEVYKgtlkGEGENTKIKVAVKT--LKEGADEEERedflEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6544 CSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFS 6622
Cdd:pfam07714   83 MPGGDLLDFLRKhKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLV--VKISDFGLSRDIYDDDYYRK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6623 QYGSPEFV---SPEIIQQNPVSEASDIWAMGV-----ISYlsltCSSPFAGESDRATLLNVLEGRVswsSPMAAHLSEDA 6694
Cdd:pfam07714  161 RGGGKLPIkwmAPESLKDGKFTSKSDVWSFGVllweiFTL----GEQPYPGMSNEEVLEFLEDGYR---LPQPENCPDEL 233

                          250       260
                   ....*....|....*....|....
gi 215274225  6695 KDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:pfam07714  234 YDLMKQCWAYDPEDRPTFSELVED 257
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
 6474-6720 1.01e-17

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 89.42  E-value: 1.01e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIP-----LRSRTRAqaYRERDILAALSHPLVTGLLD-----QFETRKTLILILEL 6543
Cdd:cd07853     8 IGYGAFGVVWSVTDPRDGKRVALKKMPnvfqnLVSCKRV--FRELKMLCFFKHDNVLSALDilqppHIDPFEEIYVVTEL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEeLLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAElqfSQ 6623
Cdd:cd07853    86 MQSD-LHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCV--LKICDFGLARVEEPDE---SK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFV-----SPEIIQQNP-VSEASDIWAMGVI------------------------SYLSLTCSSPF--AGESDRAT 6671
Cdd:cd07853   160 HMTQEVVtqyyrAPEILMGSRhYTSAVDIWSVGCIfaellgrrilfqaqspiqqldlitDLLGTPSLEAMrsACEGARAH 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6672 LLNVLEGRVSWSS--PMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd07853   240 ILRGPHKPPSLPVlyTLSSQATHEAVHLLCRMLVFDPDKRISAADALAHPY 290
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
 7681-7905 1.14e-17

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 88.23  E-value: 1.14e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKI-----IPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd05584    10 GKVFQVRKTTGSDKGKIFAMKVlkkasIVRNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILEYLSGGELFM 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK---FKDYLE 7832
Cdd:cd05584    90 HLEREGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFG----LCKESIHDGTVthtFCGTIE 165

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTL 7905
Cdd:cd05584   166 YMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLNLP---PYLTNEARDLLKKLL 235
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 7707-7924 1.22e-17

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 86.71  E-value: 1.22e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL----LPCLAERASYSESEVKDYLWQMLSATQYL 7782
Cdd:cd08222    43 PDETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCIVTEYCEGGDLddkiSEYKKSGTTIDENQILDWFIQLLLAVQYM 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7783 HNQHILHLDLRSENmIITEYNLLKVVDLGNAQSLSQEKVLPSdKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLS 7862
Cdd:cd08222   123 HERRILHRDLKAKN-IFLKNNVIKVGDFGISRILMGTSDLAT-TFTGTPYYMSPEVLKHEGYNSKSDIWSLGCILYEMCC 200

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7863 AEYPVSSEGARDLQRGLRKGLV-RLSRCYaglSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd08222   201 LKHAFDGQNLLSVMYKIVEGETpSLPDKY---SKELNAIYSRMLNKDPALRPSAAEILKIPFI 260
PKc_YAK1 cd14212
Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze ...
 6468-6652 1.27e-17

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271114 [Multi-domain]  Cd Length: 330  Bit Score: 88.08  E-value: 1.27e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAAL--------SHPLVTgLLDQFETRKTLIL 6539
Cdd:cd14212     1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLLntkydpedKHHIVR-LLDHFMHHGHLCI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSE--ELLDRLYRKGVVTEAeVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFA--QNIT 6615
Cdd:cd14212    80 VFELLGVNlyELLKQNQFRGLSLQL-IRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDSPEIKLIDFGSAcfENYT 158

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 6616 paelQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd14212   159 ----LYTYIQSRFYRSPEVLLGLPYSTAIDMWSLGCI 191
I-set pfam07679
Immunoglobulin I-set domain;
248-328 1.36e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 81.15  E-value: 1.36e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQeNFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLVV 327
Cdd:pfam07679   11 EVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGG-TYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89


                   .
gi 215274225   328 V 328
Cdd:pfam07679   90 V 90
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 7678-7921 1.37e-17

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 86.96  E-value: 1.37e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPK--DKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd13996    14 LGSGGFGSVYKVRNKVDGVTYAIKKIRLTEKssASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGTLRD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYS---ESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT-EYNLLKVVDLGNAQSLSQEKV-LPSDKFKDY 7830
Cdd:cd13996    94 WIDRRNSSSkndRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFLDnDDLQVKIGDFGLATSIGNQKReLNNLNNNNN 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 LET------------MAPELLEGQGAVPQTDIWAIGVTAFIMLsaeYPVS--SEGARDLQrGLRKGLVRLS---RCYAGL 7893
Cdd:cd13996   174 GNTsnnsvgigtplyASPEQLDGENYNEKADIYSLGIILFEML---HPFKtaMERSTILT-DLRNGILPESfkaKHPKEA 249

                         250       260
                  ....*....|....*....|....*...
gi 215274225 7894 SggavaFLRSTLCAQPWGRPCASSCLQC 7921
Cdd:cd13996   250 D-----LIQSLLSKNPEERPSAEQLLRS 272
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
 6445-6721 1.41e-17

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 88.50  E-value: 1.41e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6445 LVLGGDNEPDSEKQSHRRKLHSF--YEVKEEIGRGVFGFVKRVQHKGNKILCAA-----KFIPLRSRTRAQAYRERDILA 6517
Cdd:PTZ00426    7 LQLHKKKDSDSTKEPKRKNKMKYedFNFIRTLGTGSFGRVILATYKNEDFPPVAikrfeKSKIIKQKQVDHVFSERKILN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6518 ALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVH 6597
Cdd:PTZ00426   87 YINHPFCVNLYGSFKDESYLYLVLEFVIGGEFFTFLRRNKRFPNDVGCFYAAQIVLIFEYLQSLNIVYRDLKPENLLLDK 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6598 PARedIKICDFGFAQNITPAelQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE 6677
Cdd:PTZ00426  167 DGF--IKMTDFGFAKVVDTR--TYTLCGTPEYIAPEILLNVGHGKAADWWTLGIFIYEILVGCPPFYANEPLLIYQKILE 242

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 6678 GRVSWSSPMAAHLSEDAKDFIKATL-QRAPQARPSAAQCLSHPWF 6721
Cdd:PTZ00426  243 GIIYFPKFLDNNCKHLMKKLLSHDLtKRYGNLKKGAQNVKEHPWF 287
I-set pfam07679
Immunoglobulin I-set domain;
7463-7548 1.44e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 81.15  E-value: 1.44e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATlKNFQLLTILVVVAEDLGVYTCSVSNAL 7542
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSGKYTCVATNSA 79


                   ....*.
gi 215274225  7543 GTVTTT 7548
Cdd:pfam07679   80 GEAEAS 85
STKc_MRCK_alpha cd05623
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ...
 6452-6699 1.54e-17

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270773 [Multi-domain]  Cd Length: 409  Bit Score: 89.30  E-value: 1.54e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6452 EPDSEKQSHRRKLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRE-RDILAALSHPLVTGL 6527
Cdd:cd05623    58 KPFTSKVKQMRLHKEDFEILKVIGRGAFGEVAVVKLKNADKVFAMKILnkwEMLKRAETACFREeRDVLVNGDSQWITTL 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6528 LDQFETRKTLILILELCSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKIC 6606
Cdd:cd05623   138 HYAFQDDNNLYLVMDYYVGGDLLTLLSKfEDRLPEDMARFYLAEMVLAIDSVHQLHYVHRDIKPDNILM--DMNGHIRLA 215

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6607 DFGFAQNITP-AELQFS-QYGSPEFVSPEIIQ-----QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGR 6679
Cdd:cd05623   216 DFGSCLKLMEdGTVQSSvAVGTPDYISPEILQamedgKGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHK 295

                         250       260
                  ....*....|....*....|.
gi 215274225 6680 VSWSSPM-AAHLSEDAKDFIK 6699
Cdd:cd05623   296 ERFQFPTqVTDVSENAKDLIR 316
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
 7678-7866 1.77e-17

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 86.50  E-value: 1.77e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPyhpKDKTA-------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd05579     1 ISRGAYGRVYLAKKKSTGDLYAIKVIK---KRDMIrknqvdsVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG-----------NAQSLSQE 7819
Cdd:cd05579    78 GDLYSLLENVGALDEDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGlskvglvrrqiKLSIQKKS 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7820 KVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05579   158 NGAPEKEDRRIVGTpdyLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPP 207
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
 7672-7922 1.86e-17

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 86.29  E-value: 1.86e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd08530     2 FKVLKKLGKGSYGSVYKVKRLSDNQVYALKEVnlgSLSQKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERAS----YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqslsqeKVLPS 7824
Cdd:cd08530    82 PFGDLSKLISKRKKkrrlFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGIS------KVLKK 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 DKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL-QRGLRKGLVRLSRCYaglSGGAVAF 7900
Cdd:cd08530   156 NLAKTQIGTplyAAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEARTMQELrYKVCRGKFPPIPPVY---SQDLQQI 232

                         250       260
                  ....*....|....*....|..
gi 215274225 7901 LRSTLCAQPWGRPCASSCLQCP 7922
Cdd:cd08530   233 IRSLLQVNPKKRPSCDKLLQSP 254
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
 7680-7925 1.90e-17

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 86.16  E-value: 1.90e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAV----LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14116    15 KGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVehqlRREVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYR 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSlsqekvLPSDKFKDY---LE 7832
Cdd:cd14116    95 ELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVH------APSSRRTTLcgtLD 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRglrkglvRLSRCY----AGLSGGAVAFLRSTLCAQ 7908
Cdd:cd14116   169 YLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYK-------RISRVEftfpDFVTEGARDLISRLLKHN 241

                         250
                  ....*....|....*..
gi 215274225 7909 PWGRPCASSCLQCPWLT 7925
Cdd:cd14116   242 PSQRPMLREVLEHPWIT 258
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
 7677-7934 2.09e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 86.96  E-value: 2.09e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd06659    28 KIGEGSTGVVCIAREKHSGRQVAVKMMDLRKQQRRELLfNEVVIMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGALTD 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvLPsdKFKDYLET-- 7833
Cdd:cd06659   108 IVSQ-TRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKD--VP--KRKSLVGTpy 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 -MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd06659   183 wMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRDSPPPKLKNSHKASPVLRDFLERMLVRDPQER 262

                         250       260
                  ....*....|....*....|...
gi 215274225 7913 PCASSCLQCPWLTEEG-PACSRP 7934
Cdd:cd06659   263 ATAQELLDHPFLLQTGlPECLVP 285
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
 7678-7854 2.28e-17

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 86.61  E-value: 2.28e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---KTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELcsgpeL 7753
Cdd:cd07832     8 IGEGAHGIVFKAKDRETGETVALKKVALRKLEggiPNQALREIKALQACQgHPYVVKLRDVFPHGTGFVLVFEY-----M 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAE-----RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPsdkfk 7828
Cdd:cd07832    83 LSSLSEvlrdeERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDPRL----- 157

                         170       180       190
                  ....*....|....*....|....*....|...
gi 215274225 7829 dYLET------MAPELLEG-QGAVPQTDIWAIG 7854
Cdd:cd07832   158 -YSHQvatrwyRAPELLYGsRKYDEGVDLWAVG 189
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
 6469-6718 2.63e-17

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270939 [Multi-domain]  Cd Length: 277  Bit Score: 86.18  E-value: 2.63e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAY-RERDILAALS-HPLVTGLLDQFETR------KTLILi 6540
Cdd:cd14037     6 TIEKYLAEGGFAHVYLVKTSNGGNRAALKRVYVNDEHDLNVCkREIEIMKRLSgHKNIVGYIDSSANRsgngvyEVLLL- 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLD----RLYRKgvVTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPAreDIKICDFGFA--- 6611
Cdd:cd14037    85 MEYCKGGGVIDlmnqRLQTG--LTESEILKIFCDVCEAVAAMHYLKppLIHRDLKVENVLISDSG--NYKLCDFGSAttk 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 -------QNITPAELQFSQYGSPEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFaGESDRATLLNvlegrVS 6681
Cdd:cd14037   161 ilppqtkQGVTYVEEDIKKYTTLQYRAPEMIdlyRGKPITEKSDIWALGCLLYKLCFYTTPF-EESGQLAILN-----GN 234

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 215274225 6682 WSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14037   235 FTFPDNSRYSKRLHKLIRYMLEEDPEKRPNIYQVSYE 271
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
 6474-6721 2.79e-17

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 86.23  E-value: 2.79e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05630     8 LGKGGFGEVCACQVRATgKMYACKKLEKKRIKKRkgeAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLMNGGDL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVV--TEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQFSQYGSP 6627
Cdd:cd05630    88 KFHIYHMGQAgfPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGH--IRISDLGLAVHVPEGQTIKGRVGTV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQ 6707
Cdd:cd05630   166 GYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPFQQRKKKIKREEVERLVKEVPEEYSEKFSPQARSLCSMLLCKDPA 245

                         250
                  ....*....|....*....
gi 215274225 6708 AR-----PSAAQCLSHPWF 6721
Cdd:cd05630   246 ERlgcrgGGAREVKEHPLF 264
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
 6468-6611 2.82e-17

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 86.65  E-value: 2.82e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSHPLVTGLLDQFET--------RKT 6536
Cdd:cd07865    14 YEKLAKIGQGTFGEVFKARHRKTGQIVALKKVLMENEKEGfpiTALREIKILQLLKHENVVNLIEICRTkatpynryKGS 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6537 LILILELCSSE--ELLDRLYRKgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDI-KICDFGFA 6611
Cdd:cd07865    94 IYLVFEFCEHDlaGLLSNKNVK--FTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILI---TKDGVlKLADFGLA 166
I-set pfam07679
Immunoglobulin I-set domain;
5260-5350 2.82e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 80.38  E-value: 2.82e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:pfam07679    1 PKFTQKPKDVEVQEGES-ARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  5340 GAAYSSARLLV 5350
Cdd:pfam07679   80 GEAEASAELTV 90
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
 6468-6723 3.70e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 86.32  E-value: 3.70e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd06654    22 YTRFEKIGQGASGTVYTAMDVATGQEVAIRQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAG 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFS-QYG 6625
Cdd:cd06654   102 GSLTD-VVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDG--SVKLTDFGFCAQITPEQSKRStMVG 178

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVLEGRVSWSSPmaAHLSEDAKDFIKATLQR 6704
Cdd:cd06654   179 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPlRALYLIATNGTPELQNP--EKLSAIFRDFLNRCLEM 256

                         250
                  ....*....|....*....
gi 215274225 6705 APQARPSAAQCLSHPwFLK 6723
Cdd:cd06654   257 DVEKRGSAKELLQHQ-FLK 274
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
 6468-6721 4.45e-17

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 85.85  E-value: 4.45e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNkilcAAKFIPLRsRTRAQAYRE-------RDI-----LAALSHPLVTGLLDQFETRK 6535
Cdd:cd07862     3 YECVAEIGEGAYGKVFKARDLKN----GGRFVALK-RVRVQTGEEgmplstiREVavlrhLETFEHPNVVRLFDVCTVSR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 T-----LILILELCSSE--ELLDRLYRKGVVTEAeVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDF 6608
Cdd:cd07862    78 TdretkLTLVFEHVDQDltTYLDKVPEPGVPTET-IKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQ--IKLADF 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6609 GFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSWS 6683
Cdd:cd07862   155 GLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDviglpGEEDWP 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6684 ----------SPMAAH--------LSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07862   235 rdvalprqafHSKSAQpiekfvtdIDELGKDLLLKCLTFNPAKRISAYSALSHPYF 290
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
 6473-6726 5.09e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 85.84  E-value: 5.09e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQA-YRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLD 6551
Cdd:cd06657    27 KIGEGSTGIVCIATVKSSGKLVAVKKMDLRKQQRRELlFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTD 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6552 rLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGF-AQNITPAELQFSQYGSPEFV 6630
Cdd:cd06657   107 -IVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGR--VKLSDFGFcAQVSKEVPRRKSLVGTPYWM 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6631 SPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATlLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARP 6710
Cdd:cd06657   184 APELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKA-MKMIRDNLPPKLKNLHKVSPSLKGFLDRLLVRDPAQRA 262

                         250
                  ....*....|....*.
gi 215274225 6711 SAAQCLSHPWFLKSMP 6726
Cdd:cd06657   263 TAAELLKHPFLAKAGP 278
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
 6468-6720 5.37e-17

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 86.30  E-value: 5.37e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNK--ILCAAKFIP-------LRSRtraqAYRERDILAAL-SHPLVTGLLD-------Q 6530
Cdd:cd07857     2 YELIKELGQGAYGIVCSARNAETSeeETVAIKKITnvfskkiLAKR----ALRELKLLRHFrGHKNITCLYDmdivfpgN 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6531 FEtrktlililELCSSEELLD----RLYRKGV-VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKI 6605
Cdd:cd07857    78 FN---------ELYLYEELMEadlhQIIRSGQpLTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLV--NADCELKI 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6606 CDFGFAQNITPAELQFSQYGSpEFVS------PEIIQQN-PVSEASDIWAMGVISYLSLTCSSPFAGES----------- 6667
Cdd:cd07857   147 CDFGLARGFSENPGENAGFMT-EYVAtrwyraPEIMLSFqSYTKAIDVWSVGCILAELLGRKPVFKGKDyvdqlnqilqv 225

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6668 ----DRATL--------------LNVLEGR-VSWSSPMAAHlseDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd07857   226 lgtpDEETLsrigspkaqnyirsLPNIPKKpFESIFPNANP---LALDLLEKLLAFDPTKRISVEEALEHPY 294
PKc_DYRK1 cd14226
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
 6468-6677 5.37e-17

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271128 [Multi-domain]  Cd Length: 339  Bit Score: 86.60  E-value: 5.37e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAAL-SHP-----LVTGLLDQFETRKTLILIL 6541
Cdd:cd14226    15 YEIDSLIGKGSFGQVVKAYDHVEQEWVAIKIIKNKKAFLNQAQIEVRLLELMnKHDtenkyYIVRLKRHFMFRNHLCLVF 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEeLLDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSH--GVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPA 6617
Cdd:cd14226    95 ELLSYN-LYDLLRNTNFrgVSLNLTRKFAQQLCTALLFLSTPelSIIHCDLKPENILLCNPKRSAIKIIDFGSSCQLGQR 173

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQygSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE 6677
Cdd:cd14226   174 IYQYIQ--SRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLFSGANEVDQMNKIVE 231
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 4523-4608 5.80e-17

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 79.46  E-value: 5.80e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4523 PDPPEDAEVVARSSHTVTLSWAAPmSDGGGGLCGYRVEVKEGATGQWRLCH-ELVPGPECVVDGLAPGETYRFRVAAVGP 4601
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPP-EDDGGPITGYVVEYREKGSGDWKEVEvTPGSETSYTLTGLKPGTEYEFRVRAVNG 79


                  ....*..
gi 215274225 4602 VGAGEPV 4608
Cdd:cd00063    80 GGESPPS 86
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
 6464-6725 5.85e-17

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 85.88  E-value: 5.85e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ--------AYRERDILAALSHPLVTGLLDQFE-TR 6534
Cdd:cd14040     4 LNERYLLLHLLGRGGFSEVYKAFDLYEQRYAAVKIHQLNKSWRDEkkenyhkhACREYRIHKELDHPRIVKLYDYFSlDT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHS--HGVLHLDIKPSNILMVH-PAREDIKICDFGFA 6611
Cdd:cd14040    84 DTFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIVMQIVNALRYLNEikPPIIHYDLKPGNILLVDgTACGEIKITDFGLS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 Q-------NITPAELQFSQYGSPEFVSPE--IIQQNP--VSEASDIWAMGVISYLSLTCSSPFAGESDRATLL--NVLEG 6678
Cdd:cd14040   164 KimdddsyGVDGMDLTSQGAGTYWYLPPEcfVVGKEPpkISNKVDVWSVGVIFFQCLYGRKPFGHNQSQQDILqeNTILK 243

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 6679 RVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKSM 6725
Cdd:cd14040   244 ATEVQFPVKPVVSNEAKAFIRRCLAYRKEDRFDVHQLASDPYLLPHM 290
I-set pfam07679
Immunoglobulin I-set domain;
4898-4988 6.03e-17

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 79.22  E-value: 6.03e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGdGTCSLLITGLDRADAGCYTCQVSNKF 4977
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 215274225  4978 GQVTHSACVVV 4988
Cdd:pfam07679   80 GEAEASAELTV 90
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
 6474-6709 6.13e-17

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270741 [Multi-domain]  Cd Length: 326  Bit Score: 86.20  E-value: 6.13e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKfiplrsrtraqAYRERDILA------------------ALSHPLVTGLLDQFETRK 6535
Cdd:cd05589     7 LGRGHFGKVLLAEYKPTGELFAIK-----------ALKKGDIIArdeveslmcekrifetvnSARHPFLVNLFACFQTPE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 TLILILELCSSEELLDRLYRKgVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNI 6614
Cdd:cd05589    76 HVCFVMEYAAGGDLMMHIHED-VFSEPRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLL--DTEGYVKIADFGLCkEGM 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRatllNVLEGRVSWSSPMAAHLSEDA 6694
Cdd:cd05589   153 GFGDRTSTFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLIYEMLVGESPFPGDDEE----EVFDSIVNDEVRYPRFLSTEA 228

                         250
                  ....*....|....*
gi 215274225 6695 KDFIKATLQRAPQAR 6709
Cdd:cd05589   229 ISIMRRLLRKNPERR 243
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
 6463-6721 6.21e-17

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271038 [Multi-domain]  Cd Length: 320  Bit Score: 86.09  E-value: 6.21e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDIL-----AALSHPL---VTGLLDQFETR 6534
Cdd:cd14136     7 VYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLkcvreADPKDPGrehVVQLLDDFKHT 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 ----KTLILILELCSSEEL-LDRLYR-KGVVTEAeVKVYIQQLVEGLHYLHSH-GVLHLDIKPSNILMVHPaREDIKICD 6607
Cdd:cd14136    87 gpngTHVCMVFEVLGPNLLkLIKRYNyRGIPLPL-VKKIARQVLQGLDYLHTKcGIIHTDIKPENVLLCIS-KIEVKIAD 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6608 FGFA----QNITpAELQFSQYGspefvSPEIIQQNPVSEASDIWAMGVI-------SYL--------------------- 6655
Cdd:cd14136   165 LGNAcwtdKHFT-EDIQTRQYR-----SPEVILGAGYGTPADIWSTACMafelatgDYLfdphsgedysrdedhlaliie 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6656 -------SLTCSSPFAGE--SDRATLLN-----------VLEGRVSWSSPMAAHLSedakDFIKATLQRAPQARPSAAQC 6715
Cdd:cd14136   239 llgriprSIILSGKYSREffNRKGELRHisklkpwpledVLVEKYKWSKEEAKEFA----SFLLPMLEYDPEKRATAAQC 314


                  ....*.
gi 215274225 6716 LSHPWF 6721
Cdd:cd14136   315 LQHPWL 320
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
 7680-7924 6.42e-17

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 84.80  E-value: 6.42e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVrQCWEKASGRALAAKIIPYHPKDKTAVLREYEA-------LKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd06631    11 KGAYGTV-YCGLTSTGQLIAVKQVELDTSDKEKAEKEYEKlqeevdlLKTLKHVNIVGYLGTCLEDNVVSIFMEFVPGGS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL-------SQEKVLPSD 7825
Cdd:cd06631    90 IASILARFGALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLcinlssgSQSQLLKSM 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYLetMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG--ARDLQRGLRKGLV-RLSRCYaglSGGAVAFLR 7902
Cdd:cd06631   170 RGTPYW--MAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMNpmAAIFAIGSGRKPVpRLPDKF---SPEARDFVH 244

                         250       260
                  ....*....|....*....|..
gi 215274225 7903 STLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd06631   245 ACLTRDQDERPSAEQLLKHPFI 266
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
 7674-7872 7.22e-17

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 84.39  E-value: 7.22e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA--------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd14074     7 LEETLGRGHFAVVKLARHVFTGEKVAVKVI-----DKTKlddvskahLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLIL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN-LLKVVDLGNAQSLSQEKVLp 7823
Cdd:cd14074    82 ELGDGGDMYDYIMKHENgLNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFEKQgLVKLTDFGFSNKFQPGEKL- 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7824 sDKFKDYLETMAPELLEGQG-AVPQTDIWAIGVTAFIMLSAEYPVSSEGA 7872
Cdd:cd14074   161 -ETSCGSLAYSAPEILLGDEyDAPAVDIWSLGVILYMLVCGQPPFQEAND 209
STKc_HIPK3 cd14229
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; ...
 6468-6657 7.28e-17

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271131 [Multi-domain]  Cd Length: 330  Bit Score: 85.85  E-value: 7.28e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALS------HPLVTGLlDQFETRKTLILIL 6541
Cdd:cd14229     2 YEVLDFLGRGTFGQVVKCWKRGTNEIVAVKILKNHPSYARQGQIEVGILARLSnenadeFNFVRAY-ECFQHRNHTCLVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCssEELLDRLYRKGVVTEAEVKVY---IQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED--IKICDFGFAQNITP 6616
Cdd:cd14229    81 EML--EQNLYDFLKQNKFSPLPLKVIrpiLQQVATALKKLKSLGLIHADLKPENIMLVDPVRQPyrVKVIDFGSASHVSK 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 6617 A----ELQfSQYgspeFVSPEIIQQNPVSEASDIWAMG-VISYLSL 6657
Cdd:cd14229   159 TvcstYLQ-SRY----YRAPEIILGLPFCEAIDMWSLGcVIAELFL 199
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
 6464-6722 7.74e-17

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 85.50  E-value: 7.74e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6464 LHSFYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ--------AYRERDILAALSHPLVTGLLDQFE-TR 6534
Cdd:cd14041     4 LNDRYLLLHLLGRGGFSEVYKAFDLTEQRYVAVKIHQLNKNWRDEkkenyhkhACREYRIHKELDHPRIVKLYDYFSlDT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHS--HGVLHLDIKPSNILMVH-PAREDIKICDFGFA 6611
Cdd:cd14041    84 DSFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEikPPIIHYDLKPGNILLVNgTACGEIKITDFGLS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 Q--------NITPAELQFSQYGSPEFVSPE--IIQQNP--VSEASDIWAMGVISYLSLTCSSPFAGESDRATLL--NVLE 6677
Cdd:cd14041   164 KimdddsynSVDGMELTSQGAGTYWYLPPEcfVVGKEPpkISNKVDVWSVGVIFYQCLYGRKPFGHNQSQQDILqeNTIL 243

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 6678 GRVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFL 6722
Cdd:cd14041   244 KATEVQFPPKPVVTPEAKAFIRRCLAYRKEDRIDVQQLACDPYLL 288
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 6474-6663 7.88e-17

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 85.01  E-value: 7.88e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTL------ILILELCS 6545
Cdd:cd14038     2 LGTGGFGNVLRWINQETGEQVAIKQCrqELSPKNRERWCLEIQIMKRLNHPNVVAARDVPEGLQKLapndlpLLAMEYCQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEEL---LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVH-PAREDIKICDFGFAQNITPAELQF 6621
Cdd:cd14038    82 GGDLrkyLNQFENCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQgEQRLIHKIIDLGYAKELDQGSLCT 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF 6663
Cdd:cd14038   162 SFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPF 203
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 7706-7858 8.14e-17

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 85.19  E-value: 8.14e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7706 HPKDKTAVLREYEALKGLRHPH-----LAQLHAAYLSPRHL-VLILELCSGPELLPCLAERASYS---ESEVKDYLWQML 7776
Cdd:cd13989    33 SDKNRERWCLEVQIMKKLNHPNvvsarDVPPELEKLSPNDLpLLAMEYCSGGDLRKVLNQPENCCglkESEVRTLLSDIS 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7777 SATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKVLPSdkFKDYLETMAPELLEGQGAVPQTDIWAI 7853
Cdd:cd13989   113 SAISYLHENRIIHRDLKPENIVLQQGGgrvIYKLIDLGYAKELDQGSLCTS--FVGTLQYLAPELFESKKYTCTVDYWSF 190


                  ....*
gi 215274225 7854 GVTAF 7858
Cdd:cd13989   191 GTLAF 195
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
 7681-7874 8.55e-17

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 85.53  E-value: 8.55e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIpyhpkdKTAVLR---------EYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd05582     9 GKVFLVRKITGPDAGTLYAMKVL------KKATLKvrdrvrtkmERDILADVNHPFIVKLHYAFQTEGKLYLILDFLRGG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK---FK 7828
Cdd:cd05582    83 DLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFG----LSKESIDHEKKaysFC 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7829 DYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd05582   159 GTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKE 204
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 7681-7885 9.97e-17

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 84.67  E-value: 9.97e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHP---KDKTA--VLREYEALKGLRH-PHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd05613    14 GKVFLVRKVSGHDAGKLYAMKVLKKATivqKAKTAehTRTERQVLEHIRQsPFLVTLHYAFQTDTKLHLILDYINGGELF 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETM 7834
Cdd:cd05613    94 THLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDENERAYSFCGTIEYM 173

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7835 APELLEG--QGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVR 7885
Cdd:cd05613   174 APEIVRGgdSGHDKAVDWWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILK 226
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 6474-6663 1.01e-16

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 84.81  E-value: 1.01e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQaYRER-----DILAALSHP-LVTGLLDQFETRKTLI-----LILE 6542
Cdd:cd13989     1 LGSGGFGYVTLWKHQDTGEYVAIKKCRQELSPSDK-NRERwclevQIMKKLNHPnVVSARDVPPELEKLSPndlplLAME 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEEL---LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDI-KICDFGFAQNITPAE 6618
Cdd:cd13989    80 YCSGGDLrkvLNQPENCCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQQGGGRVIyKLIDLGYAKELDQGS 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 6619 LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF 6663
Cdd:cd13989   160 LCTSFVGTLQYLAPELFESKKYTCTVDYWSFGTLAFECITGYRPF 204
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 5886-5999 1.15e-16

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 79.93  E-value: 1.15e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5886 YPGTLQALGEPIRQGHFIVW-EGAPGARMP---WKGHNRHVFLFRNHLVICKpRRDSRTDTVSYVFRNMMKLSSIDLNDQ 5961
Cdd:cd01227     5 YDGNLGDLGKLLMQGSFNVWtEHKKGHTKKlarFKPMQRHIFLYEKAVLFCK-KRGENGEAPSYSYKNSLNTTAVGLTEN 83

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 215274225 5962 VEGDDRAFEVWQEREDSVrkYLLQARTAIIKSSWVKEI 5999
Cdd:cd01227    84 VKGDTKKFEIWLNGREEV--FIIQAPTPEIKAAWVKAI 119
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
 7678-7880 1.18e-16

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 83.36  E-value: 1.18e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRqcweKAS--GRALAAKII---PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd13999     1 IGSGSFGEVY----KGKwrGTDVAIKKLkveDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASY-SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYL 7831
Cdd:cd13999    77 LYDLLHKKKIPlSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFG----LSRIKNSTTEKMTGVV 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7832 ET---MAPELLEGQGAVPQTDIWAIGVTAFIMLS-----AEYPVSSEGARDLQRGLR 7880
Cdd:cd13999   153 GTprwMAPEVLRGEPYTEKADVYSFGIVLWELLTgevpfKELSPIQIAAAVVQKGLR 209
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
 7681-7855 1.18e-16

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 84.55  E-value: 1.18e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKII----PYHPKD---KTAvLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPel 7753
Cdd:cd07841    11 GTYAVVYKARDKETGRIVAIKKIklgeRKEAKDginFTA-LREIKLLQELKHPNIIGLLDVFGHKSNINLVFEFMETD-- 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQekvlPSDKFKDYL 7831
Cdd:cd07841    88 LEKVIKDKSivLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSFGS----PNRKMTHQV 163

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 7832 ETM---APELLEGQ----GAVpqtDIWAIGV 7855
Cdd:cd07841   164 VTRwyrAPELLFGArhygVGV---DMWSVGC 191
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
 7672-7924 1.32e-16

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 83.76  E-value: 1.32e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH--PKD--KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14164     2 YTLGTTIGEGSFSKVKLATSQKYCCKVAIKIVDRRraSPDfvQKFLPRELSILRRVNHPNIVQMFECIEVANGRLYIVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT-EYNLLKVVDLGNAQSLSQEKVLpSDK 7826
Cdd:cd14164    82 AAATDLLQKIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLSaDDRKIKIADFGFARFVEDYPEL-STT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYLETMAPELLEGQGAVPQT-DIWAIGVTAFIMLSAEYPVSSEGARDL---QRGLR--KGLVRLSRCYaglsggavAF 7900
Cdd:cd14164   161 FCGSRAYTPPEVILGTPYDPKKyDVWSLGVVLYVMVTGTMPFDETNVRRLrlqQRGVLypSGVALEEPCR--------AL 232

                         250       260
                  ....*....|....*....|....
gi 215274225 7901 LRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14164   233 IRTLLQFNPSTRPSIQQVAGNSWL 256
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
 6468-6749 1.33e-16

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 84.39  E-value: 1.33e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSH--PLVT-----------GLLDQfetr 6534
Cdd:cd06637     8 FELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYSHhrNIATyygafikknppGMDDQ---- 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 ktLILILELCSSEELLDRLYR-KGVVTEAEVKVYI-QQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQ 6612
Cdd:cd06637    84 --LWLVMEFCGAGSVTDLIKNtKGNTLKEEWIAYIcREILRGLSHLHQHKVIHRDIKGQNVLLTENA--EVKLVDFGVSA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 NITPAELQFSQY-GSPEFVSPEII--QQNPVSE---ASDIWAMGVISYLSLTCSSPFAGESDRATLLnvLEGRVSWSSPM 6686
Cdd:cd06637   160 QLDRTVGRRNTFiGTPYWMAPEVIacDENPDATydfKSDLWSLGITAIEMAEGAPPLCDMHPMRALF--LIPRNPAPRLK 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6687 AAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPwFLKSMPAEEAHFIntkQLKFLLARSRWQR 6749
Cdd:cd06637   238 SKKWSKKFQSFIESCLVKNHSQRPSTEQLMKHP-FIRDQPNERQVRI---QLKDHIDRTKKKR 296
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 20-99 1.38e-16

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 78.32  E-value: 1.38e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225     20 VVSVGKDATLSCQIVGNPTPQVSWEKD-QQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIGEAFAAVGLQ 98
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQgGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84


                    .
gi 215274225     99 V 99
Cdd:smart00410   85 V 85
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 7708-7924 1.39e-16

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 83.64  E-value: 1.39e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTAVLREYEALKGLRHPHLAQLHAAYLSPR-HLVLILELCSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHN 7784
Cdd:cd08223    41 RERKAAEQEAKLLSKLKHPNIVSYKESFEGEDgFLYIVMGFCEGGDLYTRLKEQKGvlLEERQVVEWFVQIAMALQYMHE 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7785 QHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIML 7861
Cdd:cd08223   121 RNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESS----SDMATTLIGTpyyMSPELFSNKPYNHKSDVWALGCCVYEMA 196

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7862 SAEYPVSsegARDLQ----RGLRKGLVRLSRCYaglSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd08223   197 TLKHAFN---AKDMNslvyKILEGKLPPMPKQY---SPELGELIKAMLHQDPEKRPSVKRILRQPYI 257
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
 6474-6721 1.41e-16

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270740 [Multi-domain]  Cd Length: 328  Bit Score: 85.16  E-value: 1.41e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIplrsrTRAQAYRERDI----------LAALSHPLVTGLLDQFETRKTLILILEL 6543
Cdd:cd05588     3 IGRGSYAKVLMVELKKTKRIYAMKVI-----KKELVNDDEDIdwvqtekhvfETASNHPFLVGLHSCFQTESRLFFVIEF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA-QNITPAELQFS 6622
Cdd:cd05588    78 VNGGDLMFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGH--IKLTDYGMCkEGLRPGDTTST 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF--AGESDRAT------LLNV-LEG--RVSWSspmaahLS 6691
Cdd:cd05588   156 FCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPFdiVGSSDNPDqntedyLFQViLEKpiRIPRS------LS 229

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 215274225 6692 EDAKDFIKATLQRAPQAR------PSAAQCLSHPWF 6721
Cdd:cd05588   230 VKAASVLKGFLNKNPAERlgchpqTGFADIQSHPFF 265
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
 7681-7866 1.52e-16

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 83.46  E-value: 1.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYH-----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPR--HLVLILELCSG--P 7751
Cdd:cd14119     4 GSYGKVKEVLDTETLCRRAVKILKKRklrriPNGEANVKREIQILRRLNHRNVIKLVDVLYNEEkqKLYMVMEYCVGglQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPcLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsqekvlpsDKF-KDY 7830
Cdd:cd14119    84 EMLD-SAPDKRLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEAL--------DLFaEDD 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7831 LETMA--------PELLEGQGAV--PQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14119   155 TCTTSqgspafqpPEIANGQDSFsgFKVDIWSAGVTLYNMTTGKYP 200
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
 7678-7866 1.59e-16

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 83.50  E-value: 1.59e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA---------VLREYEALKGLRHPHLAQLHAAYLSPR-HLVLILEL 7747
Cdd:cd14163     8 IGEGTYSKVKEAFSKKHQRKVAIKII-----DKSGgpeefiqrfLPRELQIVERLDHKNIIHVYEMLESADgKIYLVMEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNlLKVVDLGNAQSLSQEKVLPSDKF 7827
Cdd:cd14163    83 AEDGDVFDCVLHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQGFT-LKLTDFGFAKQLPKGGRELSQTF 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7828 KDYLETMAPELLEGqgaVP----QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14163   162 CGSTAYAAPEVLQG---VPhdsrKGDIWSMGVVLYVMLCAQLP 201
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
 6468-6721 1.72e-16

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 85.00  E-value: 1.72e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKE------EIGRGVFGFVKRV--QHKGNKILCAAKFIPLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTL- 6537
Cdd:cd07880    11 WEVPDryrdlkQVGSGAYGTVCSAldRRTGAKVAIKKLYRPFQSELFAKrAYRELRLLKHMKHENVIGLLDVFTPDLSLd 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 -----ILILELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGF 6610
Cdd:cd07880    91 rfhdfYLVMPFMGTD--LGKLMKHEKLSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAV----NEDceLKILDFGL 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 AQNiTPAELQ----FSQYGSPEFvspeIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPM 6686
Cdd:cd07880   165 ARQ-TDSEMTgyvvTRWYRAPEV----ILNWMHYTQTVDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEIMKVTGTPSKEF 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6687 AAHL-SEDAKDFIKA--------------------------TLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07880   240 VQKLqSEDAKNYVKKlprfrkkdfrsllpnanplavnvlekMLVLDAESRITAAEALAHPYF 301
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
 7680-7866 1.72e-16

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 83.55  E-value: 1.72e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHP------KDKTAVLREYEALKGLRHPHLAQLHAAYLSP--RHLVLILELCSGP 7751
Cdd:cd06652    12 QGAFGRVYLCYDADTGRELAVKQVQFDPespetsKEVNALECEIQLLKNLLHERIVQYYGCLRDPqeRTLSIFMEYMPGG 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsQEKVLPSDKFKDYL 7831
Cdd:cd06652    92 SIKDQLKSYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRL-QTICLSGTGMKSVT 170

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 215274225 7832 ET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06652   171 GTpywMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPP 208
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
 6474-6720 1.74e-16

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 84.93  E-value: 1.74e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQ-AYRERDILAALSHPLVTGLLDQF-ETRKTLILILELCSSEel 6549
Cdd:cd07856    18 VGMGAFGLVCSARDQLTGQNVAVKKImkPFSTPVLAKrTYRELKLLKHLRHENIISLSDIFiSPLEDIYFVTELLGTD-- 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPaelQFSQYGSPEF 6629
Cdd:cd07856    96 LHRLLTSRPLEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENC--DLKICDFGLARIQDP---QMTGYVSTRY 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6630 V-SPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGE------SDRATLL-----NVLEGRVSWSS------------ 6684
Cdd:cd07856   171 YrAPEImLTWQKYDVEVDIWSAGCIFAEMLEGKPLFPGKdhvnqfSIITELLgtppdDVINTICSENTlrfvqslpkrer 250

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 6685 -PMAAHLSE---DAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd07856   251 vPFSEKFKNadpDAIDLLEKMLVFDPKKRISAAEALAHPY 290
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
 7678-7885 1.85e-16

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 83.54  E-value: 1.85e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKiiPYHPKD----KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd14088     9 IKTEEFCEIFRAKDKTTGKLYTCK--KFLKRDgrkvRKAAKNEINILKMVKHPNILQLVDVFETRKEYFIFLELATGREV 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIteYNLLKvvdlgnaqslsQEKVLPSD----KFKD 7829
Cdd:cd14088    87 FDWILDQGYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVY--YNRLK-----------NSKIVISDfhlaKLEN 153

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7830 YL--------ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVR 7885
Cdd:cd14088   154 GLikepcgtpEYLAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEAEEDDYENHDKNLFR 217
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 5697-5873 1.87e-16

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 80.81  E-value: 1.87e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5697 VIQELLSSEQAFVEELQFLQSHHLQHLERCPHVPiavAGQKAVIFRNVRDIGRFHSS-FLQELQQC-DTDDDVAMCFIKN 5774
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSES---EEEIKTIFSNIEEIYELHRQlLLEELLKEwISIQRIGDIFLKF 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5775 QAAFEQYLEFLVGRVQAESVVvsTAIQEFYKKYAEEALLAGDPSQPPPPPLQHYLEQPVERVQRYQALLKELIRNKARNR 5854
Cdd:pfam00621   78 APGFKVYSTYCSNYPKALKLL--KKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDH 155

                          170
                   ....*....|....*....
gi 215274225  5855 QNCALLEQAYAVVSALPQR 5873
Cdd:pfam00621  156 PDYEDLKKALEAIKEVAKQ 174
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
 7677-7870 1.98e-16

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 83.74  E-value: 1.98e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKII--PYHPKDKTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLVLILELCSGpEL 7753
Cdd:cd07830     6 QLGDGTFGSVYLARNKETGELVAIKKMkkKFYSWEECMNLREVKSLRKLnEHPNIVKLKEVFRENDELYFVFEYMEG-NL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEkVLPSDKFKDYL 7831
Cdd:cd07830    85 YQLMKDRKGkpFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFG----LARE-IRSRPPYTDYV 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 7832 ET---MAPE-LLEGQGAVPQTDIWAIGVTAF--IMLSAEYPVSSE 7870
Cdd:cd07830   160 STrwyRAPEiLLRSTSYSSPVDIWALGCIMAelYTLRPLFPGSSE 204
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
 6561-6721 2.07e-16

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 83.91  E-value: 2.07e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6561 EAEVKVYIQQLVEGLHYLHSH-GVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAELQFSQYG------------SP 6627
Cdd:cd14011   113 DVEIKYGLLQISEALSFLHNDvKLVHGNICPESVVINSNG--EWKLAGFDFCISSEQATDQFPYFReydpnlpplaqpNL 190

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISY-LSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAP 6706
Cdd:cd14011   191 NYLAPEYILSKTCDPASDMFSLGVLIYaIYNKGKPLFDCVNNLLSYKKNSNQLRQLSLSLLEKVPEELRDHVKTLLNVTP 270

                         170
                  ....*....|....*
gi 215274225 6707 QARPSAAQCLSHPWF 6721
Cdd:cd14011   271 EVRPDAEQLSKIPFF 285
STKc_MAPKAPK5 cd14171
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 7686-7924 2.11e-16

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271073 [Multi-domain]  Cd Length: 289  Bit Score: 83.66  E-value: 2.11e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7686 VRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKglrHPHLAQLHAAY---------LSPR-HLVLILELCSGPELLP 7755
Cdd:cd14171    22 VRVCVKKSTGERFALKILLDRPKARTEVRLHMMCSG---HPNIVQIYDVYansvqfpgeSSPRaRLLIVMELMEGGELFD 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII---TEYNLLKVVDLGNAQSLSQEKVLPsdKFKDYLe 7832
Cdd:cd14171    99 RISQHRHFTEKQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLkdnSEDAPIKLCDFGFAKVDQGDLMTP--QFTPYY- 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 tMAPELLEGQ--------GAVPQT---------DIWAIGVTAFIMLSAEYPVSSEG-----ARDLQRGLRKGLVRL-SRC 7889
Cdd:cd14171   176 -VAPQVLEAQrrhrkersGIPTSPtpytydkscDMWSLGVIIYIMLCGYPPFYSEHpsrtiTKDMKRKIMTGSYEFpEEE 254

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 215274225 7890 YAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14171   255 WSQISEMAKDIVRKLLCVDPEERMTIEEVLHHPWL 289
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
 6474-6648 2.23e-16

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 83.33  E-value: 2.23e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRsRTRAQayrERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd13991    14 IGRGSFGEVHRMEDKQTGFQCAVKKVRLE-VFRAE---ELMACAGLTSPRVVPLYGAVREGPWVNIFMDLKEGGSLGQLI 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAReDIKICDFGFAQNITPAELQFSQY------GSP 6627
Cdd:cd13991    90 KEQGCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSDGS-DAFLCDFGHAECLDPDGLGKSLFtgdyipGTE 168

                         170       180
                  ....*....|....*....|.
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWA 6648
Cdd:cd13991   169 THMAPEVVLGKPCDAKVDVWS 189
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
 6468-6721 2.35e-16

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 83.97  E-value: 2.35e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSR--TRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd07869     7 YEKLEKLGEGSYATVYKGKSKVNGKLVALKVIRLQEEegTPFTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEYVH 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SE--ELLDRlyRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQ-NITPAELQFS 6622
Cdd:cd07869    87 TDlcQYMDK--HPGGLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTG--ELKLADFGLARaKSVPSHTYSN 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD--------------------------------R 6669
Cdd:cd07869   163 EVVTLWYRPPDVlLGSTEYSTCLDMWGVGCIFVEMIQGVAAFPGMKDiqdqleriflvlgtpnedtwpgvhslphfkpeR 242

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6670 ATLLNVLEGRVSWSSpmaAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07869   243 FTLYSPKNLRQAWNK---LSYVNHAEDLASKLLQCFPKNRLSAQAALSHEYF 291
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 7708-7912 2.38e-16

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 83.21  E-value: 2.38e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTA--VLREYEALKGLRH-PHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHN 7784
Cdd:cd05583    38 KAKTAehTMTERQVLEAVRQsPFLVTLHYAFQTDAKLHLILDYVNGGELFTHLYQREHFTESEVRIYIGEIVLALEHLHK 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7785 QHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEkVLPSDKFKDY-----LETMAPELLEG--QGAVPQTDIWAIGVTA 7857
Cdd:cd05583   118 LGIIYRDIKLENILLDSEGHVVLTDFG----LSKE-FLPGENDRAYsfcgtIEYMAPEVVRGgsDGHDKAVDWWSLGVLT 192

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7858 FIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYA-GLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd05583   193 YELLTGASPFTVDGERNSQSEISKRILKSHPPIPkTFSAEAKDFILKLLEKDPKKR 248
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 5882-5999 2.73e-16

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 78.58  E-value: 2.73e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5882 LMENYPGTLQALGEPIRQGHFIVWEGAPGARmpwKGHNRHVFLFRNHLVICKPRRDSrTDTVSYVFRNMMKLSSIDLNDQ 5961
Cdd:cd13240     1 LLEGCDEDLDSLGEVILQDSFQVWDPKQLIR---KGRERHVFLFELCLVFSKEVKDS-NGKSKYIYKSRLMTSEIGVTEH 76

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 215274225 5962 VEGDDRAFEVWQERE-DSVRKYLLQARTAIIKSSWVKEI 5999
Cdd:cd13240    77 IEGDPCKFALWTGRVpTSDNKIVLKASSLEVKQTWVKKL 115
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
 7678-7912 2.83e-16

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 82.91  E-value: 2.83e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK----TAVLREYEALKGLRH-PHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd05611     4 ISKGAFGSVYLAKKRSTGDYFAIKVLKKSDMIAknqvTNVKAERAIMMIQGEsPYVAKLYYSFQSKDYLYLVMEYLNGGD 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSqEKVLPSDKFKDYLE 7832
Cdd:cd05611    84 CASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFG----LS-RNGLEKRHNKKFVG 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 T---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL-QRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQ 7908
Cdd:cd05611   159 TpdyLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVfDNILSRRINWPEEVKEFCSPEAVDLINRLLCMD 238


                  ....
gi 215274225 7909 PWGR 7912
Cdd:cd05611   239 PAKR 242
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
 6474-6719 2.84e-16

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 82.84  E-value: 2.84e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDIL-AALSHPLVTGLLDQFETRKTLILILELCSSEELLDR 6552
Cdd:cd06624    16 LGKGTFGVVYAARDLSTQVRIAIKEIPERDSREVQPLHEEIALhSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGGSLSAL 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6553 LYRK-GVVTEAE--VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREDIKICDFGFAQ---NITPAELQFSqyGS 6626
Cdd:cd06624    96 LRSKwGPLKDNEntIGYYTKQILEGLKYLHDNKIVHRDIKGDNVL-VNTYSGVVKISDFGTSKrlaGINPCTETFT--GT 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEIIQQNP--VSEASDIWAMGVISYLSLTCSSPFAGESD-RATLLNVleGRVSWSSPMAAHLSEDAKDFIKATLQ 6703
Cdd:cd06624   173 LQYMAPEVIDKGQrgYGPPADIWSLGCTIIEMATGKPPFIELGEpQAAMFKV--GMFKIHPEIPESLSEEAKSFILRCFE 250

                         250
                  ....*....|....*.
gi 215274225 6704 RAPQARPSAAQCLSHP 6719
Cdd:cd06624   251 PDPDKRATASDLLQDP 266
I-set pfam07679
Immunoglobulin I-set domain;
2470-2553 2.89e-16

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 77.30  E-value: 2.89e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2470 VLTRPLEPKTGRELQSVVLSCDFR--PAPKaVQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA----G 2543
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtPDPE-VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  2544 SAHSSTEVTV 2553
Cdd:pfam07679   81 EAEASAELTV 90
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
 7676-7871 3.36e-16

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 82.64  E-value: 3.36e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKT--AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd06623     7 KVLGQGSSGVVYKVRHKPTGKIYALKKIHVDGDEEFrkQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGGSL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQ-HILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDYLE 7832
Cdd:cd06623    87 ADLLKKVGKIPEPVLAYIARQILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGISKVLENT----LDQCNTFVG 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7833 T---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG 7871
Cdd:cd06623   163 TvtyMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLPPG 204
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
 7678-7866 3.64e-16

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 83.25  E-value: 3.64e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKI--IP--YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd05612     9 IGTGTFGRVHLVRDRISEHYYALKVmaIPevIRLKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLMEYVPGGEL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqEKVLPSDKFKDYLet 7833
Cdd:cd05612    89 FSYLRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKLR-DRTWTLCGTPEYL-- 165

                         170       180       190
                  ....*....|....*....|....*....|...
gi 215274225 7834 mAPELLEGQGAVPQTDIWAIGVTAFIMLSAeYP 7866
Cdd:cd05612   166 -APEVIQSKGHNKAVDWWALGILIYEMLVG-YP 196
I-set pfam07679
Immunoglobulin I-set domain;
6108-6197 3.95e-16

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 76.91  E-value: 3.95e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPrsGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|
gi 215274225  6188 LGSARASAEL 6197
Cdd:pfam07679   79 AGEAEASAEL 88
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
 6470-6716 4.16e-16

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 82.40  E-value: 4.16e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6470 VKEEIGRGVFGFVKRVQHKGNKI-LCAAKFIPLR--SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS 6546
Cdd:cd14145    10 LEEIIGIGGFGKVYRAIWIGDEVaVKAARHDPDEdiSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARG 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEAEVKvYIQQLVEGLHYLHSHG---VLHLDIKPSNILMVHPARED------IKICDFGFAQNITPA 6617
Cdd:cd14145    90 GPLNRVLSGKRIPPDILVN-WAVQIARGMNYLHCEAivpVIHRDLKSSNILILEKVENGdlsnkiLKITDFGLAREWHRT 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ElQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAAHLSEDAKDF 6697
Cdd:cd14145   169 T-KMSAAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLTGEVPFRGIDGLAVAYGVAMNKLSL--PIPSTCPEPFARL 245

                         250
                  ....*....|....*....
gi 215274225 6698 IKATLQRAPQARPSAAQCL 6716
Cdd:cd14145   246 MEDCWNPDPHSRPPFTNIL 264
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
 7674-7856 4.50e-16

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 82.16  E-value: 4.50e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7674 FQTQIQRGRFSVVRQCWEKASGRAL----AAKIIP--YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:pfam07714    3 LGEKLGEGAFGEVYKGTLKGEGENTkikvAVKTLKegADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7748 CSGPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqslsqekvLPSDK 7826
Cdd:pfam07714   83 MPGGDLLDFLrKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFG----------LSRDI 152

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 215274225  7827 FKDYLET-----------MAPELLEGQGAVPQTDIWAIGVT 7856
Cdd:pfam07714  153 YDDDYYRkrgggklpikwMAPESLKDGKFTSKSDVWSFGVL 193
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
 7681-7926 4.93e-16

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 82.77  E-value: 4.93e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd06644    23 GAFGKVYKAKNKETGALAAAKVIETKSEEELEdYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGGAVDAIMLE 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 -RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG----NAQSLSQEkvlpsDKFKDYLETM 7834
Cdd:cd06644   103 lDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGvsakNVKTLQRR-----DSFIGTPYWM 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7835 APELL--EGQGAVP---QTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQP 7909
Cdd:cd06644   178 APEVVmcETMKDTPydyKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLSQPSKWSMEFRDFLKTALDKHP 257

                         250
                  ....*....|....*..
gi 215274225 7910 WGRPCASSCLQCPWLTE 7926
Cdd:cd06644   258 ETRPSAAQLLEHPFVSS 274
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
 7749-7924 5.22e-16

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 82.05  E-value: 5.22e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsqeKVLPSDKFK 7828
Cdd:cd14004    92 SGMDLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAYI---KSGPFDTFV 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 DYLETMAPELLEGQGAV-PQTDIWAIGVTAFIMLSAEYPVSSegardlqrgLRKGLVRLSRCYAGLSGGAVAFLRSTLCA 7907
Cdd:cd14004   169 GTIDYAAPEVLRGNPYGgKEQDIWALGVLLYTLVFKENPFYN---------IEEILEADLRIPYAVSEDLIDLISRMLNR 239

                         170
                  ....*....|....*..
gi 215274225 7908 QPWGRPCASSCLQCPWL 7924
Cdd:cd14004   240 DVGDRPTIEELLTDPWL 256
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 5126-5203 5.30e-16

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 76.45  E-value: 5.30e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGhQLIITAVVPADMGVYRCLAEN 5203
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNS-TLTISNVTRSDAGTYTCVASN 78
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
 7674-7862 5.31e-16

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 81.81  E-value: 5.31e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7674 FQTQIQRGRFSVVRQC-WEKASGRAL---AAKII--PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:smart00219    3 LGKKLGEGAFGEVYKGkLKGKGGKKKvevAVKTLkeDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEY 82

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7748 CSGPELLPCLAERASY-SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSqeKVLPSDK 7826
Cdd:smart00219   83 MEGGDLLSYLRKNRPKlSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFG----LS--RDLYDDD 156

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|..
gi 215274225   7827 FKDYLET------MAPELLEGQGAVPQTDIWAIGVTAFIMLS 7862
Cdd:smart00219  157 YYRKRGGklpirwMAPESLKEGKFTSKSDVWSFGVLLWEIFT 198
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
 6460-6721 5.37e-16

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 83.55  E-value: 5.37e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6460 HRRKLH-SFYEVKEE------IGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQ-AYRERDILAALSHPLVTGLLD 6529
Cdd:cd07877     4 YRQELNkTIWEVPERyqnlspVGSGAYGSVCAAFDTKTGLRVAVKKLsrPFQSIIHAKrTYRELRLLKHMKHENVIGLLD 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6530 QFETRKTL------ILILELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED- 6602
Cdd:cd07877    84 VFTPARSLeefndvYLVTHLMGAD--LNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAV----NEDc 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 -IKICDFGFAQNiTPAELQfSQYGSPEFVSPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGES--DRATLLNVLEG 6678
Cdd:cd07877   158 eLKILDFGLARH-TDDEMT-GYVATRWYRAPEImLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDhiDQLKLILRLVG 235

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6679 rVSWSSPMAAHLSEDAKDFIKATLQRA------------PQA--------------RPSAAQCLSHPWF 6721
Cdd:cd07877   236 -TPGAELLKKISSESARNYIQSLTQMPkmnfanvfiganPLAvdllekmlvldsdkRITAAQALAHAYF 303
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
 6472-6722 5.40e-16

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 82.74  E-value: 5.40e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE-- 6547
Cdd:cd07873     8 DKLGEGTYATVYKGRSKLTDNLVALKEIRLEHEEGApcTAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLDKDlk 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLyrKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNIT-PAELQFSQYGS 6626
Cdd:cd07873    88 QYLDDC--GNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLI--NERGELKLADFGLARAKSiPTKTYSNEVVT 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 PEFVSPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVL-----------------EGRVSWSSPM-- 6686
Cdd:cd07873   164 LWYRPPDIlLGSTDYSTQIDMWGVGCIFYEMSTGRPLFPGSTVEEQLHFIFrilgtpteetwpgilsnEEFKSYNYPKyr 243

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 215274225 6687 -------AAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFL 6722
Cdd:cd07873   244 adalhnhAPRLDSDGADLLSKLLQFEGRKRISAEEAMKHPYFH 286
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
 7677-7934 5.43e-16

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 82.78  E-value: 5.43e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd06658    29 KIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLfNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFLEGGALTD 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 cLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvLPsdKFKDYLET-- 7833
Cdd:cd06658   109 -IVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKE--VP--KRKSLVGTpy 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 -MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd06658   184 wMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDNLPPRVKDSHKVSSVLRGFLDLMLVREPSQR 263

                         250       260
                  ....*....|....*....|...
gi 215274225 7913 PCASSCLQCPWLTEEG-PACSRP 7934
Cdd:cd06658   264 ATAQELLQHPFLKLAGpPSCIVP 286
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 5132-5216 5.47e-16

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 76.46  E-value: 5.47e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5132 LQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:cd20973     4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCS 83


                  ....*
gi 215274225 5212 AELRV 5216
Cdd:cd20973    84 AELTV 88
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
 6466-6718 5.73e-16

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 82.00  E-value: 5.73e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6466 SFYEVK--EEIGRGVFGFVKRVQHKGNKI-LCAAKFIPLR--SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd14147     1 SFQELRleEVIGIGGFGKVYRGSWRGELVaVKAARQDPDEdiSVTAESVRQEARLFAMLAHPNIIALKAVCLEEPNLCLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKvYIQQLVEGLHYLHSHG---VLHLDIKPSNILMVHPARED------IKICDFGFA 6611
Cdd:cd14147    81 MEYAAGGPLSRALAGRRVPPHVLVN-WAVQIARGMHYLHCEAlvpVIHRDLKSNNILLLQPIENDdmehktLKITDFGLA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAElQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAAHLS 6691
Cdd:cd14147   160 REWHKTT-QMSAAGTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLTGEVPYRGIDCLAVAYGVAVNKLTL--PIPSTCP 236

                         250       260
                  ....*....|....*....|....*..
gi 215274225 6692 EDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14147   237 EPFAQLMADCWAQDPHRRPDFASILQQ 263
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
 6474-6718 5.80e-16

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 82.01  E-value: 5.80e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKI-LCAAKFIPLR--SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14146     2 IGVGGFGKVYRATWKGQEVaVKAARQDPDEdiKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTLN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRL--------YRKGVVTEAEVKV-YIQQLVEGLHYLHSHGV---LHLDIKPSNILMVHPARED------IKICDFGFAQ 6612
Cdd:cd14146    82 RALaaanaapgPRRARRIPPHILVnWAVQIARGMLYLHEEAVvpiLHRDLKSSNILLLEKIEHDdicnktLKITDFGLAR 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 NITPAElQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWssPMAAHLSE 6692
Cdd:cd14146   162 EWHRTT-KMSAAGTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLTGEVPYRGIDGLAVAYGVAVNKLTL--PIPSTCPE 238

                         250       260
                  ....*....|....*....|....*.
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd14146   239 PFAKLMKECWEQDPHIRPSFALILEQ 264
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
 6474-6711 6.31e-16

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 81.71  E-value: 6.31e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKIlcAAKFIPLRSRTRAqAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd14058     1 VGRGSFGVVCKARWRNQIV--AVKIIESESEKKA-FEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGV---VTEAEVKVYIQQLVEGLHYLHS---HGVLHLDIKPSNILMVHPArEDIKICDFGFAQNITpaELQFSQYGSP 6627
Cdd:cd14058    78 HGKEPkpiYTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLTNGG-TVLKICDFGTACDIS--THMTNNKGSA 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF---AGESDRATLLnVLEGRvswSSPMAAHLSEDAKDFIKATLQR 6704
Cdd:cd14058   155 AWMAPEVFEGSKYSEKCDVFSWGIILWEVITRRKPFdhiGGPAFRIMWA-VHNGE---RPPLIKNCPKPIESLMTRCWSK 230


                  ....*..
gi 215274225 6705 APQARPS 6711
Cdd:cd14058   231 DPEKRPS 237
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
 6467-6721 6.74e-16

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 81.59  E-value: 6.74e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAakFIPLRSRTRAQAYRER-----DILAALSHPLVTGLLDQFET----RKTL 6537
Cdd:cd14033     2 FLKFNIEIGRGSFKTVYRGLDTETTVEVA--WCELQTRKLSKGERQRfseevEMLKGLQHPNIVRFYDSWKStvrgHKCI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDRLYRkgvVTEAEVKV---YIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPArEDIKICDFGFAq 6612
Cdd:cd14033    80 ILVTELMTSGTLKTYLKR---FREMKLKLlqrWSRQILKGLHFLHSRCppILHRDLKCDNIFITGPT-GSVKIGDLGLA- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 NITPAELQFSQYGSPEFVSPEIIQQNpVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSE 6692
Cdd:cd14033   155 TLKRASFAKSVIGTPEFMAPEMYEEK-YDEAVDVYAFGMCILEMATSEYPYSECQNAAQIYRKVTSGIKPDSFYKVKVPE 233

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6693 dAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14033   234 -LKEIIEGCIRTDKDERFTIQDLLEHRFF 261
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
 7680-7866 8.57e-16

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 82.79  E-value: 8.57e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd05571     5 KGTFGKVILCREKATGELYAIKILKKEviiAKDEVAhTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGGELFF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYL---E 7832
Cdd:cd05571    85 HLSRERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFG----LCKEEISYGATTKTFCgtpE 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05571   161 YLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLP 194
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
 7672-7869 8.79e-16

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 81.52  E-value: 8.79e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPY-HPKDK-TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd06609     3 FTLLERIGKGSFGEVYKGIDKRTNQVVAIKVIDLeEAEDEiEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPcLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKD 7829
Cdd:cd06609    83 GGSVLD-LLKPGPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTST----MSKRNT 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7830 YLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSS 7869
Cdd:cd06609   158 FVGTpfwMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSD 200
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 7680-7854 1.02e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 80.93  E-value: 1.02e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd08220    10 RGAYGTVYLCRRKDDNKLVIIKQIPVEqmtKEERQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYAPGGTLFEY 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEY-NLLKVVDLGNAqslsqeKVLpSDKFKDYLET 7833
Cdd:cd08220    90 IQQRKGslLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKrTVVKIGDFGIS------KIL-SSKSKAYTVV 162

                         170       180
                  ....*....|....*....|....*.
gi 215274225 7834 -----MAPELLEGQGAVPQTDIWAIG 7854
Cdd:cd08220   163 gtpcyISPELCEGKPYNQKSDIWALG 188
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
 7677-7862 1.05e-15

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 81.55  E-value: 1.05e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAV--LREYEALKGLR-HPHLAQLHAAYLSPRH--LVLILELCSGP 7751
Cdd:cd07831     6 KIGEGTFSEVLKAQSRKTGKYYAIKCMKKHFKSLEQVnnLREIQALRRLSpHPNILRLIEVLFDRKTgrLALVFELMDMN 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 --ELLPclAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEyNLLKVVDLGNAQSLSQEkvLPsdkFKD 7829
Cdd:cd07831    86 lyELIK--GRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKD-DILKLADFGSCRGIYSK--PP---YTE 157

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7830 YLET---MAPELLEGQGAV-PQTDIWAIGVTAFIMLS 7862
Cdd:cd07831   158 YISTrwyRAPECLLTDGYYgPKMDIWAVGCVFFEILS 194
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
 6468-6651 1.05e-15

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 82.40  E-value: 1.05e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd06649     7 FERISELGAGNGGVVTKVQHKPSGLIMARKLIHLeiKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMD 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELlDRLYRKGVVTEAEV--KVYIQQLvEGLHYL-HSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAeLQFS 6622
Cdd:cd06649    87 GGSL-DQVLKEAKRIPEEIlgKVSIAVL-RGLAYLrEKHQIMHRDVKPSNILV--NSRGEIKLCDFGVSGQLIDS-MANS 161

                         170       180
                  ....*....|....*....|....*....
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGV 6651
Cdd:cd06649   162 FVGTRSYMSPERLQGTHYSVQSDIWSMGL 190
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
 6461-6723 1.11e-15

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 81.62  E-value: 1.11e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6461 RRKLHSFYEvkeeIGRGVFGFV--KRVQHKGNKIlcAAKFIPLRSRTRAQA-YRERDILAALSHPLVTGLLDQFETRKTL 6537
Cdd:cd06658    21 REYLDSFIK----IGEGSTGIVciATEKHTGKQV--AVKKMDLRKQQRRELlFNEVVIMRDYHHENVVDMYNSYLVGDEL 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDrLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGF-AQNITP 6616
Cdd:cd06658    95 WVVMEFLEGGALTD-IVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGR--IKLSDFGFcAQVSKE 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNV---LEGRVSWSSPMAAHLsed 6693
Cdd:cd06658   172 VPKRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIrdnLPPRVKDSHKVSSVL--- 248

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6694 aKDFIKATLQRAPQARPSAAQCLSHPwFLK 6723
Cdd:cd06658   249 -RGFLDLMLVREPSQRATAQELLQHP-FLK 276
I-set pfam07679
Immunoglobulin I-set domain;
6014-6106 1.12e-15

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 75.76  E-value: 1.12e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHiLIEDPDGSCALILDSLTGVDSGQYMCFAASAA 6093
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRF-KVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|...
gi 215274225  6094 GNCSTlgKILVQV 6106
Cdd:pfam07679   80 GEAEA--SAELTV 90
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
 6468-6721 1.19e-15

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270830 [Multi-domain]  Cd Length: 294  Bit Score: 81.81  E-value: 1.19e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSH-PLVTGLLDQFET----RKTLIL 6539
Cdd:cd07837     3 YEKLEKIGEGTYGKVYKARDKNTGKLVALKKTRLEMEEEgvpSTALREVSLLQMLSQsIYIVRLLDVEHVeengKPLLYL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSE--ELLDRlYRKGVVTEAE---VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPAREDIKICDFGFAQNI 6614
Cdd:cd07837    83 VFEYLDTDlkKFIDS-YGRGPHNPLPaktIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLL-VDKQKGLLKIADLGLGRAF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 T-PAELQFSQYGSPEFVSPEI-IQQNPVSEASDIWAMGVIsYLSLTCSSP-FAGESDRATLLNVLE-----GRVSWS--- 6683
Cdd:cd07837   161 TiPIKSYTHEIVTLWYRAPEVlLGSTHYSTPVDMWSVGCI-FAEMSRKQPlFPGDSELQQLLHIFRllgtpNEEVWPgvs 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6684 ----------------SPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07837   240 klrdwheypqwkpqdlSRAVPDLEPEGVDLLTKMLAYDPAKRISAKAALQHPYF 293
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
 6474-6692 1.21e-15

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 82.15  E-value: 1.21e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAK-FIPLRSRTRAQA-YRERDILAALSHPLVTGLL---DQFETRKTlILILELCSSEE 6548
Cdd:cd13988     1 LGQGATANVFRGRHKKTGDLYAVKvFNNLSFMRPLDVqMREFEVLKKLNHKNIVKLFaieEELTTRHK-VLVMELCPCGS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 L---LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaRED----IKICDFGFAQNITPAELQF 6621
Cdd:cd13988    80 LytvLEEPSNAYGLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRVI--GEDgqsvYKLTDFGAARELEDDEQFV 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQYGSPEFVSPEIIQ--------QNPVSEASDIWAMGVISYLSLTCSSPF----AGESDRATLLNVL------------- 6676
Cdd:cd13988   158 SLYGTEEYLHPDMYEravlrkdhQKKYGATVDLWSIGVTFYHAATGSLPFrpfeGPRRNKEVMYKIItgkpsgaisgvqk 237

                         250       260
                  ....*....|....*....|
gi 215274225 6677 --EGRVSWSS--PMAAHLSE 6692
Cdd:cd13988   238 seNGPIEWSGelPVSCSLSQ 257
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
 6467-6721 1.23e-15

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 81.31  E-value: 1.23e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR---ERDILAALSHPLVTGLLDQFET----RKTLIL 6539
Cdd:cd14031    11 FLKFDIELGRGAFKTVYKGLDTETWVEVAWCELQDRKLTKAEQQRfkeEAEMLKGLQHPNIVRFYDSWESvlkgKKCIVL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPArEDIKICDFGFAqNITPA 6617
Cdd:cd14031    91 VTELMTSGTLKTYLKRFKVMKPKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGPT-GSVKIGDLGLA-TLMRT 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNpVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSpMAAHLSEDAKDF 6697
Cdd:cd14031   169 SFAKSVIGTPEFMAPEMYEEH-YDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRKVTSGIKPAS-FNKVTDPEVKEI 246

                         250       260
                  ....*....|....*....|....
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14031   247 IEGCIRQNKSERLSIKDLLNHAFF 270
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
 6451-6721 1.33e-15

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 82.77  E-value: 1.33e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6451 NEPDSEKQSHRRKLHSFyEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ----AYRERDIL-AALSHPLVT 6525
Cdd:cd05618     6 NSRESGKASSSLGLQDF-DLLRVIGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEdidwVQTEKHVFeQASNHPFLV 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6526 GLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKI 6605
Cdd:cd05618    85 GLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLL--DSEGHIKL 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6606 CDFGFA-QNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF--AGESDRAT------LLNV- 6675
Cdd:cd05618   163 TDYGMCkEGLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFdiVGSSDNPDqntedyLFQVi 242

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6676 LEGRVSwsspMAAHLSEDAKDFIKATLQRAPQAR----PSA--AQCLSHPWF 6721
Cdd:cd05618   243 LEKQIR----IPRSLSVKAASVLKSFLNKDPKERlgchPQTgfADIQGHPFF 290
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 5126-5216 1.41e-15

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 75.53  E-value: 1.41e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLE---EDDHYMInEDQQGGHQLIITAVVPADMGVYRCLAE 5202
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpssIPGKYKI-ESEYGVHVLHIRRVTVEDSAVYSAVAK 79

                          90
                  ....*....|....
gi 215274225 5203 NSMGVSSTKAELRV 5216
Cdd:cd20951    80 NIHGEASSSASVVV 93
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
 7681-7928 1.42e-15

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 81.33  E-value: 1.42e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd06611    16 GAFGKVYKAQHKETGLFAAAKIIQIESEEELEdFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGALDSIMLE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 -RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsDKFKDYLET---MA 7835
Cdd:cd06611    96 lERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKSTL----QKRDTFIGTpywMA 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7836 PELL--EGQGAVP---QTDIWAIGVTAFIMLSAEYPVSS-EGARDLQRGLRKGLVRLSRCyAGLSGGAVAFLRSTLCAQP 7909
Cdd:cd06611   172 PEVVacETFKDNPydyKADIWSLGITLIELAQMEPPHHElNPMRVLLKILKSEPPTLDQP-SKWSSSFNDFLKSCLVKDP 250

                         250
                  ....*....|....*....
gi 215274225 7910 WGRPCASSCLQCPWLTEEG 7928
Cdd:cd06611   251 DDRPTAAELLKHPFVSDQS 269
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 4523-4605 1.60e-15

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 74.96  E-value: 1.60e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4523 PDPPEDAEVVARSSHTVTLSWAAPMSDGGGG-LCGYRVEvKEGATGQWRLCHELVPGPECVVDGLAPGETYRFRVAAVGP 4601
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGyIVGYRVE-YREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 215274225   4602 VGAG 4605
Cdd:smart00060   80 AGEG 83
STKc_beta_ARK cd05606
Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs ...
 6474-6721 2.04e-15

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270757 [Multi-domain]  Cd Length: 279  Bit Score: 80.56  E-value: 2.04e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFV-------------------KRVQHKGNKILcaakfiplrsrtraqAYRERDILAALSH----PLVTGLLDQ 6530
Cdd:cd05606     2 IGRGGFGEVygcrkadtgkmyamkcldkKRIKMKQGETL---------------ALNERIMLSLVSTggdcPFIVCMTYA 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6531 FETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGF 6610
Cdd:cd05606    67 FQTPDKLCFILDLMNGGDLHYHLSQHGVFSEAEMRFYAAEVILGLEHMHNRFIVYRDLKPANILLDEHGH--VRISDLGL 144

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6611 AQNITpAELQFSQYGSPEFVSPEIIQQNPVSEASDIW-AMGVISYLSLTCSSPF-------AGESDRATLLNVLEGRVSW 6682
Cdd:cd05606   145 ACDFS-KKKPHASVGTHGYMAPEVLQKGVAYDSSADWfSLGCMLYKLLKGHSPFrqhktkdKHEIDRMTLTMNVELPDSF 223

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 215274225 6683 SSPMaahlsedaKDFIKATLQRAPQAR-----PSAAQCLSHPWF 6721
Cdd:cd05606   224 SPEL--------KSLLEGLLQRDVSKRlgclgRGATEVKEHPFF 259
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
 6474-6720 2.13e-15

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 80.45  E-value: 2.13e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPL------RSRTRAQAYRERDILAALSHPLVT---GLLDQFETRKtLILILELC 6544
Cdd:cd06653    10 LGRGAFGEVYLCYDADTGRELAVKQVPFdpdsqeTSKEVNALECEIQLLKNLRHDRIVqyyGCLRDPEEKK-LSIFVEYM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmvHPAREDIKICDFGFAQNITPAELQ---- 6620
Cdd:cd06653    89 PGGSVKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANIL--RDSAGNVKLGDFGASKRIQTICMSgtgi 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLegrvswSSPMAAHLSEDAKDFIKA 6700
Cdd:cd06653   167 KSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIA------TQPTKPQLPDGVSDACRD 240

                         250       260
                  ....*....|....*....|...
gi 215274225 6701 TLQR---APQARPSAAQCLSHPW 6720
Cdd:cd06653   241 FLRQifvEEKRRPTAEFLLRHPF 263
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
 6468-6663 2.16e-15

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 81.99  E-value: 2.16e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIplrsrTRAQAYRERDI----------LAALSHPLVTGLLDQFETRKTL 6537
Cdd:cd05617    17 FDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVV-----KKELVHDDEDIdwvqtekhvfEQASSNPFLVGLHSCFQTTSRL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFA-QNITP 6616
Cdd:cd05617    92 FLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLL--DADGHIKLTDYGMCkEGLGP 169

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 6617 AELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF 6663
Cdd:cd05617   170 GDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPF 216
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
 6472-6721 2.66e-15

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 80.39  E-value: 2.66e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd07870     6 EKLGEGSYATVYKGISRINGQLVALKVISMKTEEGVpfTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYMHTDLA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNIT-PAELQFSQYGSPE 6628
Cdd:cd07870    86 QYMIQHPGGLHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLG--ELKLADFGLARAKSiPSQTYSSEVVTLW 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQ-QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRA-------TLLNVLEGRV---------------SWSSP 6685
Cdd:cd07870   164 YRPPDVLLgATDYSSALDIWGAGCIFIEMLQGQPAFPGVSDVFeqlekiwTVLGVPTEDTwpgvsklpnykpewfLPCKP 243

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 215274225 6686 MAAH-----LSE--DAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07870   244 QQLRvvwkrLSRppKAEDLASQMLMMFPKDRISAQDALLHPYF 286
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
 7672-7922 2.73e-15

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 80.16  E-value: 2.73e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEK-ASGRALAAKIIPYH---PKDKTAVLREYEALKGLR---HPHLAQLHAAYLSPRHLVLI 7744
Cdd:cd14052     2 FANVELIGSGEFSQVYKVSERvPTGKVYAVKKLKPNyagAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAErasYSESEVKD--YLWQML----SATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQ 7818
Cdd:cd14052    82 TELCENGSLDVFLSE---LGLLGRLDefRVWKILvelsLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7819 EKVLPSDKFKDYLetmAPELLEGQGAVPQTDIWAIGVTAF-IMLSAEYPVSSEGARDLQRGLRKGLVRLSRC-------- 7889
Cdd:cd14052   159 IRGIEREGDREYI---APEILSEHMYDKPADIFSLGLILLeAAANVVLPDNGDAWQKLRSGDLSDAPRLSSTdlhsassp 235

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7890 ----------YAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCP 7922
Cdd:cd14052   236 ssnpppdppnMPILSGSLDRVVRWMLSPEPDRRPTADDVLATP 278
STKc_LATS2 cd05626
Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs ...
 6467-6721 2.83e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173715 [Multi-domain]  Cd Length: 381  Bit Score: 81.98  E-value: 2.83e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEeIGRGVFGFVKRVQHKGNKILCAAKFIP----LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd05626     3 FVKIKT-LGIGAFGEVCLACKVDTHALYAMKTLRkkdvLNRNQVAHVKAERDILAEADNEWVVKLYYSFQDKDNLYFVMD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFA----------- 6611
Cdd:cd05626    82 YIPGGDMMSLLIRMEVFPEVLARFYIAELTLAIESVHKMGFIHRDIKPDNILIDLDGH--IKLTDFGLCtgfrwthnsky 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 ---------QNITPAE----------------------------LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISY 6654
Cdd:cd05626   160 yqkgshirqDSMEPSDlwddvsncrcgdrlktleqratkqhqrcLAHSLVGTPNYIAPEVLLRKGYTQLCDWWSVGVILF 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6655 LSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQ--ARPSAAQCLSHPWF 6721
Cdd:cd05626   240 EMLVGQPPFLAPTPTETQLKVINWENTLHIPPQVKLSPEAVDLITKLCCSAEErlGRNGADDIKAHPFF 308
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
 6474-6716 3.03e-15

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 79.80  E-value: 3.03e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC---SSE 6547
Cdd:cd13978     1 LGSGGFGTVSKARHVSWFGMVAIKCLhssPNCIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMengSLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKgvvTEAEVKV-YIQQLVEGLHYLHSH--GVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQF--- 6621
Cdd:cd13978    81 SLLEREIQD---VPWSLRFrIIHEIALGMNFLHNMdpPLLHHDLKPENILL--DNHFHVKISDFGLSKLGMKSISANrrr 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 ---SQYGSPEFVSPEIIQ--QNPVSEASDIWAMGVISYLSLTCSSPFAGES------------DRATLLNVLEGRVswsS 6684
Cdd:cd13978   156 gteNLGGTPIYMAPEAFDdfNKKPTSKSDVYSFAIVIWAVLTRKEPFENAInpllimqivskgDRPSLDDIGRLKQ---I 232

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 6685 PMAAHLSEdakdFIKATLQRAPQARPSAAQCL 6716
Cdd:cd13978   233 ENVQELIS----LMIRCWDGNPDARPTFLECL 260
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
 6474-6714 3.19e-15

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 79.61  E-value: 3.19e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKIlcAAKFIPLRSRTRAqAYRERDILAALSHPLVTGLLDQfeTRKTLILILELcSSEELLDRL 6553
Cdd:cd14068     2 LGDGGFGSVYRAVYRGEDV--AVKIFNKHTSFRL-LRQELVVLSHLHHPSLVALLAA--GTAPRMLVMEL-APKGSLDAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YR--KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM--VHPAREDI-KICDFGFAQNITPAELQFSQyGSPE 6628
Cdd:cd14068    76 LQqdNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftLYPNCAIIaKIADYGIAQYCCRMGIKTSE-GTPG 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 FVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSS------PFAGESDRATLLNVLEGRVS------WssPMAAHLsedak 6695
Cdd:cd14068   155 FRAPEVARGNVIyNQQADVYSFGLLLYDILTCGEriveglKFPNEFDELAIQGKLPDPVKeygcapW--PGVEAL----- 227

                         250
                  ....*....|....*....
gi 215274225 6696 dfIKATLQRAPQARPSAAQ 6714
Cdd:cd14068   228 --IKDCLKENPQCRPTSAQ 244
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
 7674-7862 3.38e-15

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 79.51  E-value: 3.38e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7674 FQTQIQRGRFSVVRQC-WEKASGRAL---AAKII--PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:smart00221    3 LGKKLGEGAFGEVYKGtLKGKGDGKEvevAVKTLkeDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEY 82

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7748 CSGPELLPCLAERASY--SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSqeKVLPSD 7825
Cdd:smart00221   83 MPGGDLLDYLRKNRPKelSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFG----LS--RDLYDD 156

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|...
gi 215274225   7826 KFKDYLET------MAPELLEGQGAVPQTDIWAIGVTAFIMLS 7862
Cdd:smart00221  157 DYYKVKGGklpirwMAPESLKEGKFTSKSDVWSFGVLLWEIFT 199
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 6356-6433 3.44e-15

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 74.14  E-value: 3.44e-15
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  6356 PPSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQN 6433
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
 7672-7866 3.60e-15

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 81.23  E-value: 3.60e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd05594    27 FEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEvivAKDEVAhTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEY 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQ-HILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK 7826
Cdd:cd05594   107 ANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEkNVVYRDLKLENLMLDKDGHIKITDFG----LCKEGIKDGAT 182

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7827 FKDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05594   183 MKTFCgtpEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLP 225
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
 6460-6723 3.86e-15

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 80.86  E-value: 3.86e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6460 HRRKLH-SFYEVKEE------IGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQ-AYRERDILAALSHPLVTGLLD 6529
Cdd:cd07878     2 YRQELNkTVWEVPERyqnltpVGSGAYGSVCSAYDTRLRQKVAVKKLsrPFQSLIHARrTYRELRLLKHMKHENVIGLLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6530 QF------ETRKTLILILELCSSEelLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED- 6602
Cdd:cd07878    82 VFtpatsiENFNEVYLVTNLMGAD--LNNIVKCQKLSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAV----NEDc 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 -IKICDFGFAQNitpAELQFSQYGSPE-FVSPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGR 6679
Cdd:cd07878   156 eLRILDFGLARQ---ADDEMTGYVATRwYRAPEImLNWMHYNQTVDIWSVGCIMAELLKGKALFPGNDYIDQLKRIMEVV 232

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6680 VSWSSPMAAHL-SEDAKDFIKaTLQRAPQ---------------------------ARPSAAQCLSHPWFLK 6723
Cdd:cd07878   233 GTPSPEVLKKIsSEHARKYIQ-SLPHMPQqdlkkifrganplaidllekmlvldsdKRISASEALAHPYFSQ 303
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 7686-7926 4.30e-15

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 80.08  E-value: 4.30e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7686 VRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGlrhPHLAQL----HAAYLSPRHLVLILELCSGPELLPCLAERA 7761
Cdd:cd14170    18 VLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQC---PHIVRIvdvyENLYAGRKCLLIVMECLDGGELFSRIQDRG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7762 --SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKVLPSDKFKDYLetMAP 7836
Cdd:cd14170    95 dqAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRpnaILKLTDFGFAKETTSHNSLTTPCYTPYY--VAP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7837 ELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKgLVRLSRC------YAGLSGGAVAFLRSTLCAQPW 7910
Cdd:cd14170   173 EVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKT-RIRMGQYefpnpeWSEVSEEVKMLIRNLLKTEPT 251

                         250
                  ....*....|....*.
gi 215274225 7911 GRPCASSCLQCPWLTE 7926
Cdd:cd14170   252 QRMTITEFMNHPWIMQ 267
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
 6463-6721 4.43e-15

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 80.05  E-value: 4.43e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVkEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd07871     3 KLETYVKL-DKLGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKNLKHANIVTLHDIIHTERCLTLV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSE--ELLDRLyrKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAE 6618
Cdd:cd07871    82 FEYLDSDlkQYLDNC--GNLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLI--NEKGELKLADFGLARAKSVPT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQ------YGSPEFVSPEIIQQNPVseasDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSW----- 6682
Cdd:cd07871   158 KTYSNevvtlwYRPPDVLLGSTEYSTPI----DMWGVGCILYEMATGRPMFPGSTVKEELHLIFRllgtpTEETWpgvts 233

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6683 -------------SSPMAAH---LSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07871   234 neefrsylfpqyrAQPLINHaprLDTDGIDLLSSLLLYETKSRISAEAALRHSYF 288
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 110-188 4.57e-15

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 73.75  E-value: 4.57e-15
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgePDGPRVRVEELGEASALRIRAARPRDGGTYEVRAEN 188
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI--SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
 7678-7924 4.59e-15

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 79.35  E-value: 4.59e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKI--IPYH------PKDKTAV--LR-EYEALKGLRHPHLAQlhaaYL----SPRHLV 7742
Cdd:cd06629     9 IGKGTYGRVYLAMNATTGEMLAVKQveLPKTssdradSRQKTVVdaLKsEIDTLKDLDHPNIVQ----YLgfeeTEDYFS 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG------NAQSL 7816
Cdd:cd06629    85 IFLEYVPGGSIGSCLRKYGKFEEDLVRFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGiskksdDIYGN 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7817 SQEKVLPSDKFkdyleTMAPELLE--GQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGArdLQRGLRKGLVRLSRCY---A 7891
Cdd:cd06629   165 NGATSMQGSVF-----WMAPEVIHsqGQGYSAKVDIWSLGCVVLEMLAGRRPWSDDEA--IAAMFKLGNKRSAPPVpedV 237

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 7892 GLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd06629   238 NLSPEALDFLNACFAIDPRDRPTAAELLSHPFL 270
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 6107-6199 5.11e-15

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 73.77  E-value: 5.11e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6107 PPRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEprSGLLVLVIRAASKEDLGLYECELVN 6186
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQE--GDLHSLIIAEAFEEDTGRYSCLATN 78

                          90
                  ....*....|...
gi 215274225 6187 RLGSARASAELRI 6199
Cdd:cd20972    79 SVGSDTTSAEIFV 91
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
 7677-7881 6.27e-15

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 79.74  E-value: 6.27e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKT--AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE-----LCS 7749
Cdd:cd07869    12 KLGEGSYATVYKGKSKVNGKLVALKVIRLQEEEGTpfTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEyvhtdLCQ 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPclaerASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKD 7829
Cdd:cd07869    92 YMDKHP-----GGLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFG----LARAKSVPSHTYSN 162

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 7830 YLETM---APELLEGQGAVPQT-DIWAIGVTAFIMLS--AEYPvsseGARDLQRGLRK 7881
Cdd:cd07869   163 EVVTLwyrPPDVLLGSTEYSTClDMWGVGCIFVEMIQgvAAFP----GMKDIQDQLER 216
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 6524-6720 6.49e-15

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 78.47  E-value: 6.49e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6524 VTGLLDQFETRKTLILILELCSS-EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPARED 6602
Cdd:cd14100    67 VIRLLDWFERPDSFVLVLERPEPvQDLFDFITERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENIL-IDLNTGE 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 IKICDFGfaqniTPAELQFSQY----GSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFagESDRatllNVLE 6677
Cdd:cd14100   146 LKLIDFG-----SGALLKDTVYtdfdGTRVYSPPEWIRFHRYhGRSAAVWSLGILLYDMVCGDIPF--EHDE----EIIR 214

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 6678 GRVSWSSpmaaHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14100   215 GQVFFRQ----RVSSECQHLIKWCLALRPSDRPSFEDIQNHPW 253
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
 7678-7866 7.36e-15

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 78.68  E-value: 7.36e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKAS-----GRALAAKIIP----YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd14076     9 LGEGEFGKVKLGWPLPKanhrsGVQVAIKLIRrdtqQENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIGIVLEFV 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsdkfK 7828
Cdd:cd14076    89 SGGELFDYILARRRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFDHFN-------G 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7829 DYLET-------MAPELLEGQGAVP--QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14076   162 DLMSTscgspcyAAPELVVSDSMYAgrKADIWSCGVILYAMLAGYLP 208
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
 7674-7868 7.40e-15

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 78.42  E-value: 7.40e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQCWEKASGRALA---AKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSP--RHLVLILELC 7748
Cdd:cd13983     5 FNEVLGRGSFKTVYRAFDTEEGIEVAwneIKLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDSWESKskKEVIFITELM 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMIIT-EYNLLKVVDLGNAQSLSQEK---VL 7822
Cdd:cd13983    85 TSGTLKQYLKRFKRLKLKVIKSWCRQILEGLNYLHTRDppIIHRDLKCDNIFINgNTGEVKIGDLGLATLLRQSFaksVI 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7823 PSDKFkdyletMAPELLEgQGAVPQTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd13983   165 GTPEF------MAPEMYE-EHYDEKVDIYAFGMCLLEMATGEYPYS 203
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
 6468-6721 7.56e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 79.24  E-value: 7.56e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFV--KRVQHKGnkilcaaKFIPLRSrTRAQAYRE-------RDI-----LAALSHPLVTGLLDQFET 6533
Cdd:cd07863     2 YEPVAEIGVGAYGTVykARDPHSG-------HFVALKS-VRVQTNEDglplstvREVallkrLEAFDHPNIVRLMDVCAT 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKT-----LILILELCSSE--ELLDRLYRKGVVTEaEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKIC 6606
Cdd:cd07863    74 SRTdretkVTLVFEHVDQDlrTYLDKVPPPGLPAE-TIKDLMRQFLRGLDFLHANCIVHRDLKPENILVT--SGGQVKLA 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6607 DFGFAQ------NITPAELQFSqygspeFVSPEIIQQNPVSEASDIWAMGVIsYLSLTCSSP-FAGESDRATLLNV---- 6675
Cdd:cd07863   151 DFGLARiyscqmALTPVVVTLW------YRAPEVLLQSTYATPVDMWSVGCI-FAEMFRRKPlFCGNSEADQLGKIfdli 223

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6676 -LEGRVSWS----------SPMAAH--------LSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07863   224 gLPPEDDWPrdvtlprgafSPRGPRpvqsvvpeIEESGAQLLLEMLTFNPHKRISAFRALQHPFF 288
PTKc_Wee1 cd14051
Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the ...
 6467-6719 7.64e-15

Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Wee1 is a nuclear cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. There are two distinct Wee1 proteins in vertebrates showing different expression patterns, called Wee1a and Wee1b. They are functionally dstinct and are implicated in different steps of egg maturation and embryo development. The Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270953 [Multi-domain]  Cd Length: 275  Bit Score: 78.98  E-value: 7.64e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVkEEIGRGVFGFVKRVQHKGNKILCAAK--FIPLR-SRTRAQAYRERDILAAL-SHPLVTGLLDQFETRKTLILILE 6542
Cdd:cd14051     2 FHEV-EKIGSGEFGSVYKCINRLDGCVYAIKksKKPVAgSVDEQNALNEVYAHAVLgKHPHVVRYYSAWAEDDHMIIQNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRL---YRKG-VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDI--------------- 6603
Cdd:cd14051    81 YCNGGSLADAIsenEKAGeRFSEAELKDLLLQVAQGLKYIHSQNLVHMDIKPGNIFISRTPNPVSseeeeedfegeednp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6604 -------KICDFGFAQNITPAELqfsQYGSPEFVSPEIIQQN----PvseASDIWAMGVISYLSLTCSS-PFAGESdrat 6671
Cdd:cd14051   161 esnevtyKIGDLGHVTSISNPQV---EEGDCRFLANEILQENyshlP---KADIFALALTVYEAAGGGPlPKNGDE---- 230

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6672 LLNVLEGRVswssPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd14051   231 WHEIRQGNL----PPLPQCSPEFNELLRSMIHPDPEKRPSAAALLQHP 274
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
 7681-7870 8.13e-15

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 78.61  E-value: 8.13e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIP---YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14082    14 GQFGIVYGGKHRKTGRDVAIKVIDklrFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKLHGDMLEMIL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 A-ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII---TEYNLLKVVDLGNAqslsqeKVLPSDKFKD---- 7829
Cdd:cd14082    94 SsEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLasaEPFPQVKLCDFGFA------RIIGEKSFRRsvvg 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7830 ---YLetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd14082   168 tpaYL---APEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNED 208
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
 6468-6721 8.67e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 79.01  E-value: 8.67e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELC 6544
Cdd:cd07839     2 YEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEgvpSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSE--ELLDRLyrKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFS 6622
Cdd:cd07839    82 DQDlkKYFDSC--NGDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLI--NKNGELKLADFGLARAFGIPVRCYS 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QygspEFV-----SPEIIQQNPVSEAS-DIWAMGVI-SYLSLTCSSPFAGES--DRATLLNVLEG---RVSWSS------ 6684
Cdd:cd07839   158 A----EVVtlwyrPPDVLFGAKLYSTSiDMWSAGCIfAELANAGRPLFPGNDvdDQLKRIFRLLGtptEESWPGvsklpd 233

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6685 ----PM----------AAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07839   234 ykpyPMypattslvnvVPKLNSTGRDLLQNLLVCNPVQRISAEEALQHPYF 284
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
 7672-7868 1.02e-14

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 78.12  E-value: 1.02e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd06613     2 YELIQRIGSGTYGDVYKARNIATGELAAVKVIKLEPGDDFEIIQqEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDY 7830
Cdd:cd06613    82 GSLQDIYQVTGPLSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQLTAT----IAKRKSF 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7831 LET---MAPELLEGQGAVP---QTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06613   158 IGTpywMAPEVAAVERKGGydgKCDIWALGITAIELAELQPPMF 201
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 5143-5211 1.06e-14

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 72.36  E-value: 1.06e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 5143 VSFDCVVTGQPMPSVRWFKDGKLLEEDDHYmINEDQQGGHQLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRD-SRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68
I-set pfam07679
Immunoglobulin I-set domain;
3890-3974 1.07e-14

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 73.06  E-value: 1.07e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCTC----G 3964
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3965 SQATSATLTV 3974
Cdd:pfam07679   81 EAEASAELTV 90
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
 7678-7870 1.18e-14

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 79.24  E-value: 1.18e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVLREYEA----------LKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd05603     3 IGKGSFGKVLLAKRKCDGKFYAVKVL-----QKKTILKKKEQnhimaernvlLKNLKHPFLVGLHYSFQTSEKLYFVLDY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKF 7827
Cdd:cd05603    78 VNGGELFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFG----LCKEGMEPEETT 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7828 KDYL---ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd05603   154 STFCgtpEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSR 199
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 5133-5216 1.28e-14

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 72.54  E-value: 1.28e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5133 QNQEVQDGYPVSFDCVVTGQPMPSVRWFKDG-KLLEEDDHYMINEDQqGGHQLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSG-STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   5212 AELRV 5216
Cdd:smart00410   81 TTLTV 85
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 6362-6446 1.32e-14

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 72.61  E-value: 1.32e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6362 TIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTY-SLVLRHVASKDAGVYTCLAQNTGGQVLC 6440
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                  ....*.
gi 215274225 6441 KAELLV 6446
Cdd:cd20973    83 SAELTV 88
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
 7681-7866 1.37e-14

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270992 [Multi-domain]  Cd Length: 289  Bit Score: 78.23  E-value: 1.37e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPK-DKTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLA 7758
Cdd:cd14090    13 GAYASVQTCINLYTGKEYAVKIIEKHPGhSRSRVFREVETLHQCQgHPNILQLIEYFEDDERFYLVFEKMRGGPLLSHIE 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVV-----DLGNAQSLSQEKVLPSdKFKDYL-- 7831
Cdd:cd14090    93 KRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCESMDKVSPVkicdfDLGSGIKLSSTSMTPV-TTPELLtp 171

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7832 ----ETMAPELLE---GQGAV--PQTDIWAIGVTAFIMLSAeYP 7866
Cdd:cd14090   172 vgsaEYMAPEVVDafvGEALSydKRCDLWSLGVILYIMLCG-YP 214
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 6471-6724 1.42e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 78.00  E-value: 1.42e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6471 KEEIGRGVFGFVKRVQHKGNKILCAAKFIPL--RSRTRAQAYRERDILAALSHPLVTGLLDQF--ETRktliliLELCSs 6546
Cdd:cd06619     6 QEILGHGNGGTVYKAYHLLTRRILAVKVIPLdiTVELQKQIMSELEILYKCDSPYIIGFYGAFfvENR------ISICT- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 eELLD----RLYRKgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAeLQFS 6622
Cdd:cd06619    79 -EFMDggslDVYRK--IPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLV--NTRGQVKLCDFGVSTQLVNS-IAKT 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGvISYLSLTCSS-PFAG-ESDRATL--LNVLEGRVSWSSPM--AAHLSEDAKD 6696
Cdd:cd06619   153 YVGTNAYMAPERISGEQYGIHSDVWSLG-ISFMELALGRfPYPQiQKNQGSLmpLQLLQCIVDEDPPVlpVGQFSEKFVH 231

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6697 FIKATLQRAPQARPSAAQCLSHPWFLKS 6724
Cdd:cd06619   232 FITQCMRKQPKERPAPENLMDHPFIVQY 259
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 6474-6663 1.64e-14

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 78.04  E-value: 1.64e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKF--IPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLI-----LILELCSS 6546
Cdd:cd14039     1 LGTGGFGNVCLYQNQETGEKIAIKScrLELSVKNKDRWCHEIQIMKKLNHPNVVKACDVPEEMNFLVndvplLAMEYCSG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 ---EELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDI-KICDFGFAQNITPAELQFS 6622
Cdd:cd14039    81 gdlRKLLNKPENCCGLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEINGKIVhKIIDLGYAKDLDQGSLCTS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 215274225 6623 QYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF 6663
Cdd:cd14039   161 FVGTLQYLAPELFENKSYTVTVDYWSFGTMVFECIAGFRPF 201
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 7682-7875 2.00e-14

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 77.16  E-value: 2.00e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7682 RFSVVRQCWEKASGRALAAK--------------IIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd08218     1 KYVRIKKIGEGSFGKALLVKskedgkqyvikeinISKMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCL-AERA-SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPsd 7825
Cdd:cd08218    81 CDGGDLYKRInAQRGvLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELA-- 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7826 kfKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:cd08218   159 --RTCIGTpyyLSPEICENKPYNNKSDIWALGCVLYEMCTLKHAFEAGNMKNL 209
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
 7672-7924 2.02e-14

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 77.21  E-value: 2.02e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14186     3 FKVLNLLGKGSFACVYRARSLHTGLEVAIKMIDKKAMQKAGmvqrVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvLPSDK 7826
Cdd:cd14186    83 CHNGEMSRYLKNRKKpFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLK----MPHEK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGardLQRGLRKGLVRLSRCYAGLSGGAVAFLRS 7903
Cdd:cd14186   159 HFTMCGTpnyISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPFDTDT---VKNTLNKVVLADYEMPAFLSREAQDLIHQ 235

                         250       260
                  ....*....|....*....|.
gi 215274225 7904 TLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14186   236 LLRKNPADRLSLSSVLDHPFM 256
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 10-86 2.09e-14

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 71.83  E-value: 2.09e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225    10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARN 86
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
STKc_HIPK2 cd14227
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; ...
 6468-6678 2.10e-14

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271129 [Multi-domain]  Cd Length: 355  Bit Score: 78.98  E-value: 2.10e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGL-----LDQFETRKTLILILE 6542
Cdd:cd14227    17 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTESADDYnfvraYECFQHKNHTCLVFE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSsEELLDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED--IKICDFGFAQNITPAE 6618
Cdd:cd14227    97 MLE-QNLYDFLKQNKFspLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPSRQPyrVKVIDFGSASHVSKAV 175

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6619 LQfSQYGSPEFVSPEIIQQNPVSEASDIWAMG-VISYLSLTCS-SPFAGESDRATLLNVLEG 6678
Cdd:cd14227   176 CS-TYLQSRYYRAPEIILGLPFCEAIDMWSLGcVIAELFLGWPlYPGASEYDQIRYISQTQG 236
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 7677-7858 2.26e-14

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 77.19  E-value: 2.26e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQC-WEKASGRAL--AAKIIPYH--PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd00192     2 KLGEGAFGEVYKGkLKGGDGKTVdvAVKTLKEDasESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYL---------WQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVL 7822
Cdd:cd00192    82 DLLDFLRKSRPVFPSPEPSTLslkdllsfaIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDYY 161

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7823 PSDK-FKDYLETMAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd00192   162 RKKTgGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLW 198
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 7708-7858 2.26e-14

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 77.65  E-value: 2.26e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLV-----LILELCSGPELLPCLAERAS---YSESEVKDYLWQMLSAT 7779
Cdd:cd14039    33 KNKDRWCHEIQIMKKLNHPNVVKACDVPEEMNFLVndvplLAMEYCSGGDLRKLLNKPENccgLKESQVLSLLSDIGSGI 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7780 QYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKVLPSdkFKDYLETMAPELLEGQGAVPQTDIWAIGVT 7856
Cdd:cd14039   113 QYLHENKIIHRDLKPENIVLQEINgkiVHKIIDLGYAKDLDQGSLCTS--FVGTLQYLAPELFENKSYTVTVDYWSFGTM 190


                  ..
gi 215274225 7857 AF 7858
Cdd:cd14039   191 VF 192
I-set pfam07679
Immunoglobulin I-set domain;
1176-1251 2.29e-14

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 71.90  E-value: 2.29e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1176 VQAEAGTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSC----EAGGQRVSFQLH 1250
Cdd:pfam07679   10 VEVQEGESARFTCTVtGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAELT 89


                   .
gi 215274225  1251 I 1251
Cdd:pfam07679   90 V 90
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
 7680-7861 2.30e-14

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 77.36  E-value: 2.30e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKI---IPYHPKDKTA-----VLREYEALKGLRHPHLAQL-HAAYLSPRHLVLILELCSG 7750
Cdd:cd13990    10 KGGFSEVYKAFDLVEQRYVACKIhqlNKDWSEEKKQnyikhALREYEIHKSLDHPRIVKLyDVFEIDTDSFCTVLEYCDG 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHN--QHILHLDLRSENMIITEYNL---LKVVDLGnaqsLSqeKVLPSD 7825
Cdd:cd13990    90 NDLDFYLKQHKSIPEREARSIIMQVVSALKYLNEikPPIIHYDLKPGNILLHSGNVsgeIKITDFG----LS--KIMDDE 163

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7826 KFKD--------------YLetmAPELLEGQGAVP----QTDIWAIGVTAFIML 7861
Cdd:cd13990   164 SYNSdgmeltsqgagtywYL---PPECFVVGKTPPkissKVDVWSVGVIFYQML 214
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 6014-6105 2.56e-14

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 72.07  E-value: 2.56e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQV--DPHHILIEDPDGSCALILDSLTGVDSGQYMCFAAS 6091
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 215274225 6092 AAGNCSTLGKILVQ 6105
Cdd:cd20951    81 IHGEASSSASVVVE 94
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
 6467-6721 2.65e-14

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 77.40  E-value: 2.65e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYR---ERDILAALSHPLVTGLLDQFET----RKTLIL 6539
Cdd:cd14030    26 FLKFDIEIGRGSFKTVYKGLDTETTVEVAWCELQDRKLSKSERQRfkeEAGMLKGLQHPNIVRFYDSWEStvkgKKCIVL 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPArEDIKICDFGFAqNITPA 6617
Cdd:cd14030   106 VTELMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGPT-GSVKIGDLGLA-TLKRA 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEIIQQNpVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEdAKDF 6697
Cdd:cd14030   184 SFAKSVIGTPEFMAPEMYEEK-YDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRRVTSGVKPASFDKVAIPE-VKEI 261

                         250       260
                  ....*....|....*....|....
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14030   262 IEGCIRQNKDERYAIKDLLNHAFF 285
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 7668-7866 2.74e-14

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 77.76  E-value: 2.74e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVL 7743
Cdd:cd08229    22 TLANFRIEKKIGRGQFSEVYRATCLLDGVPVALKKVQifdlMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNI 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCSGPELLPCL----AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQe 7819
Cdd:cd08229   102 VLELADAGDLSRMIkhfkKQKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSS- 180

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7820 KVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd08229   181 KTTAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSP 227
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
 6474-6717 2.99e-14

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 77.27  E-value: 2.99e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN----------------KILCAAKFIPLRSRTRAQAYR----ERDILAALSHPLVTGLLDQfeT 6533
Cdd:cd14000     2 LGDGGFGSVYRASYKGEpvavkifnkhtssnfaNVPADTMLRHLRATDAMKNFRllrqELTVLSHLHHPSIVYLLGI--G 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKTLILILELCSSEELlDRLYRKGVVTEAEVKVYIQQ-----LVEGLHYLHSHGVLHLDIKPSNIL---MVHPAREDIKI 6605
Cdd:cd14000    80 IHPLMLVLELAPLGSL-DHLLQQDSRSFASLGRTLQQrialqVADGLRYLHSAMIIYRDLKSHNVLvwtLYPNSAIIIKI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6606 CDFGFAQNITPAELQFSQyGSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEG-RVSWS 6683
Cdd:cd14000   159 ADYGISRQCCRMGAKGSE-GTPGFRAPEIARGNVIyNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDIHGGlRPPLK 237

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 6684 SPMAAHLSEdAKDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd14000   238 QYECAPWPE-VEVLMKKCWKENPQQRPTAVTVVS 270
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
 6468-6720 3.43e-14

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 76.97  E-value: 3.43e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKT-------LILI 6540
Cdd:cd06636    18 FELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSppghddqLWLV 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYR-KGVVTEAEVKVYI-QQLVEGLHYLHSHGVLHLDIKPSNILMVHPAreDIKICDFGFAQNITPAE 6618
Cdd:cd06636    98 MEFCGAGSVTDLVKNtKGNALKEDWIAYIcREILRGLAHLHAHKVIHRDIKGQNVLLTENA--EVKLVDFGVSAQLDRTV 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQY-GSPEFVSPEII--QQNPVSE---ASDIWAMGVISYLSLTCSSPFAGESDRATLLnvLEGRVSWSSPMAAHLSE 6692
Cdd:cd06636   176 GRRNTFiGTPYWMAPEVIacDENPDATydyRSDIWSLGITAIEMAEGAPPLCDMHPMRALF--LIPRNPPPKLKSKKWSK 253

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd06636   254 KFIDFIEGCLVKNYLSRPSTEQLLKHPF 281
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 6468-6720 3.50e-14

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271004 [Multi-domain]  Cd Length: 253  Bit Score: 76.53  E-value: 3.50e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTraqayrERDILAALSHPL--------------VTGLLDQFET 6533
Cdd:cd14102     2 YQVGSVLGSGGFGTVYAGSRIADGLPVAVKHVVKERVT------EWGTLNGVMVPLeivllkkvgsgfrgVIKLLDWYER 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKTLILILELCS-SEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNiLMVHPAREDIKICDFGfaq 6612
Cdd:cd14102    76 PDGFLIVMERPEpVKDLFDFITEKGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDEN-LLVDLRTGELKLIDFG--- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 niTPAELQFSQY----GSPEFVSPEIIQQNPV-SEASDIWAMGVISYLSLTCSSPFagESDRatllNVLEGRVSWSSpma 6687
Cdd:cd14102   152 --SGALLKDTVYtdfdGTRVYSPPEWIRYHRYhGRSATVWSLGVLLYDMVCGDIPF--EQDE----EILRGRLYFRR--- 220

                         250       260       270
                  ....*....|....*....|....*....|...
gi 215274225 6688 aHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14102   221 -RVSPECQQLIKWCLSLRPSDRPTLEQIFDHPW 252
PKc_DYRK4 cd14225
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
 6454-6677 3.81e-14

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271127 [Multi-domain]  Cd Length: 341  Bit Score: 77.82  E-value: 3.81e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6454 DSEKQSHRRKLHSF----YEVKEEIGRGVFG-FVKRVQHKGNKILcAAKFIPLRSRTRAQAYRERDILAAL-------SH 6521
Cdd:cd14225    27 DDENGSYLKVLHDHiayrYEILEVIGKGSFGqVVKALDHKTNEHV-AIKIIRNKKRFHHQALVEVKILDALrrkdrdnSH 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6522 PlVTGLLDQFETRKTLILILELCSSE--ELLDRLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPA 6599
Cdd:cd14225   106 N-VIHMKEYFYFRNHLCITFELLGMNlyELIKKNNFQGF-SLSLIRRFAISLLQCLRLLYRERIIHCDLKPENILLRQRG 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6600 REDIKICDFG---FAQNITPAELQfSQYgspeFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVL 6676
Cdd:cd14225   184 QSSIKVIDFGsscYEHQRVYTYIQ-SRF----YRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLFPGENEVEQLACIM 258


                  .
gi 215274225 6677 E 6677
Cdd:cd14225   259 E 259
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 6364-6446 4.18e-14

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 71.00  E-value: 4.18e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6364 EDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVD-STRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGGQVLCKA 6442
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAeSGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 215274225   6443 ELLV 6446
Cdd:smart00410   82 TLTV 85
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 7678-7872 4.18e-14

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 76.74  E-value: 4.18e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYH-PKDKTA-VLREYEALKGLRH---PHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd06917     9 VGRGSYGAVYRGYHVKTGRVVALKVLNLDtDDDDVSdIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDYCEGGS 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LlPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDYLE 7832
Cdd:cd06917    89 I-RTLMRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQN----SSKRSTFVG 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7833 T---MAPE-LLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGA 7872
Cdd:cd06917   164 TpywMAPEvITEGKYYDTKADIWSLGITTYEMATGNPPYSDVDA 207
I-set pfam07679
Immunoglobulin I-set domain;
5371-5466 4.40e-14

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 71.13  E-value: 4.40e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDtPGYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQP-----LRSS-DRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74

                           90
                   ....*....|....*.
gi 215274225  5451 ASNAAGQALCSASLHV 5466
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 7676-7925 4.58e-14

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 76.31  E-value: 4.58e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKG-------LRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd06630     6 PLLGTGAFSSCYQARDVKTGTLMAVKQVSFCRNSSSEQEEVVEAIREeirmmarLNHPNIVRMLGATQHKSHFNIFVEWM 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII-TEYNLLKVVDLGNAQSLsQEKVLPSDKF 7827
Cdd:cd06630    86 AGGSVASLLSKYGAFSENVIINYTLQILRGLAYLHDNQIIHRDLKGANLLVdSTGQRLRIADFGAAARL-ASKGTGAGEF 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 K-DYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP----------------VSSEGARDLQRGLRKGLVRLS 7887
Cdd:cd06630   165 QgQLLGTiafMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPwnaekisnhlalifkiASATTPPPIPEHLSPGLRDVT 244

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 215274225 7888 -RCyaglsggavaflrstLCAQPWGRPCASSCLQCPWLT 7925
Cdd:cd06630   245 lRC---------------LELQPEDRPPARELLKHPVFT 268
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
 5894-5999 4.74e-14

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270062  Cd Length: 136  Bit Score: 72.71  E-value: 4.74e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5894 GEPIRQGHFIVWEGApgarmpwKGHNRHVFLFRNHLVICKPRRDSRTDTVsYVFRNMMKLSSIDLNDQVEGDDRAFEVWQ 5973
Cdd:cd13242    27 GQLLRQDEFLVWQGR-------KKCLRHVFLFEDLILFSKPKKTPGGKDV-YIYKHSIKTSDIGLTENVGDSGLKFEIWF 98

                          90       100
                  ....*....|....*....|....*.
gi 215274225 5974 EREDSVRKYLLQARTAIIKSSWVKEI 5999
Cdd:cd13242    99 RRRKARDTYILQATSPEIKQAWTSDI 124
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
 7680-7866 4.78e-14

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 76.27  E-value: 4.78e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHP------KDKTAVLREYEALKGLRHPHLAQLHAAYL--SPRHLVLILELCSGP 7751
Cdd:cd06651    17 QGAFGRVYLCYDVDTGRELAAKQVQFDPespetsKEVSALECEIQLLKNLQHERIVQYYGCLRdrAEKTLTIFMEYMPGG 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsQEKVLPSDKFKDYL 7831
Cdd:cd06651    97 SVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRL-QTICMSGTGIRSVT 175

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 215274225 7832 ET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06651   176 GTpywMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPP 213
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
 7672-7926 4.80e-14

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 76.62  E-value: 4.80e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP-KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG 7750
Cdd:cd06645    13 FELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEPgEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEFCGG 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpsdKFKDY 7830
Cdd:cd06645    93 GSLQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIA----KRKSF 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 LET---MAPEL--LEGQGAVPQ-TDIWAIGVTAFIMLSAEYPVSS---------EGARDLQRGLRKGLVRLSRCYAglsg 7895
Cdd:cd06645   169 IGTpywMAPEVaaVERKGGYNQlCDIWAVGITAIELAELQPPMFDlhpmralflMTKSNFQPPKLKDKMKWSNSFH---- 244

                         250       260       270
                  ....*....|....*....|....*....|.
gi 215274225 7896 gavAFLRSTLCAQPWGRPCASSCLQCPWLTE 7926
Cdd:cd06645   245 ---HFVKMALTKNPKKRPTAEKLLQHPFVTQ 272
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
 7680-7912 4.82e-14

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 77.25  E-value: 4.82e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd05590     5 KGSFGKVMLARLKESGRLYAVKVLKkdviLQDDDVECTMTEKRILSLARnHPFLTQLYCCFQTPDRLFFVMEFVNGGDLM 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSdKFKDYLETM 7834
Cdd:cd05590    85 FHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKTTS-TFCGTPDYI 163

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7835 APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVrlsrCYAG-LSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd05590   164 APEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEV----VYPTwLSQDAVDILKAFMTKNPTMR 238
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
 7686-7881 4.95e-14

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 76.17  E-value: 4.95e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7686 VRQCWEKASGRALAAKIIPYHPKDKtavlREYEA-LKGLRHPHLAQL----HAAYLSPRHLVLILELCSGPELLPCLAER 7760
Cdd:cd14089    17 VLECFHKKTGEKFALKVLRDNPKAR----REVELhWRASGCPHIVRIidvyENTYQGRKCLLVVMECMEGGELFSRIQER 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7761 AS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---LLKVVDLGNAQSLSQEKVLPSDKFKDYLetMA 7835
Cdd:cd14089    93 ADsaFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGpnaILKLTDFGFAKETTTKKSLQTPCYTPYY--VA 170

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7836 PELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRK 7881
Cdd:cd14089   171 PEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKK 216
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
 7678-7876 5.07e-14

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 76.20  E-value: 5.07e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVV-RQCWEKASGRALAAKIIPYHPKDKTAVL--REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14201    14 VGHGAFAVVfKGRHRKKTDWEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGGDLA 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN---------LLKVVDLGNAQSLsQEKVLPSD 7825
Cdd:cd14201    94 DYLQAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSYASrkkssvsgiRIKIADFGFARYL-QSNMMAAT 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7826 KFKDYLeTMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQ 7876
Cdd:cd14201   173 LCGSPM-YMAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPFQANSPQDLR 222
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
 7681-7866 5.84e-14

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 76.67  E-value: 5.84e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPyhpKDKTA-------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd14209    12 GSFGRVMLVRHKETGNYYAMKILD---KQKVVklkqvehTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEYVPGGEM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQslsqekvlpsdKFKDYL-- 7831
Cdd:cd14209    89 FSHLRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAK-----------RVKGRTwt 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 215274225 7832 -----ETMAPELLEGQGAVPQTDIWAIGVTAFIMlSAEYP 7866
Cdd:cd14209   158 lcgtpEYLAPEIILSKGYNKAVDWWALGVLIYEM-AAGYP 196
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 6468-6721 5.90e-14

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 76.27  E-value: 5.90e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd07844     2 YKKLDKLGEGSYATVYKGRSKLTGQLVALKEIRLEHEEGApfTAIREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SE--ELLDRlyRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQnitpAELQFSQ 6623
Cdd:cd07844    82 TDlkQYMDD--CGGGLSMHNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISE--RGELKLADFGLAR----AKSVPSK 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 YGSPEFVS-----PEII-QQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNV------------------LEGR 6679
Cdd:cd07844   154 TYSNEVVTlwyrpPDVLlGSTEYSTSLDMWGVGCIFYEMATGRPLFPGSTDVEDQLHKifrvlgtpteetwpgvssNPEF 233

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6680 VSWSSPM---------AAHLS--EDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07844   234 KPYSFPFypprplinhAPRLDriPHGEELALKFLQYEPKKRISAAEAMKHPYF 286
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 7681-7866 6.22e-14

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 77.17  E-value: 6.22e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHP----KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:PTZ00263   29 GSFGRVRIAKHKGTGEYYAIKCLKKREilkmKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVGGELFTH 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqEKVLPSDKFKDYLetmAP 7836
Cdd:PTZ00263  109 LRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVP-DRTFTLCGTPEYL---AP 184

                         170       180       190
                  ....*....|....*....|....*....|
gi 215274225 7837 ELLEGQGAVPQTDIWAIGVTAFIMLsAEYP 7866
Cdd:PTZ00263  185 EVIQSKGHGKAVDWWTMGVLLYEFI-AGYP 213
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
 7670-7957 6.24e-14

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 76.99  E-value: 6.24e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd06634    15 KLFSDLREIGHGSFGAVYFARDVRNNEVVAIKKMSYSGKQSNEkwqdIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVM 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSD 7825
Cdd:cd06634    95 EYCLGSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMA-----PAN 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYLETMAPELL----EGQ--GAVpqtDIWAIGVTA----------FIM--LSAEYPVSSEGARDLQRGLRKGLVRls 7887
Cdd:cd06634   170 SFVGTPYWMAPEVIlamdEGQydGKV---DVWSLGITCielaerkpplFNMnaMSALYHIAQNESPALQSGHWSEYFR-- 244

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7888 rcyaglsggavAFLRSTLCAQPWGRPCASSCLQCPWLTEEGPacsrpapvtfPTARLRVFVRNREKRRAL 7957
Cdd:cd06634   245 -----------NFVDSCLQKIPQDRPTSDVLLKHRFLLRERP----------PTVIMDLIQRTKDAVREL 293
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
 7670-7914 6.47e-14

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 75.93  E-value: 6.47e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVrqcWEK--ASGRALAAKIIPyhpKDKTAVLREY----EALKGLRHPHLAQLHAAYLSPRHLVL 7743
Cdd:cd05148     6 EEFTLERKLGSGYFGEV---WEGlwKNRVRVAIKILK---SDDLLKQQDFqkevQALKRLRHKHLISLFAVCSVGEPVYI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCSGPELLPCL--AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKV 7821
Cdd:cd05148    80 ITELMEKGSLLAFLrsPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDVY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7822 LPSDKFKDYLETmAPELLEGQGAVPQTDIWAIGVTAFIMLS---AEYP--VSSEGARDLQRGLRkgLVRLSRCYAGLsgg 7896
Cdd:cd05148   160 LSSDKKIPYKWT-APEAASHGTFSTKSDVWSFGILLYEMFTygqVPYPgmNNHEVYDQITAGYR--MPCPAKCPQEI--- 233

                         250
                  ....*....|....*...
gi 215274225 7897 aVAFLRSTLCAQPWGRPC 7914
Cdd:cd05148   234 -YKIMLECWAAEPEDRPS 250
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
 7677-7920 6.75e-14

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 76.26  E-value: 6.75e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA--VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd06641    11 KIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDEIedIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGSAL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLaERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpsdKFKDYLET- 7833
Cdd:cd06641    91 DLL-EPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQI----KRN*FVGTp 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 --MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRcyAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:cd06641   166 fwMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLIPKNNPPTLE--GNYSKPLKEFVEACLNKEPSF 243


                  ....*....
gi 215274225 7912 RPCASSCLQ 7920
Cdd:cd06641   244 RPTAKELLK 252
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 6108-6200 7.69e-14

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 70.53  E-value: 7.69e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLT-TGNKFQTLSEPRSGLLVLVIRAASKEDLGLYECELVN 6186
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 215274225 6187 RLGSARASAELRIQ 6200
Cdd:cd20951    81 IHGEASSSASVVVE 94
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
 6470-6717 7.89e-14

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 75.87  E-value: 7.89e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6470 VKEEIGRGVFGFVKRVQHKGNkilCAAKFIPLRSRT--RAQAYR-ERDILAALSHPLVTgLLDQFETRKTLILILELCSS 6546
Cdd:cd14151    12 VGQRIGSGSFGTVYKGKWHGD---VAVKMLNVTAPTpqQLQAFKnEVGVLRKTRHVNIL-LFMGYSTKPQLAIVTQWCEG 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYrkGVVTEAEVKVYI---QQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFA--QNITPAEL 6619
Cdd:cd14151    88 SSLYHHLH--IIETKFEMIKLIdiaRQTAQGMDYLHAKSIIHRDLKSNNIFL----HEDltVKIGDFGLAtvKSRWSGSH 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6620 QFSQY-GSPEFVSPEIIQ---QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLeGRVSWS---SPMAAHLSE 6692
Cdd:cd14151   162 QFEQLsGSILWMAPEVIRmqdKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMV-GRGYLSpdlSKVRSNCPK 240

                         250       260
                  ....*....|....*....|....*
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd14151   241 AMKRLMAECLKKKRDERPLFPQILA 265
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
 7677-7866 7.94e-14

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 76.61  E-value: 7.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELC--SG 7750
Cdd:cd06633    28 EIGHGSFGAVYFATNSHTNEVVAIKKMSYSGKQTNEkwqdIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEYClgSA 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPclAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSDKFKDY 7830
Cdd:cd06633   108 SDLLE--VHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIAS-----PANSFVGT 180

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7831 LETMAPELL----EGQ--GAVpqtDIWAIGVTAfIMLSAEYP 7866
Cdd:cd06633   181 PYWMAPEVIlamdEGQydGKV---DIWSLGITC-IELAERKP 218
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
 7678-7854 9.27e-14

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 75.80  E-value: 9.27e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgPELL 7754
Cdd:cd07848     9 VGEGAYGVVLKCRHKETKEIVAIKKFKDSEENeevKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVE-KNML 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESE-VKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpSDKFKDYLET 7833
Cdd:cd07848    88 ELLEEMPNGVPPEkVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGS---NANYTEYVAT 164

                         170       180
                  ....*....|....*....|....
gi 215274225 7834 ---MAPELLEGQGAVPQTDIWAIG 7854
Cdd:cd07848   165 rwyRSPELLLGAPYGKAVDMWSVG 188
PTKc_Wee1a cd14138
Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the ...
 7677-7922 9.44e-14

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271040 [Multi-domain]  Cd Length: 276  Bit Score: 75.83  E-value: 9.44e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWE---------KASGRALAAKIipyhpkDKTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd14138    12 KIGSGEFGSVFKCVKrldgciyaiKRSKKPLAGSV------DEQNALREVYAHAVLgQHSHVVRYYSAWAEDDHMLIQNE 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAE---RASY-SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL------------------ 7804
Cdd:cd14138    86 YCNGGSLADAISEnyrIMSYfTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFISRTSIpnaaseegdedewasnkv 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7805 -LKVVDLGNAQSLSQEKVLPSDKfkdylETMAPELL-EGQGAVPQTDIWAIGVTAFIMLSAEyPVSSEGarDLQRGLRKG 7882
Cdd:cd14138   166 iFKIGDLGHVTRVSSPQVEEGDS-----RFLANEVLqENYTHLPKADIFALALTVVCAAGAE-PLPTNG--DQWHEIRQG 237

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 7883 lvRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCP 7922
Cdd:cd14138   238 --KLPRIPQVLSQEFLDLLKVMIHPDPERRPSAVALVKHS 275
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
 6467-6721 9.77e-14

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 75.50  E-value: 9.77e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVKEEIGRGVFGFVkrvqHKG--NKILCAAKFIPLRSRTRAQAYRER-----DILAALSHPLVTGLLDQFET----RK 6535
Cdd:cd14032     2 FLKFDIELGRGSFKTV----YKGldTETWVEVAWCELQDRKLTKVERQRfkeeaEMLKGLQHPNIVRFYDFWEScakgKR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 TLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPArEDIKICDFGFAqN 6613
Cdd:cd14032    78 CIVLVTELMTSGTLKTYLKRFKVMKPKVLRSWCRQILKGLLFLHTRTppIIHRDLKCDNIFITGPT-GSVKIGDLGLA-T 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQFSQYGSPEFVSPEIIQQNpVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEd 6693
Cdd:cd14032   156 LKRASFAKSVIGTPEFMAPEMYEEH-YDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRKVTCGIKPASFEKVTDPE- 233

                         250       260
                  ....*....|....*....|....*...
gi 215274225 6694 AKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14032   234 IKEIIGECICKNKEERYEIKDLLSHAFF 261
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 10-94 1.01e-13

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 70.66  E-value: 1.01e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPV-----AAGARFRLAQDGDLYRLTILDLALG--DSGQYVC 82
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkdDPRSHRIVLPSGSLFFLRVVHGRKGrsDEGVYVC 80

                          90
                  ....*....|..
gi 215274225   83 RARNAIGEAFAA 94
Cdd:cd07693    81 VAHNSLGEAVSR 92
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6122-6199 1.07e-13

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 69.87  E-value: 1.07e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6122 GEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRsgllvLVIRAASKEDLGLYECELVNRLGSARASAELRI 6199
Cdd:cd20957    16 GRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-----LVIPSVKREDKGMYQCFVRNDGDSAQATAELKL 88
STKc_HIPK1 cd14228
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; ...
 6468-6678 1.08e-13

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271130 [Multi-domain]  Cd Length: 355  Bit Score: 76.67  E-value: 1.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALS------HPLVTGLlDQFETRKTLILIL 6541
Cdd:cd14228    17 YEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSsenadeYNFVRSY-ECFQHKNHTCLVF 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSsEELLDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED--IKICDFGFAQNITPA 6617
Cdd:cd14228    96 EMLE-QNLYDFLKQNKFspLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPVRQPyrVKVIDFGSASHVSKA 174

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6618 ELQfSQYGSPEFVSPEIIQQNPVSEASDIWAMG-VISYLSLTCS-SPFAGESDRATLLNVLEG 6678
Cdd:cd14228   175 VCS-TYLQSRYYRAPEIILGLPFCEAIDMWSLGcVIAELFLGWPlYPGASEYDQIRYISQTQG 236
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 5382-5466 1.12e-13

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 69.84  E-value: 1.12e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5382 VKKGSSITFSVKVEGRPVPTVHWLREEAErgvlWIGPDtPGYTVASSAQQHSLVLLDVGRQHQGTYTCIASNAAGQALCS 5461
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPEVTWYKQGGK----LLAES-GRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   5462 ASLHV 5466
Cdd:smart00410   81 TTLTV 85
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
 7678-7868 1.13e-13

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 75.42  E-value: 1.13e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLV------LILELCSG 7750
Cdd:cd06608    14 IGEGTYGKVYKARHKKTGQLAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPPGgddqlwLVMEYCGG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 ---PELLPCLAERASYSESEVKDY-LWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG-NAQSLSQekvlpSD 7825
Cdd:cd06608    94 gsvTDLVKGLRKKGKRLKEEWIAYiLRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGvSAQLDST-----LG 168

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7826 KFKDYLET---MAPELLEGQGAVPQT-----DIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06608   169 RRNTFIGTpywMAPEVIACDQQPDASydarcDVWSLGITAIELADGKPPLC 219
PTKc_Wee1a cd14138
Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the ...
 6462-6719 1.18e-13

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271040 [Multi-domain]  Cd Length: 276  Bit Score: 75.44  E-value: 1.18e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6462 RKLHSFYEVkEEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQ-AYRERDILAAL-SHPLVTGLLDQFETRKTL 6537
Cdd:cd14138     2 RYATEFHEL-EKIGSGEFGSVFKCVKRLDGCIYAIKRSkkPLAGSVDEQnALREVYAHAVLgQHSHVVRYYSAWAEDDHM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6538 ILILELCSSEELLDRL---YRK-GVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM---------VHPARED-- 6602
Cdd:cd14138    81 LIQNEYCNGGSLADAIsenYRImSYFTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFIsrtsipnaaSEEGDEDew 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 ------IKICDFGFAQNITPAELqfsQYGSPEFVSPEIIQQNPVS-EASDIWAMGvISYLSLTCSSPFAGESDRATllNV 6675
Cdd:cd14138   161 asnkviFKIGDLGHVTRVSSPQV---EEGDSRFLANEVLQENYTHlPKADIFALA-LTVVCAAGAEPLPTNGDQWH--EI 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 6676 LEGRVswssPMAAH-LSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd14138   235 RQGKL----PRIPQvLSQEFLDLLKVMIHPDPERRPSAVALVKHS 275
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
 7681-7888 1.18e-13

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 75.07  E-value: 1.18e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQC-WEKASGRAL--AAKII----PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRhLVLILELCSGPEL 7753
Cdd:cd05040     6 GSFGVVRRGeWTTPSGKVIqvAVKCLksdvLSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLSSP-LMMVTELAPLGSL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERA-SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpsdkfKDYLE 7832
Cdd:cd05040    85 LDRLRKDQgHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQN--------EDHYV 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 7833 TM----------APELLEGQGAVPQTDIWAIGVTAFIMLS-AEYP-VSSEGARDLQRGLRKGlVRLSR 7888
Cdd:cd05040   157 MQehrkvpfawcAPESLKTRKFSHASDVWMFGVTLWEMFTyGEEPwLGLNGSQILEKIDKEG-ERLER 223
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
 7680-7924 1.21e-13

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 75.29  E-value: 1.21e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAV----LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14117    16 KGKFGNVYLAREKQSKFIVALKVLFKSQIEKEGVehqlRREIEIQSHLRHPNILRLYNYFHDRKRIYLILEYAPRGELYK 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG---NAQSLSQEKVLPSdkfkdyLE 7832
Cdd:cd14117    96 ELQKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGwsvHAPSLRRRTMCGT------LD 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd14117   170 YLPPEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFESASHTETYRRIVKVDLKFP---PFLSDGSRDLISKLLRYHPSER 246

                         250
                  ....*....|..
gi 215274225 7913 PCASSCLQCPWL 7924
Cdd:cd14117   247 LPLKGVMEHPWV 258
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 6365-6446 1.21e-13

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 69.83  E-value: 1.21e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6365 DVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQ-QQEGTTYSLVLRHVASKDAGVYTCLAQNTGGQVLCKAE 6443
Cdd:cd05744     9 DLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMlVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAE 88


                  ...
gi 215274225 6444 LLV 6446
Cdd:cd05744    89 LVV 91
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 6472-6651 1.27e-13

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 74.69  E-value: 1.27e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKR---VQHKGNKILCAAKFipLRSRT----RAQAYRERDILAALSHPLVTGLLDQFETrKTLILILELC 6544
Cdd:cd05060     1 KELGHGNFGSVRKgvyLMKSGKEVEVAVKT--LKQEHekagKKEFLREASVMAQLDHPCIVRLIGVCKG-EPLMLVMELA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPAE--LQFS 6622
Cdd:cd05060    78 PLGPLLKYLKKRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLV--NRHQAKISDFGMSRALGAGSdyYRAT 155

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 6623 QYGS-P-EFVSPEIIQQNPVSEASDIWAMGV 6651
Cdd:cd05060   156 TAGRwPlKWYAPECINYGKFSSKSDVWSYGV 186
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
 6468-6721 1.32e-13

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 75.62  E-value: 1.32e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTR---AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELc 6544
Cdd:PLN00009    4 YEKVEKIGEGTYGVVYKARDRVTNETIALKKIRLEQEDEgvpSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFEY- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 sseelLDRLYRKGVVTEAE-------VKVYIQQLVEGLHYLHSHGVLHLDIKPSNiLMVHPAREDIKICDFGFAQNITPA 6617
Cdd:PLN00009   83 -----LDLDLKKHMDSSPDfaknprlIKTYLYQILRGIAYCHSHRVLHRDLKPQN-LLIDRRTNALKLADFGLARAFGIP 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQ------YGSPEFVSPEIIQQNPVseasDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE-----GRVSW---- 6682
Cdd:PLN00009  157 VRTFTHevvtlwYRAPEILLGSRHYSTPV----DIWSVGCIFAEMVNQKPLFPGDSEIDELFKIFRilgtpNEETWpgvt 232

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6683 -------------SSPMAA---HLSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:PLN00009  233 slpdyksafpkwpPKDLATvvpTLEPAGVDLLSKMLRLDPSKRITARAALEHEYF 287
STKc_GRK2 cd14223
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs ...
 6468-6704 1.38e-13

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271125 [Multi-domain]  Cd Length: 321  Bit Score: 75.85  E-value: 1.38e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ----AYRERDILAALSH---PLVTGLLDQFETRKTLILI 6540
Cdd:cd14223     2 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQgetlALNERIMLSLVSTgdcPFIVCMSYAFHTPDKLSFI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQ 6620
Cdd:cd14223    82 LDLMNGGDLHYHLSQHGVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFGH--VRISDLGLACDFSKKKPH 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSqYGSPEFVSPEIIQQNPVSEASDIW-AMGVISYLSLTCSSPF-------AGESDRATLLNVLEgrvswsspMAAHLSE 6692
Cdd:cd14223   160 AS-VGTHGYMAPEVLQKGVAYDSSADWfSLGCMLFKLLRGHSPFrqhktkdKHEIDRMTLTMAVE--------LPDSFSP 230

                         250
                  ....*....|..
gi 215274225 6693 DAKDFIKATLQR 6704
Cdd:cd14223   231 ELRSLLEGLLQR 242
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
 7676-7924 1.47e-13

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 74.79  E-value: 1.47e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd06648    13 VKIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALT 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvLPsdKFKDYLET- 7833
Cdd:cd06648    93 DIVTH-TRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKE--VP--RRKSLVGTp 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 --MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWG 7911
Cdd:cd06648   168 ywMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNEPPKLKNLHKVSPRLRSFLDRMLVRDPAQ 247

                         250
                  ....*....|...
gi 215274225 7912 RPCASSCLQCPWL 7924
Cdd:cd06648   248 RATAAELLNHPFL 260
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
 7724-7909 1.48e-13

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 75.71  E-value: 1.48e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7724 RHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN 7803
Cdd:cd05570    54 RHPFLTGLHACFQTEDRLYFVMEYVNGGDLMFHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEG 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7804 LLKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLR 7880
Cdd:cd05570   134 HIKIADFG----MCKEGIWGGNTTSTFCGTpdyIAPEILREQDYGFSVDWWALGVLLYEMLAGQSPFEGDDEDELFEAIL 209

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7881 KGLVRLSRcyaGLSGGAVAFLRSTLCAQP 7909
Cdd:cd05570   210 NDEVLYPR---WLSREAVSILKGLLTKDP 235
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
 6474-6663 1.64e-13

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 74.64  E-value: 1.64e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKI-LCAAKFIPLR--SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14148     2 IGVGGFGKVYKGLWRGEEVaVKAARQDPDEdiAVTAENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKGVVTEAEVKvYIQQLVEGLHYLHSHG---VLHLDIKPSNILMVHPARED------IKICDFGFAQNITPAElQF 6621
Cdd:cd14148    82 RALAGKKVPPHVLVN-WAVQIARGMNYLHNEAivpIIHRDLKSSNILILEPIENDdlsgktLKITDFGLAREWHKTT-KM 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 6622 SQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPF 6663
Cdd:cd14148   160 SAAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLTGEVPY 201
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
 7677-7934 1.64e-13

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 75.44  E-value: 1.64e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVL-REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd06657    27 KIGEGSTGIVCIATVKSSGKLVAVKKMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTD 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 cLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDYLET-- 7833
Cdd:cd06657   107 -IVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKE----VPRRKSLVGTpy 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 -MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd06657   182 wMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPKLKNLHKVSPSLKGFLDRLLVRDPAQR 261

                         250       260
                  ....*....|....*....|...
gi 215274225 7913 PCASSCLQCPWLTEEG-PACSRP 7934
Cdd:cd06657   262 ATAAELLKHPFLAKAGpPSCIVP 284
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
 7670-7870 1.67e-13

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 75.81  E-value: 1.67e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH---PKDKTAVLREYEALKGLRH-PHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd05601     1 KDFEVKNVIGRGHFGEVQVVKEKATGDIYAMKVLKKSetlAQEEVSFFEEERDIMAKANsPWITKLQYAFQDSENLYLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd05601    81 EYHPGGDLLSLLSRYDDiFEESMARFYLAELVLAIHSLHSMGYVHRDIKPENILIDRTGHIKLADFGSAAKLSSDKTVTS 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7825 D---KFKDYletMAPELLE------GQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd05601   161 KmpvGTPDY---IAPEVLTsmnggsKGTYGVECDWWSLGIVAYEMLYGKTPFTED 212
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
 7678-7861 1.92e-13

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 75.77  E-value: 1.92e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKI----IPYHPKDKTAVLREYEAL-KGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd05604     4 IGKGSFGKVLLAKRKRDGKYYAVKVlqkkVILNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDFVNGGE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSD---KFKD 7829
Cdd:cd05604    84 LFFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFG----LCKEGISNSDtttTFCG 159

                         170       180       190
                  ....*....|....*....|....*....|..
gi 215274225 7830 YLETMAPELLEGQGAVPQTDIWAIGVTAFIML 7861
Cdd:cd05604   160 TPEYLAPEVIRKQPYDNTVDWWCLGSVLYEML 191
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
 7678-7877 1.97e-13

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 75.30  E-value: 1.97e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKII-PYHPKDKTAV---LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd05585     2 IGKGSFGKVMQVRKKDTSRIYALKTIrKAHIVSRSEVthtLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFINGGEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQsLSQEKVLPSDKFKDYLET 7833
Cdd:cd05585    82 FHHLQREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCK-LNMKDDDKTNTFCGTPEY 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7834 MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQR 7877
Cdd:cd05585   161 LAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYR 204
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
 7668-7940 2.24e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 75.10  E-value: 2.24e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPY-HPKDKTAV--LREYEALKGLRHPHLAQLHAAYLSpRHL--- 7741
Cdd:cd07845     5 SVTEFEKLNRIGEGTYGIVYRARDTTSGEIVALKKVRMdNERDGIPIssLREITLLLNLRHPNIVELKEVVVG-KHLdsi 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7742 VLILELCSgpELLPCLAE--RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqe 7819
Cdd:cd07845    84 FLVMEYCE--QDLASLLDnmPTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYG-- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7820 kvLPSDKFKDYLETM---APELLegQGAVPQT---DIWAIGVTAFIMLSAE--YPVSSE--------------------G 7871
Cdd:cd07845   160 --LPAKPMTPKVVTLwyrAPELL--LGCTTYTtaiDMWAVGCILAELLAHKplLPGKSEieqldliiqllgtpnesiwpG 235

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7872 ARDLQrGLRKGLVR------LSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWLTEEGPACSRPAPVTFP 7940
Cdd:cd07845   236 FSDLP-LVGKFTLPkqpynnLKHKFPWLSEAGLRLLNFLLMYDPKKRATAEEALESSYFKEKPLPCEPEMMPTFP 309
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
 7678-7866 2.47e-13

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 74.49  E-value: 2.47e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd05577     1 LGRGGFGEVCACQVKATGKMYACKKLDKKrikkKKGETMALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGGDL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAE--RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsdKFKDYL 7831
Cdd:cd05577    81 KYHIYNvgTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFKGGK-----KIKGRV 155

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7832 ET---MAPELLEGQGAVP-QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05577   156 GThgyMAPEVLQKEVAYDfSVDWFALGCMLYEMIAGRSP 194
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 6120-6199 2.61e-13

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 68.69  E-value: 2.61e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   6120 VEGEDAQFTCTIEGAPYPQIRWYKDGA-LLTTGNKFQtlSEPRSGLLVLVIRAASKEDLGLYECELVNRLGSARASAELR 6198
Cdd:smart00410    7 KEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFS--VSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84


                    .
gi 215274225   6199 I 6199
Cdd:smart00410   85 V 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 116-201 2.66e-13

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 68.69  E-value: 2.66e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    116 PTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGpRVRVEELGEASALRIRAARPRDGGTYEVRAENPLGAASA 195
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESG-RFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*.
gi 215274225    196 AAALVV 201
Cdd:smart00410   80 GTTLTV 85
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 6114-6199 2.71e-13

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 68.76  E-value: 2.71e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6114 VRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEpRSGLLVLVIRAASKEDLGLYECELVNRLGSARA 6193
Cdd:cd20973     4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQD-EDGLCSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                  ....*.
gi 215274225 6194 SAELRI 6199
Cdd:cd20973    83 SAELTV 88
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 5126-5216 2.83e-13

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 68.97  E-value: 2.83e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLE-EDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENS 5204
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISpKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 215274225 5205 MGVSSTKAELRV 5216
Cdd:cd05893    81 QGRISCTGRLMV 92
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
 7665-7875 2.87e-13

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 75.44  E-value: 2.87e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7665 PLPSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVLREYEA----------LKGLRHPHLAQLHAA 7734
Cdd:cd05602     2 PHAKPSDFHFLKVIGKGSFGKVLLARHKSDEKFYAVKVL-----QKKAILKKKEEkhimsernvlLKNVKHPFLVGLHFS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7735 YLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaq 7814
Cdd:cd05602    77 FQTTDKLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFG--- 153

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7815 sLSQEKVLP---SDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:cd05602   154 -LCKENIEPngtTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEM 216
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 6472-6678 2.89e-13

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 73.64  E-value: 2.89e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGnKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLD 6551
Cdd:cd05059    10 KELGSGQFGVVHLGKWRG-KIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANGCLLN 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6552 RLY-RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQyGSP--- 6627
Cdd:cd05059    89 YLReRRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLV--GEQNVVKVSDFGLARYVLDDEYTSSV-GTKfpv 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6628 EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSS-PFAGESDRATLLNVLEG 6678
Cdd:cd05059   166 KWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKmPYERFSNSEVVEHISQG 217
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
 7681-7866 2.99e-13

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 74.29  E-value: 2.99e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd06643    16 GAFGKVYKAQNKETGILAAAKVIDTKSEEELEdYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGAVDAVMLE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 -RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG----NAQSLSQEkvlpsDKFKDYLETM 7834
Cdd:cd06643    96 lERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGvsakNTRTLQRR-----DSFIGTPYWM 170

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7835 APELL--EGQGAVP---QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06643   171 APEVVmcETSKDRPydyKADVWSLGVTLIEMAQIEPP 207
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 5260-5350 2.99e-13

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 68.76  E-value: 2.99e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRLaKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKV-RLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 215274225 5340 GAAYSSARLLV 5350
Cdd:cd20972    81 GSDTTSAEIFV 91
STKc_GRK3 cd05633
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs ...
 6468-6709 3.02e-13

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270781 [Multi-domain]  Cd Length: 346  Bit Score: 75.48  E-value: 3.02e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQ----AYRERDILAALSH---PLVTGLLDQFETRKTLILI 6540
Cdd:cd05633     7 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQgetlALNERIMLSLVSTgdcPFIVCMTYAFHTPDKLCFI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREdiKICDFGFAQNITPAELQ 6620
Cdd:cd05633    87 LDLMNGGDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHV--RISDLGLACDFSKKKPH 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6621 FSqYGSPEFVSPEIIQQNPVSEASDIW-AMGVISYLSLTCSSPF-------AGESDRATLLNVLEgrvswsspMAAHLSE 6692
Cdd:cd05633   165 AS-VGTHGYMAPEVLQKGTAYDSSADWfSLGCMLFKLLRGHSPFrqhktkdKHEIDRMTLTVNVE--------LPDSFSP 235

                         250
                  ....*....|....*..
gi 215274225 6693 DAKDFIKATLQRAPQAR 6709
Cdd:cd05633   236 ELKSLLEGLLQRDVSKR 252
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
 6468-6720 3.39e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 74.45  E-value: 3.39e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSH-------PLVTGLLDQFETRK-- 6535
Cdd:cd07864     9 FDIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLDNEKEGfpiTAIREIKILRQLNHrsvvnlkEIVTDKQDALDFKKdk 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 -TLILILELCSSEelLDRLYRKGVV--TEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFA- 6611
Cdd:cd07864    89 gAFYLVFEYMDHD--LMGLLESGLVhfSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNN--KGQIKLADFGLAr 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 ------------QNIT----PAELQFSQ--YG------SPEFVSPEIIQQNPVSEASDiwAMGVISYLSLTCSSPFAG-- 6665
Cdd:cd07864   165 lynseesrpytnKVITlwyrPPELLLGEerYGpaidvwSCGCILGELFTKKPIFQANQ--ELAQLELISRLCGSPCPAvw 242

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6666 -ESDRATLLNVLEGRVSWSSPMA---AHLSEDAKDFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd07864   243 pDVIKLPYFNTMKPKKQYRRRLReefSFIPTPALDLLDHMLTLDPSKRCTAEQALNSPW 301
STKc_PINK1 cd14018
Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze ...
 6566-6712 3.54e-13

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270920 [Multi-domain]  Cd Length: 313  Bit Score: 74.45  E-value: 3.54e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6566 VYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARE--DIKICDFG--FAQNITPAELQFSQY-----GSPEFVSPEIIQ 6636
Cdd:cd14018   142 VMILQLLEGVDHLVRHGIAHRDLKSDNILLELDFDGcpWLVIADFGccLADDSIGLQLPFSSWyvdrgGNACLMAPEVST 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6637 QNPVS------EASDIWAMGVISYLSLTCSSPFAGESDraTLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRAPQARP 6710
Cdd:cd14018   222 AVPGPgvvinySKADAWAVGAIAYEIFGLSNPFYGLGD--TMLESRSYQESQLPALPSAVPPDVRQVVKDLLQRDPNKRV 299


                  ..
gi 215274225 6711 SA 6712
Cdd:cd14018   300 SA 301
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 6469-6652 5.03e-13

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 73.15  E-value: 5.03e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKIlcAAKFIPlRSRTRAQAY-RERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd05039     9 KLGELIGKGEFGDVMLGDYRGQKV--AVKCLK-DDSTAAQAFlAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKG 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaREDI--KICDFGFAQnitpaELQFSQ 6623
Cdd:cd05039    86 SLVDYLRSRGraVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLV----SEDNvaKVSDFGLAK-----EASSNQ 156

                         170       180       190
                  ....*....|....*....|....*....|..
gi 215274225 6624 YGS--P-EFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd05039   157 DGGklPiKWTAPEALREKKFSTKSDVWSFGIL 188
PTKc_Wee1b cd14139
Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the ...
 6467-6719 5.57e-13

Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1b (also called Wee2), Xenopus laevis Wee1a (XeWee1a) and similar vertebrate proteins. XeWee1a accumulates after exiting the metaphase II stage in oocytes and in early mitotic cells. It functions during the first zygotic cell division and not during subsequent divisions. Mammalian Wee2/Wee1b is an oocyte-specific inhibitor of meiosis that functions downstream of cAMP. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1b subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271041 [Multi-domain]  Cd Length: 274  Bit Score: 73.42  E-value: 5.57e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVkEEIGRGVFGFVKRVQHKGNKILCAAK--FIPLRSRTRAQ-AYRERDILAALSH-PLVTGLLDQFETRKTLILILE 6542
Cdd:cd14139     2 FLEL-EKIGVGEFGSVYKCIKRLDGCVYAIKrsMRPFAGSSNEQlALHEVYAHAVLGHhPHVVRYYSAWAEDDHMIIQNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6543 LCSSEELLDRLYRKG----VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVH------PAREDI--------- 6603
Cdd:cd14139    81 YCNGGSLQDAISENTksgnHFEEPELKDILLQVSMGLKYIHNSGLVHLDIKPSNIFICHkmqsssGVGEEVsneedefls 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6604 -----KICDFGFAQNITPAELqfsQYGSPEFVSPEIIQQNPVS-EASDIWAMGVISYLSLTCSS-PFAGesdrATLLNVL 6676
Cdd:cd14139   161 anvvyKIGDLGHVTSINKPQV---EEGDSRFLANEILQEDYRHlPKADIFALGLTVALAAGAEPlPTNG----AAWHHIR 233

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 215274225 6677 EGRVswsSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHP 6719
Cdd:cd14139   234 KGNF---PDVPQELPESFSSLLKNMIQPDPEQRPSATALARHT 273
I-set pfam07679
Immunoglobulin I-set domain;
3097-3177 5.82e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 5.82e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3097 VFSRELTDATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA---GGA 3172
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsAGE 81


                   ....*
gi 215274225  3173 CSSSI 3177
Cdd:pfam07679   82 AEASA 86
I-set pfam07679
Immunoglobulin I-set domain;
1541-1608 5.99e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 5.99e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  1541 SREVQAEAGTSATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA 1608
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
I-set pfam07679
Immunoglobulin I-set domain;
2648-2731 6.48e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 68.05  E-value: 6.48e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2648 VFLKALDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV----GS 2722
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 215274225  2723 EETRARVRV 2731
Cdd:pfam07679   82 AEASAELTV 90
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
 7680-7924 6.63e-13

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 72.83  E-value: 6.63e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEAL-KGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLA 7758
Cdd:cd06624    18 KGTFGVVYAARDLSTQVRIAIKEIPERDSREVQPLHEEIALhSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGGSLSALLR 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ER---ASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN-LLKVVDLGNAQSLSqeKVLP-SDKFKDYLET 7833
Cdd:cd06624    98 SKwgpLKDNENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVNTYSgVVKISDFGTSKRLA--GINPcTETFTGTLQY 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7834 MAPELLE-GQ-GAVPQTDIWAIGVTAFIMLSAEYPVSSEG---ARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCAQ 7908
Cdd:cd06624   176 MAPEVIDkGQrGYGPPADIWSLGCTIIEMATGKPPFIELGepqAAMFKVGMFKIHPEIP---ESLSEEAKSFILRCFEPD 252

                         250
                  ....*....|....*.
gi 215274225 7909 PWGRPCASSCLQCPWL 7924
Cdd:cd06624   253 PDKRATASDLLQDPFL 268
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 7686-7858 6.80e-13

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 73.46  E-value: 6.80e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7686 VRQCWEKASgralaakiipyhPKDKTAVLREYEALKGLRHPHLAQLHAA-----YLSPRHL-VLILELCSGPEL---LPC 7756
Cdd:cd14038    24 IKQCRQELS------------PKNRERWCLEIQIMKRLNHPNVVAARDVpeglqKLAPNDLpLLAMEYCQGGDLrkyLNQ 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT--EYNLL-KVVDLGNAQSLSQEKVLPSdkFKDYLET 7833
Cdd:cd14038    92 FENCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQqgEQRLIhKIIDLGYAKELDQGSLCTS--FVGTLQY 169

                         170       180
                  ....*....|....*....|....*
gi 215274225 7834 MAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd14038   170 LAPELLEQQKYTVTVDYWSFGTLAF 194
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 27-94 7.01e-13

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 66.97  E-value: 7.01e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   27 ATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIGEAFAA 94
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 6014-6104 7.14e-13

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 67.81  E-value: 7.14e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKavQVDP---HHILIEDPDGSCALILDSLTGVDSGQYMCFAA 6090
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGK--QISPksdHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAA 78

                          90
                  ....*....|....
gi 215274225 6091 SAAGNCSTLGKILV 6104
Cdd:cd05893    79 NPQGRISCTGRLMV 92
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
 6472-6717 7.18e-13

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 72.74  E-value: 7.18e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNkilCAAKFIPLRSRT--RAQAYR-ERDILAALSHPLVTgLLDQFETRKTLILILELCSSEE 6548
Cdd:cd14150     6 KRIGTGSFGTVFRGKWHGD---VAVKILKVTEPTpeQLQAFKnEMQVLRKTRHVNIL-LFMGFMTRPNFAIITQWCEGSS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LldrlYRKGVVTEAEVKVY-----IQQLVEGLHYLHSHGVLHLDIKPSNILMvHPAREdIKICDFGFAQNIT--PAELQF 6621
Cdd:cd14150    82 L----YRHLHVTETRFDTMqlidvARQTAQGMDYLHAKNIIHRDLKSNNIFL-HEGLT-VKIGDFGLATVKTrwSGSQQV 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6622 SQ-YGSPEFVSPEIIQQ---NPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLnVLEGRvSWSSPMAAHLSEDA--- 6694
Cdd:cd14150   156 EQpSGSILWMAPEVIRMqdtNPYSFQSDVYAYGVVLYELMSGTLPYSNINNRDQII-FMVGR-GYLSPDLSKLSSNCpka 233

                         250       260
                  ....*....|....*....|....
gi 215274225 6695 -KDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd14150   234 mKRLLIDCLKFKREERPLFPQILV 257
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
 7665-7868 7.61e-13

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 73.12  E-value: 7.61e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7665 PLPStKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKII-PYHPKDKTaVLREYEALKGLR-HPHLAQLHAAYLSPR--- 7739
Cdd:cd06638    14 PDPS-DTWEIIETIGKGTYGKVFKVLNKKNGSKAAVKILdPIHDIDEE-IEAEYNILKALSdHPNVVKFYGMYYKKDvkn 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7740 --HLVLILELCSG---PELLPCLAERASYSESEVKDY-LWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNA 7813
Cdd:cd06638    92 gdQLWLVLELCNGgsvTDLVKGFLKRGERMEEPIIAYiLHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVS 171

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7814 QSLSQEKVLPSDKFKDYLeTMAPELLEGQGAVPQT-----DIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06638   172 AQLTSTRLRRNTSVGTPF-WMAPEVIACEQQLDSTydarcDVWSLGITAIELGDGDPPLA 230
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 4901-4988 8.56e-13

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 67.60  E-value: 8.56e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4901 SHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKFGQV 4980
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80


                  ....*...
gi 215274225 4981 THSACVVV 4988
Cdd:cd20973    81 TCSAELTV 88
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 114-188 8.94e-13

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 67.53  E-value: 8.94e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  114 LRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDgPRVRVEELGeaSALRIRAARPRDGGTYEVRAEN 188
Cdd:cd20970     7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFN-TRYIVRENG--TTLTIRNIRRSDMGIYLCIASN 78
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 248-328 9.66e-13

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 67.52  E-value: 9.66e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLVV 327
Cdd:cd05744    11 EVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAELV 90


                  .
gi 215274225  328 V 328
Cdd:cd05744    91 V 91
I-set pfam07679
Immunoglobulin I-set domain;
3186-3269 9.66e-13

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 67.28  E-value: 9.66e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3186 RFQEALKDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC----SFGD 3260
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGE 81


                   ....*....
gi 215274225  3261 QTTSATLTV 3269
Cdd:pfam07679   82 AEASAELTV 90
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 515-602 9.83e-13

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 67.52  E-value: 9.83e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  515 PPVDPVVKARMESSVILSWSPPPHGERPvtIDGYLVEKKKLGTYTWIRChEAEWVATPELTVADVAEEGNFQFRVSALNS 594
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDDGGP--ITGYVVEYREKGSGDWKEV-EVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79


                  ....*...
gi 215274225  595 FGQSPYLE 602
Cdd:cd00063    80 GGESPPSE 87
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
 7670-7870 1.03e-12

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 72.83  E-value: 1.03e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH--PKdKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd06655    19 KKYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQkqPK-KELIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEY 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsDKF 7827
Cdd:cd06655    98 LAGGSLTDVVTE-TCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQ----SKR 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7828 KDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd06655   173 STMVGTpywMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNE 218
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5133-5216 1.03e-12

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 67.04  E-value: 1.03e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5133 QNQEVQDGYPVSFDCVVTGQPMPSVRWFK-DGKLleEDDHYMINEDqqggHQLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKeDGEL--PKGRYEILDD----HSLKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                  ....*
gi 215274225 5212 AELRV 5216
Cdd:cd05725    79 ATLTV 83
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
 6459-6652 1.08e-12

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 73.93  E-value: 1.08e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6459 SHRRKLHSFYEVkeEIGRGVFGFVKRVQH------KGNKILCAA-----------KFI--PLRSRTRAQ-AYRERDILAA 6518
Cdd:cd07875     2 SRSKRDNNFYSV--EIGDSTFTVLKRYQNlkpigsGAQGIVCAAydailernvaiKKLsrPFQNQTHAKrAYRELVLMKC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6519 LSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAE---VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM 6595
Cdd:cd07875    80 VNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDherMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVV 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6596 vhpaRED--IKICDFGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd07875   160 ----KSDctLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCI 214
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 7708-7862 1.18e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 72.08  E-value: 1.18e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP--CLAERASYSESEVKDYLWQMLSATQYLHNQ 7785
Cdd:cd08221    41 KERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCNGGNLHDkiAQQKNQLFPEEVVLWYLYQIVSAVSHIHKA 120

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7786 HILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLpSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLS 7862
Cdd:cd08221   121 GILHRDIKTLNIFLTKADLVKLGDFGISKVLDSESSM-AESIVGTPYYMSPELVQGVKYNFKSDIWAVGCVLYELLT 196
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
 7720-7866 1.21e-12

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 71.37  E-value: 1.21e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7720 LKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII 7799
Cdd:cd14059    35 LRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEVLRAGREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLV 114

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7800 TEYNLLKVVDLGNAQSLSQEKVLPSdkFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14059   115 TYNDVLKISDFGTSKELSEKSTKMS--FAGTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTGEIP 179
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
 7676-7877 1.23e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 73.17  E-value: 1.23e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKII--PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd06650    11 SELGAGNGGVVFKVSHKPSGLVMARKLIhlEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpSDKFKDYLE 7832
Cdd:cd06650    91 DQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSM---ANSFVGTRS 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQR 7877
Cdd:cd06650   168 YMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELEL 212
STKc_HIPK cd14211
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs ...
 6468-6657 1.23e-12

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271113 [Multi-domain]  Cd Length: 329  Bit Score: 73.25  E-value: 1.23e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFI---PLRSRtraQAYRERDILAALS------HPLVTGLlDQFETRKTLI 6538
Cdd:cd14211     1 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILknhPSYAR---QGQIEVSILSRLSqenadeFNFVRAY-ECFQHKNHTC 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSsEELLDRLYRKGV--VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED--IKICDFGFAQNI 6614
Cdd:cd14211    77 LVFEMLE-QNLYDFLKQNKFspLPLKYIRPILQQVLTALLKLKSLGLIHADLKPENIMLVDPVRQPyrVKVIDFGSASHV 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 6615 TPA----ELQfSQYgspeFVSPEIIQQNPVSEASDIWAMG-VISYLSL 6657
Cdd:cd14211   156 SKAvcstYLQ-SRY----YRAPEIILGLPFCEAIDMWSLGcVIAELFL 198
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
 6465-6652 1.30e-12

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 73.58  E-value: 1.30e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVkeEIGRGVFGFVKRVQH------KGNKILCAAKFI-------------PLRSRTRAQ-AYRERDILAALSHPLV 6524
Cdd:cd07874     1 NQFYSV--EVGDSTFTVLKRYQNlkpigsGAQGIVCAAYDAvldrnvaikklsrPFQNQTHAKrAYRELVLMKCVNHKNI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6525 TGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAE---VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRE 6601
Cdd:cd07874    79 ISLLNVFTPQKSLEEFQDVYLVMELMDANLCQVIQMELDherMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVV----KS 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6602 D--IKICDFGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd07874   155 DctLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCI 207
PTKc_Wee1b cd14139
Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the ...
 7677-7917 1.31e-12

Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1b (also called Wee2), Xenopus laevis Wee1a (XeWee1a) and similar vertebrate proteins. XeWee1a accumulates after exiting the metaphase II stage in oocytes and in early mitotic cells. It functions during the first zygotic cell division and not during subsequent divisions. Mammalian Wee2/Wee1b is an oocyte-specific inhibitor of meiosis that functions downstream of cAMP. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1b subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271041 [Multi-domain]  Cd Length: 274  Bit Score: 72.27  E-value: 1.31e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAK--IIPY-HPKDKTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd14139     7 KIGVGEFGSVYKCIKRLDGCVYAIKrsMRPFaGSSNEQLALHEVYAHAVLgHHPHVVRYYSAWAEDDHMIIQNEYCNGGS 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERAS----YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLL----------------------K 7806
Cdd:cd14139    87 LQDAISENTKsgnhFEEPELKDILLQVSMGLKYIHNSGLVHLDIKPSNIFICHKMQSssgvgeevsneedeflsanvvyK 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7807 VVDLGNAQSLSQEKVLPSDKfkdylETMAPELLEGQGA-VPQTDIWAIGVTAFIMLSAEyPVSSEGArdLQRGLRKGlvR 7885
Cdd:cd14139   167 IGDLGHVTSINKPQVEEGDS-----RFLANEILQEDYRhLPKADIFALGLTVALAAGAE-PLPTNGA--AWHHIRKG--N 236

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 7886 LSRCYAGLSGGAVAFLRSTLCAQPWGRPCASS 7917
Cdd:cd14139   237 FPDVPQELPESFSSLLKNMIQPDPEQRPSATA 268
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 7677-7924 1.32e-12

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 72.47  E-value: 1.32e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFS-VVRQCWEKASGRALAAKIIP--------YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd14096     8 KIGEGAFSnVYKAVPLRNTGKPVAIKVVRkadlssdnLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYYIVLEL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT--------------------------- 7800
Cdd:cd14096    88 ADGGEIFHQIVRLTYFSEDLSRHVITQVASAVKYLHEIGVVHRDIKPENLLFEpipfipsivklrkadddetkvdegefi 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7801 ------EYNLLKVVDLGnaqsLSqeKVLPSDKFKDYLETM---APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEG 7871
Cdd:cd14096   168 pgvgggGIGIVKLADFG----LS--KQVWDSNTKTPCGTVgytAPEVVKDERYSKKVDMWALGCVLYTLLCGFPPFYDES 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7872 ARDLQRGLRKG-LVRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14096   242 IETLTEKISRGdYTFLSPWWDEISKSAKDLISHLLTVDPAKRYDIDEFLAHPWI 295
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 6014-6098 1.44e-12

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 67.14  E-value: 1.44e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFAASAA 6093
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80


                  ....*
gi 215274225 6094 GNCST 6098
Cdd:cd05744    81 GENSF 85
I-set pfam07679
Immunoglobulin I-set domain;
2167-2250 1.48e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 66.90  E-value: 1.48e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2167 SFSRPLQDVVTTEKEKVTLECELS-RPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAHD---- 2241
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNsage 81


                   ....*....
gi 215274225  2242 AQSSASVKV 2250
Cdd:pfam07679   82 AEASAELTV 90
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 7682-7919 1.49e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 71.54  E-value: 1.49e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7682 RFSVVRQCWEKASGRAL-----------AAKIIPYhPKDKTAV---LREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd08219     1 QYNVLRVVGEGSFGRALlvqhvnsdqkyAMKEIRL-PKSSSAVedsRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQekvlPSD 7825
Cdd:cd08219    80 CDGGDLMQKIKLQRGklFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTS----PGA 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGlvrlsrCYAGLSGGAVAFLR 7902
Cdd:cd08219   156 YACTYVGTpyyVPPEIWENMPYNNKSDIWSLGCILYELCTLKHPFQANSWKNLILKVCQG------SYKPLPSHYSYELR 229

                         250       260
                  ....*....|....*....|..
gi 215274225 7903 StLCAQ-----PWGRPCASSCL 7919
Cdd:cd08219   230 S-LIKQmfkrnPRSRPSATTIL 250
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 7463-7540 1.53e-12

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 66.43  E-value: 1.53e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNfQLLTILVVVAEDLGVYTCSVSN 7540
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-STLTISNVTRSDAGTYTCVASN 78
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 248-315 1.56e-12

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 66.43  E-value: 1.56e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGrRHVVYEDAQENFVLKILFCKQSDRGLYTCTASN 315
Cdd:pfam13927   12 TVREGETVTLTCEATGSPPPTITWYKNGEPISSG-STRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 7672-7870 1.59e-12

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 71.98  E-value: 1.59e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd08228     4 FQIEKKIGRGQFSEVYRATCLLDRKPVALKKVQifemMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLEL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCL----AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQeKVLP 7823
Cdd:cd08228    84 ADAGDLSQMIkyfkKQKRLIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSS-KTTA 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7824 SDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd08228   163 AHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGD 209
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
 6468-6721 1.61e-12

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 72.89  E-value: 1.61e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRV--QHKGNKIlcAAK-----FIPLRSRTRAqaYRERDILAALSHPLVTGLLDQF-----ETRK 6535
Cdd:cd07859     2 YKIQEVIGKGSYGVVCSAidTHTGEKV--AIKkindvFEHVSDATRI--LREIKLLRLLRHPDIVEIKHIMlppsrREFK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6536 TLILILELCSSEeLLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmvhpARED--IKICDFGFAQ- 6612
Cdd:cd07859    78 DIYVVFELMESD-LHQVIKANDDLTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNIL----ANADckLKICDFGLARv 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6613 --NITPAELQFSQYGSPE-FVSPEIIQQ--NPVSEASDIWAMGVISYLSLTCSSPFAGES--DRATLLNVLEGRVSwSSP 6685
Cdd:cd07859   153 afNDTPTAIFWTDYVATRwYRAPELCGSffSKYTPAIDIWSIGCIFAEVLTGKPLFPGKNvvHQLDLITDLLGTPS-PET 231

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6686 MAAHLSEDAKDFIKAT----------------------LQRA----PQARPSAAQCLSHPWF 6721
Cdd:cd07859   232 ISRVRNEKARRYLSSMrkkqpvpfsqkfpnadplalrlLERLlafdPKDRPTAEEALADPYF 293
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 7677-7855 1.67e-12

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 71.61  E-value: 1.67e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKasGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd05039    13 LIGKGEFGDVMLGDYR--GQKVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKGSLVDY 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LA--ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvLPSDKFKdyLETM 7834
Cdd:cd05039    91 LRsrGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEASSN--QDGGKLP--IKWT 166

                         170       180
                  ....*....|....*....|.
gi 215274225 7835 APELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05039   167 APEALREKKFSTKSDVWSFGI 187
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
 7678-7900 1.75e-12

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 71.66  E-value: 1.75e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFS-VVRQCWekaSGRALAAKIIPYHPKDKTA-----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14061     2 IGVGGFGkVYRGIW---RGEEVAVKAARQDPDEDISvtlenVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVkDYLWQMLSATQYLHNQH---ILHLDLRSENMIITE--------YNLLKVVDLGNAQSLSQEK 7820
Cdd:cd14061    79 ALNRVLAGRKIPPHVLV-DWAIQIARGMNYLHNEApvpIIHRDLKSSNILILEaienedleNKTLKITDFGLAREWHKTT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7821 VLPSDKFKDYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPvssegardlqrglrkglvrlsrcYAGLSGGAVAF 7900
Cdd:cd14061   158 RMSAAGTYAW---MAPEVIKSSTFSKASDVWSYGVLLWELLTGEVP-----------------------YKGIDGLAVAY 211
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 11-91 1.85e-12

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 66.59  E-value: 1.85e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   11 RFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIGE 90
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSI 80


                  .
gi 215274225   91 A 91
Cdd:cd20949    81 A 81
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
 7677-7866 1.85e-12

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 71.60  E-value: 1.85e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKT-AVLREYEALKGL-RHPHLAQ-LHAAYLS--PRHLVLIL-ELCSG 7750
Cdd:cd13985     7 QLGEGGFSYVYLAHDVNTGRRYALKRMYFNDEEQLrVAIKEIEIMKRLcGHPNIVQyYDSAILSseGRKEVLLLmEYCPG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 pELLPCLAERAS--YSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDk 7826
Cdd:cd13985    87 -SLVDILEKSPPspLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFGSATTEHYPLERAEE- 164

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7827 FKDYLETM---------APELLEGQGAVP---QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd13985   165 VNIIEEEIqknttpmyrAPEMIDLYSKKPigeKADIWALGCLLYKLCFFKLP 216
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 7677-7866 2.20e-12

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 72.27  E-value: 2.20e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTA---------VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd05574     8 LLGKGDVGRVYLVRLKGTGKLFAMKVL-----DKEEmikrnkvkrVLTEREILATLDHPFLPTLYASFQTSTHLCFVMDY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII--------TEYNL---------LKVV 7808
Cdd:cd05574    83 CPGGELFRLLQKQPGkrLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILLhesghimlTDFDLskqssvtppPVRK 162

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7809 DLGNAQSLSQEKVLPSDKFKDYL-----------ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05574   163 SLRKGSRRSSVKSIEKETFVAEPsarsnsfvgteEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTP 231
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
 6467-6744 2.42e-12

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 72.75  E-value: 2.42e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6467 FYEVkeEIGRGVFGFVKRVQH------KGNKILCAA------------KFI-PLRSRTRAQ-AYRERDILAALSHPLVTG 6526
Cdd:cd07876     7 FYSV--QVADSTFTVLKRYQQlkpigsGAQGIVCAAfdtvlginvavkKLSrPFQNQTHAKrAYRELVLLKCVNHKNIIS 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6527 LLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAE---VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED- 6602
Cdd:cd07876    85 LLNVFTPQKSLEEFQDVYLVMELMDANLCQVIHMELDherMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVV----KSDc 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 -IKICDFGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVS 6681
Cdd:cd07876   161 tLKILDFGLARTACTNFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGSVIFQGTDHIDQWNKVIEQLGT 240

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6682 WSSPMAAHLSEDAKDFIkatlQRAPQARPSAAQCLSHPWflkSMPAEEAH-FINTKQLKFLLAR 6744
Cdd:cd07876   241 PSAEFMNRLQPTVRNYV----ENRPQYPGISFEELFPDW---IFPSESERdKLKTSQARDLLSK 297
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 5883-6005 2.53e-12

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270061  Cd Length: 140  Bit Score: 68.06  E-value: 2.53e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5883 MENYPGTLQALGEPIRQGHFIVWEGAPGARmpWKGHNRHVFLFRNHLVICKP-RRDSRTDTVSYVFRNMMKLSSIDLNDQ 5961
Cdd:cd13241     4 LQGFDGKITAQGKLLLQGTLLVSEPSAGLL--QKGKERRVFLFEQIIIFSEIlGKKTQFSNPGYIYKNHIKVNKMSLEEN 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 5962 VEGDDRAFEVW-QEREDSVRKYLLQARTAIIKSSWVKEICGI--QQR 6005
Cdd:cd13241    82 VDGDPLRFALKsRDPNNPSETFILQAASPEVRQEWVDTINQIldTQR 128
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 5126-5216 2.63e-12

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 66.26  E-value: 2.63e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGY-PVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDqqggHQLIITAVVPADMGVYRCLAENS 5204
Cdd:cd20978     1 PKFIQKPEKNVVVKGGqDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVED----GTLTIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|..
gi 215274225 5205 MGVSSTKAELRV 5216
Cdd:cd20978    77 IGDIYTETLLHV 88
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 20-99 2.73e-12

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 66.06  E-value: 2.73e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   20 VVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGD-LYRLTILDLALGDSGQYVCRARNAIGEAFAAVGLQ 98
Cdd:cd20973     8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDgLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87


                  .
gi 215274225   99 V 99
Cdd:cd20973    88 V 88
I-set pfam07679
Immunoglobulin I-set domain;
3803-3885 2.77e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 66.13  E-value: 2.77e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3803 RFIEDVKNQEAREGATAVLQCELSkAAP---VEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVC----G 3875
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3876 QERTSATLTV 3885
Cdd:pfam07679   81 EAEASAELTV 90
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
 6474-6652 2.80e-12

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 70.97  E-value: 2.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFIPLRSrTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSS---EELL 6550
Cdd:cd14155     1 IGSGFFSEVYKVRHRTSGQVMALKMNTLSS-NRANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGgnlEQLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRlyrkGVVTEAEVKVYIQ-QLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKIC-DFGFAQNITPAE---LQFSQYG 6625
Cdd:cd14155    80 DS----NEPLSWTVRVKLAlDIARGLSYLHSKGIFHRDLTSKNCLIKRDENGYTAVVgDFGLAEKIPDYSdgkEKLAVVG 155

                         170       180
                  ....*....|....*....|....*..
gi 215274225 6626 SPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd14155   156 SPYWMAPEVLRGEPYNEKADVFSYGII 182
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
 7667-7870 2.96e-12

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 70.73  E-value: 2.96e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQtQIQRGRFSVVRQCWEKASGRALAAKII--PYHPKdKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLI 7744
Cdd:cd06647     5 PKKKYTRFE-KIGQGASGTVYTAIDVATGQEVAIKQMnlQQQPK-KELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlps 7824
Cdd:cd06647    83 MEYLAGGSLTDVVTE-TCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQ---- 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 7825 DKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd06647   158 SKRSTMVGTpywMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNE 206
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
 7678-7874 3.07e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 70.84  E-value: 3.07e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK--TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd06605     9 LGEGNGGVVSKVRHRPSGQIMAVKVIRLEIDEAlqKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDGGSLDK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVlpSDKFKDYLET- 7833
Cdd:cd06605    89 ILKEVGRIPERILGKIAVAVVKGLIYLHEKHkIIHRDVKPSNILVNSRGQVKLCDFG----VSGQLV--DSLAKTFVGTr 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7834 --MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd06605   163 syMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPPPNAKP 205
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
 7674-7866 3.12e-12

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 70.84  E-value: 3.12e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVV-RQCWEkasGRAlAAKI--IPYHPKDK-TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCS 7749
Cdd:cd14063     4 IKEVIGKGRFGRVhRGRWH---GDV-AIKLlnIDYLNEEQlEAFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSLCK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 GPELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENM-------IITEYNLLKVVDLGNAQSLSQEKV 7821
Cdd:cd14063    80 GRTLYSLIHERKEkFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIflengrvVITDFGLFSLSGLLQPGRREDTLV 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7822 LPsdkfKDYLETMAPEL-------LEGQGAVP---QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14063   160 IP----NGWLCYLAPEIiralspdLDFEESLPftkASDVYAFGTVWYELLAGRWP 210
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
 7670-7925 3.23e-12

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 70.56  E-value: 3.23e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd06607     1 KIFEDLREIGHGSFGAVYYARNKRTSEVVAIKKMSYSGKQSTEkwqdIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSD 7825
Cdd:cd06607    81 EYCLGSASDIVEVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLVC-----PAN 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KFKDYLETMAPELL----EGQ--GAVpqtDIWAIGVTA----------FIM--LSAEYPVSSEGARDLQRGlrkglvrls 7887
Cdd:cd06607   156 SFVGTPYWMAPEVIlamdEGQydGKV---DVWSLGITCielaerkpplFNMnaMSALYHIAQNDSPTLSSG--------- 223

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 215274225 7888 rcyaGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWLT 7925
Cdd:cd06607   224 ----EWSDDFRNFVDSCLQKIPQDRPSAEDLLKHPFVT 257
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
 7677-7867 3.37e-12

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 71.30  E-value: 3.37e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK----TAVlREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG-- 7750
Cdd:cd07861     7 KIGEGTYGVVYKGRNKKTGQIVAMKKIRLESEEEgvpsTAI-REISLLKELQHPNIVCLEDVLMQENRLYLVFEFLSMdl 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvLPSDKFKDY 7830
Cdd:cd07861    86 KKYLDSLPKGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFG----IPVRVYTHE 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7831 LETM---APELLEGQG--AVPqTDIWAIGvTAFIMLSAEYPV 7867
Cdd:cd07861   162 VVTLwyrAPEVLLGSPrySTP-VDIWSIG-TIFAEMATKKPL 201
fn3 pfam00041
Fibronectin type III domain;
4524-4607 3.37e-12

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 65.51  E-value: 3.37e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4524 DPPEDAEVVARSSHTVTLSWAAPmSDGGGGLCGYRVEVKE-GATGQWRlcHELVPGPE--CVVDGLAPGETYRFRVAAVG 4600
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPP-PDGNGPITGYEVEYRPkNSGEPWN--EITVPGTTtsVTLTGLKPGTEYEVRVQAVN 77


                   ....*..
gi 215274225  4601 PVGAGEP 4607
Cdd:pfam00041   78 GGGEGPP 84
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 11-99 3.41e-12

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 66.13  E-value: 3.41e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   11 RFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKD--------QQPVAAGARFRLAQDGDlyrLTILDLALGDSGQYVC 82
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEgsqnllfpYQPPQPSSRFSVSPTGD---LTITNVQRSDVGYYIC 77

                          90
                  ....*....|....*..
gi 215274225   83 RARNAIGEAFAAVGLQV 99
Cdd:cd05726    78 QALNVAGSILAKAQLEV 94
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 248-328 3.49e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.60  E-value: 3.49e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    248 TVTEGKHARLSCYVTGEPKPETVWKKDG-QLVTEGRRHVVYEDAQeNFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLV 326
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGS-TSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83


                    ..
gi 215274225    327 VV 328
Cdd:smart00410   84 TV 85
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
 6475-6682 3.62e-12

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 70.37  E-value: 3.62e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6475 GRGVFGFVKRvqhkgnkilcaAKFIP----LRSRTRAQAYRERDILAALSHPLVT------------GLLDQFETRKTLI 6538
Cdd:cd14060     2 GGGSFGSVYR-----------AIWVSqdkeVAVKKLLKIEKEAEILSVLSHRNIIqfygaileapnyGIVTEYASYGSLF 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELldrlyrkgvvTEAEVKVYIQQLVEGLHYLHSHG---VLHLDIKPSNILMVhpAREDIKICDFGfAQNIT 6615
Cdd:cd14060    71 DYLNSNESEEM----------DMDQIMTWATDIAKGMHYLHMEApvkVIHRDLKSRNVVIA--ADGVLKICDFG-ASRFH 137

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6616 PAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGesdratllnvLEG-RVSW 6682
Cdd:cd14060   138 SHTTHMSLVGTFPWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPFKG----------LEGlQVAW 195
I-set pfam07679
Immunoglobulin I-set domain;
3363-3445 3.71e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 65.74  E-value: 3.71e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3363 HFIGRLRHQESIEGATATLRCELSkAAP---VEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVC----G 3435
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3436 EERTSATLTV 3445
Cdd:pfam07679   81 EAEASAELTV 90
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 5260-5350 3.89e-12

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 65.59  E-value: 3.89e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGtRLAKFQLKVKGYPAPRLYWFKDGQPLT-ASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNA 5338
Cdd:cd05744     1 PHFLQAPGDLEVQEG-RLCRFDCKVSGLPTPDLFWQLNGKPVRpDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNR 79

                          90
                  ....*....|..
gi 215274225 5339 MGAAYSSARLLV 5350
Cdd:cd05744    80 AGENSFNAELVV 91
STKc_CDK8 cd07868
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs ...
 6459-6662 3.99e-12

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270851 [Multi-domain]  Cd Length: 333  Bit Score: 71.63  E-value: 3.99e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6459 SHRRKLHSFYEVKE-EIGRGVFGFVKRVQHKGNKilcAAKFIPLR----SRTRAQAYRERDILAALSHPLVTGLLDQFET 6533
Cdd:cd07868     9 GERERVEDLFEYEGcKVGRGTYGHVYKAKRKDGK---DDKDYALKqiegTGISMSACREIALLRELKHPNVISLQKVFLS 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6534 RKTLILILELCSSEELLDRLYRKGVVTEAE----------VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV--HPARE 6601
Cdd:cd07868    86 HADRKVWLLFDYAEHDLWHIIKFHRASKANkkpvqlprgmVKSLLYQILDGIHYLHANWVLHRDLKPANILVMgeGPERG 165

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6602 DIKICDFGFAQ----------NITPAELQFsQYGSPEFvspeIIQQNPVSEASDIWAMGVIsYLSLTCSSP 6662
Cdd:cd07868   166 RVKIADMGFARlfnsplkplaDLDPVVVTF-WYRAPEL----LLGARHYTKAIDIWAIGCI-FAELLTSEP 230
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 6107-6186 4.17e-12

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 65.28  E-value: 4.17e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6107 PPRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGllVLVIRAASKEDLGLYECELVN 6186
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNS--TLTISNVTRSDAGTYTCVASN 78
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2834-2911 4.20e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.60  E-value: 4.20e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2834 EDQWVAPGEDVELRCELSRAGTP-VHWLKDR-KAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEAS----KSTA 2907
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSsgsaSSGT 81


                    ....
gi 215274225   2908 SLHV 2911
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
2829-2911 4.29e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 65.36  E-value: 4.29e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2829 IIKPLEDQWVAPGEDVELRCELSraGTP---VHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEAS-- 2903
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVT--GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSag 80

                           90
                   ....*....|
gi 215274225  2904 --KSTASLHV 2911
Cdd:pfam07679   81 eaEASAELTV 90
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
 7667-7854 4.37e-12

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 70.99  E-value: 4.37e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTavlREYEALKGLRHPHLAQLHAAYLS----PRHLV 7742
Cdd:cd14137     1 PVEISYTIEKVIGSGSFGVVYQAKLLETGEVVAIKKVLQDKRYKN---RELQIMRRLKHPNIVKLKYFFYSsgekKDEVY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELcsgpELLP-CLAERASY--------SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII-TEYNLLKVVDLGN 7812
Cdd:cd14137    78 LNLVM----EYMPeTLYRVIRHysknkqtiPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVdPETGVLKLCDFGS 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7813 AQSLsqekvLPSDKFKDYLETM---APELLegQGAV---PQTDIWAIG 7854
Cdd:cd14137   154 AKRL-----VPGEPNVSYICSRyyrAPELI--FGATdytTAIDIWSAG 194
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 5260-5351 4.73e-12

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 65.52  E-value: 4.73e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRmtDKKI-----LHTLEIISVTREDSGQYAAY 5334
Cdd:cd20951     1 PEFIIRLQSHTVWEKSD-AKLRVEVQGKPDPEVKWYKNGVPIDPSSIPG--KYKIeseygVHVLHIRRVTVEDSAVYSAV 77

                          90
                  ....*....|....*..
gi 215274225 5335 ISNAMGAAYSSARLLVR 5351
Cdd:cd20951    78 AKNIHGEASSSASVVVE 94
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3809-3885 4.82e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 65.22  E-value: 4.82e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3809 KNQEAREGATAVLQCELSKAAP--VEWRK-GSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVC----GQERTSA 3881
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3882 TLTV 3885
Cdd:smart00410   82 TLTV 85
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
 6535-6677 4.87e-12

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 70.70  E-value: 4.87e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6535 KTLILILELCSSEELLDRLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpARED-IKICDFGFAQN 6613
Cdd:cd05080    81 KSLQLIMEYVPLGSLRDYLPKHSI-GLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLL---DNDRlVKIGDFGLAKA 156

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6614 ITPAELQF--SQYG-SPEF-VSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFagESDRATLLNVLE 6677
Cdd:cd05080   157 VPEGHEYYrvREDGdSPVFwYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSS--QSPPTKFLEMIG 222
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 12-99 4.93e-12

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 65.21  E-value: 4.93e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   12 FLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAA-GARFRLAQDGDlyrLTILDLALGDSGQYVCRARNAIGE 90
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGkDERITTLENGS---LQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 215274225   91 AFAAVGLQV 99
Cdd:cd20952    79 ATWSAVLDV 87
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
 7676-7861 5.21e-12

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 71.19  E-value: 5.21e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVLREYEA----------LKGLRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd05575     1 KVIGKGSFGKVLLARHKAEGKLYAVKVL-----QKKAILKRNEVkhimaernvlLKNVKHPFLVGLHYSFQTKDKLYFVL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSD 7825
Cdd:cd05575    76 DYVNGGELFFHLQRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFG----LCKEGIEPSD 151

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7826 K---FKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIML 7861
Cdd:cd05575   152 TtstFCGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEML 190
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
 7685-7920 5.25e-12

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 70.02  E-value: 5.25e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7685 VVRQCWEkasGRALAAKIIPYHPKDKTAVL-----REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14148    10 VYKGLWR---GEEVAVKAARQDPDEDIAVTaenvrQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALNRALAG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESEVkDYLWQMLSATQYLHNQH---ILHLDLRSENMIITE----YNL----LKVVDLGNAQSLSQEKVLPSDKFK 7828
Cdd:cd14148    87 KKVPPHVLV-NWAVQIARGMNYLHNEAivpIIHRDLKSSNILILEpienDDLsgktLKITDFGLAREWHKTTKMSAAGTY 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 DYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRL---SRCYAGLsggaVAFLRSTL 7905
Cdd:cd14148   166 AW---MAPEVIRLSLFSKSSDVWSFGVLLWELLTGEVPYREIDALAVAYGVAMNKLTLpipSTCPEPF----ARLLEECW 238

                         250
                  ....*....|....*
gi 215274225 7906 CAQPWGRPCASSCLQ 7920
Cdd:cd14148   239 DPDPHGRPDFGSILK 253
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
 7678-7873 5.33e-12

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270938 [Multi-domain]  Cd Length: 282  Bit Score: 70.62  E-value: 5.33e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAK-IIPYHPKDKTAVLREYEALKGLR-HPHLAQL-HAAYLSPR-------HLVLILEL 7747
Cdd:cd14036     8 IAEGGFAFVYEAQDVGTGKEYALKrLLSNEEEKNKAIIQEINFMKKLSgHPNIVQFcSAASIGKEesdqgqaEYLLLTEL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGP--ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMIITEYNLLKVVDLGNAQSLS------ 7817
Cdd:cd14036    88 CKGQlvDFVKKVEAPGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFGSATTEAhypdys 167

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7818 ---QEKVLPSDKFKDYLETM--APELLEGQGAVP---QTDIWAIGVTAFIMLSAEYPVsSEGAR 7873
Cdd:cd14036   168 wsaQKRSLVEDEITRNTTPMyrTPEMIDLYSNYPigeKQDIWALGCILYLLCFRKHPF-EDGAK 230
STKc_Mnk2 cd14173
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
 7681-7924 5.48e-12

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271075 [Multi-domain]  Cd Length: 288  Bit Score: 70.44  E-value: 5.48e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHP-KDKTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLA 7758
Cdd:cd14173    13 GAYARVQTCINLITNKEYAVKIIEKRPgHSRSRVFREVEMLYQCQgHRNVLELIEFFEEEDKFYLVFEKMRGGSILSHIH 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVV-----DLGNAQSL--------SQEKVLPSD 7825
Cdd:cd14173    93 RRRHFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILCEHPNQVSPVkicdfDLGSGIKLnsdcspisTPELLTPCG 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7826 KfkdyLETMAPELLEG---QGAV--PQTDIWAIGVTAFIMLSAEYPVSSEGARD---------------LQRGLRKGLVR 7885
Cdd:cd14173   173 S----AEYMAPEVVEAfneEASIydKRCDLWSLGVILYIMLSGYPPFVGRCGSDcgwdrgeacpacqnmLFESIQEGKYE 248

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 7886 L-SRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14173   249 FpEKDWAHISCAAKDLISKLLVRDAKQRLSAAQVLQHPWV 288
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 6024-6089 5.54e-12

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 64.89  E-value: 5.54e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  6024 TAELGETVKLACRVTGTPKPVISWYKDGKAVQvDPHHILIEDPDGSCALILDSLTGVDSGQYMCFA 6089
Cdd:pfam13927   12 TVREGETVTLTCEATGSPPPTITWYKNGEPIS-SGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 6471-6723 5.63e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 70.47  E-value: 5.63e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6471 KEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQAYRERD---ILAALSHPLVT---GLLdqFETRKTLIlILELC 6544
Cdd:cd06616    11 LGEIGRGAFGTVNKMLHKPSGTIMAVKRIRSTVDEKEQKRLLMDldvVMRSSDCPYIVkfyGAL--FREGDCWI-CMELM 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEelLDRLYR------KGVVTE---AEVKVYIqqlVEGLHYL-HSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNI 6614
Cdd:cd06616    88 DIS--LDKFYKyvyevlDSVIPEeilGKIAVAT---VKALNYLkEELKIIHRDVKPSNILL--DRNGNIKLCDFGISGQL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6615 TPAELQFSQYGSPEFVSPEIIQQNPVSEA----SDIWAMGVISYLSLTCSSPFAG-ESDRATLLNVLEG---RVSWSSPM 6686
Cdd:cd06616   161 VDSIAKTRDAGCRPYMAPERIDPSASRDGydvrSDVWSLGITLYEVATGKFPYPKwNSVFDQLTQVVKGdppILSNSEER 240

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 215274225 6687 aaHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLK 6723
Cdd:cd06616   241 --EFSPSFVNFVNLCLIKDESKRPKYKELLKHPFIKM 275
I-set pfam07679
Immunoglobulin I-set domain;
1900-1983 5.64e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 65.36  E-value: 5.64e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1900 KFMSGLSTVVAEEGGEATFQCVVS----PSdvaVVWFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEG- 1974
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtpdPE---VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNs 78

                           90
                   ....*....|..
gi 215274225  1975 ---ASSSAALRV 1983
Cdd:pfam07679   79 ageAEASAELTV 90
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
 7677-7868 5.68e-12

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 70.47  E-value: 5.68e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA--VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd06640    11 RIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDEIedIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGSAL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLaERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpsdKFKDYLET- 7833
Cdd:cd06640    91 DLL-RAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQI----KRNTFVGTp 165

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7834 --MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06640   166 fwMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNS 202
PK_TRB1 cd14023
Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein ...
 6561-6721 6.02e-12

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270925 [Multi-domain]  Cd Length: 242  Bit Score: 69.69  E-value: 6.02e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6561 EAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFS-QYGSPEFVSPEIIQQNP 6639
Cdd:cd14023    83 EEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSDEERTQLRLESLEDTHIMKGEDDALSdKHGCPAYVSPEILNTTG 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6640 V--SEASDIWAMGVISYLSLTCSSPFAgESDRATLLNVLEgRVSWSSPmaAHLSEDAKDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd14023   163 TysGKSADVWSLGVMLYTLLVGRYPFH-DSDPSALFSKIR-RGQFCIP--DHVSPKARCLIRSLLRREPSERLTAPEILL 238


                  ....
gi 215274225 6718 HPWF 6721
Cdd:cd14023   239 HPWF 242
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
 7677-7868 6.04e-12

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 70.47  E-value: 6.04e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA--VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd06642    11 RIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDEIedIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGSAL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLaERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpsdKFKDYLET- 7833
Cdd:cd06642    91 DLL-KPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQI----KRNTFVGTp 165

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7834 --MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06642   166 fwMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNS 202
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 6024-6095 6.33e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 64.83  E-value: 6.33e-12
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225   6024 TAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFAASAAGN 6095
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76
I-set pfam07679
Immunoglobulin I-set domain;
3715-3797 6.53e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 64.97  E-value: 6.53e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3715 KFIEGLRNEEATEGDTATLWCELSkAAP---VEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVC----G 3787
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3788 QERTSATLTV 3797
Cdd:pfam07679   81 EAEASAELTV 90
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
 7711-7854 6.77e-12

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 70.29  E-value: 6.77e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7711 TAvLREYEALKGLRHPHLAQLHAAYLSPRH------LVLILELC----SGpellpcLAERASY--SESEVKDYLWQMLSA 7778
Cdd:cd07840    44 TA-IREIKLLQKLDHPNVVRLKEIVTSKGSakykgsIYMVFEYMdhdlTG------LLDNPEVkfTESQIKCYMKQLLEG 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7779 TQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlpSDKFKDYLETM------APELLEGQ---GavPQTD 7849
Cdd:cd07840   117 LQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYT------KENNADYTNRVitlwyrPPELLLGAtryG--PEVD 188


                  ....*
gi 215274225 7850 IWAIG 7854
Cdd:cd07840   189 MWSVG 193
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 6013-6104 7.11e-12

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 64.91  E-value: 7.11e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6013 PPDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPhHILIEDPDGSCALILDSLTGVDSGQYMCFAASA 6092
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSP-DIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNS 79

                          90
                  ....*....|..
gi 215274225 6093 AGNCSTLGKILV 6104
Cdd:cd20972    80 VGSDTTSAEIFV 91
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
 7678-7854 7.16e-12

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 70.01  E-value: 7.16e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK----TAvLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE------- 7746
Cdd:cd07835     7 IGEGTYGVVYKARDKLTGEIVALKKIRLETEDEgvpsTA-IREISLLKELNHPNIVRLLDVVHSENKLYLVFEfldldlk 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 --LCSGPELlpclaeraSYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvLPS 7824
Cdd:cd07835    86 kyMDSSPLT--------GLDPPLIKSYLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAFG----VPV 153

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 215274225 7825 DKFKDYLETM---APELLEG--QGAVPqTDIWAIG 7854
Cdd:cd07835   154 RTYTHEVVTLwyrAPEILLGskHYSTP-VDIWSVG 187
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
 7678-7867 7.28e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 70.06  E-value: 7.28e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQR---GRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd06646    14 IQRvgsGTYGDVYKARNLHTGELAAVKIIKLEPGDDFSLIQqEIFMVKECKHCNIVAYFGSYLSREKLWICMEYCGGGSL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpsdKFKDYLET 7833
Cdd:cd06646    94 QDIYHVTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATIA----KRKSFIGT 169

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 215274225 7834 ---MAPEL--LEGQGAVPQ-TDIWAIGVTAFIMLSAEYPV 7867
Cdd:cd06646   170 pywMAPEVaaVEKNGGYNQlCDIWAVGITAIELAELQPPM 209
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 4898-4988 7.40e-12

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 64.82  E-value: 7.40e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKF 4977
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 215274225 4978 GQVTHSACVVV 4988
Cdd:cd05744    81 GENSFNAELVV 91
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
 7675-7866 7.54e-12

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 69.85  E-value: 7.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7675 QTQIQRGRFSVVRQCWEKASGRALAAKIIPYhpkdKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd13991    11 QLRIGRGSFGEVHRMEDKQTGFQCAVKKVRL----EVFRAEELMACAGLTSPRVVPLYGAVREGPWVNIFMDLKEGGSLG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE---YNLLkvVDLGNAQSLSQE----KVLPSDKF 7827
Cdd:cd13991    87 QLIKEQGCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSdgsDAFL--CDFGHAECLDPDglgkSLFTGDYI 164

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7828 KDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd13991   165 PGTETHMAPEVVLGKPCDAKVDVWSSCCMMLHMLNGCHP 203
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
 6449-6721 7.57e-12

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 71.99  E-value: 7.57e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6449 GDNEPDSEKQSHRRKLHSfYEVKEEIGRGVFGFVKRVqhkgnkiLC--AAKFIPLRSRTRAQAYRERD--ILAALSHPLV 6524
Cdd:PTZ00036   50 EDEEKMIDNDINRSPNKS-YKLGNIIGNGSFGVVYEA-------ICidTSEKVAIKKVLQDPQYKNREllIMKNLNHINI 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6525 TGLLDQFETR------KTLILILELcsseELLDRLYRKGVVTEAE---------VKVYIQQLVEGLHYLHSHGVLHLDIK 6589
Cdd:PTZ00036  122 IFLKDYYYTEcfkkneKNIFLNVVM----EFIPQTVHKYMKHYARnnhalplflVKLYSYQLCRALAYIHSKFICHRDLK 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6590 PSNiLMVHPAREDIKICDFGFAQNITPAELQFSQYGSPEFVSPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESD 6668
Cdd:PTZ00036  198 PQN-LLIDPNTHTLKLCDFGSAKNLLAGQRSVSYICSRFYRAPELmLGATNYTTHIDLWSLGCIIAEMILGYPIFSGQSS 276

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6669 RATLLNVL-------EGRVSWSSPMAAHLS------------------EDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:PTZ00036  277 VDQLVRIIqvlgtptEDQLKEMNPNYADIKfpdvkpkdlkkvfpkgtpDDAINFISQFLKYEPLKRLNPIEALADPFF 354
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2479-2553 7.84e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 64.83  E-value: 7.84e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2479 TGRELQSVVLSCDFRPAPKA-VQWYKDD-TPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA----GSAHSSTEVT 2552
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLT 84


                    .
gi 215274225   2553 V 2553
Cdd:smart00410   85 V 85
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 6020-6104 7.98e-12

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 64.90  E-value: 7.98e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6020 LADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFAASAAGNCSTL 6099
Cdd:cd20973     4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCS 83


                  ....*
gi 215274225 6100 GKILV 6104
Cdd:cd20973    84 AELTV 88
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 7678-7873 8.25e-12

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 69.90  E-value: 8.25e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKII--PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLS--PR---------HLVLI 7744
Cdd:cd14048    14 LGRGGFGVVFEAKNKVDDCNYAVKRIrlPNNELAREKVLREVRALAKLDHPGIVRYFNAWLErpPEgwqekmdevYLYIQ 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERASYSESE---VKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEK- 7820
Cdd:cd14048    94 MQLCRKENLKDWMNRRCTMESRElfvCLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVTAMDQGEp 173

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7821 ---VL-PSDKFKDYLET------MAPELLEGQGAVPQTDIWAIGVTAFIMLsaeYPVSSEGAR 7873
Cdd:cd14048   174 eqtVLtPMPAYAKHTGQvgtrlyMSPEQIHGNQYSEKVDIFALGLILFELI---YSFSTQMER 233
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3897-3974 8.31e-12

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 64.45  E-value: 8.31e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3897 QSLQAEEGSTATLQCELS-EPTATVVWSKGGLQ-LQANGRREPRLQGCTAELVLQDLQREDTGEYTCTC----GSQATSA 3970
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3971 TLTV 3974
Cdd:smart00410   82 TLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
2918-3000 8.33e-12

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 64.59  E-value: 8.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2918 FTEELTNLQVEEKGTAVFTCK-TEHPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC----DIGQA 2992
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTvTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEA 82


                   ....*...
gi 215274225  2993 QSRAQLLV 3000
Cdd:pfam07679   83 EASAELTV 90
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
 7681-7864 8.46e-12

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 69.99  E-value: 8.46e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDK---TAVlREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgPELLPCL 7757
Cdd:cd07870    11 GSYATVYKGISRINGQLVALKVISMKTEEGvpfTAI-REASLLKGLKHANIVLLHDIIHTKETLTFVFEYMH-TDLAQYM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AER-ASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLETM-- 7834
Cdd:cd07870    89 IQHpGGLHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFG----LARAKSIPSQTYSSEVVTLwy 164

                         170       180       190
                  ....*....|....*....|....*....|..
gi 215274225 7835 -APELLEGQGAVP-QTDIWAIGVTAFIMLSAE 7864
Cdd:cd07870   165 rPPDVLLGATDYSsALDIWGAGCIFIEMLQGQ 196
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 109-201 8.98e-12

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 64.53  E-value: 8.98e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  109 APHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgePDGPRVRVEELGEASALRIRAARPRDGGTYEVRAEN 188
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL--QNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATN 78

                          90
                  ....*....|...
gi 215274225  189 PLGAASAAAALVV 201
Cdd:cd20972    79 SVGSDTTSAEIFV 91
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
 7669-7868 9.43e-12

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 70.02  E-value: 9.43e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKII-PYHPKDKTaVLREYEALKGL-RHPHLAQLHAAYLSPRHLV---- 7742
Cdd:cd06639    21 SDTWDIIETIGKGTYGKVYKVTNKKDGSLAAVKILdPISDVDEE-IEAEYNILRSLpNHPNVVKFYGMFYKADQYVggql 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 -LILELCSG---PELLPCLAERASYSESEVKDY-LWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLS 7817
Cdd:cd06639   100 wLVLELCNGgsvTELVKGLLKCGQRLDEAMISYiLYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLT 179

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7818 QEKVLPSDKFKDYLeTMAPELLEGQGAV-----PQTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd06639   180 SARLRRNTSVGTPF-WMAPEVIACEQQYdysydARCDVWSLGITAIELADGDPPLF 234
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
 6470-6716 9.81e-12

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270938 [Multi-domain]  Cd Length: 282  Bit Score: 69.85  E-value: 9.81e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6470 VKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRAQA-YRERDILAALS-HPLVTGLLDQFETRKT--------LIL 6539
Cdd:cd14036     4 IKRVIAEGGFAFVYEAQDVGTGKEYALKRLLSNEEEKNKAiIQEINFMKKLSgHPNIVQFCSAASIGKEesdqgqaeYLL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEeLLDRLYR---KGVVTEAEVKVYIQQLVEGLHYLHSHG--VLHLDIKPSNILMVHPARedIKICDFG----- 6609
Cdd:cd14036    84 LTELCKGQ-LVDFVKKveaPGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQ--IKLCDFGsatte 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6610 --------FAQNITPAELQFSQYGSPEFVSPEII---QQNPVSEASDIWAMGVISYLSLTCSSPFAgESDRATLLNvleg 6678
Cdd:cd14036   161 ahypdyswSAQKRSLVEDEITRNTTPMYRTPEMIdlySNYPIGEKQDIWALGCILYLLCFRKHPFE-DGAKLRIIN---- 235

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 215274225 6679 rVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCL 6716
Cdd:cd14036   236 -AKYTIPPNDTQYTVFHDLIRSTLKVNPEERLSITEIV 272
PKc_DYRK2_3 cd14224
Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and ...
 6446-6720 1.13e-11

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271126 [Multi-domain]  Cd Length: 380  Bit Score: 70.93  E-value: 1.13e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6446 VLGGDNEP--DSEKQSHRRKLHSF----YEVKEEIGRGVFG-FVKRVQHKGNKILcAAKFIPLRSRTRAQAYRERDILAA 6518
Cdd:cd14224    39 VIGGPNNGgyDDEQGSYIHVPHDHiayrYEVLKVIGKGSFGqVVKAYDHKTHQHV-ALKMVRNEKRFHRQAAEEIRILEH 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6519 LSHPLVTG------LLDQFETRKTLILILELCSSE--ELLDRLYRKGVVTEAeVKVYIQQLVEGLHYLHSHGVLHLDIKP 6590
Cdd:cd14224   118 LKKQDKDNtmnvihMLESFTFRNHICMTFELLSMNlyELIKKNKFQGFSLQL-VRKFAHSILQCLDALHRNKIIHCDLKP 196

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6591 SNILMVHPAREDIKICDFGFA----QNItpaelqFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGE 6666
Cdd:cd14224   197 ENILLKQQGRSGIKVIDFGSScyehQRI------YTYIQSRFYRAPEVILGARYGMPIDMWSFGCILAELLTGYPLFPGE 270

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6667 -----------------------SDRA-------------TLLNVLEGRVSWSS-----------PMAAHLSEDAK---- 6695
Cdd:cd14224   271 degdqlacmiellgmppqklletSKRAknfisskgyprycTVTTLPDGSVVLNGgrsrrgkmrgpPGSKDWVTALKgcdd 350

                         330       340
                  ....*....|....*....|....*....
gi 215274225 6696 ----DFIKATLQRAPQARPSAAQCLSHPW 6720
Cdd:cd14224   351 plflDFLKRCLEWDPAARMTPSQALRHPW 379
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
 5604-5664 1.15e-11

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 63.04  E-value: 1.15e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 5604 IYVVTADYLPLGaeQDAITLREGQYVEVLDAAHPLRWLVRTKPtksspsRQGWVSPAYLDR 5664
Cdd:cd11856     1 SYVAIADYEAQG--DDEISLQEGEVVEVLEKNDSGWWYVRKGD------KEGWVPASYLEP 53
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 6363-6446 1.21e-11

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 64.36  E-value: 1.21e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6363 IEDVQAQT---GGTAQFEAIIEGDPQPSVTWYKDSVQL---VDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd20951     4 IIRLQSHTvweKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHG 83

                          90
                  ....*....|
gi 215274225 6437 QVLCKAELLV 6446
Cdd:cd20951    84 EASSSASVVV 93
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
 6474-6729 1.21e-11

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 70.32  E-value: 1.21e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTL------ILILELC 6544
Cdd:cd07879    23 VGSGAYGSVCSAIDKRTGEKVAIKKLsrPFQSEIFAKrAYRELTLLKHMQHENVIGLLDVFTSAVSGdefqdfYLVMPYM 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6545 SSEelLDRLyRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFAQNitpAELQFS 6622
Cdd:cd07879   103 QTD--LQKI-MGHPLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAV----NEDceLKILDFGLARH---ADAEMT 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPE-FVSPEII-QQNPVSEASDIWAMGVISYLSLTCSSPFAGES--DRAT-LLNV-----------LEGRVSWS--- 6683
Cdd:cd07879   173 GYVVTRwYRAPEVIlNWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKDylDQLTqILKVtgvpgpefvqkLEDKAAKSyik 252

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6684 ----------SPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPWFLKSMPAEE 6729
Cdd:cd07879   253 slpkyprkdfSTLFPKASPQAVDLLEKMLELDVDKRLTATEALEHPYFDSFRDADE 308
STKc_GRK3 cd05633
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs ...
 7672-7874 1.24e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270781 [Multi-domain]  Cd Length: 346  Bit Score: 70.48  E-value: 1.24e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRH---PHLAQLHAAYLSPRHLVLI 7744
Cdd:cd05633     7 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKrikmKQGETLALNERIMLSLVSTgdcPFIVCMTYAFHTPDKLCFI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd05633    87 LDLMNGGDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHAS 166

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7825 DKFKDYletMAPELLE-GQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd05633   167 VGTHGY---MAPEVLQkGTAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKD 214
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
 7672-7854 1.30e-11

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 69.65  E-value: 1.30e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAK-IIPYHPKDK---TAvLREYEALKGLRHPHLAQL-HAAYLSP---RHLVL 7743
Cdd:cd07866    10 YEILGKLGEGTFGEVYKARQIKTGRVVALKkILMHNEKDGfpiTA-LREIKILKKLKHPNVVPLiDMAVERPdksKRKRG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCSgPELLPCLA-----ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQ 7818
Cdd:cd07866    89 SVYMVT-PYMDHDLSgllenPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYDG 167

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7819 EKVLPSDKF----KDYLETM------APELLEGQ----GAVpqtDIWAIG 7854
Cdd:cd07866   168 PPPNPKGGGgggtRKYTNLVvtrwyrPPELLLGErrytTAV---DIWGIG 214
STKc_CDC2L6 cd07867
Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the ...
 6473-6662 1.32e-11

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270850 [Multi-domain]  Cd Length: 318  Bit Score: 70.10  E-value: 1.32e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNKilcAAKFIPLR----SRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd07867     9 KVGRGTYGHVYKAKRKDGK---DEKEYALKqiegTGISMSACREIALLRELKHPNVIALQKVFLSHSDRKVWLLFDYAEH 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLYRKGVVTEAE----------VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV--HPAREDIKICDFGFAQ---- 6612
Cdd:cd07867    86 DLWHIIKFHRASKANkkpmqlprsmVKSLLYQILDGIHYLHANWVLHRDLKPANILVMgeGPERGRVKIADMGFARlfns 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6613 ------NITPAELQFsQYGSPEFvspeIIQQNPVSEASDIWAMGVIsYLSLTCSSP 6662
Cdd:cd07867   166 plkplaDLDPVVVTF-WYRAPEL----LLGARHYTKAIDIWAIGCI-FAELLTSEP 215
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
 7680-7866 1.40e-11

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 68.89  E-value: 1.40e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPyhpKDKT---AVLREYEALKGLR-HPHLAQLHA-AYLSPRHLVLILELCSGPELL 7754
Cdd:cd13987     3 EGTYGKVLLAVHKGSGTKMALKFVP---KPSTklkDFLREYNISLELSvHPHIIKTYDvAFETEDYYVFAQEYAPYGDLF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII--TEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLE 7832
Cdd:cd13987    80 SIIPPQVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLfdKDCRRVKLCDFG----LTRRVGSTVKRVSGTIP 155

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7833 TMAPELL-----EGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd13987   156 YTAPEVCeakknEGFVVDPSIDVWAFGVLLFCCLTGNFP 194
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 5134-5214 1.40e-11

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 63.75  E-value: 1.40e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5134 NQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMInedqQGGHQLIITAVVPADMGVYRCLAENSMGVSSTKAE 5213
Cdd:cd05723     6 NIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKI----VKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQ 81


                  .
gi 215274225 5214 L 5214
Cdd:cd05723    82 L 82
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 245-328 1.40e-11

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 64.13  E-value: 1.40e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  245 RTCTVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSV 324
Cdd:cd20973     5 RDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSA 84


                  ....
gi 215274225  325 LVVV 328
Cdd:cd20973    85 ELTV 88
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
 6463-6721 1.47e-11

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 69.64  E-value: 1.47e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6463 KLHSFYEVkEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRSRTRA--QAYRERDILAALSHPLVTGLLDQFETRKTLILI 6540
Cdd:cd07872     4 KMETYIKL-EKLGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6541 LELCSSE--ELLDRLyrKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQ-NITPA 6617
Cdd:cd07872    83 FEYLDKDlkQYMDDC--GNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLI--NERGELKLADFGLARaKSVPT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 ELQFSQYGSPEFVSPEI-IQQNPVSEASDIWAMGVISYLSLTCSSPFAGES--DRATLLNVLEGRVS---W--------- 6682
Cdd:cd07872   159 KTYSNEVVTLWYRPPDVlLGSSEYSTQIDMWGVGCIFFEMASGRPLFPGSTveDELHLIFRLLGTPTeetWpgissndef 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6683 ---------SSPMAAH---LSEDAKDFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd07872   239 knynfpkykPQPLINHaprLDTEGIELLTKFLQYESKKRISAEEAMKHAYF 289
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4905-4988 1.52e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 63.68  E-value: 1.52e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4905 GDTEAQVGDALRLECVVASKADVRARWLKDGVE-LTDGRHHHIDQLGdGTCSLLITGLDRADAGCYTCQVSNKFGQVTHS 4983
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSG-STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   4984 ACVVV 4988
Cdd:smart00410   81 TTLTV 85
STKc_GRK2 cd14223
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs ...
 7672-7874 1.56e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271125 [Multi-domain]  Cd Length: 321  Bit Score: 69.69  E-value: 1.56e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRH---PHLAQLHAAYLSPRHLVLI 7744
Cdd:cd14223     2 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKrikmKQGETLALNERIMLSLVSTgdcPFIVCMSYAFHTPDKLSFI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd14223    82 LDLMNGGDLHYHLSQHGVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFGHVRISDLGLACDFSKKKPHAS 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7825 DKFKDYletMAPELLE-GQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd14223   162 VGTHGY---MAPEVLQkGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKD 209
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
 6511-6711 1.56e-11

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 69.33  E-value: 1.56e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6511 RERDILAALSHPLVTGLLDQFET--RKTLILILELCSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLD 6587
Cdd:cd05038    55 REIEILRTLDHEYIVKYKGVCESpgRRSLRLIMEYLPSGSLRDYLQRhRDQIDLKRLLLFASQICKGMEYLGSQRYIHRD 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6588 IKPSNILMVHPARedIKICDFGFAQNIT----------PAElqfsqygSPEF-VSPEIIQQNPVSEASDIWAMGVISYLS 6656
Cdd:cd05038   135 LAARNILVESEDL--VKISDFGLAKVLPedkeyyyvkePGE-------SPIFwYAPECLRESRFSSASDVWSFGVTLYEL 205

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6657 LT-C---SSPFA----------GESDRATLLNVLEGrvSWSSPMAAHLSEDAKDFIKATLQRAPQARPS 6711
Cdd:cd05038   206 FTyGdpsQSPPAlflrmigiaqGQMIVTRLLELLKS--GERLPRPPSCPDEVYDLMKECWEYEPQDRPS 272
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
 7671-7854 1.57e-11

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 69.62  E-value: 1.57e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRFSVVRQCWEKAS--GRALAAKIIPYHPKDKTAV----LREYEALKGLRHPHLAQLHAAYLSP--RHLV 7742
Cdd:cd07842     1 KYEIEGCIGRGTYGRVYKAKRKNGkdGKEYAIKKFKGDKEQYTGIsqsaCREIALLRELKHENVVSLVEVFLEHadKSVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELCSGpELLPCL-----AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT----EYNLLKVVDLGNA 7813
Cdd:cd07842    81 LLFDYAEH-DLWQIIkfhrqAKRVSIPPSMVKSLLWQILNGIHYLHSNWVLHRDLKPANILVMgegpERGVVKIGDLGLA 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7814 --------QSLSQEKVLPSDKFKdyletmAPELLEG-QGAVPQTDIWAIG 7854
Cdd:cd07842   160 rlfnaplkPLADLDPVVVTIWYR------APELLLGaRHYTKAIDIWAIG 203
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
 6500-6652 1.58e-11

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 69.75  E-value: 1.58e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6500 PLRSRTRAQ-AYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAE---VKVYIQQLVEGL 6575
Cdd:cd07850    36 PFQNVTHAKrAYRELVLMKLVNHKNIIGLLNVFTPQKSLEEFQDVYLVMELMDANLCQVIQMDLDherMSYLLYQMLCGI 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6576 HYLHSHGVLHLDIKPSNIlmVHPAREDIKICDFGFAQNitpAELQFSQygSPEFVS-----PEIIQQNPVSEASDIWAMG 6650
Cdd:cd07850   116 KHLHSAGIIHRDLKPSNI--VVKSDCTLKILDFGLART---AGTSFMM--TPYVVTryyraPEVILGMGYKENVDIWSVG 188


                  ..
gi 215274225 6651 VI 6652
Cdd:cd07850   189 CI 190
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
 7677-7870 1.60e-11

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 69.46  E-value: 1.60e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK---TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE------- 7746
Cdd:PLN00009    9 KIGEGTYGVVYKARDRVTNETIALKKIRLEQEDEgvpSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFEyldldlk 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 --LCSGPELlpclaeraSYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE-YNLLKVVDLGNAQSLSqekvLP 7823
Cdd:PLN00009   89 khMDSSPDF--------AKNPRLIKTYLYQILRGIAYCHSHRVLHRDLKPQNLLIDRrTNALKLADFGLARAFG----IP 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7824 SDKFKDYLETM---APELLEG--QGAVPqTDIWAIGVTAFIMLSAE--YPVSSE 7870
Cdd:PLN00009  157 VRTFTHEVVTLwyrAPEILLGsrHYSTP-VDIWSVGCIFAEMVNQKplFPGDSE 209
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 5371-5466 1.63e-11

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 63.98  E-value: 1.63e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAERGVLWIGPDtpgYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGK---YKIESEYGVHVLHIRRVTVEDSAVYSAV 77

                          90
                  ....*....|....*.
gi 215274225 5451 ASNAAGQALCSASLHV 5466
Cdd:cd20951    78 AKNIHGEASSSASVVV 93
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 6374-6436 1.66e-11

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 63.12  E-value: 1.66e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 6374 AQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 7470-7548 1.66e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 63.68  E-value: 1.66e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7470 SDETVVLGQSVTLACQVSAQPAAQATWSKDGA-PLESSSRVLISATLKNFQlLTILVVVAEDLGVYTCSVSNALGTVTTT 7548
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSRSGSTST-LTISNVTPEDSGTYTCAATNSSGSASSG 80
I-set pfam07679
Immunoglobulin I-set domain;
1634-1711 1.68e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 63.82  E-value: 1.68e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1634 REVQAEAGASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSC----EAGGQQLSFR 1708
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAE 87


                   ...
gi 215274225  1709 LQV 1711
Cdd:pfam07679   88 LTV 90
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 5370-5466 1.83e-11

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 63.76  E-value: 1.83e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5370 PPRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAERgvlwigPDTPGYTVASSAQQHSLVLLDVGRQHQGTYTC 5449
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL------QNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSC 74

                          90
                  ....*....|....*..
gi 215274225 5450 IASNAAGQALCSASLHV 5466
Cdd:cd20972    75 LATNSVGSDTTSAEIFV 91
PTKc_Wee1 cd14051
Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the ...
 7677-7922 1.83e-11

Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Wee1 is a nuclear cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. There are two distinct Wee1 proteins in vertebrates showing different expression patterns, called Wee1a and Wee1b. They are functionally dstinct and are implicated in different steps of egg maturation and embryo development. The Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270953 [Multi-domain]  Cd Length: 275  Bit Score: 68.97  E-value: 1.83e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKiipyhpKDKTAV---------LREYEALKGL-RHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd14051     7 KIGSGEFGSVYKCINRLDGCVYAIK------KSKKPVagsvdeqnaLNEVYAHAVLgKHPHVVRYYSAWAEDDHMIIQNE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERAS----YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT---------------EYNLL-- 7805
Cdd:cd14051    81 YCNGGSLADAISENEKagerFSEAELKDLLLQVAQGLKYIHSQNLVHMDIKPGNIFISrtpnpvsseeeeedfEGEEDnp 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7806 -------KVVDLGNAQSLSQEKVLPSD-KFkdyletMAPELL-EGQGAVPQTDIWAIGVTAFIMLSAEyPVSSEGArDLQ 7876
Cdd:cd14051   161 esnevtyKIGDLGHVTSISNPQVEEGDcRF------LANEILqENYSHLPKADIFALALTVYEAAGGG-PLPKNGD-EWH 232

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7877 RgLRKG-LVRLSRCyaglSGGAVAFLRSTLCAQPWGRPCASSCLQCP 7922
Cdd:cd14051   233 E-IRQGnLPPLPQC----SPEFNELLRSMIHPDPEKRPSAAALLQHP 274
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 110-201 1.84e-11

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 63.91  E-value: 1.84e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGPRVRVEELGEASALRIRAARPRDGGTYEVRAENP 189
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 215274225  190 LGAASAAAALVV 201
Cdd:cd20974    81 SGQATSTAELLV 92
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
 7670-7867 1.89e-11

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 69.31  E-value: 1.89e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd06635    25 KLFSDLREIGHGSFGAVYFARDVRTSEVVAIKKMSYSGKQSNEkwqdIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVM 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvlPSD 7825
Cdd:cd06635   105 EYCLGSASDLLEVHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIAS-----PAN 179

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7826 KFKDYLETMAPELL----EGQ--GAVpqtDIWAIGVTAFIMLSAEYPV 7867
Cdd:cd06635   180 SFVGTPYWMAPEVIlamdEGQydGKV---DVWSLGITCIELAERKPPL 224
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 7463-7551 1.90e-11

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 63.57  E-value: 1.90e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVV-LGQSVTLACQVSAQPAAQATWSKDGAPLESSSRvliSATLKNFQlLTILVVVAEDLGVYTCSVSNA 7541
Cdd:cd20978     1 PKFIQKPEKNVVVkGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPME---RATVEDGT-LTIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|
gi 215274225 7542 LGTVTTTGVL 7551
Cdd:cd20978    77 IGDIYTETLL 86
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 6014-6097 1.96e-11

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 63.58  E-value: 1.96e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFAASAA 6093
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                  ....
gi 215274225 6094 GNCS 6097
Cdd:cd20990    81 GQNS 84
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
 7653-7874 1.98e-11

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 70.06  E-value: 1.98e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7653 ASEEESQGRSAQPLpSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEAL-KGLRHPH 7727
Cdd:cd05618     4 AMNSRESGKASSSL-GLQDFDLLRVIGRGSYAKVLLVRLKKTERIYAMKVVKKElvndDEDIDWVQTEKHVFeQASNHPF 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7728 LAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKV 7807
Cdd:cd05618    83 LVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKL 162

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7808 VDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd05618   163 TDYG----MCKEGLRPGDTTSTFCGTpnyIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIVGSSD 228
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
 7667-7870 2.00e-11

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 68.98  E-value: 2.00e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQtQIQRGRFSVVRQCWEKASGRALAAKI--IPYHPKdKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLI 7744
Cdd:cd06654    18 PKKKYTRFE-KIGQGASGTVYTAMDVATGQEVAIRQmnLQQQPK-KELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlps 7824
Cdd:cd06654    96 MEYLAGGSLTDVVTE-TCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQ---- 170

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 7825 DKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd06654   171 SKRSTMVGTpywMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNE 219
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
 7708-7876 2.02e-11

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 68.50  E-value: 2.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHI 7787
Cdd:cd14202    43 KSQTLLGKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGGDLADYLHTMRTLSEDTIRLFLQQIAGAMKMLHSKGI 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7788 LHLDLRSENMIITEYN---------LLKVVDLGNAQSLsQEKVLPSDKFKDYLeTMAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd14202   123 IHRDLKPQNILLSYSGgrksnpnniRIKIADFGFARYL-QNNMMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTIIY 200

                         170
                  ....*....|....*...
gi 215274225 7859 IMLSAEYPVSSEGARDLQ 7876
Cdd:cd14202   201 QCLTGKAPFQASSPQDLR 218
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3890-3962 2.03e-11

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 63.35  E-value: 2.03e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  3890 PVFREPLQSLQAEEGSTATLQCE-LSEPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCT 3962
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
 7678-7854 2.13e-11

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 68.79  E-value: 2.13e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK----TAvLREYEALKGLRHPHLAQLHAAYLSPR--HLVLILE----- 7746
Cdd:cd07843    13 IEEGTYGVVYRARDKKTGEIVALKKLKMEKEKEgfpiTS-LREINILLKLQHPNIVTVKEVVVGSNldKIYMVMEyvehd 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPclaerASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK 7826
Cdd:cd07843    92 LKSLMETMK-----QPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFG----LAREYGSPLKP 162

                         170       180       190
                  ....*....|....*....|....*....|..
gi 215274225 7827 FKDYLETM---APELLEGQGAV-PQTDIWAIG 7854
Cdd:cd07843   163 YTQLVVTLwyrAPELLLGAKEYsTAIDMWSVG 194
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
 6474-6673 2.18e-11

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 68.19  E-value: 2.18e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN---KILCAAKFIPlrsrTRAQAYR-ERDILAALSHPLVTgLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14062     1 IGSGSFGTVYKGRWHGDvavKKLNVTDPTP----SQLQAFKnEVAVLRKTRHVNIL-LFMGYMTKPQLAIVTQWCEGSSL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 ldrlYRKGVVteAEVKVYIQQLVE-------GLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFAQNIT--PAE 6618
Cdd:cd14062    76 ----YKHLHV--LETKFEMLQLIDiarqtaqGMDYLHAKNIIHRDLKSNNIFL----HEDltVKIGDFGLATVKTrwSGS 145

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6619 LQFSQ-YGSPEFVSPEIIQ---QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLL 6673
Cdd:cd14062   146 QQFEQpTGSILWMAPEVIRmqdENPYSFQSDVYAFGIVLYELLTGQLPYSHINNRDQIL 204
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 9-91 2.40e-11

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 63.37  E-value: 2.40e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    9 APRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAI 88
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80


                  ...
gi 215274225   89 GEA 91
Cdd:cd20972    81 GSD 83
I-set pfam07679
Immunoglobulin I-set domain;
3539-3621 2.60e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 63.43  E-value: 2.60e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3539 RFIEDVKNQEAREGATAVLQCELnSAAP---VEWRKGSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCVC----G 3611
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTV-TGTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3612 QERTSAMLTV 3621
Cdd:pfam07679   81 EAEASAELTV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2838-2911 2.62e-11

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 63.03  E-value: 2.62e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 2838 VAPGEDVELRCELSRAGTPVHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEASKSTASLHV 2911
Cdd:cd20967     9 VSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
 7681-7854 2.71e-11

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 68.28  E-value: 2.71e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKT--AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSG--PELLPC 7756
Cdd:cd07836    11 GTYATVYKGRNRTTGEIVALKEIHLDAEEGTpsTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKdlKKYMDT 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvLPSDKFKDYLETM-- 7834
Cdd:cd07836    91 HGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAFG----IPVNTFSNEVVTLwy 166

                         170       180
                  ....*....|....*....|..
gi 215274225 7835 -APELLEGQGAVPQT-DIWAIG 7854
Cdd:cd07836   167 rAPDVLLGSRTYSTSiDIWSVG 188
I-set pfam07679
Immunoglobulin I-set domain;
1358-1424 2.87e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 63.05  E-value: 2.87e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1358 RKVQAEAGAIATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
 7711-7875 2.91e-11

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 68.95  E-value: 2.91e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7711 TAVLREYEALkGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHL 7790
Cdd:cd05592    42 TMIERRVLAL-ASQHPFLTHLFCTFQTESHLFFVMEYLNGGDLMFHIQQSGRFDEDRARFYGAEIICGLQFLHSRGIIYR 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7791 DLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPV 7867
Cdd:cd05592   121 DLKLDNVLLDREGHIKIADFG----MCKENIYGENKASTFCGTpdyIAPEILKGQKYNQSVDWWSFGVLLYEMLIGQSPF 196


                  ....*...
gi 215274225 7868 SSEGARDL 7875
Cdd:cd05592   197 HGEDEDEL 204
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 5370-5453 3.12e-11

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 62.58  E-value: 3.12e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5370 PPRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAERgvlwigPDTPGYTVASSAQQHSLVLLDVGRQHQGTYTC 5449
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI------SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74


                   ....
gi 215274225  5450 IASN 5453
Cdd:pfam13927   75 VASN 78
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 110-201 3.19e-11

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 63.21  E-value: 3.19e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRL-GEPDGPRVRVEELGEASALRIRAARPRDGGTYEVRAEN 188
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 215274225  189 PLGAASAAAALVV 201
Cdd:cd20951    81 IHGEASSSASVVV 93
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 7462-7546 3.23e-11

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 63.35  E-value: 3.23e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7462 APTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLIS------ATLKNFqlLTILVVVAEDLGVYT 7535
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGdyvtsdGDVVSY--VNISSVRVEDGGEYT 78

                          90
                  ....*....|.
gi 215274225 7536 CSVSNALGTVT 7546
Cdd:cd20956    79 CTATNDVGSVS 89
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
 7667-7870 3.24e-11

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 68.59  E-value: 3.24e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQtQIQRGRFSVVRQCWEKASGRALAAKI--IPYHPKdKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLI 7744
Cdd:cd06656    17 PKKKYTRFE-KIGQGASGTVYTAIDIATGQEVAIKQmnLQQQPK-KELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlps 7824
Cdd:cd06656    95 MEYLAGGSLTDVVTE-TCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQ---- 169

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 7825 DKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd06656   170 SKRSTMVGTpywMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNE 218
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 5125-5216 3.74e-11

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 62.96  E-value: 3.74e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5125 APVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMI----NEDQQGGHQLIITAVVPADMGVYRCL 5200
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGDVVSYVNISSVRVEDGGEYTCT 80

                          90
                  ....*....|....*.
gi 215274225 5201 AENSMGVSSTKAELRV 5216
Cdd:cd20956    81 ATNDVGSVSHSARINV 96
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
 7714-7869 3.95e-11

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 68.11  E-value: 3.95e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7714 LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgPELLPCLAERA-SYSESEVKDYLWQMLSATQYLHNQHILHLDL 7792
Cdd:cd07873    48 IREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLD-KDLKQYLDDCGnSINMHNVKLFLFQLLRGLAYCHRRKVLHRDL 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7793 RSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLETM---APELLEGQGAVP-QTDIWAIGVTAFIMLSAE--YP 7866
Cdd:cd07873   127 KPQNLLINERGELKLADFG----LARAKSIPTKTYSNEVVTLwyrPPDILLGSTDYStQIDMWGVGCIFYEMSTGRplFP 202


                  ...
gi 215274225 7867 VSS 7869
Cdd:cd07873   203 GST 205
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
 7725-7866 4.18e-11

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 68.89  E-value: 4.18e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7725 HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL 7804
Cdd:cd05617    75 NPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGH 154

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7805 LKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05617   155 IKLTDYG----MCKEGLGPGDTTSTFCGTpnyIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSP 215
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3192-3269 4.32e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 62.52  E-value: 4.32e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3192 KDLEVLEGGAATLRCVLSSVAAPVKWCY--GNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC----SFGDQTTSA 3265
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYkqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaatnSSGSASSGT 81


                    ....
gi 215274225   3266 TLTV 3269
Cdd:smart00410   82 TLTV 85
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 110-201 4.54e-11

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 62.51  E-value: 4.54e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGPRVRVEELGEASaLRIRAARPRDGGTYEVRAENP 189
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHS-LIIEPVTKRDAGIYTCIARNR 79

                          90
                  ....*....|..
gi 215274225  190 LGAASAAAALVV 201
Cdd:cd05744    80 AGENSFNAELVV 91
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
 7685-7866 4.62e-11

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 67.37  E-value: 4.62e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7685 VVRQCWEkasGRALAAKIIPYHP-KDKTA----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14146    10 VYRATWK---GQEVAVKAARQDPdEDIKAtaesVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTLNRALAA 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESE---------VKDYLWQMLSATQYLHNQH---ILHLDLRSENMIITEY--------NLLKVVDLGNAQSLSQE 7819
Cdd:cd14146    87 ANAAPGPRrarripphiLVNWAVQIARGMLYLHEEAvvpILHRDLKSSNILLLEKiehddicnKTLKITDFGLAREWHRT 166

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7820 KVLPSDKFKDYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14146   167 TKMSAAGTYAW---MAPEVIKSSLFSKGSDIWSYGVLLWELLTGEVP 210
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
 7670-7854 4.87e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 68.16  E-value: 4.87e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK----TAvLREYEALKGLRHP---HLAQLHAAYLSPRH-- 7740
Cdd:cd07865    12 SKYEKLAKIGQGTFGEVFKARHRKTGQIVALKKVLMENEKEgfpiTA-LREIKILQLLKHEnvvNLIEICRTKATPYNry 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7741 ---LVLILELCSGpELLPCLAERA-SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL 7816
Cdd:cd07865    91 kgsIYLVFEFCEH-DLAGLLSNKNvKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARAF 169

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7817 SQEKVLPSDKFKDYLETM---APELLEGQ---GavPQTDIWAIG 7854
Cdd:cd07865   170 SLAKNSQPNRYTNRVVTLwyrPPELLLGErdyG--PPIDMWGAG 211
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 5128-5216 5.22e-11

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 62.23  E-value: 5.22e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5128 FLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDdhymiNEDQQGGHQLIITAVVPADMGVYRCLAENSMGV 5207
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASE-----NRIEVEAGDLRITKLSLSDSGMYQCVAENKHGT 76


                  ....*....
gi 215274225 5208 SSTKAELRV 5216
Cdd:cd05728    77 IYASAELAV 85
I-set pfam07679
Immunoglobulin I-set domain;
1084-1159 5.26e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 62.27  E-value: 5.26e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1084 VQAEAGASAMLSCEVAQAQT-EVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSC----EAGGQRVSFHLH 1158
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAELT 89


                   .
gi 215274225  1159 I 1159
Cdd:pfam07679   90 V 90
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
 7678-7866 5.26e-11

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 67.09  E-value: 5.26e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKD---KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELl 7754
Cdd:cd13978     1 LGSGGFGTVSKARHVSWFGMVAIKCLHSSPNCieeRKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSL- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 pclaerASYSESEVKDYLW--------QMLSATQYLHNQH--ILHLDLRSENMIITEYNLLKVVDLGNAQ----SLSQEK 7820
Cdd:cd13978    80 ------KSLLEREIQDVPWslrfriihEIALGMNFLHNMDppLLHHDLKPENILLDNHFHVKISDFGLSKlgmkSISANR 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7821 VLPSDKFKDYLETMAPELLEGQGAVPQT--DIWAIGVTAFIMLSAEYP 7866
Cdd:cd13978   154 RRGTENLGGTPIYMAPEAFDDFNKKPTSksDVYSFAIVIWAVLTRKEP 201
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 10-91 5.62e-11

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 62.51  E-value: 5.62e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARF-RLAQDGDLYRLTILDLALGDSGQYVCRARNAI 88
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHkMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80


                  ...
gi 215274225   89 GEA 91
Cdd:cd05744    81 GEN 83
I-set pfam07679
Immunoglobulin I-set domain;
898-964 5.79e-11

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 62.27  E-value: 5.79e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   898 RKLQAEAGASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 7681-7862 5.82e-11

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 67.41  E-value: 5.82e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDK---TAVlREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgpellpcl 7757
Cdd:cd07844    11 GSYATVYKGRSKLTGQLVALKEIRLEHEEGapfTAI-REASLLKDLKHANIVTLHDIIHTKKTLTLVFEYLD-------- 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSE--------SEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKD 7829
Cdd:cd07844    82 TDLKQYMDdcggglsmHNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFG----LARAKSVPSKTYSN 157

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7830 YLETM---APELLEGQGAVP-QTDIWAIGVTAFIMLS 7862
Cdd:cd07844   158 EVVTLwyrPPDVLLGSTEYStSLDMWGVGCIFYEMAT 194
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
 7670-7869 6.06e-11

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 67.34  E-value: 6.06e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKT--AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd07871     5 ETYVKLDKLGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFEY 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGpELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK 7826
Cdd:cd07871    85 LDS-DLKQYLDNCGNlMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFG----LARAKSVPTKT 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYLETM---APELLEG--QGAVPqTDIWAIGVTAFIMLSAE--YPVSS 7869
Cdd:cd07871   160 YSNEVVTLwyrPPDVLLGstEYSTP-IDMWGVGCILYEMATGRpmFPGST 208
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
 6501-6659 6.22e-11

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 68.48  E-value: 6.22e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6501 LRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEeLLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHS 6580
Cdd:PHA03212  122 IKAGQRGGTATEAHILRAINHPSIIQLKGTFTYNKFTCLILPRYKTD-LYCYLAAKRNIAICDILAIERSVLRAIQYLHE 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6581 HGVLHLDIKPSNILMVHPAreDIKICDFGFAqnITPAELQFSQY----GSPEFVSPEIIQQNPVSEASDIWAMGVISYLS 6656
Cdd:PHA03212  201 NRIIHRDIKAENIFINHPG--DVCLGDFGAA--CFPVDINANKYygwaGTIATNAPELLARDPYGPAVDIWSAGIVLFEM 276


                  ...
gi 215274225 6657 LTC 6659
Cdd:PHA03212  277 ATC 279
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 5126-5216 6.22e-11

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 62.48  E-value: 6.22e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEED-DHYMINEDQQGGHQLIITAVVPADMGVYRCLAENS 5204
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                          90
                  ....*....|..
gi 215274225 5205 MGVSSTKAELRV 5216
Cdd:cd05892    81 AGVVSCNARLDV 92
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3545-3621 7.11e-11

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 61.75  E-value: 7.11e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3545 KNQEAREGATAVLQCELNSAAP--VEWRK-GSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCVC----GQERTSA 3617
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3618 MLTV 3621
Cdd:smart00410   82 TLTV 85
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
 6474-6652 7.15e-11

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 67.78  E-value: 7.15e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRA-QAYRERDILAALSHPLVTGLLD-----QFETRKTLILILELCS 6545
Cdd:cd07858    13 IGRGAYGIVCSAKNSETNEKVAIKKIanAFDNRIDAkRTLREIKLLRHLDHENVIAIKDimpppHREAFNDVYIVYELMD 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEelLDRLYRKG-VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQFSQ- 6623
Cdd:cd07858    93 TD--LHQIIRSSqTLSDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLL--NANCDLKICDFGLARTTSEKGDFMTEy 168

                         170       180       190
                  ....*....|....*....|....*....|....
gi 215274225 6624 -----YGSPEfvspEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd07858   169 vvtrwYRAPE----LLLNCSEYTTAIDVWSVGCI 198
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 7698-7924 7.26e-11

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 68.89  E-value: 7.26e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7698 LAAKIIPYHPKDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL----LPCLAERASYSESEVKDYL 7772
Cdd:PTZ00267   96 VVAKFVMLNDERQAAYARsELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSGGDLnkqiKQRLKEHLPFQEYEVGLLF 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7773 WQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLpsDKFKDYLET---MAPELLEGQGAVPQTD 7849
Cdd:PTZ00267  176 YQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQYSDSVSL--DVASSFCGTpyyLAPELWERKRYSKKAD 253

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7850 IWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGlvRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:PTZ00267  254 MWSLGVILYELLTLHRPFKGPSQREIMQQVLYG--KYDPFPCPVSSGMKALLDPLLSKNPALRPTTQQLLHTEFL 326
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
 7714-7869 7.60e-11

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 67.32  E-value: 7.60e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7714 LREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgPELLPCLAERAS-YSESEVKDYLWQMLSATQYLHNQHILHLDL 7792
Cdd:cd07872    52 IREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLD-KDLKQYMDDCGNiMSMHNVKIFLYQILRGLAYCHRRKVLHRDL 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7793 RSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLETM---APELLEGQGAVP-QTDIWAIGVTAFIMLSAE--YP 7866
Cdd:cd07872   131 KPQNLLINERGELKLADFG----LARAKSVPTKTYSNEVVTLwyrPPDVLLGSSEYStQIDMWGVGCIFFEMASGRplFP 206


                  ...
gi 215274225 7867 VSS 7869
Cdd:cd07872   207 GST 209
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
 6472-6714 7.74e-11

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 66.60  E-value: 7.74e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKR---VQHKGNKILCAAKFipLRSRTRAQA------YRERDILAALSHPLVTGL----LDQfetrkTLI 6538
Cdd:cd05040     1 EKLGDGSFGVVRRgewTTPSGKVIQVAVKC--LKSDVLSQPnamddfLKEVNAMHSLDHPNLIRLygvvLSS-----PLM 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6539 LILELCSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVhpAREDIKICDFGFAQNITPA 6617
Cdd:cd05040    74 MVTELAPLGSLLDRLRKdQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLA--SKDKVKIGDFGLMRALPQN 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6618 E----LQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLT-CSSPFAGESDRATLLNVLEGRVSWSSPmaAHLSE 6692
Cdd:cd05040   152 EdhyvMQEHRKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTyGEEPWLGLNGSQILEKIDKEGERLERP--DDCPQ 229

                         250       260
                  ....*....|....*....|..
gi 215274225 6693 DAKDFIKATLQRAPQARPSAAQ 6714
Cdd:cd05040   230 DIYNVMLQCWAHKPADRPTFVA 251
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
 7678-7866 7.81e-11

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 66.57  E-value: 7.81e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIP---YHPKDktavlreYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd13995    12 IPRGAFGKVYLAQDTKTKKRMACKLIPveqFKPSD-------VEIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVkdyLW---QMLSATQYLHNQHILHLDLRSENMIITEYNLLkVVDLGNAQSLSQEKVLPSDkFKDYL 7831
Cdd:cd13995    85 EKLESCGPMREFEI---IWvtkHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAV-LVDFGLSVQMTEDVYVPKD-LRGTE 159

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd13995   160 IYMSPEVILCRGHNTKADIYSLGATIIHMQTGSPP 194
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 5125-5212 7.85e-11

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 62.10  E-value: 7.85e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5125 APVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAV-VPADMGVYRCLAEN 5203
Cdd:cd20971     1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASvTDDDATVYQVRATN 80


                  ....*....
gi 215274225 5204 SMGVSSTKA 5212
Cdd:cd20971    81 QGGSVSGTA 89
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 7682-7924 7.98e-11

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 66.52  E-value: 7.98e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7682 RFSVVRQCWEKASGRALAAK--------------IIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILEL 7747
Cdd:cd08225     1 RYEIIKKIGEGSFGKIYLAKaksdsehcvikeidLTKMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENGRLFIVMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLL-KVVDLGNAQSL--SQEKVL 7822
Cdd:cd08225    81 CDGGDLMKRINRQRGvlFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVaKLGDFGIARQLndSMELAY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7823 PSDKFKDYLetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGlvRLSRCYAGLSGGAVAFLR 7902
Cdd:cd08225   161 TCVGTPYYL---SPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNLHQLVLKICQG--YFAPISPNFSRDLRSLIS 235

                         250       260
                  ....*....|....*....|..
gi 215274225 7903 STLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd08225   236 QLFKVSPRDRPSITSILKRPFL 257
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 5266-5350 8.29e-11

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 61.82  E-value: 8.29e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5266 LRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMT-DKKILHTLEIISVTREDSGQYAAYISNAMGAAYS 5344
Cdd:cd20973     4 LRDKEVVEGSA-ARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDqDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                  ....*.
gi 215274225 5345 SARLLV 5350
Cdd:cd20973    83 SAELTV 88
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 5126-5216 8.38e-11

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 62.04  E-value: 8.38e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 215274225 5206 GVSSTKAELRV 5216
Cdd:cd20990    81 GQNSFNLELVV 91
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 7480-7550 8.90e-11

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 61.19  E-value: 8.90e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7480 VTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNFQlLTILVVVAEDLGVYTCSVSNALGTVTTTGV 7550
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGT-LTISNVTLEDSGTYTCVASNSAGGSASASV 70
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 245-329 9.24e-11

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 62.05  E-value: 9.24e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  245 RTCTVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGR--RHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYS 322
Cdd:cd20951     8 QSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEASS 87


                  ....*..
gi 215274225  323 SVLVVVR 329
Cdd:cd20951    88 SASVVVE 94
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
 7676-7876 9.25e-11

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 67.38  E-value: 9.25e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKII--PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd06649    11 SELGAGNGGVVTKVQHKPSGLIMARKLIhlEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpSDKFKDYLE 7832
Cdd:cd06649    91 DQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHqIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSM---ANSFVGTRS 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQ 7876
Cdd:cd06649   168 YMSPERLQGTHYSVQSDIWSMGLSLVELAIGRYPIPPPDAKELE 211
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 127-191 9.91e-11

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 61.19  E-value: 9.91e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  127 ATFRCRVGGSPRPAVSWSKDGRRLgePDGPRVRVEELGEASALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPL--PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
PK_TRB cd13976
Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to ...
 6561-6721 1.04e-10

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270878 [Multi-domain]  Cd Length: 242  Bit Score: 65.91  E-value: 1.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6561 EAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFS-QYGSPEFVSPEII--QQ 6637
Cdd:cd13976    83 EPEAARLFRQIASAVAHCHRNGIVLRDLKLRKFVFADEERTKLRLESLEDAVILEGEDDSLSdKHGCPAYVSPEILnsGA 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6638 NPVSEASDIWAMGVISYLSLTCSSPFAgESDRATLLNVLEgRVSWSSPmaAHLSEDAKDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd13976   163 TYSGKAADVWSLGVILYTMLVGRYPFH-DSEPASLFAKIR-RGQFAIP--ETLSPRARCLIRSLLRREPSERLTAEDILL 238


                  ....
gi 215274225 6718 HPWF 6721
Cdd:cd13976   239 HPWL 242
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 238-328 1.06e-10

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 61.76  E-value: 1.06e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  238 SPPSTGTrTCTVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEG-RRHVVYEDAQEnfvLKILFCKQSDRGLYTCTASNL 316
Cdd:cd20970     4 STPQPSF-TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFnTRYIVRENGTT---LTIRNIRRSDMGIYLCIASNG 79

                          90
                  ....*....|..
gi 215274225  317 VGQTYSSVLVVV 328
Cdd:cd20970    80 VPGSVEKRITLQ 91
PK_TRB2 cd14022
Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein ...
 6561-6721 1.08e-10

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270924 [Multi-domain]  Cd Length: 242  Bit Score: 65.83  E-value: 1.08e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6561 EAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNITPAELQFS-QYGSPEFVSPEIIQQNP 6639
Cdd:cd14022    83 EEEAARLFYQIASAVAHCHDGGLVLRDLKLRKFVFKDEERTRVKLESLEDAYILRGHDDSLSdKHGCPAYVSPEILNTSG 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6640 V--SEASDIWAMGVISYLSLTCSSPFAgESDRATLLNVLEgRVSWSSPMAahLSEDAKDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd14022   163 SysGKAADVWSLGVMLYTMLVGRYPFH-DIEPSSLFSKIR-RGQFNIPET--LSPKAKCLIRSILRREPSERLTSQEILD 238


                  ....
gi 215274225 6718 HPWF 6721
Cdd:cd14022   239 HPWF 242
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
 7725-7880 1.12e-10

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 66.89  E-value: 1.12e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7725 HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL 7804
Cdd:cd05620    55 NPFLTHLYCTFQTKEHLFFVMEFLNGGDLMFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGH 134

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7805 LKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLR 7880
Cdd:cd05620   135 IKIADFG----MCKENVFGDNRASTFCGTpdyIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIR 209
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
 7724-7875 1.16e-10

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 67.13  E-value: 1.16e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7724 RHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN 7803
Cdd:cd05591    54 KHPFLTALHSCFQTKDRLFFVMEYVNGGDLMFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEG 133

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7804 LLKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:cd05591   134 HCKLADFG----MCKEGILNGKTTTTFCGTpdyIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDL 204
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 112-188 1.16e-10

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 61.58  E-value: 1.16e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  112 FLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRL--GEPDGPRVRveelGEASALRIRAARPRDGGTYEVRAEN 188
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPIsaSVADMSKYR----ILADGLLINKVTQDDTGEYTCRAYQ 76
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
 6474-6726 1.17e-10

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 66.59  E-value: 1.17e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNkilCAAKFIPLRSRT--RAQAYR-ERDILAALSHPLVTgLLDQFETRKTLILILELCSSEELL 6550
Cdd:cd14149    20 IGSGSFGTVYKGKWHGD---VAVKILKVVDPTpeQFQAFRnEVAVLRKTRHVNIL-LFMGYMTKDNLAIVTQWCEGSSLY 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYrkgvVTEAEVKVY-----IQQLVEGLHYLHSHGVLHLDIKPSNILMvHPAREdIKICDFGFAQNIT--PAELQFSQ 6623
Cdd:cd14149    96 KHLH----VQETKFQMFqlidiARQTAQGMDYLHAKNIIHRDMKSNNIFL-HEGLT-VKIGDFGLATVKSrwSGSQQVEQ 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6624 -YGSPEFVSPEIIQ---QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLnVLEGRvSWSSPMAAHLSEDA----K 6695
Cdd:cd14149   170 pTGSILWMAPEVIRmqdNNPFSFQSDVYSYGIVLYELMTGELPYSHINNRDQII-FMVGR-GYASPDLSKLYKNCpkamK 247

                         250       260       270
                  ....*....|....*....|....*....|..
gi 215274225 6696 DFIKATLQRAPQARPSAAQCLSHPWFLK-SMP 6726
Cdd:cd14149   248 RLVADCIKKVKEERPLFPQILSSIELLQhSLP 279
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 115-201 1.18e-10

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 61.26  E-value: 1.18e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  115 RPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgepdgPRVRVEELGEASaLRIRAARPRDGGTYEVRAENPLGAAS 194
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-----PKGRYEILDDHS-LKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 215274225  195 AAAALVV 201
Cdd:cd05725    77 ASATLTV 83
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
 7695-7870 1.23e-10

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 66.23  E-value: 1.23e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7695 GRALAAKIIPYHPKDKtaVLREYEALKGLRHPHLAQLHAAYLSPR--HLVLILELCSGPELLPCLAERaSYSESEVKDYL 7772
Cdd:cd14118    45 RRKPGALGKPLDPLDR--VYREIAILKKLDHPNVVKLVEVLDDPNedNLYMVFELVDKGAVMEVPTDN-PLSEETARSYF 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7773 WQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqslsqekvlPSDKFK---DYLET-------MAPELLEGQ 7842
Cdd:cd14118   122 RDIVLGIEYLHYQKIIHRDIKPSNLLLGDDGHVKIADFG-----------VSNEFEgddALLSStagtpafMAPEALSES 190

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 7843 GAV---PQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd14118   191 RKKfsgKALDIWAMGVTLYCFVFGRCPFEDD 221
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
 7672-7912 1.27e-10

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 66.95  E-value: 1.27e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPyhpKDK---------TAVLREYEALKGlRHPHLAQLHAAYLSPRHLV 7742
Cdd:cd05616     2 FNFLMVLGKGSFGKVMLAERKGTDELYAVKILK---KDVviqdddvecTMVEKRVLALSG-KPPFLTQLHSCFQTMDRLY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVL 7822
Cdd:cd05616    78 FVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFG----MCKENIW 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7823 PSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRcyaGLSGGAVA 7899
Cdd:cd05616   154 DGVTTKTFCGTpdyIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPK---SMSKEAVA 230

                         250
                  ....*....|...
gi 215274225 7900 FLRSTLCAQPWGR 7912
Cdd:cd05616   231 ICKGLMTKHPGKR 243
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 245-318 1.28e-10

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 61.48  E-value: 1.28e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  245 RTCTVTEGKHARLSCYVTGEPKPETVWKKDGQL----VTEGRRHVVYEDAqenfVLKILFCKQSDRGLYTCTASNLVG 318
Cdd:cd05763     7 HDITIRAGSTARLECAATGHPTPQIAWQKDGGTdfpaARERRMHVMPEDD----VFFIVDVKIEDTGVYSCTAQNSAG 80
I-set pfam07679
Immunoglobulin I-set domain;
2293-2374 1.33e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 61.12  E-value: 1.33e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2293 VRPLRDKIAMEKHRGVLECQVSRASA-QVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDA----GDVK 2367
Cdd:pfam07679    4 TQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAE 83


                   ....*..
gi 215274225  2368 TSAQFFV 2374
Cdd:pfam07679   84 ASAELTV 90
pknD PRK13184
serine/threonine-protein kinase PknD;
6574-6770 1.35e-10

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 69.03  E-value: 1.35e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6574 GLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAE-----LQFSQY--------------GSPEFVSPEI 6634
Cdd:PRK13184  125 TIEYVHSKGVLHRDLKPDNILL--GLFGEVVILDWGAAIFKKLEEedlldIDVDERnicyssmtipgkivGTPDYMAPER 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6635 IQQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATllnVLEGRVSWSSPMAAHlsEDAKDFIKATLQRA----PQARP 6710
Cdd:PRK13184  203 LLGVPASESTDIYALGVILYQMLTLSFPYRRKKGRKI---SYRDVILSPIEVAPY--REIPPFLSQIAMKAlavdPAERY 277

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6711 SAAQCL----------SHPWFLKSMpaeeahfINTKQlkfllaRSRWQrslmSYKSILVMRSIPELLRGP 6770
Cdd:PRK13184  278 SSVQELkqdlephlqgSPEWTVKAT-------LMTKK------KSCWK----FYEPILLSKYFPMLESSP 330
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1174-1240 1.36e-10

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 61.04  E-value: 1.36e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1174 NEVQAEAGTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
6468-6667 1.49e-10

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 68.28  E-value: 1.49e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRG----VfgfvkrvqHKGN----------KILCA-----AKFIpLRSRTRAQAyrerdiLAALSHPLVTGLL 6528
Cdd:NF033483    9 YEIGERIGRGgmaeV--------YLAKdtrldrdvavKVLRPdlardPEFV-ARFRREAQS------AASLSHPNIVSVY 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6529 DQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKIC 6606
Cdd:NF033483   74 DVGEDGGIPYIVMEYVDGRTLKDYIREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILI----TKDgrVKVT 149

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6607 DFGFA-----QNITpaelQFSQ-YGSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSSPFAGES 6667
Cdd:NF033483  150 DFGIAralssTTMT----QTNSvLGTVHYLSPEQARGGTVDARSDIYSLGIVLYEMLTGRPPFDGDS 212
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 5125-5216 1.51e-10

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 61.11  E-value: 1.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5125 APVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGghQLIITAVVPADMGVYRCLAENS 5204
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVG--ELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 215274225 5205 MGVSSTKAELRV 5216
Cdd:cd20976    79 AGQVSCSAWVTV 90
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 6031-6094 1.71e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 60.42  E-value: 1.71e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6031 VKLACRVTGTPKPVISWYKDGKAVQVDPHHIlIEDPDGSCALILDSLTGVDSGQYMCFAASAAG 6094
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDS-RRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
 7667-7870 1.74e-10

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270761 [Multi-domain]  Cd Length: 349  Bit Score: 66.83  E-value: 1.74e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP---KDKTA-VLREYEALKGLRHPHLAQLHAAYLSPRHLV 7742
Cdd:cd05610     1 PSIEEFVIVKPISRGAFGKVYLGRKKNNSKLYAVKVVKKADminKNMVHqVQAERDALALSKSPFIVHLYYSLQSANNVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7743 LILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQ-SLSQEKV 7821
Cdd:cd05610    81 LVMEYLIGGDVKSLLHIYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKvTLNRELN 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7822 L------PS--DKFKDYLET-------------------------------------------MAPELLEGQGAVPQTDI 7850
Cdd:cd05610   161 MmdilttPSmaKPKNDYSRTpgqvlslisslgfntptpyrtpksvrrgaarvegerilgtpdyLAPELLLGKPHGPAVDW 240

                         250       260
                  ....*....|....*....|
gi 215274225 7851 WAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd05610   241 WALGVCLFEFLTGIPPFNDE 260
I-set pfam07679
Immunoglobulin I-set domain;
1273-1332 1.80e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 60.73  E-value: 1.80e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  1273 GASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:pfam07679   15 GESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 15-90 1.82e-10

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 60.88  E-value: 1.82e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   15 RPKAFVVSVGKDATLSCQI-VGNPTPQVSWEKDQQPVA-AGARFRLAQDGDlyrLTILDLALGDSGQYVCRARNAIGE 90
Cdd:cd05724     3 EPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNlDNERVRIVDDGN---LLIAEARKSDEGTYKCVATNMVGE 77
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
 7677-7968 1.95e-10

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 67.08  E-value: 1.95e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTA---VLREYEALKGLRHPH----LAQLHAAYLSP-RHLVLILELC 7748
Cdd:cd07853     7 PIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSckrVFRELKMLCFFKHDNvlsaLDILQPPHIDPfEEIYVVTELM 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGpELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNA--QSLSQEKVLPSDK 7826
Cdd:cd07853    87 QS-DLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLArvEEPDESKHMTQEV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYLEtmAPELLEGQ----GAVpqtDIWAIG------VTAFIMLSAEYPVSS--------------------EGARD-- 7874
Cdd:cd07853   166 VTQYYR--APEILMGSrhytSAV---DIWSVGcifaelLGRRILFQAQSPIQQldlitdllgtpsleamrsacEGARAhi 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7875 LQRGLR-KGLVRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWLtEEGP------ACSrpapVTFPTARLRVF 7947
Cdd:cd07853   241 LRGPHKpPSLPVLYTLSSQATHEAVHLLCRMLVFDPDKRISAADALAHPYL-DEGRlryhtcMCK----CCYTTSGGRVY 315

                         330       340
                  ....*....|....*....|....*..
gi 215274225 7948 VRNRE----KRRALLY--KRHNLAQVR 7968
Cdd:cd07853   316 TSDFEpsanPPFDDEYekNLTSVRQVK 342
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
 7672-7960 1.98e-10

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 66.73  E-value: 1.98e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIP---YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSP-----RHLVL 7743
Cdd:cd07859     2 YKIQEVIGKGSYGVVCSAIDTHTGEKVAIKKINdvfEHVSDATRILREIKLLRLLRHPDIVEIKHIMLPPsrrefKDIYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCsGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlP 7823
Cdd:cd07859    82 VFELM-ESDLHQVIKANDDLTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVAFNDT--P 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7824 SDKF-KDYLET---MAPELLegqGA-----VPQTDIWAIGVTAFIMLSAE--YP-------------------------V 7867
Cdd:cd07859   159 TAIFwTDYVATrwyRAPELC---GSffskyTPAIDIWSIGCIFAEVLTGKplFPgknvvhqldlitdllgtpspetisrV 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7868 SSEGARDLQRGLRKGL-VRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL-----TEEGPACSRPAPVTFPT 7941
Cdd:cd07859   236 RNEKARRYLSSMRKKQpVPFSQKFPNADPLALRLLERLLAFDPKDRPTAEEALADPYFkglakVEREPSAQPITKLEFEF 315

                         330
                  ....*....|....*....
gi 215274225 7942 ARLRVfvrNREKRRALLYK 7960
Cdd:cd07859   316 ERRRL---TKEDVRELIYR 331
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
 6474-6652 1.98e-10

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 65.20  E-value: 1.98e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKfIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd14065     1 LGKGFFGEVYKVTHRETGKVMVMK-ELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGVVTEAEVKVYI-QQLVEGLHYLHSHGVLHLDIKPSNILMVHPARE-DIKICDFGFAQNI------TPAE-LQFSQY 6624
Cdd:cd14065    80 KSMDEQLPWSQRVSLaKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGrNAVVADFGLAREMpdektkKPDRkKRLTVV 159

                         170       180
                  ....*....|....*....|....*...
gi 215274225 6625 GSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd14065   160 GSPYWMAPEMLRGESYDEKVDVFSFGIV 187
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2655-2731 2.00e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 60.60  E-value: 2.00e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2655 DLSAEERGTLALQCEVS-DPEAHVVWRKDGVQ-LGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV----GSEETRAR 2728
Cdd:smart00410    3 SVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTT 82


                    ...
gi 215274225   2729 VRV 2731
Cdd:smart00410   83 LTV 85
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 6801-7076 2.14e-10

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 68.26  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6801 APFARAKSLPP--SPVTHSPLLHPRGFLRPSASLPEEAEASERSTEAPAPPASPEGAGPPAAQGCVprhsvirslfyhQA 6878
Cdd:pfam03154  198 GPTPSAPSVPPqgSPATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSP------------QP 265

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6879 GESPE-HGALAPGSrrhparrrHLLKGGyiagalpglrEPLMEHRVLEEEAAReeqatllakaPSFETALRLPASGTHLA 6957
Cdd:pfam03154  266 LPQPSlHGQMPPMP--------HSLQTG----------PSHMQHPVPPQPFPL----------TPQSSQSQVPPGPSPAA 317

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6958 PGHSHSLEHDSPSTPRPSSEACGEAQRLPSAPSG--------GAPIRDMGHPQGSKQLPSTGG----------------- 7012
Cdd:pfam03154  318 PGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSmphikpppTTPIPQLPNPQSHKHPPHLSGpspfqmnsnlppppalk 397

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  7013 --------HPGTA-----------QPERPSPDSPWGQPAPFCHPKQGSA--PQEGCSPHPAVAPCPPGSFPPGSCKEApL 7071
Cdd:pfam03154  398 plsslsthHPPSAhppplqlmpqsQQLPPPPAQPPVLTQSQSLPPPAAShpPTSGLHQVPSQSPFPQHPFVPGGPPPI-T 476


                   ....*
gi 215274225  7072 VPSSP 7076
Cdd:pfam03154  477 PPSGP 481
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
 7680-7891 2.26e-10

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 65.67  E-value: 2.26e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDK----TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd05608    11 KGGFGEVSACQMRATGKLYACKKLNKKRLKKrkgyEGAMVEKRILAKVHSRFIVSLAYAFQTKTDLCLVMTIMNGGDLRY 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CL----AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpsDKFKDYL 7831
Cdd:cd05608    91 HIynvdEENPGFQEPRACFYTAQIISGLEHLHQRRIIYRDLKPENVLLDDDGNVRISDLGLAVELKDGQ----TKTKGYA 166

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7832 ET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCYA 7891
Cdd:cd05608   167 GTpgfMAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPFRARGEKVENKELKQRILNDSVTYS 229
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 10-99 2.31e-10

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 60.48  E-value: 2.31e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRP-KAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGdlyRLTILDLALGDSGQYVCRARNAI 88
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDG---TLTIINVQPEDTGYYGCVATNEI 77

                          90
                  ....*....|.
gi 215274225   89 GEAFAAVGLQV 99
Cdd:cd20978    78 GDIYTETLLHV 88
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 10-99 2.50e-10

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 60.51  E-value: 2.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPV---AAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARN 86
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 215274225   87 AIGEAFAAVGLQV 99
Cdd:cd20951    81 IHGEASSSASVVV 93
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 7671-7870 2.55e-10

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 65.22  E-value: 2.55e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRF-SVVRQCWEKASGRALAAKIIPYH---------PKDKTA--VLREYEALK-GLRHPHLAQLHAAYLS 7737
Cdd:cd08528     1 EYAVLELLGSGAFgCVYKVRKKSNGQTLLALKEINMTnpafgrteqERDKSVgdIISEVNIIKeQLRHPNIVRYYKTFLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7738 PRHLVLILELCSGP---ELLPCLAER-ASYSESEVKDYLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGn 7812
Cdd:cd08528    81 NDRLYIVMELIEGAplgEHFSSLKEKnEHFTEDRIWNIFVQMVLALRYLHKEKqIVHRDLKPNNIMLGEDDKVTITDFG- 159

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7813 aqsLSQEKVLPSDKFKDYLETM---APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd08528   160 ---LAKQKGPESSKMTSVVGTIlysCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYST 217
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
 6474-6711 2.59e-10

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 65.30  E-value: 2.59e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVK--RVQHKGNKI--LCAAKFIPLRSRTRAQAY-RERDILAALSHPLVTGL--LDQFETRKTLILILELCSS 6546
Cdd:cd05081    12 LGKGNFGSVElcRYDPLGDNTgaLVAVKQLQHSGPDQQRDFqREIQILKALHSDFIVKYrgVSYGPGRRSLRLVMEYLPS 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKGVVTEA-EVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQnITPAELQF---S 6622
Cdd:cd05081    92 GCLRDFLQRHRARLDAsRLLLYSSQICKGMEYLGSRRCVHRDLAARNILV--ESEAHVKIADFGLAK-LLPLDKDYyvvR 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYG-SPEF-VSPEIIQQNPVSEASDIWAMGVI-----SYLSLTCSSP------FAGESDRATLLNVLEG-RVSWSSPMAA 6688
Cdd:cd05081   169 EPGqSPIFwYAPESLSDNIFSRQSDVWSFGVVlyelfTYCDKSCSPSaeflrmMGCERDVPALCRLLELlEEGQRLPAPP 248

                         250       260
                  ....*....|....*....|...
gi 215274225 6689 HLSEDAKDFIKATLQRAPQARPS 6711
Cdd:cd05081   249 ACPAEVHELMKLCWAPSPQDRPS 271
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 110-201 2.72e-10

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 60.48  E-value: 2.72e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRP-TSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGpRVRVEElgeaSALRIRAARPRDGGTYEVRAEN 188
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPME-RATVED----GTLTIINVQPEDTGYYGCVATN 75

                          90
                  ....*....|...
gi 215274225  189 PLGAASAAAALVV 201
Cdd:cd20978    76 EIGDIYTETLLHV 88
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 6014-6106 2.94e-10

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 60.10  E-value: 2.94e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCT-AELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEdpDGScaLILDSLTGVDSGQYMCFAASA 6092
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE--DGT--LTIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|....
gi 215274225 6093 AGNCSTlgKILVQV 6106
Cdd:cd20978    77 IGDIYT--ETLLHV 88
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
 6511-6726 3.09e-10

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 65.94  E-value: 3.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6511 RERDILAALSHPLVTGLLDQFETRKTLILILELCSSE--ELLDRLYRkgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDI 6588
Cdd:PTZ00024   69 RELKIMNEIKHENIMGLVDVYVEGDFINLVMDIMASDlkKVVDRKIR---LTESQVKCILLQILNGLNVLHKWYFMHRDL 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6589 KPSNILMvhPAREDIKICDFGFA---------------QNITPAELQFSQ-----YGSPEFvspeIIQQNPVSEASDIWA 6648
Cdd:PTZ00024  146 SPANIFI--NSKGICKIADFGLArrygyppysdtlskdETMQRREEMTSKvvtlwYRAPEL----LMGAEKYHFAVDMWS 219

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6649 MGVISYLSLTCSSPFAGESDRATLlnvleGRV----------SWssPMAAHL---------------------SEDAKDF 6697
Cdd:PTZ00024  220 VGCIFAELLTGKPLFPGENEIDQL-----GRIfellgtpnedNW--PQAKKLplyteftprkpkdlktifpnaSDDAIDL 292

                         250       260
                  ....*....|....*....|....*....
gi 215274225 6698 IKATLQRAPQARPSAAQCLSHPWFlKSMP 6726
Cdd:PTZ00024  293 LQSLLKLNPLERISAKEALKHEYF-KSDP 320
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
 5143-5206 3.22e-10

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 60.25  E-value: 3.22e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 5143 VSFDCVVTGQPMPSVRWFKDGKLLEEDDH---YMINEDQQgghQLIITAVVPADMGVYRCLAENSMG 5206
Cdd:cd05857    22 VKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggYKVRNQHW---SLIMESVVPSDKGNYTCVVENEYG 85
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 6125-6194 3.97e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 59.27  E-value: 3.97e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6125 AQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGllVLVIRAASKEDLGLYECELVNRLGSARAS 6194
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNG--TLTISNVTLEDSGTYTCVASNSAGGSASA 68
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 6108-6199 4.15e-10

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 59.82  E-value: 4.15e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEpRSGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVR-ENGRHSLIIEPVTKRDAGIYTCIARNR 79

                          90
                  ....*....|..
gi 215274225 6188 LGSARASAELRI 6199
Cdd:cd05744    80 AGENSFNAELVV 91
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 4898-4975 4.61e-10

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 59.50  E-value: 4.61e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHhIDQLGDGTCSLLITGLDRADAGCYTCQVSN 4975
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTR-SRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
I-set pfam07679
Immunoglobulin I-set domain;
3275-3357 4.76e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.58  E-value: 4.76e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3275 QFIGKLRNKEATEGATATLRCELSkAAP---VEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVC----G 3347
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-GTPdpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaG 80

                           90
                   ....*....|
gi 215274225  3348 EERTSASLTI 3357
Cdd:pfam07679   81 EAEASAELTV 90
I-set pfam07679
Immunoglobulin I-set domain;
335-418 4.90e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.58  E-value: 4.90e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   335 FKKRLQDLEVREKESATFLCEV---PQPSTEaaWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYIC--ETPEG 409
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVtgtPDPEVS--WFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvaTNSAG 80

                           90
                   ....*....|
gi 215274225   410 SRTV-AELAV 418
Cdd:pfam07679   81 EAEAsAELTV 90
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
 5888-5999 5.33e-10

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270134  Cd Length: 114  Bit Score: 60.44  E-value: 5.33e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5888 GTLQALGEPIRQGHFIVWEGAPgarmpwKGHNRHVFLFRNHLVICKPRRDSRTDTVsYVFRNMMKLSSIDLNdQVEGDDR 5967
Cdd:cd13325     1 GNIHKLGRLLRHDWFTVTDGEG------KAKERYLFLFKSRILITKVRRISEDRSV-FILKDIIRLPEVNVK-QHPDDER 72

                          90       100       110
                  ....*....|....*....|....*....|...
gi 215274225 5968 AFEVWQEREDSVRKYL-LQARTAIIKSSWVKEI 5999
Cdd:cd13325    73 TFELQPKLPAFGILPIdFKAHKDEIKDYWLNEI 105
pk1 PHA03390
serine/threonine-protein kinase 1; Provisional
 7725-7866 5.35e-10

serine/threonine-protein kinase 1; Provisional


Pssm-ID: 223069 [Multi-domain]  Cd Length: 267  Bit Score: 64.11  E-value: 5.35e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7725 HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL 7804
Cdd:PHA03390   68 NPNFIKLYYSVTTLKGHVLIMDYIKDGDLFDLLKKEGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLYDRAKD 147

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7805 -LKVVDLGNAQSLSQEKVLpsDKFKDYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:PHA03390  148 rIYLCDYGLCKIIGTPSCY--DGTLDY---FSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHP 205
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3721-3797 5.57e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 59.44  E-value: 5.57e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3721 RNEEATEGDTATLWCELSKAAP--VEWRK-GHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVC----GQERTSA 3793
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3794 TLTV 3797
Cdd:smart00410   82 TLTV 85
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
 6469-6651 5.70e-10

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 64.37  E-value: 5.70e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKR---VQHKGNKILCAAKFIP------LRSRTRAQAYrerdILAALSHPLVTGLLDQFETRKTLIl 6539
Cdd:cd05056     9 TLGRCIGEGQFGDVYQgvyMSPENEKIAVAVKTCKnctspsVREKFLQEAY----IMRQFDHPHIVKLIGVITENPVWI- 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELldRLY---RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHParEDIKICDFGFAQNITP 6616
Cdd:cd05056    84 VMELAPLGEL--RSYlqvNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSP--DCVKLGDFGLSRYMED 159

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 6617 AELQFSQYGS-P-EFVSPEIIQQNPVSEASDIWAMGV 6651
Cdd:cd05056   160 ESYYKASKGKlPiKWMAPESINFRRFTSASDVWMFGV 196
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2666-2720 6.16e-10

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 58.88  E-value: 6.16e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2666 LQCEVS-DPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV 2720
Cdd:cd00096     3 LTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 24-91 6.19e-10

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 59.50  E-value: 6.19e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225   24 GKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQ----DGDL--YrLTILDLALGDSGQYVCRARNAIGEA 91
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDyvtsDGDVvsY-VNISSVRVEDGGEYTCTATNDVGSV 88
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2924-3000 6.84e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 59.06  E-value: 6.84e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2924 NLQVEEKGTAVFTCKTE-HPAATVTWRK-GLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC----DIGQAQSRAQ 2997
Cdd:smart00410    3 SVTVKEGESVTLSCEASgSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaatnSSGSASSGTT 82


                    ...
gi 215274225   2998 LLV 3000
Cdd:smart00410   83 LTV 85
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
 6473-6654 6.97e-10

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 63.83  E-value: 6.97e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKR--VQHKGNKILCAAKFIPLRSRTRA---QAYRERDILAALSHPLVTGLLDQFETrKTLILILELCSSE 6547
Cdd:cd05116     2 ELGSGNFGTVKKgyYQMKKVVKTVAVKILKNEANDPAlkdELLREANVMQQLDNPYIVRMIGICEA-ESWMLVMEMAELG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV--HPArediKICDFGFAQNITPAELQFSQYG 6625
Cdd:cd05116    81 PLNKFLQKNRHVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVtqHYA----KISDFGLSKALRADENYYKAQT 156

                         170       180       190
                  ....*....|....*....|....*....|...
gi 215274225 6626 S---P-EFVSPEIIQQNPVSEASDIWAMGVISY 6654
Cdd:cd05116   157 HgkwPvKWYAPECMNYYKFSSKSDVWSFGVLMW 189
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 3-99 7.18e-10

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 59.19  E-value: 7.18e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    3 QPQFSGAPRFLTrpkafvVSVGKDATLSCQIVGNPTPQVSWEKDQQPVA-AGARFRLaqDGDLYRLTILDLALGDSGQYV 81
Cdd:cd20976     1 APSFSSVPKDLE------AVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTC--EAGVGELHIQDVLPEDHGTYT 72

                          90
                  ....*....|....*...
gi 215274225   82 CRARNAIGEAFAAVGLQV 99
Cdd:cd20976    73 CLAKNAAGQVSCSAWVTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1906-1983 7.25e-10

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 59.06  E-value: 7.25e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1906 STVVAEEGGEATFQCVVSPSDVAVV-WFRDGA-LLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEG----ASSSA 1979
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVtWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNssgsASSGT 81


                    ....
gi 215274225   1980 ALRV 1983
Cdd:smart00410   82 TLTV 85
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 5371-5467 7.50e-10

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 59.49  E-value: 7.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAERGVLWIGPDTPGYTVASSaqqhSLVLLDV-----GRQHQG 5445
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSG----SLFFLRVvhgrkGRSDEG 76

                          90       100
                  ....*....|....*....|...
gi 215274225 5446 TYTCIASNAAGQALC-SASLHVS 5467
Cdd:cd07693    77 VYVCVAHNSLGEAVSrNASLEVA 99
I-set pfam07679
Immunoglobulin I-set domain;
992-1056 7.53e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 59.19  E-value: 7.53e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225   992 VQAEAGASATLSCEVAQAQT-EVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEA 1056
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 5143-5206 7.56e-10

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 59.54  E-value: 7.56e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 5143 VSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENSMG 5206
Cdd:cd05729    22 VRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
 7678-7866 7.57e-10

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 63.54  E-value: 7.57e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVV-RQCWEKASGRALAAKIIPYHPKDKTAVL--REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd14120     1 IGHGAFAVVfKGRHRKKPDLPVAIKCITKKNLSKSQNLlgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE--------YNL-LKVVDLGNAQSLsQEKVLP-- 7823
Cdd:cd14120    81 DYLQAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHnsgrkpspNDIrLKIADFGFARFL-QDGMMAat 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7824 ---SDKFkdyletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14120   160 lcgSPMY------MAPEVIMSLQYDAKADLWSIGTIVYQCLTGKAP 199
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 119-191 7.98e-10

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 58.76  E-value: 7.98e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  119 IRVREGSeaTFRCRVG--GSPRPAVSWSKDGRRLGEPDgpRVRVEELGEASALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd05748     2 IVVRAGE--SLRLDIPikGRPTPTVTWSKDGQPLKETG--RVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAG 72
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 4069-4154 8.05e-10

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 58.79  E-value: 8.05e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4069 KFKTRLQSleqETGDIARLCCQLSDAesGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACVTGGQKT 4148
Cdd:cd20967     2 KAQPAVQV---SKGHKIRLTVELADP--DAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKC 76


                  ....*.
gi 215274225 4149 AASLRV 4154
Cdd:cd20967    77 SFELFV 82
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 7463-7551 8.21e-10

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 59.05  E-value: 8.21e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNFQLLTILVVVAEDLGVYTCSVSNAL 7542
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80


                  ....*....
gi 215274225 7543 GTVTTTGVL 7551
Cdd:cd05744    81 GENSFNAEL 89
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
 7636-7871 9.36e-10

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 64.46  E-value: 9.36e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7636 PYSSPSEQVLLGGPSHLASEEESQGRSAQPLPSTKTFAFQ-----TQIQRGRFSVVRQCWEKASGRALAAKII-PYHPKD 7709
Cdd:PLN00034   35 PQRDPSLAVPLPLPPPSSSSSSSSSSSASGSAPSAAKSLSelervNRIGSGAGGTVYKVIHRPTGRLYALKVIyGNHEDT 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7710 -KTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELlpclAERASYSESEVKDYLWQMLSATQYLHNQHIL 7788
Cdd:PLN00034  115 vRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGSL----EGTHIADEQFLADVARQILSGIAYLHRRHIV 190

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7789 HLDLRSENMIITEYNLLKVVDLGNAQSLSQeKVLPSDKFKDYLETMAPE-----LLEGQGAVPQTDIWAIGVT--AFIML 7861
Cdd:PLN00034  191 HRDIKPSNLLINSAKNVKIADFGVSRILAQ-TMDPCNSSVGTIAYMSPErintdLNHGAYDGYAGDIWSLGVSilEFYLG 269

                         250
                  ....*....|
gi 215274225 7862 SAEYPVSSEG 7871
Cdd:PLN00034  270 RFPFGVGRQG 279
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 5371-5466 9.51e-10

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 59.05  E-value: 9.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDTPGYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKP-----VRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCI 75

                          90
                  ....*....|....*.
gi 215274225 5451 ASNAAGQALCSASLHV 5466
Cdd:cd05744    76 ARNRAGENSFNAELVV 91
PHA03207 PHA03207
serine/threonine kinase US3; Provisional
 6511-6726 9.55e-10

serine/threonine kinase US3; Provisional


Pssm-ID: 165473 [Multi-domain]  Cd Length: 392  Bit Score: 64.87  E-value: 9.55e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6511 RERDILAALSHPLVTGLLDQFETRKTLILILelcsseelldRLYRKGVVTEAEVK--------VYIQQ-LVEGLHYLHSH 6581
Cdd:PHA03207  135 REIDILKTISHRAIINLIHAYRWKSTVCMVM----------PKYKCDLFTYVDRSgplpleqaITIQRrLLEALAYLHGR 204

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6582 GVLHLDIKPSNILMVHParEDIKICDFGFAQNITPAELQFSQY---GSPEFVSPEIIQQNPVSEASDIWAMGVISYLSLT 6658
Cdd:PHA03207  205 GIIHRDVKTENIFLDEP--ENAVLGDFGAACKLDAHPDTPQCYgwsGTLETNSPELLALDPYCAKTDIWSAGLVLFEMSV 282

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6659 CSSPFAGESD-----------RATLLNVLEGRVSWSSPMAAH----------------------LSEDAKDFIKATLQRA 6705
Cdd:PHA03207  283 KNVTLFGKQVkssssqlrsiiRCMQVHPLEFPQNGSTNLCKHfkqyaivlrppytippvirkygMHMDVEYLIAKMLTFD 362

                         250       260
                  ....*....|....*....|.
gi 215274225 6706 PQARPSAAQCLSHPWFLKSMP 6726
Cdd:PHA03207  363 QEFRPSAQDILSLPLFTKEPI 383
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
 7677-7854 9.59e-10

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 63.61  E-value: 9.59e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK---TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd07839     7 KIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEgvpSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYCDQDLK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSqekvLPSDKFKDYLET 7833
Cdd:cd07839    87 KYFDSCNGDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARAFG----IPVRCYSAEVVT 162

                         170       180
                  ....*....|....*....|....*
gi 215274225 7834 M---APELLEG-QGAVPQTDIWAIG 7854
Cdd:cd07839   163 LwyrPPDVLFGaKLYSTSIDMWSAG 187
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 112-201 9.84e-10

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 58.66  E-value: 9.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  112 FLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDgPRVRVEELGeasALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKD-ERITTLENG---SLQIKGAEKSDTGEYTCVALNLSG 77

                          90
                  ....*....|
gi 215274225  192 AASAAAALVV 201
Cdd:cd20952    78 EATWSAVLDV 87
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5385-5466 1.06e-09

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 58.56  E-value: 1.06e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5385 GSSITFSVKVEGRPVPTVHWLREEAE--RGVLWIGPDtpgytvassaqqHSLVLLDVGRQHQGTYTCIASNAAGQALCSA 5462
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDGElpKGRYEILDD------------HSLKIRKVTAGDMGSYTCVAENMVGKIEASA 79


                  ....
gi 215274225 5463 SLHV 5466
Cdd:cd05725    80 TLTV 83
I-set pfam07679
Immunoglobulin I-set domain;
3627-3709 1.07e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 58.81  E-value: 1.07e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3627 KFTEGLRNEEATEGATAVLRCELS-KMAP-VEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLC----MCGK 3700
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGE 81


                   ....*....
gi 215274225  3701 ERTSAMLTV 3709
Cdd:pfam07679   82 AEASAELTV 90
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 7667-7871 1.11e-09

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270747 [Multi-domain]  Cd Length: 352  Bit Score: 64.32  E-value: 1.11e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIpyhpkDKTAVLR---------EYEALKGLRHPHLAQLHAAYLS 7737
Cdd:cd05596    23 MNAEDFDVIKVIGRGAFGEVQLVRHKSTKKVYAMKLL-----SKFEMIKrsdsaffweERDIMAHANSEWIVQLHYAFQD 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7738 PRHLVLILELCSGPELLPcLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLS 7817
Cdd:cd05596    98 DKYLYMVMDYMPGGDLVN-LMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDASGHLKLADFGTCMKMD 176

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7818 QEKVLPSDK---FKDYLetmAPELLEGQGAVP----QTDIWAIGVTAFIMLSAEYPVSSEG 7871
Cdd:cd05596   177 KDGLVRSDTavgTPDYI---SPEVLKSQGGDGvygrECDWWSVGVFLYEMLVGDTPFYADS 234
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
 7716-7866 1.19e-09

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 63.57  E-value: 1.19e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7716 EYEALKGLRHPHLAQLHAAYLSPR-HLVLILELCsGPELLPCLAERASYSE-----SEVKDYLWQMLSATQYLHNQ-HIL 7788
Cdd:cd14001    55 EAKILKSLNHPNIVGFRAFTKSEDgSLCLAMEYG-GKSLNDLIEERYEAGLgpfpaATILKVALSIARALEYLHNEkKIL 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7789 HLDLRSENMIIT-EYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLET---MAPELLEGQGAVP-QTDIWAIGVTAFIMLSA 7863
Cdd:cd14001   134 HGDIKSGNVLIKgDFESVKLCDFGVSLPLTENLEVDSDPKAQYVGTepwKAKEALEEGGVITdKADIFAYGLVLWEMMTL 213


                  ...
gi 215274225 7864 EYP 7866
Cdd:cd14001   214 SVP 216
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
 7667-7883 1.22e-09

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 63.20  E-value: 1.22e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAFQTQIQRGRFSVV-----RQCWEKASGRALAAKIIPYHPKDKTAvlREYEALKGLRHPHLAQLHAAYLS---- 7737
Cdd:cd14031     7 PGGRFLKFDIELGRGAFKTVykgldTETWVEVAWCELQDRKLTKAEQQRFK--EEAEMLKGLQHPNIVRFYDSWESvlkg 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7738 PRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMIIT-EYNLLKVVDLGNAQ 7814
Cdd:cd14031    85 KKCIVLVTELMTSGTLKTYLKRFKVMKPKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITgPTGSVKIGDLGLAT 164

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7815 SLSQ---EKVLPSDKFkdyletMAPELLEgQGAVPQTDIWAIGVTAFIMLSAEYPVSS-EGARDLQRGLRKGL 7883
Cdd:cd14031   165 LMRTsfaKSVIGTPEF------MAPEMYE-EHYDESVDVYAFGMCMLEMATSEYPYSEcQNAAQIYRKVTSGI 230
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
 6474-6677 1.22e-09

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 63.67  E-value: 1.22e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRvQHKGNKILCAAKFIPLRSRT----RAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd14158    23 LGEGGFGVVFK-GYINDKNVAVKKLAAMVDIStedlTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMPNGSL 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKG----VVTEAEVKVyIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREdiKICDFGFAQnitpAELQFSQ-- 6623
Cdd:cd14158   102 LDRLACLNdtppLSWHMRCKI-AQGTANGINYLHENNHIHRDIKSANILLDETFVP--KISDFGLAR----ASEKFSQti 174

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6624 -----YGSPEFVSPEIIqQNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLE 6677
Cdd:cd14158   175 mteriVGTTAYMAPEAL-RGEITPKSDIFSFGVVLLEIITGLPPVDENRDPQLLLDIKE 232
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3106-3181 1.22e-09

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 58.29  E-value: 1.22e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3106 TITEGEDLTLVCETSTCDIPVC-WTKDG-KTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA--GGACSSSIVRVH 3181
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVtWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnSSGSASSGTTLT 84
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 12-99 1.28e-09

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 58.40  E-value: 1.28e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   12 FLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKD---QQPVAAGARFRLAQDGDLYrlTILDLALGDSGQYVCRARNAI 88
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPEDDVF--FIVDVKIEDTGVYSCTAQNSA 79

                          90
                  ....*....|.
gi 215274225   89 GEAFAAVGLQV 99
Cdd:cd05763    80 GSISANATLTV 90
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3094-3169 1.31e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 57.96  E-value: 1.31e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  3094 KPSVFSrELTDATITEGEDLTLVCETSTCDIPVC-WTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA 3169
Cdd:pfam13927    1 KPVITV-SPSSVTVREGETVTLTCEATGSPPPTItWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 20-99 1.32e-09

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 58.67  E-value: 1.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   20 VVSVGKDATLSCQIVGNPTPQVSW-EKDQQPVAAGARFRLAQDGDLyrLTILDLALGDSGQYVCRARN-AIGEAFAAVGL 97
Cdd:cd20970    13 TAREGENATFMCRAEGSPEPEISWtRNGNLIIEFNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASNgVPGSVEKRITL 90


                  ..
gi 215274225   98 QV 99
Cdd:cd20970    91 QV 92
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
 7713-7870 1.35e-09

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 63.45  E-value: 1.35e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7713 VLREYEALKGLRHPHLAQLHAAYLSPR--HLVLILELCS-GPEL-LPCLAeraSYSESEVKDYLWQMLSATQYLHNQHIL 7788
Cdd:cd14199    72 VYQEIAILKKLDHPNVVKLVEVLDDPSedHLYMVFELVKqGPVMeVPTLK---PLSEDQARFYFQDLIKGIEYLHYQKII 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7789 HLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDyLETMAPELLEGQGAV---PQTDIWAIGVTAFIMLSAEY 7865
Cdd:cd14199   149 HRDVKPSNLLVGEDGHIKIADFGVSNEFEGSDALLTNTVGT-PAFMAPETLSETRKIfsgKALDVWAMGVTLYCFVFGQC 227


                  ....*
gi 215274225 7866 PVSSE 7870
Cdd:cd14199   228 PFMDE 232
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 109-201 1.35e-09

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 58.42  E-value: 1.35e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  109 APHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgEPDGPRVRVE-ELGEasaLRIRAARPRDGGTYEVRAE 187
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPL-QYAADRSTCEaGVGE---LHIQDVLPEDHGTYTCLAK 76

                          90
                  ....*....|....
gi 215274225  188 NPLGAASAAAALVV 201
Cdd:cd20976    77 NAAGQVSCSAWVTV 90
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
 7672-7912 1.41e-09

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 63.86  E-value: 1.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIP----YHPKDKTAVLREYEALKGL-RHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd05615    12 FNFLMVLGKGSFGKVMLAERKGSDELYAIKILKkdvvIQDDDVECTMVEKRVLALQdKPPFLTQLHSCFQTVDRLYFVME 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlPSDK 7826
Cdd:cd05615    92 YVNGGDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVEGV-TTRT 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7827 FKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRcyaGLSGGAVAFLRSTLC 7906
Cdd:cd05615   171 FCGTPDYIAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPK---SLSKEAVSICKGLMT 247


                  ....*.
gi 215274225 7907 AQPWGR 7912
Cdd:cd05615   248 KHPAKR 253
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 7686-7875 1.41e-09

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 63.21  E-value: 1.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7686 VRQCWEKASGRALAAKIIPYHPKD--KTAVLREYEALKGLRHPHLAQLHAAYL--SPRHLVLILELCSGPEL----LPCL 7757
Cdd:cd06621    17 VTKCRLRNTKTIFALKTITTDPNPdvQKQILRELEINKSCASPYIVKYYGAFLdeQDSSIGIAMEYCEGGSLdsiyKKVK 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK-FKDYLETMAP 7836
Cdd:cd06621    97 KKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFG----VSGELVNSLAGtFTGTSYYMAP 172

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7837 ELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:cd06621   173 ERIQGGPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPPL 211
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
 7680-7855 1.46e-09

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 63.04  E-value: 1.46e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAK-IIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLA 7758
Cdd:cd14222     3 KGFFGQAIKVTHKATGKVMVMKeLIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLR 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLP--------------S 7824
Cdd:cd14222    83 ADDPFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKKKPppdkpttkkrtlrkN 162

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 215274225 7825 DKFKDYLET-----MAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd14222   163 DRKKRYTVVgnpywMAPEMLNGKSYDEKVDIFSFGI 198
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2486-2542 1.48e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 57.72  E-value: 1.48e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 2486 VVLSCDFRPAPKA-VQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA 2542
Cdd:cd00096     1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
 7678-7855 1.50e-09

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 62.51  E-value: 1.50e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPyHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14065     1 LGKGFFGEVYKVTHRETGKVMVMKELK-RFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AE-RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLK---VVDLGNAQSLSQEKVLPSDKFKDYLET 7833
Cdd:cd14065    80 KSmDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRnavVADFGLAREMPDEKTKKPDRKKRLTVV 159

                         170       180
                  ....*....|....*....|....*..
gi 215274225 7834 -----MAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd14065   160 gspywMAPEMLRGESYDEKVDVFSFGI 186
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 248-328 1.56e-09

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 58.35  E-value: 1.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYedaqENFVLKIL-FCKQSDRGLYTCTASNLVGQTYS-SVL 325
Cdd:cd20958    11 TAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVF----PNGTLVIEnVQRSSDEGEYTCTARNQQGQSASrSVF 86


                  ...
gi 215274225  326 VVV 328
Cdd:cd20958    87 VKV 89
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1184-1240 1.65e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 57.72  E-value: 1.65e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1184 AMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
 7707-7888 1.66e-09

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 62.82  E-value: 1.66e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLvLILELCSgpelLPCLAERASYSESEVKDYL---W--QMLSATQY 7781
Cdd:cd05057    50 PKANEEILDEAYVMASVDHPHLVRLLGICLSSQVQ-LITQLMP----LGCLLDYVRNHRDNIGSQLllnWcvQIAKGMSY 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7782 LHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLS-QEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAF-I 7859
Cdd:cd05057   125 LEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDvDEKEYHAEGGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWeL 204

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7860 MLSAEYPVSSEGARDLQRGLRKGLvRLSR 7888
Cdd:cd05057   205 MTFGAKPYEGIPAVEIPDLLEKGE-RLPQ 232
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
 6472-6716 1.69e-09

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 62.57  E-value: 1.69e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVK----RVQHKgnkilCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSE 6547
Cdd:cd05114    10 KELGSGLFGVVRlgkwRAQYK-----VAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQfSQYGS 6626
Cdd:cd05114    85 CLLNYLrQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLV--NDTGVVKVSDFGMTRYVLDDQYT-SSSGA 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 P---EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSS-PFAGESDRATLLNVLEGRVSWSSPMAAHLsedAKDFIKATL 6702
Cdd:cd05114   162 KfpvKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKmPFESKSNYEVVEMVSRGHRLYRPKLASKS---VYEVMYSCW 238

                         250
                  ....*....|....
gi 215274225 6703 QRAPQARPSAAQCL 6716
Cdd:cd05114   239 HEKPEGRPTFADLL 252
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6355-6446 1.71e-09

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 57.79  E-value: 1.71e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6355 RPPSMQVTIedvqaqTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDStRLSQQQEgttYSLVLRHVASKDAGVYTCLAQNT 6434
Cdd:cd05725     2 KRPQNQVVL------VDDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDD---HSLKIRKVTAGDMGSYTCVAENM 71

                          90
                  ....*....|..
gi 215274225 6435 GGQVLCKAELLV 6446
Cdd:cd05725    72 VGKIEASATLTV 83
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 5134-5212 1.72e-09

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 58.29  E-value: 1.72e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5134 NQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEE-DDHYMINEDqqgGHQLIITAVVPADMGVYRCLAENSMGVSSTKA 5212
Cdd:cd20970    11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVREN---GTTLTIRNIRRSDMGIYLCIASNGVPGSVEKR 87
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 7677-7920 1.73e-09

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 62.91  E-value: 1.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHP---KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE--LCSgP 7751
Cdd:cd14049    13 RLGKGGYGKVYKVRNKLDGQYYAIKKILIKKvtkRDCMKVLREVKVLAGLQHPNIVGYHTAWMEHVQLMLYIQmqLCE-L 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVK--------------DYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL-LKVVDLGNA--- 7813
Cdd:cd14049    92 SLWDWIVERNKRPCEEEFksapytpvdvdvttKILQQLLEGVTYIHSMGIVHRDLKPRNIFLHGSDIhVRIGDFGLAcpd 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7814 QSLSQEKVLPSDKFKDYLET--------MAPELLEGQGAVPQTDIWAIGVTAFIMLSaeyPVSSEGAR-DLQRGLRKGLV 7884
Cdd:cd14049   172 ILQDGNDSTTMSRLNGLTHTsgvgtclyAAPEQLEGSHYDFKSDMYSIGVILLELFQ---PFGTEMERaEVLTQLRNGQI 248

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 215274225 7885 RLSRCYAGLSggAVAFLRSTLCAQPWGRPCASSCLQ 7920
Cdd:cd14049   249 PKSLCKRWPV--QAKYIKLLTSTEPSERPSASQLLE 282
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 255-318 1.82e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 57.34  E-value: 1.82e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  255 ARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDaQENFVLKILFCKQSDRGLYTCTASNLVG 318
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-LGNGTLTISNVTLEDSGTYTCVASNSAG 63
STKc_SNT7_plant cd14013
Catalytic domain of the Serine/Threonine kinase, Plant SNT7; STKs catalyze the transfer of the ...
 6564-6721 2.01e-09

Catalytic domain of the Serine/Threonine kinase, Plant SNT7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNT7 is a plant thylakoid-associated kinase that is essential in short- and long-term acclimation responses to cope with various light conditions in order to maintain photosynthetic redox poise for optimal photosynthetic performance. Short-term response involves state transitions over periods of minutes while the long-term response (LTR) occurs over hours to days and involves changing the relative amounts of photosystems I and II. SNT7 acts as a redox sensor and a signal transducer for both responses, which are triggered by the redox state of the plastoquinone (PQ) pool. It is positioned at the top of a phosphorylation cascade that induces state transitions by phosphorylating light-harvesting complex II (LHCII), and triggers the LTR through the phosphorylation of chloroplast proteins. The SNT7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270915 [Multi-domain]  Cd Length: 318  Bit Score: 63.23  E-value: 2.01e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6564 VKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREdIKICDFGFAQ------NITPAELQFS-QYGSPE-------- 6628
Cdd:cd14013   122 IKSIMRQILVALRKLHSTGIVHRDVKPQNIIVSEGDGQ-FKIIDLGAAAdlrigiNYIPKEFLLDpRYAPPEqyimstqt 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6629 ----------FVSPEIIQQNpVSEASDIWAMGVIsYLSLTCSSPfagESDRATLLNVLEGR------VSWSSPMAAHLSE 6692
Cdd:cd14013   201 psappapvaaALSPVLWQMN-LPDRFDMYSAGVI-LLQMAFPNL---RSDSNLIAFNRQLKqcdydlNAWRMLVEPRASA 275

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 6693 DAK--------------DFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14013   276 DLRegfeildlddgagwDLVTKLIRYKPRGRLSASAALAHPYF 318
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 29-99 2.02e-09

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 57.19  E-value: 2.02e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225   29 LSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGdlyRLTILDLALGDSGQYVCRARNAIGeaFAAVGLQV 99
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVARNTIG--YASVSMVL 68
I-set pfam07679
Immunoglobulin I-set domain;
1716-1793 2.08e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 58.04  E-value: 2.08e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1716 PQISERPcrrEPLVVKEHEDIILTATLATPSAATVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:pfam07679    1 PKFTQKP---KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA 75
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
 7694-7870 2.10e-09

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 62.84  E-value: 2.10e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7694 SGRALAAKIIPYHPKDK--TAVLREYEALKGLRHPHLAQLHAAYLSPR-HLVLILELCSGPELLPCLAERASYSESEVKD 7770
Cdd:cd06620    29 TGTIMAKKVIHIDAKSSvrKQILRELQILHECHSPYIVSFYGAFLNENnNIIICMEYMDCGSLDKILKKKGPFPEEVLGK 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7771 YLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpSDKFKDYLETMAPELLEGQGAVPQTD 7849
Cdd:cd06620   109 IAVAVLEGLTYLYNVHrIIHRDIKPSNILVNSKGQIKLCDFGVSGELINSI---ADTFVGTSTYMSPERIQGGKYSVKSD 185

                         170       180
                  ....*....|....*....|.
gi 215274225 7850 IWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd06620   186 VWSLGLSIIELALGEFPFAGS 206
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
 7676-7874 2.18e-09

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 62.74  E-value: 2.18e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAqLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd14149    18 TRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNIL-LFMGYMTKDNLAIVTQWCEGSSLYK 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CL-AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQ-----SLSQEKVLPSDKfkd 7829
Cdd:cd14149    97 HLhVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATvksrwSGSQQVEQPTGS--- 173

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7830 yLETMAPELLEGQGAVP---QTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd14149   174 -ILWMAPEVIRMQDNNPfsfQSDVYSYGIVLYELMTGELPYSHINNRD 220
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 6356-6446 2.24e-09

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 57.98  E-value: 2.24e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6356 PPSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTG 6435
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 215274225 6436 GQVLCKAELLV 6446
Cdd:cd20972    81 GSDTTSAEIFV 91
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 5129-5216 2.26e-09

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 57.91  E-value: 2.26e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5129 LTELQNQEVQDGYPVSFDCVVTG-QPMPSVRWFKDGKLL--EEDDHYMInEDQQGGHQLIITAVVPADMGVYRCLAENSM 5205
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELnrKRPKNIKI-RNKKKNSELQINKAKLEDSGEYTCVVENIL 81

                          90
                  ....*....|.
gi 215274225 5206 GVSSTKAELRV 5216
Cdd:cd05750    82 GKDTVTGNVTV 92
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3108-3180 2.29e-09

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 57.64  E-value: 2.29e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 3108 TEGEDLTLVCETSTCDIPVCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEAGGACSSSIVRV 3180
Cdd:cd20967    10 SKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
 7677-7861 2.29e-09

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270879 [Multi-domain]  Cd Length: 322  Bit Score: 62.96  E-value: 2.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYH-PKDKTAVLREYEALKGL--RHPHLAQL---------------HAAYLSP 7738
Cdd:cd13977     7 EVGRGSYGVVYEAVVRRTGARVAVKKIRCNaPENVELALREFWALSSIqrQHPNVIQLeecvlqrdglaqrmsHGSSKSD 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7739 RHLVLI---------------------LELCSGPELLPCLAERaSYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENM 7797
Cdd:cd13977    87 LYLLLVetslkgercfdprsacylwfvMEFCDGGDMNEYLLSR-RPDRQTNTSFMLQLSSALAFLHRNQIVHRDLKPDNI 165

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7798 IITEYN---LLKVVDLGNAQSLSQEKVLPSDKF---KDYLET-------MAPELLEGQgAVPQTDIWAIGVTAFIML 7861
Cdd:cd13977   166 LISHKRgepILKVADFGLSKVCSGSGLNPEEPAnvnKHFLSSacgsdfyMAPEVWEGH-YTAKADIFALGIIIWAMV 241
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 5267-5350 2.36e-09

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 57.52  E-value: 2.36e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   5267 RDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDG-QPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMGAAYSS 5345
Cdd:smart00410    2 PSVTVKEGES-VTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 215274225   5346 ARLLV 5350
Cdd:smart00410   81 TTLTV 85
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
 7707-7874 2.44e-09

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 62.39  E-value: 2.44e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAqLHAAYLSPRHLVLILELCSGPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQ 7785
Cdd:cd14151    45 PQQLQAFKNEVGVLRKTRHVNIL-LFMGYSTKPQLAIVTQWCEGSSLYHHLhIIETKFEMIKLIDIARQTAQGMDYLHAK 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7786 HILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlPSDKFKDYLET---MAPELLEGQGAVP---QTDIWAIGVTAFI 7859
Cdd:cd14151   124 SIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWS--GSHQFEQLSGSilwMAPEVIRMQDKNPysfQSDVYAFGIVLYE 201

                         170
                  ....*....|....*
gi 215274225 7860 MLSAEYPVSSEGARD 7874
Cdd:cd14151   202 LMTGQLPYSNINNRD 216
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
 7713-7854 2.55e-09

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 63.24  E-value: 2.55e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7713 VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGpELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDL 7792
Cdd:PTZ00024   67 TLRELKIMNEIKHENIMGLVDVYVEGDFINLVMDIMAS-DLKKVVDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDL 145

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7793 RSENMIITEYNLLKVVDLGNAQSLSQEKVLPS---DKFKDYLETM----------APELLEGQGAVPQT-DIWAIG 7854
Cdd:PTZ00024  146 SPANIFINSKGICKIADFGLARRYGYPPYSDTlskDETMQRREEMtskvvtlwyrAPELLMGAEKYHFAvDMWSVG 221
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 242-319 2.56e-09

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 57.75  E-value: 2.56e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  242 TGTRTCTVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVyEDAQENFVLKILFCKQSDRGLYTCTASNLVGQ 319
Cdd:cd05747     8 TKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQI-TSTEYKSTFEISKVQMSDEGNYTVVVENSEGK 84
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
 7715-7915 2.56e-09

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 61.99  E-value: 2.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSPR------HLVLILELCSGPellpCLAERASYSES----EVKDYLWQMLSATQYLHN 7784
Cdd:cd14012    47 KELESLKKLRHPNLVSYLAFSIERRgrsdgwKVYLLTEYAPGG----SLSELLDSVGSvpldTARRWTLQLLEALEYLHR 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7785 QHILHLDLRSENMIIT----EYNlLKVVD------LGNAQSLSQEKVLPSDKFKdyletmAPELLEGQGAV-PQTDIWAI 7853
Cdd:cd14012   123 NGVVHKSLHAGNVLLDrdagTGI-VKLTDyslgktLLDMCSRGSLDEFKQTYWL------PPELAQGSKSPtRKTDVWDL 195

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7854 GVTAFIMLSaeypvsseGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCAQPWGRPCA 7915
Cdd:cd14012   196 GLLFLQMLF--------GLDVLEKYTSPNPVLVS---LDLSASLQDFLSKCLSLDPKKRPTA 246
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
 7674-7883 2.83e-09

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 61.94  E-value: 2.83e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRF----------SVVRQCWEKASGRALAAKiipyhpkDKTAVLREYEALKGLRHPHLAQLHAAYLSP----R 7739
Cdd:cd14033     5 FNIEIGRGSFktvyrgldteTTVEVAWCELQTRKLSKG-------ERQRFSEEVEMLKGLQHPNIVRFYDSWKSTvrghK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7740 HLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMIIT-EYNLLKVVDLGNAqsl 7816
Cdd:cd14033    78 CIILVTELMTSGTLKTYLKRFREMKLKLLQRWSRQILKGLHFLHSRCppILHRDLKCDNIFITgPTGSVKIGDLGLA--- 154

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7817 sqekVLPSDKFKDYL----ETMAPELLEgQGAVPQTDIWAIGVTAFIMLSAEYPVSS-EGARDLQRGLRKGL 7883
Cdd:cd14033   155 ----TLKRASFAKSVigtpEFMAPEMYE-EKYDEAVDVYAFGMCILEMATSEYPYSEcQNAAQIYRKVTSGI 221
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 248-328 2.94e-09

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 57.40  E-value: 2.94e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTE--GRRHVvyedaqENFVLKILFCKQSDRGLYTCTASNLVGQTYSSVL 325
Cdd:cd20978    12 VVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGpmERATV------EDGTLTIINVQPEDTGYYGCVATNEIGDIYTETL 85


                  ...
gi 215274225  326 VVV 328
Cdd:cd20978    86 LHV 88
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 6108-6197 2.95e-09

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 57.47  E-value: 2.95e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                          90
                  ....*....|
gi 215274225 6188 LGSARASAEL 6197
Cdd:cd05892    81 AGVVSCNARL 90
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 110-201 3.31e-09

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 57.41  E-value: 3.31e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGPRVRVEELGEASALRIRAARPRDGGTYEVRAENP 189
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 215274225  190 LGAASAAAALVV 201
Cdd:cd05893    81 QGRISCTGRLMV 92
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2645-2720 3.35e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 56.80  E-value: 3.35e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  2645 KPVVFLKAlDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHV 2720
Cdd:pfam13927    1 KPVITVSP-SSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 7466-7552 3.36e-09

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 57.02  E-value: 3.36e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7466 LRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPL-ESSSRVLISATLKnfqlltILVVVAEDLGVYTCSVSNALGT 7544
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELpKGRYEILDDHSLK------IRKVTAGDMGSYTCVAENMVGK 74


                  ....*...
gi 215274225 7545 VTTTGVLR 7552
Cdd:cd05725    75 IEASATLT 82
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 7670-7863 3.39e-09

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 61.74  E-value: 3.39e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDktaVLREYEALKGLRHPHLAQLHAAYLSPRH--------- 7740
Cdd:cd14047     6 QDFKEIELIGSGGFGQVFKAKHRIDGKTYAIKRVKLNNEK---AEREVKALAKLDHPNIVRYNGCWDGFDYdpetsssns 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7741 -------LVLILELCSGPELLPCLAERASYSESEVK--DYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLG 7811
Cdd:cd14047    83 srsktkcLFIQMEFCEKGTLESWIEKRNGEKLDKVLalEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFG 162

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7812 NAQSLSQEkvLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSA 7863
Cdd:cd14047   163 LVTSLKND--GKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELLHV 212
PK_TRB cd13976
Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to ...
 7694-7924 3.41e-09

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270878 [Multi-domain]  Cd Length: 242  Bit Score: 61.29  E-value: 3.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7694 SGRALAAKIIPYhpKDKTAVLREYEALKGlrHPHLAQLHAAYLSPRHLVLILELCSGpELLPCLAERASYSESEVKDYLW 7773
Cdd:cd13976    17 TGEELVCKVVPV--PECHAVLRAYFRLPS--HPNISGVHEVIAGETKAYVFFERDHG-DLHSYVRSRKRLREPEAARLFR 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7774 QMLSATQYLHNQHILHLDLRSENMIIT--EYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETmAPELLEGQGAVP--QTD 7849
Cdd:cd13976    92 QIASAVAHCHRNGIVLRDLKLRKFVFAdeERTKLRLESLEDAVILEGEDDSLSDKHGCPAYV-SPEILNSGATYSgkAAD 170

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7850 IWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd13976   171 VWSLGVILYTMLVGRYPFHDSEPASLFAKIRRGQFAIP---ETLSPRARCLIRSLLRREPSERLTAEDILLHPWL 242
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 711-791 3.73e-09

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 56.87  E-value: 3.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  711 AAAREVLARLHEEAQLLAELSDQAAAVTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECVSRGGRIAYQLS 790
Cdd:cd20967     2 KAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELF 81


                  .
gi 215274225  791 V 791
Cdd:cd20967    82 V 82
STKc_SHIK cd13974
Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs ...
 6530-6718 3.99e-09

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270876 [Multi-domain]  Cd Length: 290  Bit Score: 62.04  E-value: 3.99e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6530 QFETRKTLILILE-LCSSE------ELLD------RLYRkgvVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMV 6596
Cdd:cd13974    90 TGRVRKRLCLVLDcLCAHDfsdktaDLINlqhyviREKR---LSEREALVIFYDVVRVVEALHKKNIVHRDLKLGNMVLN 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6597 HPAREdIKICDFGFAQN-ITPAELQFSQYGSPEFVSPEIIQQNPVS-EASDIWAMGVISYLSLTCSSPFAgESDRATLLN 6674
Cdd:cd13974   167 KRTRK-ITITNFCLGKHlVSEDDLLKDQRGSPAYISPDVLSGKPYLgKPSDMWALGVVLFTMLYGQFPFY-DSIPQELFR 244

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 6675 VLEGrVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSH 6718
Cdd:cd13974   245 KIKA-AEYTIPEDGRVSENTVCLIRKLLVLNPQKRLTASEVLDS 287
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
 7678-7924 4.00e-09

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 61.52  E-value: 4.00e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLR------HPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd14133     7 LGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLNkkdkadKYHIVRLKDVFYFKNHLCIVFELLSQN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 --ELLPCLAERAsYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN--LLKVVDLGNAQSLSQEkvLPSdkf 7827
Cdd:cd14133    87 lyEFLKQNKFQY-LSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSrcQIKIIDFGSSCFLTQR--LYS--- 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 kdYLETM---APELLEGQGAVPQTDIWAIGVTAFIMLSAE--YPVSSEGarDLqrgLRKGLVRLSRCYAGL--SGGA--- 7897
Cdd:cd14133   161 --YIQSRyyrAPEVILGLPYDEKIDMWSLGCILAELYTGEplFPGASEV--DQ---LARIIGTIGIPPAHMldQGKAdde 233

                         250       260
                  ....*....|....*....|....*....
gi 215274225 7898 --VAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14133   234 lfVDFLKKLLEIDPKERPTASQALSHPWL 262
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 4915-4984 4.10e-09

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 56.57  E-value: 4.10e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 4915 LRLECVVASKADVRARWLKDGVELTDGrHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKF-GQVTHSA 4984
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPS-SRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 6381-6436 4.17e-09

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 56.42  E-value: 4.17e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6381 EGDPQPSVTWYKDSVQLVDSTRLSQQQEGTtysLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd05746     8 QGDPEPTITWNKDGVQVTESGKFHISPEGY---LAIRDVGVADQGRYECVARNTIG 60
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6359-6444 4.23e-09

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 57.16  E-value: 4.23e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6359 MQVTIeDVQAQT---GGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTtysLVLRHVASKDAGVYTCLAQNTG 6435
Cdd:cd20957     2 LSATI-DPPVQTvdfGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV---LVIPSVKREDKGMYQCFVRNDG 77


                  ....*....
gi 215274225 6436 GQVLCKAEL 6444
Cdd:cd20957    78 DSAQATAEL 86
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 13-99 4.33e-09

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 56.63  E-value: 4.33e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   13 LTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGaRFRLAQDgdlYRLTILDLALGDSGQYVCRARNAIGEAF 92
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDD---HSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 215274225   93 AAVGLQV 99
Cdd:cd05725    77 ASATLTV 83
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2829-2901 4.49e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 56.42  E-value: 4.49e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  2829 IIKPLEDQWVAPGEDVELRCELSRAGTP-VHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVE 2901
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPtITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
 7712-7893 4.81e-09

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 61.60  E-value: 4.81e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7712 AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLA--ERASYSESEVKDYLWQMLSATQYLHNQHILH 7789
Cdd:cd05072    48 AFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEYMAKGSLLDFLKsdEGGKVLLPKLIDFSAQIAEGMAYIERKNYIH 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7790 LDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLS---AEYP 7866
Cdd:cd05072   128 RDLRAANVLVSESLMCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTygkIPYP 207

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7867 --VSSEGARDLQRGLRkgLVRLSRCYAGL 7893
Cdd:cd05072   208 gmSNSDVMSALQRGYR--MPRMENCPDEL 234
STKc_beta_ARK cd05606
Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs ...
 7678-7874 5.18e-09

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270757 [Multi-domain]  Cd Length: 279  Bit Score: 61.30  E-value: 5.18e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkDK---------TAVLREYEALK----GLRHPHLAQLHAAYLSPRHLVLI 7744
Cdd:cd05606     2 IGRGGFGEVYGCRKADTGKMYAMKCL-----DKkrikmkqgeTLALNERIMLSlvstGGDCPFIVCMTYAFQTPDKLCFI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd05606    77 LDLMNGGDLHYHLSQHGVFSEAEMRFYAAEVILGLEHMHNRFIVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHAS 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7825 DKFKDYletMAPE-LLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd05606   157 VGTHGY---MAPEvLQKGVAYDSSADWFSLGCMLYKLLKGHSPFRQHKTKD 204
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
 6469-6717 5.21e-09

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 61.21  E-value: 5.21e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNkilCAAKFIPLRSRTRAQAYRERDILAALS---HPLVTGLLDQFETRKTLILILELCS 6545
Cdd:cd14063     3 EIKEVIGKGRFGRVHRGRWHGD---VAIKLLNIDYLNEEQLEAFKEEVAAYKntrHDNLVLFMGACMDPPHLAIVTSLCK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLY-RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILmVHPARedIKICDFGFAqNITpaelQFSQY 6624
Cdd:cd14063    80 GRTLYSLIHeRKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIF-LENGR--VVITDFGLF-SLS----GLLQP 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 GSPE-----------FVSPEIIQ----------QNPVSEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGrvsws 6683
Cdd:cd14063   152 GRREdtlvipngwlcYLAPEIIRalspdldfeeSLPFTKASDVYAFGTVWYELLAGRWPFKEQPAESIIWQVGCG----- 226

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 215274225 6684 spMAAHLSE-----DAKDFIKATLQRAPQARPSAAQCLS 6717
Cdd:cd14063   227 --KKQSLSQldigrEVKDILMQCWAYDPEKRPTFSDLLR 263
I-set pfam07679
Immunoglobulin I-set domain;
3451-3533 5.45e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 56.88  E-value: 5.45e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3451 KFTEGLRNEEAVEGATAMLWCELSKVAP--VEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVC----GQ 3524
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDpeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 215274225  3525 ERTSATLTI 3533
Cdd:pfam07679   82 AEASAELTV 90
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 7462-7548 5.46e-09

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 56.87  E-value: 5.46e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7462 APTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLE-SSSRVLISATLKnfqLLTILVVVAEDLGVYTCSVSN 7540
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEAGVG---ELHIQDVLPEDHGTYTCLAKN 77


                  ....*...
gi 215274225 7541 ALGTVTTT 7548
Cdd:cd20976    78 AAGQVSCS 85
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 13-93 5.62e-09

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 56.48  E-value: 5.62e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   13 LTRPKAFVVSV-GKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDlyrLTILDLALGDSGQYVCRARNAIGEA 91
Cdd:cd20968     2 ITRPPTNVTIIeGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGS---LRIHNVQKEDAGQYRCVAKNSLGIA 78


                  ..
gi 215274225   92 FA 93
Cdd:cd20968    79 YS 80
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 5131-5214 5.66e-09

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 56.43  E-value: 5.66e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5131 ELQNQEVQDGYPVSFDC-VVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGHQLIITAVVPADMGVYRCLAENSMGVSS 5209
Cdd:pfam00047    2 APPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81


                   ....*
gi 215274225  5210 TKAEL 5214
Cdd:pfam00047   82 LSTSL 86
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
 7685-7912 5.85e-09

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 61.21  E-value: 5.85e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7685 VVRQCWekaSGRALAAKIIPYHPKDKTA-----VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAE 7759
Cdd:cd14145    22 VYRAIW---IGDEVAVKAARHDPDEDISqtienVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSG 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESEVkDYLWQMLSATQYLHNQHI---LHLDLRSENMIITEY--------NLLKVVDLGNAQSLSQEKVLPSDKFK 7828
Cdd:cd14145    99 KRIPPDILV-NWAVQIARGMNYLHCEAIvpvIHRDLKSSNILILEKvengdlsnKILKITDFGLAREWHRTTKMSAAGTY 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7829 DYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVssegardlqrglrKGLVRLSRCYaGLSGGAVAFLRSTLCAQ 7908
Cdd:cd14145   178 AW---MAPEVIRSSMFSKGSDVWSYGVLLWELLTGEVPF-------------RGIDGLAVAY-GVAMNKLSLPIPSTCPE 240


                  ....
gi 215274225 7909 PWGR 7912
Cdd:cd14145   241 PFAR 244
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 115-191 5.87e-09

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 56.69  E-value: 5.87e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  115 RPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgEPDGPRVRveELGEASALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd04978     5 EPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPI-EPAPEDMR--RTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 6357-6447 5.97e-09

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 56.59  E-value: 5.97e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6357 PSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSvQLVDSTRLSQQQEGTT---YSLVLRHVASKDAGVYTCLAQN 6433
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDG-QVISTSTLPGVQISFSdgrAKLSIPAVTKANSGRYSLTATN 79

                          90
                  ....*....|....
gi 215274225 6434 TGGQVLCKAELLVL 6447
Cdd:cd20974    80 GSGQATSTAELLVL 93
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
 6469-6652 6.07e-09

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 60.77  E-value: 6.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVKRVQHKGNKIlcAAKFIplRSRTRAQAY-RERDILAALSHPLVTGLLDQF-ETRKTLILILELCSS 6546
Cdd:cd05082     9 KLLQTIGKGEFGDVMLGDYRGNKV--AVKCI--KNDATAQAFlAEASVMTQLRHSNLVQLLGVIvEEKGGLYIVTEYMAK 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6547 EELLDRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpAREDI-KICDFGFAQNITpaELQFSQ 6623
Cdd:cd05082    85 GSLVDYLRSRGrsVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLV---SEDNVaKVSDFGLTKEAS--STQDTG 159

                         170       180
                  ....*....|....*....|....*....
gi 215274225 6624 YGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd05082   160 KLPVKWTAPEALREKKFSTKSDVWSFGIL 188
I-set pfam07679
Immunoglobulin I-set domain;
1450-1527 6.07e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 56.50  E-value: 6.07e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1450 REVQAQAGASTTLSCEVAQAQT-EVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSC----EAGSQRLSFH 1524
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnSAGEAEASAE 87


                   ...
gi 215274225  1525 LHV 1527
Cdd:pfam07679   88 LTV 90
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
 7680-7874 6.28e-09

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 61.23  E-value: 6.28e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDK--TAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPcL 7757
Cdd:cd14046    16 KGAFGQVVKVRNKLDGRYYAIKKIKLRSESKnnSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCEKSTLRD-L 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSEsevKDYLW----QMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS--------- 7824
Cdd:cd14046    95 IDSGLFQD---TDRLWrlfrQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLATSNKLNVELATqdinkstsa 171

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 -DKFKDYLETM-------APELLEGQGAV--PQTDIWAIGVTAFIMLsaeYPVSSEGARD 7874
Cdd:cd14046   172 aLGSSGDLTGNvgtalyvAPEVQSGTKSTynEKVDMYSLGIIFFEMC---YPFSTGMERV 228
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 807-883 6.32e-09

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 56.48  E-value: 6.32e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  807 VDAVAGGPAQFECETSEAHVHVHWYKDGMELGHSGeRFLQEDVGTRHRLVAATVTRQDEGTYSCRVGEDSVDFRLRV 883
Cdd:cd20967     7 VQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSS-KVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
4511-4603 6.91e-09

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 63.10  E-value: 6.91e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4511 AVASArLTVLGLPDPPEDAEVVARSSHTVTLSWAAPMSdggGGLCGYRVEVKEGATGQWRLCHELVPGPECVVDGLAPGE 4590
Cdd:COG3401   316 NVVSV-TTDLTPPAAPSGLTATAVGSSSITLSWTASSD---ADVTGYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPGT 391

                          90
                  ....*....|...
gi 215274225 4591 TYRFRVAAVGPVG 4603
Cdd:COG3401   392 TYYYKVTAVDAAG 404
STKc_CK1 cd14016
Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the ...
 6468-6611 7.02e-09

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270918 [Multi-domain]  Cd Length: 266  Bit Score: 60.93  E-value: 7.02e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPlRSRTRAQAYRERDILAALS-HPLVTGLLDQFETRKTLILILEL--C 6544
Cdd:cd14016     2 YKLVKKIGSGSFGEVYLGIDLKTGEEVAIKIEK-KDSKHPQLEYEAKVYKLLQgGPGIPRLYWFGQEGDYNVMVMDLlgP 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6545 SSEELLDrlYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARED-IKICDFGFA 6611
Cdd:cd14016    81 SLEDLFN--KCGRKFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLMGLGKNSNkVYLIDFGLA 146
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 11-99 7.21e-09

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 56.30  E-value: 7.21e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   11 RFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPV-AAGARFRLAQDGDLYRLTIldLALGDSGQYVCRARNAIG 89
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIePAPEDMRRTVDGRTLIFSN--LQPNDTAVYQCNASNVHG 78

                          90
                  ....*....|
gi 215274225   90 EAFAAVGLQV 99
Cdd:cd04978    79 YLLANAFLHV 88
PHA03210 PHA03210
serine/threonine kinase US3; Provisional
 7774-7889 7.42e-09

serine/threonine kinase US3; Provisional


Pssm-ID: 165476 [Multi-domain]  Cd Length: 501  Bit Score: 62.79  E-value: 7.42e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7774 QMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAI 7853
Cdd:PHA03210  275 QLLCAVEYIHDKKLIHRDIKLENIFLNCDGKIVLGDFGTAMPFEKEREAFDYGWVGTVATNSPEILAGDGYCEITDIWSC 354

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 215274225 7854 GVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRC 7889
Cdd:PHA03210  355 GLILLDMLSHDFCPIGDGGGKPGKQLLKIIDSLSVC 390
STKc_Mnk1 cd14174
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
 7680-7866 8.25e-09

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271076 [Multi-domain]  Cd Length: 289  Bit Score: 61.20  E-value: 8.25e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHP-KDKTAVLREYEALKGLR-HPHLAQLHAAYLSPRHLVLILELCSGPELLPCL 7757
Cdd:cd14174    12 EGAYAKVQGCVSLQNGKEYAVKIIEKNAgHSRSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLRGGSILAHI 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7758 AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI-----------ITEYNLLKVVDLGNAQS--LSQEKVLPS 7824
Cdd:cd14174    92 QKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILcespdkvspvkICDFDLGSGVKLNSACTpiTTPELTTPC 171

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7825 DKfkdyLETMAPELLE--GQGAV---PQTDIWAIGVTAFIMLSAeYP 7866
Cdd:cd14174   172 GS----AEYMAPEVVEvfTDEATfydKRCDLWSLGVILYIMLSG-YP 213
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
 7671-7866 8.32e-09

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 60.81  E-value: 8.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP----KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd05630     1 TFRQYRVLGKGGFGEVCACQVRATGKMYACKKLEKKRikkrKGEAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAE--RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLps 7824
Cdd:cd05630    81 LMNGGDLKFHIYHmgQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHVPEGQTI-- 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 7825 dkfKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05630   159 ---KGRVGTvgyMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSP 200
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
 6469-6725 8.50e-09

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 61.16  E-value: 8.50e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFG--FVKRVQHKGNKILCAAKFIPLRSR-----TRAQAyrERDILAALSHPLVTGLLDQFETRKTLILIL 6541
Cdd:cd08216     1 ELLYEIGKCFKGggVVHLAKHKPTNTLVAVKKINLESDskedlKFLQQ--EILTSRQLQHPNILPYVTSFVVDNDLYVVT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELC---SSEELLDRLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaREDIKICDFGFAQNITPAE 6618
Cdd:cd08216    79 PLMaygSCRDLLKTHFPEGL-PELAIAFILRDVLNALEYIHSKGYIHRSVKASHILI----SGDGKVVLSGLRYAYSMVK 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6619 LQFSQ---YGSPEF-------VSPEIIQQN--PVSEASDIWAMGVISylsltCS-----SPFAGESDRATLLNVLEG--- 6678
Cdd:cd08216   154 HGKRQrvvHDFPKSseknlpwLSPEVLQQNllGYNEKSDIYSVGITA-----CElangvVPFSDMPATQMLLEKVRGttp 228

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 6679 ----------------------------RVSWSSPMAAHLSEDAKDFIKATLQRAPQARPSAAQCLSHPwFLKSM 6725
Cdd:cd08216   229 qlldcstypleedsmsqsedsstehpnnRDTRDIPYQRTFSEAFHQFVELCLQRDPELRPSASQLLAHS-FFKQC 302
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
 7678-7874 8.58e-09

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270740 [Multi-domain]  Cd Length: 328  Bit Score: 61.28  E-value: 8.58e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyhpkdKTAVLREYEALKGLR-----------HPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd05588     3 IGRGSYAKVLMVELKKTKRIYAMKVI------KKELVNDDEDIDWVQtekhvfetasnHPFLVGLHSCFQTESRLFFVIE 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK 7826
Cdd:cd05588    77 FVNGGDLMFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGHIKLTDYG----MCKEGLRPGDT 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7827 FKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARD 7874
Cdd:cd05588   153 TSTFCGTpnyIAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPFDIVGSSD 203
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 7709-7855 8.60e-09

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 60.50  E-value: 8.60e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7709 DKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSE-SEVKDYLWQMLSATQYLHNQHI 7787
Cdd:cd05068    46 DPEDFLREAQIMKKLRHPKLIQLYAVCTLEEPIYIITELMKHGSLLEYLQGKGRSLQlPQLIDMAAQVASGMAYLESQNY 125

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7788 LHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSD---KFKdyLETMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05068   126 IHRDLAARNVLVGENNICKVADFGLARVIKVEDEYEARegaKFP--IKWTAPEAANYNRFSIKSDVWSFGI 194
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 5260-5331 8.65e-09

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 55.65  E-value: 8.65e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQY 5331
Cdd:pfam13927    2 PVITVSPSSVTVREGET-VTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTY 72
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
 7674-7855 9.16e-09

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270939 [Multi-domain]  Cd Length: 277  Bit Score: 60.76  E-value: 9.16e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVV--RQCWEKASGRALAAKIIPyHPKDKTAVLREYEALKGLR-HPHLAQL---HAAYLSP-RHLVLIL- 7745
Cdd:cd14037     7 IEKYLAEGGFAHVylVKTSNGGNRAALKRVYVN-DEHDLNVCKREIEIMKRLSgHKNIVGYidsSANRSGNgVYEVLLLm 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHN--QHILHLDLRSENMIITEYNLLKVVDLGNAqslsQEKV 7821
Cdd:cd14037    86 EYCKGGGVIDLMNQRLQtgLTESEILKIFCDVCEAVAAMHYlkPPLIHRDLKVENVLISDSGNYKLCDFGSA----TTKI 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 7822 LPSDKFKD--YLE-------TM---APELLE---GQGAVPQTDIWAIGV 7855
Cdd:cd14037   162 LPPQTKQGvtYVEedikkytTLqyrAPEMIDlyrGKPITEKSDIWALGC 210
PHA03211 PHA03211
serine/threonine kinase US3; Provisional
 6507-6652 9.41e-09

serine/threonine kinase US3; Provisional


Pssm-ID: 223009 [Multi-domain]  Cd Length: 461  Bit Score: 62.22  E-value: 9.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6507 AQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHL 6586
Cdd:PHA03211  205 ASSVHEARLLRRLSHPAVLALLDVRVVGGLTCLVLPKYRSDLYTYLGARLRPLGLAQVTAVARQLLSAIDYIHGEGIIHR 284

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6587 DIKPSNILMVHParEDIKICDFG---FAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:PHA03211  285 DIKTENVLVNGP--EDICLGDFGaacFARGSWSTPFHYGIAGTVDTNAPEVLAGDPYTPSVDIWSAGLV 351
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
 7678-7854 9.70e-09

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 61.23  E-value: 9.70e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPyHPKD--KTA--VLREYEALKGLRHPHLAQLHAAYLSP------RHLVLILEL 7747
Cdd:cd07855    13 IGSGAYGVVCSAIDTKSGQKVAIKKIP-NAFDvvTTAkrTLRELKILRHFKHDNIIAIRDILRPKvpyadfKDVYVVLDL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 ----------CSGPellpclaerasYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLS 7817
Cdd:cd07855    92 mesdlhhiihSDQP-----------LTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGLC 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7818 QEKVLPSDKFKDYLETM---APELL----EGQGAVpqtDIWAIG 7854
Cdd:cd07855   161 TSPEEHKYFMTEYVATRwyrAPELMlslpEYTQAI---DMWSVG 201
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
 7725-7880 1.01e-08

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 61.09  E-value: 1.01e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7725 HPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL 7804
Cdd:cd05619    65 HPFLTHLFCTFQTKENLFFVMEYLNGGDLMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGH 144

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7805 LKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLR 7880
Cdd:cd05619   145 IKIADFG----MCKENMLGDAKTSTFCGTpdyIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEEELFQSIR 219
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
 6472-6717 1.04e-08

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 60.28  E-value: 1.04e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGnKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLD 6551
Cdd:cd05113    10 KELGTGQFGVVKYGKWRG-QYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLN 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6552 --RLYRKGVvTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQfSQYGSP-- 6627
Cdd:cd05113    89 ylREMRKRF-QTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLV--NDQGVVKVSDFGLSRYVLDDEYT-SSVGSKfp 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 -EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSS-PFAGESDRATLLNVLEGRVSWSSPMAahlSEDAKDFIKATLQRA 6705
Cdd:cd05113   165 vRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKmPYERFTNSETVEHVSQGLRLYRPHLA---SEKVYTIMYSCWHEK 241

                         250
                  ....*....|..
gi 215274225 6706 PQARPSAAQCLS 6717
Cdd:cd05113   242 ADERPTFKILLS 253
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 23-102 1.06e-08

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 56.09  E-value: 1.06e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   23 VGKDATLSCQIVGNPTPQVSWEKDQQPVAAGA-RFRLAQDGDlyRLTILDLALGDSGQYVCRARNAIGEAFAAVGLQVDA 101
Cdd:cd05730    17 LGQSVTLACDADGFPEPTMTWTKDGEPIESGEeKYSFNEDGS--EMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVFA 94


                  .
gi 215274225  102 E 102
Cdd:cd05730    95 K 95
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
 7707-7874 1.07e-08

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 60.42  E-value: 1.07e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAqLHAAYLSPRHLVLILELCSGPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQ 7785
Cdd:cd14150    37 PEQLQAFKNEMQVLRKTRHVNIL-LFMGFMTRPNFAIITQWCEGSSLYRHLhVTETRFDTMQLIDVARQTAQGMDYLHAK 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7786 HILHLDLRSENMIITEYNLLKVVDLGNAQ-----SLSQEKVLPSDKfkdyLETMAPELLEGQGAVP---QTDIWAIGVTA 7857
Cdd:cd14150   116 NIIHRDLKSNNIFLHEGLTVKIGDFGLATvktrwSGSQQVEQPSGS----ILWMAPEVIRMQDTNPysfQSDVYAYGVVL 191

                         170
                  ....*....|....*..
gi 215274225 7858 FIMLSAEYPVSSEGARD 7874
Cdd:cd14150   192 YELMSGTLPYSNINNRD 208
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2170-2250 1.08e-08

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 55.71  E-value: 1.08e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2170 RPLQDVVTTEK-EKVTLECELSRPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAHDAQSSASV 2248
Cdd:cd20967     1 KKAQPAVQVSKgHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 2249 KV 2250
Cdd:cd20967    81 FV 82
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1541-1608 1.09e-08

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 55.65  E-value: 1.09e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  1541 SREVQAEAGTSATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA 1608
Cdd:pfam13927    8 PSSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
 6472-6652 1.11e-08

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 60.27  E-value: 1.11e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKIlcAAKFIplRSRTRAQAY-RERDILAALSHPLVTGLLDQFeTRKTLILILELCSSEELL 6550
Cdd:cd05083    12 EIIGEGEFGAVLQGEYMGQKV--AVKNI--KCDVTAQAFlEETAVMTKLQHKNLVRLLGVI-LHNGLYIVMELMSKGNLV 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6551 DRLYRKG--VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFAQnITPAELQFSQYgS 6626
Cdd:cd05083    87 NFLRSRGraLVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILV----SEDgvAKISDFGLAK-VGSMGVDNSRL-P 160

                         170       180
                  ....*....|....*....|....*.
gi 215274225 6627 PEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd05083   161 VKWTAPEALKNKKFSSKSDVWSYGVL 186
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 7468-7543 1.18e-08

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 55.48  E-value: 1.18e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  7468 ELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISAtlknfqlltilvVVAEDLGVYTCSVSNALG 7543
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTLS------------VSAEDSGTYTCVARNGRG 68
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 7462-7548 1.20e-08

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 55.67  E-value: 1.20e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7462 APTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISatlKNFQLLTILVVVA--EDLGVYTCSVS 7539
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIH---QEGDLHSLIIAEAfeEDTGRYSCLAT 77


                  ....*....
gi 215274225 7540 NALGTVTTT 7548
Cdd:cd20972    78 NSVGSDTTS 86
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 6358-6447 1.21e-08

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 55.70  E-value: 1.21e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6358 SMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYS-LVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd05763     1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDvFFIVDVKIEDTGVYSCTAQNSAG 80

                          90
                  ....*....|.
gi 215274225 6437 QVLCKAELLVL 6447
Cdd:cd05763    81 SISANATLTVL 91
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 249-328 1.22e-08

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 55.54  E-value: 1.22e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  249 VTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQenfvLKILFCKQSDRGLYTCTASNLVGQTYSSVLVVV 328
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS----LKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3894-3974 1.24e-08

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 55.33  E-value: 1.24e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3894 EPLQ-SLQAEEGSTATLQCELSEPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCTCGSQATSATL 3972
Cdd:cd20967     1 KKAQpAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 3973 TV 3974
Cdd:cd20967    81 FV 82
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
 7678-7855 1.24e-08

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 59.84  E-value: 1.24e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIipYHPK-DKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd14156     1 IGSGFFSKVYKVTHGATGKVMVVKI--YKNDvDQHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEEL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LA-ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSEN-----------MIITEYNLLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd14156    79 LArEELPLSWREKVELACDISRGMVYLHSKNIYHRDLNSKNclirvtprgreAVVTDFGLAREVGEMPANDPERKLSLVG 158

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 7825 DKFkdyleTMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd14156   159 SAF-----WMAPEMLRGEPYDRKVDVFSFGI 184
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
 6472-6662 1.26e-08

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 60.41  E-value: 1.26e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKR-----VQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVT---GLLDQfETRKTLILILEL 6543
Cdd:cd14205    10 QQLGKGNFGSVEMcrydpLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVkykGVCYS-AGRRNLRLIMEY 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQnITPAELQFS 6622
Cdd:cd14205    89 LPYGSLRDYLQKhKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENR--VKIGDFGLTK-VLPQDKEYY 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6623 QYGSPE-----FVSPEIIQQNPVSEASDIWAMGVI-----SYLSLTCSSP 6662
Cdd:cd14205   166 KVKEPGespifWYAPESLTESKFSVASDVWSFGVVlyelfTYIEKSKSPP 215
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1170-1248 1.29e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 55.62  E-value: 1.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1170 QSVHnevqaeAGTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKGctrRLVVQQVGKADAGEYSCEAGGQRVSFQ 1248
Cdd:cd20957    11 QTVD------FGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQ 81
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
 7672-7870 1.29e-08

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 60.35  E-value: 1.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKII-----------PYHPK---DKTA-------------VLREYEALKGLR 7724
Cdd:cd14200     2 YKLQSEIGKGSYGVVKLAYNESDDKYYAMKVLskkkllkqygfPRRPPprgSKAAqgeqakplaplerVYQEIAILKKLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7725 HPHLAQLHAAYLSPR--HLVLILELC-SGPEL-LPClaeRASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT 7800
Cdd:cd14200    82 HVNIVKLIEVLDDPAedNLYMVFDLLrKGPVMeVPS---DKPFSEDQARLYFRDIVLGIEYLHYQKIVHRDIKPSNLLLG 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7801 EYNLLKVVDL-------GNAQSLSQEKVLPSdkfkdyleTMAPELLE--GQGAVPQT-DIWAIGVTAFIMLSAEYPVSSE 7870
Cdd:cd14200   159 DDGHVKIADFgvsnqfeGNDALLSSTAGTPA--------FMAPETLSdsGQSFSGKAlDVWAMGVTLYCFVYGKCPFIDE 230
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 5265-5350 1.31e-08

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 55.60  E-value: 1.31e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5265 ELRDLQVAPGTRLAKFQLKVKGYPAPRLYWFKDGQPLTA--SAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMGAA 5342
Cdd:cd05750     5 EMKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRkrPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKD 84


                  ....*...
gi 215274225 5343 YSSARLLV 5350
Cdd:cd05750    85 TVTGNVTV 92
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
 6472-6711 1.44e-08

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 59.82  E-value: 1.44e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFIPL---RSRTRAQAYRE---------RDIL---AALSHPLvtGLLDQFETRKT 6536
Cdd:cd14025     2 EKVGSGGFGQVYKVRHKHWKTWLAIKCPPSlhvDDSERMELLEEakkmemakfRHILpvyGICSEPV--GLVMEYMETGS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6537 LILILelcSSEELLDRLyRKGVVTEAEVkvyiqqlveGLHYLHSHG--VLHLDIKPSNILMvhPAREDIKICDFGFAQ-N 6613
Cdd:cd14025    80 LEKLL---ASEPLPWEL-RFRIIHETAV---------GMNFLHCMKppLLHLDLKPANILL--DAHYHVKISDFGLAKwN 144

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6614 ITPAELQFSQ---YGSPEFVSPEIIQQN--PVSEASDIWAMGVISYLSLTCSSPFAGESDRAT-LLNVLEGR------VS 6681
Cdd:cd14025   145 GLSHSHDLSRdglRGTIAYLPPERFKEKnrCPDTKHDVYSFAIVIWGILTQKKPFAGENNILHiMVKVVKGHrpslspIP 224

                         250       260       270
                  ....*....|....*....|....*....|
gi 215274225 6682 WSSPMAAhlsEDAKDFIKATLQRAPQARPS 6711
Cdd:cd14025   225 RQRPSEC---QQMICLMKRCWDQDPRKRPT 251
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
 7707-7882 1.44e-08

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 60.47  E-value: 1.44e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPrhlvlILELCSgpELLP--CLAERASYSESEVKDYL---W--QMLSAT 7779
Cdd:cd05110    50 PKANVEFMDEALIMASMDHPHLVRLLGVCLSP-----TIQLVT--QLMPhgCLLDYVHEHKDNIGSQLllnWcvQIAKGM 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7780 QYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLS-QEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd05110   123 MYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEgDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIW 202

                         170       180
                  ....*....|....*....|....*
gi 215274225 7859 -IMLSAEYPVSSEGARDLQRGLRKG 7882
Cdd:cd05110   203 eLMTFGGKPYDGIPTREIPDLLEKG 227
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3633-3709 1.55e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 55.20  E-value: 1.55e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3633 RNEEATEGATAVLRCELSKMAP--VEWWK-GHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLCMC----GKERTSA 3705
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3706 MLTV 3709
Cdd:smart00410   82 TLTV 85
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 5133-5216 1.58e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 55.23  E-value: 1.58e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5133 QNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQqgghQLIITAVVPADMGVYRCLAENSMGVSSTKA 5212
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED----VLVIPSVKREDKGMYQCFVRNDGDSAQATA 84


                  ....
gi 215274225 5213 ELRV 5216
Cdd:cd20957    85 ELKL 88
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
 7677-7880 1.68e-08

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 59.56  E-value: 1.68e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAK----IIPyhPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd05084     3 RIGRGNFGEVFSGRLRADNTPVAVKscreTLP--PDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCL-AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDY- 7830
Cdd:cd05084    81 FLTFLrTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREEEDGVYAATGGMKQIp 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7831 LETMAPELLEGQGAVPQTDIWAIGV---TAFIMLSAEYP-VSSEGARD-LQRGLR 7880
Cdd:cd05084   161 VKWTAPEALNYGRYSSESDVWSFGIllwETFSLGAVPYAnLSNQQTREaVEQGVR 215
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
 6473-6651 1.71e-08

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 59.57  E-value: 1.71e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6473 EIGRGVFGFVKRVQHKGNK--ILCAAKFIPLRSR--TRAQAYRERDILAALSHPLVTGLLDQFETrKTLILILELCSSEE 6548
Cdd:cd05115    11 ELGSGNFGCVKKGVYKMRKkqIDVAIKVLKQGNEkaVRDEMMREAQIMHQLDNPYIVRMIGVCEA-EALMLVMEMASGGP 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLY-RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQNITPAElqfSQYGSP 6627
Cdd:cd05115    90 LNKFLSgKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVN--QHYAKISDFGLSKALGADD---SYYKAR 164

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 6628 EF-------VSPEIIQQNPVSEASDIWAMGV 6651
Cdd:cd05115   165 SAgkwplkwYAPECINFRKFSSRSDVWSYGV 195
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
 6567-6711 1.71e-08

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 61.19  E-value: 1.71e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6567 YIQQLVEGLHYLHSHGVLHLDIKPSNILMVHParEDIKICDFGFAQNITpAELQFSQYGSP----EFVSPEIIQQNPVSE 6642
Cdd:cd05105   242 FTYQVARGMEFLASKNCVHRDLAARNVLLAQG--KIVKICDFGLARDIM-HDSNYVSKGSTflpvKWMAPESIFDNLYTT 318

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6643 ASDIWAMGVISY--LSLTcSSPFAGESDRATLLNVLEGRVSWSSPmaAHLSEDAKDFIKATLQRAPQARPS 6711
Cdd:cd05105   319 LSDVWSYGILLWeiFSLG-GTPYPGMIVDSTFYNKIKSGYRMAKP--DHATQEVYDIMVKCWNSEPEKRPS 386
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 7471-7552 1.72e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 55.23  E-value: 1.72e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7471 DETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATlknfQLLTILVVVAEDLGVYTCSVSNALGTVTTTGV 7550
Cdd:cd20957    10 VQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSE----DVLVIPSVKREDKGMYQCFVRNDGDSAQATAE 85


                  ..
gi 215274225 7551 LR 7552
Cdd:cd20957    86 LK 87
I-set pfam07679
Immunoglobulin I-set domain;
2560-2642 1.83e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 55.34  E-value: 1.83e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2560 VTGPLQDAEATEEGWASFSCELS-HEDEEVEWSLNGMPLYNDSFHEISHKGRRHTLVLKSIQRADAGI--VRA--SSLKV 2634
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKytCVAtnSAGEA 82


                   ....*...
gi 215274225  2635 STSARLEV 2642
Cdd:pfam07679   83 EASAELTV 90
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 5380-5456 1.84e-08

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 55.21  E-value: 1.84e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 5380 KKVKKGSSITFSVKVEGRPVPTVHWLREeaerGVLWIGPDTpGYTVASSAQqhSLVLLDVGRQHQGTYTCIASNAAG 5456
Cdd:cd20970    12 VTAREGENATFMCRAEGSPEPEISWTRN----GNLIIEFNT-RYIVRENGT--TLTIRNIRRSDMGIYLCIASNGVP 81
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 7678-7924 1.91e-08

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 59.17  E-value: 1.91e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPyhpkdKTAVlREYEALKGLR----------------HPHLAQLHAAYLSPRHL 7741
Cdd:cd14005     8 LGKGGFGTVYSGVRIRDGLPVAVKFVP-----KSRV-TEWAMINGPVpvpleialllkaskpgVPGVIRLLDWYERPDGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7742 VLILELcsgPEllPC------LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL-LKVVDLGNAQ 7814
Cdd:cd14005    82 LLIMER---PE--PCqdlfdfITERGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLINLRTGeVKLIDFGCGA 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7815 sLSQEKVlpsdkFKDYLET---MAPELLEGQ--GAVPQTdIWAIGVTAFIMLSAEYPVSsegaRDLQRGLRKGLVRlsrc 7889
Cdd:cd14005   157 -LLKDSV-----YTDFDGTrvySPPEWIRHGryHGRPAT-VWSLGILLYDMLCGDIPFE----NDEQILRGNVLFR---- 221

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 215274225 7890 yAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14005   222 -PRLSKECCDLISRCLQFDPSKRPSLEQILSHPWF 255
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
 6477-6715 1.94e-08

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 59.44  E-value: 1.94e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6477 GVFGFVKRVQHK--GNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLy 6554
Cdd:cd14027     4 GGFGKVSLCFHRtqGLVVLKTVYTGPNCIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVL- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6555 rKGVVTEAEVKV-YIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaRED--IKICDFGFAQNITPAELQFSQY------- 6624
Cdd:cd14027    83 -KKVSVPLSVKGrIILEIIEGMAYLHGKGVIHKDLKPENILV----DNDfhIKIADLGLASFKMWSKLTKEEHneqrevd 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6625 -------GSPEFVSPEIIQQNPV--SEASDIWAMGVISYLSLTCSSPFagESDRATlLNVLEGRVSWSSPMAAHLSE--- 6692
Cdd:cd14027   158 gtakknaGTLYYMAPEHLNDVNAkpTEKSDVYSFAIVLWAIFANKEPY--ENAINE-DQIIMCIKSGNRPDVDDITEycp 234

                         250       260
                  ....*....|....*....|....
gi 215274225 6693 -DAKDFIKATLQRAPQARPSAAQC 6715
Cdd:cd14027   235 rEIIDLMKLCWEANPEARPTFPGI 258
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 6107-6199 1.96e-08

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 55.33  E-value: 1.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6107 PPRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLT-TGNKFQtlSEPRSGLlvLVIRAASKEDLGLYECELV 6185
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRST--CEAGVGE--LHIQDVLPEDHGTYTCLAK 76

                          90
                  ....*....|....
gi 215274225 6186 NRLGSARASAELRI 6199
Cdd:cd20976    77 NAAGQVSCSAWVTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1541-1619 1.96e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.82  E-value: 1.96e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1541 SREVQAEAGTSATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA----GDQRLS 1614
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSG 80


                    ....*
gi 215274225   1615 FHLHV 1619
Cdd:smart00410   81 TTLTV 85
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
 6472-6669 1.98e-08

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 59.65  E-value: 1.98e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFV-----------KRVQHKGNKILCAAKFIPLRSRTRAQAY-RERdilaaLSHPLVTGLLDQFETRKTLIL 6539
Cdd:cd05091    12 EELGEDRFGKVykghlfgtapgEQTQAVAIKTLKDKAEGPLREEFRHEAMlRSR-----LQHPNIVCLLGVVTKEQPMSM 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6540 ILELCSSEELLDRLYR----------------KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHpaREDI 6603
Cdd:cd05091    87 IFSYCSHGDLHEFLVMrsphsdvgstdddktvKSTLEPADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFD--KLNV 164

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6604 KICDFGFAQNITPAELQFSQYGSP---EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCS-SPFAGESDR 6669
Cdd:cd05091   165 KISDLGLFREVYAADYYKLMGNSLlpiRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGlQPYCGYSNQ 234
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
 7691-7856 2.07e-08

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 60.20  E-value: 2.07e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7691 EKASGRALAAKII-PY-HPKDKTAVLREYEALKGLRHPHLAQLHAAY--LSPRHLVLILELCSGPELLPCLAERA-SY-- 7763
Cdd:cd13988    14 HKKTGDLYAVKVFnNLsFMRPLDVQMREFEVLKKLNHKNIVKLFAIEeeLTTRHKVLVMELCPCGSLYTVLEEPSnAYgl 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7764 SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI--ITE--YNLLKVVDLGNAQSLSQekvlpSDKF------KDYLEt 7833
Cdd:cd13988    94 PESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMrvIGEdgQSVYKLTDFGAARELED-----DEQFvslygtEEYLH- 167

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 7834 maPELLE--------GQGAVPQTDIWAIGVT 7856
Cdd:cd13988   168 --PDMYEravlrkdhQKKYGATVDLWSIGVT 196
I-set pfam07679
Immunoglobulin I-set domain;
1810-1893 2.08e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 54.96  E-value: 2.08e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1810 KFCRLLEPVCGELGGTVTLACELS----PacaEVVWRCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVC----E 1881
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtpdP---EVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCvatnS 78

                           90
                   ....*....|..
gi 215274225  1882 SRDDHTSAQLTV 1893
Cdd:pfam07679   79 AGEAEASAELTV 90
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3907-3962 2.10e-08

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 54.26  E-value: 2.10e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3907 ATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCT 3962
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
 6477-6714 2.14e-08

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 59.33  E-value: 2.14e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6477 GVFGFVKRVQHKgnkilcAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRLYRK 6556
Cdd:cd13992    17 VKKVGVYGGRTV------AIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6557 GVVTEAEVKV-YIQQLVEGLHYLH-SHGVLHLDIKPSNILMvhPAREDIKICDFG---FAQNITPAELQFSQYGSPE-FV 6630
Cdd:cd13992    91 EIKMDWMFKSsFIKDIVKGMNYLHsSSIGYHGRLKSSNCLV--DSRWVVKLTDFGlrnLLEEQTNHQLDEDAQHKKLlWT 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6631 SPEIIQQNPV----SEASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSWSSPMAAHLSEDAKDFIKATLQRA- 6705
Cdd:cd13992   169 APELLRGSLLevrgTQKGDVYSFAIILYEILFRSDPFALEREVAIVEKVISGGNKPFRPELAVLLDEFPPRLVLLVKQCw 248

                         250
                  ....*....|..
gi 215274225 6706 ---PQARPSAAQ 6714
Cdd:cd13992   249 aenPEKRPSFKQ 260
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1176-1240 2.15e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.82  E-value: 2.15e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   1176 VQAEAGTTAMLSCEVAQ-PQTEVTWYKDG-KKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:smart00410    4 VTVKEGESVTLSCEASGsPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 4902-4984 2.15e-08

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 54.91  E-value: 2.15e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4902 HTFGDTEAQVGDALRLECVVASKADVRARWLKDGVEL-TDGRhhhiDQLGDGTcsLLITGLDRADAGCYTCQVSNKFGQV 4980
Cdd:cd05728     4 KVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLaSENR----IEVEAGD--LRITKLSLSDSGMYQCVAENKHGTI 77


                  ....
gi 215274225 4981 THSA 4984
Cdd:cd05728    78 YASA 81
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
 6468-6618 2.26e-08

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270919 [Multi-domain]  Cd Length: 263  Bit Score: 59.19  E-value: 2.26e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6468 YEVKEEIGRGVFGFVKRVQHKGNKILCAAKFIPLRsrTRAQAYR-ERDILAALS-HPLVTGLLDQFETRKTLILILELC- 6544
Cdd:cd14017     2 WKVVKKIGGGGFGEIYKVRDVVDGEEVAMKVESKS--QPKQVLKmEVAVLKKLQgKPHFCRLIGCGRTERYNYIVMTLLg 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6545 -SSEELLdRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILM-VHPARE-DIKICDFGFAQNITPAE 6618
Cdd:cd14017    80 pNLAELR-RSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIgRGPSDErTVYILDFGLARQYTNKD 155
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 5137-5216 2.27e-08

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 54.93  E-value: 2.27e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5137 VQDGYPVSFDCVVTGQPMPSVRWFKDGKL-----LEEDDHYMINEDQqgghqLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:cd05763    11 IRAGSTARLECAATGHPTPQIAWQKDGGTdfpaaRERRMHVMPEDDV-----FFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                  ....*
gi 215274225 5212 AELRV 5216
Cdd:cd05763    86 ATLTV 90
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
 6472-6654 2.32e-08

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 59.19  E-value: 2.32e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVkrvqHKG---NKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEE 6548
Cdd:cd05112    10 QEIGSGQFGLV----HLGywlNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6549 LLDRLY-RKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNITPAELQfSQYGSP 6627
Cdd:cd05112    86 LSDYLRtQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLV--GENQVVKVSDFGMTRFVLDDQYT-SSTGTK 162

                         170       180       190
                  ....*....|....*....|....*....|
gi 215274225 6628 ---EFVSPEIIQQNPVSEASDIWAMGVISY 6654
Cdd:cd05112   163 fpvKWSSPEVFSFSRYSSKSDVWSFGVLMW 192
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
 7678-7854 2.32e-08

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 59.60  E-value: 2.32e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDK---TAVLREYEALKGLR---HPHLAQLHAAYLSPR-----HLVLILE 7746
Cdd:cd07838     7 IGEGAYGTVYKARDLQDGRFVALKKVRVPLSEEgipLSTIREIALLKQLEsfeHPNVVRLLDVCHGPRtdrelKLTLVFE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSgpELLPCLAERAS---YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLP 7823
Cdd:cd07838    87 HVD--QDLATYLDKCPkpgLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIYSFEMALT 164

                         170       180       190
                  ....*....|....*....|....*....|....
gi 215274225 7824 SdkfkdYLETM---APELLEGQGAVPQTDIWAIG 7854
Cdd:cd07838   165 S-----VVVTLwyrAPEVLLQSSYATPVDMWSVG 193
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 4890-4988 2.35e-08

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 54.82  E-value: 2.35e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4890 KEMKQQEGpmfshtfgdteaQVGDALRLECVVASK-ADVRARWLKDGVELTDGRHHHID-QLGDGTCSLLITGLDRADAG 4967
Cdd:cd05750     4 KEMKSQTV------------QEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRPKNIKiRNKKKNSELQINKAKLEDSG 71

                          90       100
                  ....*....|....*....|.
gi 215274225 4968 CYTCQVSNKFGQVTHSACVVV 4988
Cdd:cd05750    72 EYTCVVENILGKDTVTGNVTV 92
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1082-1148 2.39e-08

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 54.49  E-value: 2.39e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1082 NEVQAEAGASAMLSCEV-AQAQTEVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
 6449-6652 2.41e-08

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 60.27  E-value: 2.41e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6449 GDNEPDSE-----KQSHRRKLHSF-YEVKEEIGRGVFGFVKRVQHKGNkilcaAKFIPLRSRTRAQAYRERDILAALSHP 6522
Cdd:PHA03209   43 ESDDDDDDgliptKQKAREVVASLgYTVIKTLTPGSEGRVFVATKPGQ-----PDPVVLKIGQKGTTLIEAMLLQNVNHP 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6523 LVTGLLDQFETRKTLILILELCSSEELLDRLYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPARED 6602
Cdd:PHA03209  118 SVIRMKDTLVSGAITCMVLPHYSSDLYTYLTKRSRPLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFI--NDVDQ 195

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 6603 IKICDFGFAQNITPAELQFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:PHA03209  196 VCIGDLGAAQFPVVAPAFLGLAGTVETNAPEVLARDKYNSKADIWSAGIV 245
IgI_VEGFR cd04976
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member ...
 5269-5337 2.42e-08

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409365  Cd Length: 90  Bit Score: 54.91  E-value: 2.42e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 5269 LQVAPGTRLAKFQLKVKGYPAPRLYWFKDGQPLTASAHIrmtdkKILHTLEIISVTREDSGQYAAYISN 5337
Cdd:cd04976    12 LEATAGKRSVRLPMKVKAYPPPEVVWYKDGLPLTEKARY-----LTRHSLIIKEVTEEDTGNYTILLSN 75
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
 7671-7873 2.52e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 59.99  E-value: 2.52e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP----KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd05632     3 TFRQYRVLGKGGFGEVCACQVRATGKMYACKRLEKKRikkrKGESMALNEKQILEKVNSQFVVNLAYAYETKDALCLVLT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQslsqeKVLPS 7824
Cdd:cd05632    83 IMNGGDLKFHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAV-----KIPEG 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7825 DKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGAR 7873
Cdd:cd05632   158 ESIRGRVGTvgyMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPFRGRKEK 209
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
 6512-6716 2.54e-08

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 59.72  E-value: 2.54e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6512 ERDILAALSHPLVTGLlDQFETRK--TLILILELC--SSEELLDRLY--RKGVVTEAEVKVYIQQLVEGLHYLHSHG-VL 6584
Cdd:cd14001    55 EAKILKSLNHPNIVGF-RAFTKSEdgSLCLAMEYGgkSLNDLIEERYeaGLGPFPAATILKVALSIARALEYLHNEKkIL 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6585 HLDIKPSNILmVHPAREDIKICDFGFA----QNITPAELQFSQY-GSPEFVSPEIIQQN-PVSEASDIWAMGVISYLSLT 6658
Cdd:cd14001   134 HGDIKSGNVL-IKGDFESVKLCDFGVSlpltENLEVDSDPKAQYvGTEPWKAKEALEEGgVITDKADIFAYGLVLWEMMT 212

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6659 CSSP-----FAGESDRATLLNVLE-------GRVSWSSPMAAHLSEDAKDFI----KATLQRAPQARPSAAQCL 6716
Cdd:cd14001   213 LSVPhlnllDIEDDDEDESFDEDEedeeayyGTLGTRPALNLGELDDSYQKVielfYACTQEDPKDRPSAAHIV 286
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
 7674-7939 2.61e-08

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 59.85  E-value: 2.61e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQCWEKASGRALAAKIIP---YHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSP-----RHLVLIL 7745
Cdd:cd07834     4 LLKPIGSGAYGVVCSAYDKRTGRKVAIKKISnvfDDLIDAKRILREIKILRHLKHENIIGLLDILRPPspeefNDVYIVT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELC---------SGPELlpclaerasySESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL 7816
Cdd:cd07834    84 ELMetdlhkvikSPQPL----------TDDHIQYFLYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGV 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7817 SQEkvlPSDKFK-DYLETM---APEL-LEGQGAVPQTDIWAIGVTAFIML-------------------------SAE-- 7864
Cdd:cd07834   154 DPD---EDKGFLtEYVVTRwyrAPELlLSSKKYTKAIDIWSVGCIFAELLtrkplfpgrdyidqlnlivevlgtpSEEdl 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7865 YPVSSEGARDLQRGLRKG-LVRLSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL-----TEEGPACSRPAPVT 7938
Cdd:cd07834   231 KFISSEKARNYLKSLPKKpKKPLSEVFPGASPEAIDLLEKMLVFNPKKRITADEALAHPYLaqlhdPEDEPVAKPPFDFP 310


                  .
gi 215274225 7939 F 7939
Cdd:cd07834   311 F 311
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 248-328 2.67e-08

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 54.81  E-value: 2.67e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDG-QLVTEGRRHVvyedAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLV 326
Cdd:cd20952    10 TVAVGGTVVLNCQATGEPVPTISWLKDGvPLLGKDERIT----TLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85


                  ..
gi 215274225  327 VV 328
Cdd:cd20952    86 DV 87
STKc_SRPK1 cd14216
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs ...
 6564-6721 2.67e-08

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271118 [Multi-domain]  Cd Length: 349  Bit Score: 60.04  E-value: 2.67e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6564 VKVYIQQLVEGLHYLHSH-GVLHLDIKPSNILM-------------------------VHPARED---IKICDFGFA--- 6611
Cdd:cd14216   121 VKKIIRQVLQGLDYLHTKcRIIHTDIKPENILLsvneqyirrlaaeatewqrnflvnpLEPKNAEklkVKIADLGNAcwv 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6612 QNITPAELQFSQYGSPEfvspeIIQQNPVSEASDIWAMGVISYLSLTCS---SPFAGES-----DRATLLNVLEGRVSWS 6683
Cdd:cd14216   201 HKHFTEDIQTRQYRSLE-----VLIGSGYNTPADIWSTACMAFELATGDylfEPHSGEDysrdeDHIALIIELLGKVPRK 275

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6684 SPMAAHLS---------------------------------EDAK---DFIKATLQRAPQARPSAAQCLSHPWF 6721
Cdd:cd14216   276 LIVAGKYSkefftkkgdlkhitklkpwglfevlvekyewsqEEAAgftDFLLPMLELIPEKRATAAECLRHPWL 349
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 7472-7551 2.72e-08

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 54.77  E-value: 2.72e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7472 ETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISA--TLKnfqlltILVVVAEDLGVYTCSVSNALGTVTTTG 7549
Cdd:cd04969    12 ILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPdgSLK------IKNVTKSDEGKYTCFAVNFFGKANSTG 85


                  ..
gi 215274225 7550 VL 7551
Cdd:cd04969    86 SL 87
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
 6474-6665 2.73e-08

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 59.20  E-value: 2.73e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVkrvqHKGN--------KILCAAKFIplRSRTRAQAYRE--RDILA--ALSHPLVTGLLDqFETRKTLILIL 6541
Cdd:cd05111    15 LGSGVFGTV----HKGIwipegdsiKIPVAIKVI--QDRSGRQSFQAvtDHMLAigSLDHAYIVRLLG-ICPGASLQLVT 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6542 ELCSSEELLDRL-YRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQ 6620
Cdd:cd05111    88 QLLPLGSLLDHVrQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQ--VQVADFGVADLLYPDDKK 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 215274225 6621 --FSQYGSP-EFVSPEIIQQNPVSEASDIWAMGVISYLSLTC-SSPFAG 6665
Cdd:cd05111   166 yfYSEAKTPiKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFgAEPYAG 214
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 6356-6446 2.87e-08

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 54.56  E-value: 2.87e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6356 PPSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQL-VDSTRLsqQQEGTTYSLVLRHVASKDAGVYTCLAQNT 6434
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLqYAADRS--TCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 215274225 6435 GGQVLCKAELLV 6446
Cdd:cd20976    79 AGQVSCSAWVTV 90
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 6361-6446 2.94e-08

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 54.42  E-value: 2.94e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6361 VTIEDVQAQT---GGTAQFEAIIEGDPQPSVTWYKDSVQL-VDSTRLSQQQEGttySLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd20952     1 IILQGPQNQTvavGGTVVLNCQATGEPVPTISWLKDGVPLlGKDERITTLENG---SLQIKGAEKSDTGEYTCVALNLSG 77

                          90
                  ....*....|
gi 215274225 6437 QVLCKAELLV 6446
Cdd:cd20952    78 EATWSAVLDV 87
PK_TRB3 cd14024
Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein ...
 6559-6720 3.00e-08

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270926 [Multi-domain]  Cd Length: 242  Bit Score: 58.74  E-value: 3.00e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6559 VTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDIKICDFGFAQNIT-PAELQFSQYGSPEFVSPEIIQQ 6637
Cdd:cd14024    81 LSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVLVNLEDSCPLNgDDDSLTDKHGCPAYVGPEILSS 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6638 NPVS--EASDIWAMGVISYLSLTCSSPFAGESDRATLLNVLEGRVSwsspMAAHLSEDAKDFIKATLQRAPQARPSAAQC 6715
Cdd:cd14024   161 RRSYsgKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFS----LPAWLSPGARCLVSCMLRRSPAERLKASEI 236


                  ....*
gi 215274225 6716 LSHPW 6720
Cdd:cd14024   237 LLHPW 241
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 7469-7551 3.03e-08

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 54.50  E-value: 3.03e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7469 LSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNFQLLTILVVVAEDLGVYTCSVSNALGTVTTT 7548
Cdd:cd20973     4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCS 83


                  ...
gi 215274225 7549 GVL 7551
Cdd:cd20973    84 AEL 86
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 5267-5340 3.10e-08

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 54.67  E-value: 3.10e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 5267 RDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMG 5340
Cdd:cd05747    11 RSLTVSEGES-ARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEG 83
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 5276-5348 3.19e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 54.46  E-value: 3.19e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 5276 RLAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHtleIISVTREDSGQYAAYISNAMGAAYSSARL 5348
Cdd:cd20957    17 RTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLV---IPSVKREDKGMYQCFVRNDGDSAQATAEL 86
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 809-883 3.33e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.43  E-value: 3.33e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    809 AVAGGPAQFECE-TSEAHVHVHWYKDGMELGHSGERFLQEDVGTRHRLVAATVTRQDEGTYSCRV----GEDSVDFRLRV 883
Cdd:smart00410    6 VKEGESVTLSCEaSGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
3980-4050 3.38e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 54.57  E-value: 3.38e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  3980 RFLRELQHQEVDEGGTAHLCCELSraGA---SVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC 4050
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT--GTpdpEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 5380-5466 3.41e-08

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 54.50  E-value: 3.41e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5380 KKVKKGSSITFSVKVEGRPVPTVHWLREE---AERGVLWIGPDTPGYTvassaqqhSLVLLDVGRQHQGTYTCIASNAAG 5456
Cdd:cd20973     7 KEVVEGSAARFDCKVEGYPDPEVKWMKDDnpiVESRRFQIDQDEDGLC--------SLIISDVCGDDSGKYTCKAVNSLG 78

                          90
                  ....*....|
gi 215274225 5457 QALCSASLHV 5466
Cdd:cd20973    79 EATCSAELTV 88
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
 6474-6651 3.61e-08

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 58.97  E-value: 3.61e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVK----RVQHKGNKILCAAKFipLRSRTRAQAY----RERDILAALSHPLVTGLLDQFETrKTLILILELCS 6545
Cdd:cd05057    15 LGSGAFGTVYkgvwIPEGEKVKIPVAIKV--LREETGPKANeeilDEAYVMASVDHPHLVRLLGICLS-SQVQLITQLMP 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6546 SEELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHParEDIKICDFGFAQNITPAELQFSQY 6624
Cdd:cd05057    92 LGCLLDYVRNhRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTP--NHVKITDFGLAKLLDVDEKEYHAE 169

                         170       180       190
                  ....*....|....*....|....*....|
gi 215274225 6625 GS--P-EFVSPEIIQQNPVSEASDIWAMGV 6651
Cdd:cd05057   170 GGkvPiKWMALESIQYRIYTHKSDVWSYGV 199
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
 7715-7866 3.64e-08

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270741 [Multi-domain]  Cd Length: 326  Bit Score: 59.24  E-value: 3.64e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERAsYSESEVKDYLWQMLSATQYLHNQHILHLDLRS 7794
Cdd:cd05589    51 RIFETVNSARHPFLVNLFACFQTPEHVCFVMEYAAGGDLMMHIHEDV-FSEPRAVFYAACVVLGLQFLHEHKIVYRDLKL 129

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7795 ENMIITEYNLLKVVDLGnaqsLSQEKVLPSDK---FKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05589   130 DNLLLDTEGYVKIADFG----LCKEGMGFGDRtstFCGTPEFLAPEVLTDTSYTRAVDWWGLGVLIYEMLVGESP 200
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
 7681-7864 3.76e-08

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 59.51  E-value: 3.76e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKII--PYhpkdKTAVL-----REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd07856    21 GAFGLVCSARDQLTGQNVAVKKImkPF----STPVLakrtyRELKLLKHLRHENIISLSDIFISPLEDIYFVTELLGTDL 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERaSYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQslsqekvLPSDKFKDYLET 7833
Cdd:cd07856    97 HRLLTSR-PLEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLAR-------IQDPQMTGYVST 168

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 215274225 7834 ---MAPE-LLEGQGAVPQTDIWAIGVTAFIMLSAE 7864
Cdd:cd07856   169 ryyRAPEiMLTWQKYDVEVDIWSAGCIFAEMLEGK 203
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
 6472-6711 3.77e-08

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 58.90  E-value: 3.77e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVkRVQHKGNKILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLD 6551
Cdd:cd05072    13 KKLGAGQFGEV-WMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEYMAKGSLLD 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6552 RLYRK--GVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPARedIKICDFGFAQNITPAELQfSQYGSP-- 6627
Cdd:cd05072    92 FLKSDegGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLM--CKIADFGLARVIEDNEYT-AREGAKfp 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6628 -EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSS-PFAGESDRATLLNVLEGrvsWSSPMAAHLSEDAKDFIKATLQRA 6705
Cdd:cd05072   169 iKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKiPYPGMSNSDVMSALQRG---YRMPRMENCPDELYDIMKTCWKEK 245


                  ....*.
gi 215274225 6706 PQARPS 6711
Cdd:cd05072   246 AEERPT 251
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 248-328 4.22e-08

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 54.34  E-value: 4.22e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRH--VVYEDAQENFVLKILFCKqsDRGLYTCTASNLVGQTYSSVL 325
Cdd:cd20990    11 TVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHkmLVRENGVHSLIIEPVTSR--DAGIYTCIATNRAGQNSFNLE 88


                  ...
gi 215274225  326 VVV 328
Cdd:cd20990    89 LVV 91
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 16-99 4.35e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 54.07  E-value: 4.35e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   16 PKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGdlyRLTILDLALGDSGQYVCRARNAIGEAFAAV 95
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQATA 84


                  ....
gi 215274225   96 GLQV 99
Cdd:cd20957    85 ELKL 88
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4169-4245 4.46e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 54.05  E-value: 4.46e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4169 EVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRIHTLRLKGVTPEDAGT----VSFHLGNHASSAQLT 4244
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGTTLT 84


                    .
gi 215274225   4245 V 4245
Cdd:smart00410   85 V 85
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 515-598 4.49e-08

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 53.77  E-value: 4.49e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    515 PPVDPVVKARMESSVILSWSPPPHGERPVTIDGYLVEKKKLGTyTWIRCHEAewVATPELTVADVAEEGNFQFRVSALNS 594
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGS-EWKEVNVT--PSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 215274225    595 FGQS 598
Cdd:smart00060   80 AGEG 83
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 7725-7924 4.57e-08

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 58.32  E-value: 4.57e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7725 HPHLAQLHAAYLSPRHLVLILElcsGPE----LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII- 7799
Cdd:cd14101    66 HRGVIRLLDWFEIPEGFLLVLE---RPQhcqdLFDYITERGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILVd 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7800 TEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYletMAPELLEGQG--AVPQTdIWAIGVTAFIMLSAEYPVSsegaRDlqr 7877
Cdd:cd14101   143 LRTGDIKLIDFGSGATLKDSMYTDFDGTRVY---SPPEWILYHQyhALPAT-VWSLGILLYDMVCGDIPFE----RD--- 211

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 215274225 7878 glrKGLVRLSRCY-AGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14101   212 ---TDILKAKPSFnKRVSNDCRSLIRSCLAYNPSDRPSLEQILLHPWM 256
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 335-405 5.02e-08

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 53.96  E-value: 5.02e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  335 FKKRLQDLEVREKESATFLCEVP-QPSTEAAWFKEE---TRLWASAKYGIEEEGTERRLTVRNVSADDDAVYICE 405
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGvpiDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAV 77
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1266-1332 5.17e-08

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 53.72  E-value: 5.17e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1266 NEVRTEAGASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 110-201 5.71e-08

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 53.95  E-value: 5.71e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGPRVRVEELGeASALRIRAARPRDGGTYEVRAENP 189
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENG-VHSLIIEPVTSRDAGIYTCIATNR 79

                          90
                  ....*....|..
gi 215274225  190 LGAASAAAALVV 201
Cdd:cd20990    80 AGQNSFNLELVV 91
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 6122-6199 5.71e-08

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 53.76  E-value: 5.71e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6122 GEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPrsgllvLVIRAASKEDLGLYECELVNRLGSARASAELRI 6199
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD------LRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3812-3885 5.86e-08

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 53.40  E-value: 5.86e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3812 EAREGATAVLQCELSKA-APVEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCVCGQERTSATLTV 3885
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 6358-6433 6.48e-08

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 53.67  E-value: 6.48e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6358 SMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVD-STRLSQQQEGTTysLVLRHVASKDAGVYTCLAQN 6433
Cdd:cd20970     4 STPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASN 78
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 110-191 6.49e-08

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 54.09  E-value: 6.49e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRL-GEPDGPRVRVEELGEASA--LRI---RAARPrDGGTYE 183
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLeTDKDDPRSHRIVLPSGSLffLRVvhgRKGRS-DEGVYV 79


                  ....*...
gi 215274225  184 VRAENPLG 191
Cdd:cd07693    80 CVAHNSLG 87
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
 7715-7866 6.53e-08

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 57.66  E-value: 6.53e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSgpelLPCLAERASYSESEVKDYLWQMLSATQ------YLHNQ--- 7785
Cdd:cd14060    31 KEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYAS----YGSLFDYLNSNESEEMDMDQIMTWATDiakgmhYLHMEapv 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7786 HILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLpsdKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEY 7865
Cdd:cd14060   107 KVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHM---SLVGTFPWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREV 183


                  .
gi 215274225 7866 P 7866
Cdd:cd14060   184 P 184
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 5370-5466 6.53e-08

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 53.72  E-value: 6.53e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5370 PPRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIgPDTPGYT----VASSAQQHSLV-LLDVGRQHQ 5444
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFP-----I-PESPRFRvgdyVTSDGDVVSYVnISSVRVEDG 74

                          90       100
                  ....*....|....*....|..
gi 215274225 5445 GTYTCIASNAAGQALCSASLHV 5466
Cdd:cd20956    75 GEYTCTATNDVGSVSHSARINV 96
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 5137-5216 6.75e-08

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 54.09  E-value: 6.75e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5137 VQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDdhyminEDQQGGHQLIITA-------VVP-----ADMGVYRCLAENS 5204
Cdd:cd07693    12 VSKGDPATLNCKAEGRPTPTIQWLKNGQPLETD------KDDPRSHRIVLPSgslfflrVVHgrkgrSDEGVYVCVAHNS 85

                          90
                  ....*....|...
gi 215274225 5205 MGVS-STKAELRV 5216
Cdd:cd07693    86 LGEAvSRNASLEV 98
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 9-97 6.84e-08

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 53.90  E-value: 6.84e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    9 APRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAI 88
Cdd:cd05747     3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSE 82


                  ....*....
gi 215274225   89 GEAFAAVGL 97
Cdd:cd05747    83 GKQEAQFTL 91
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3113-3177 7.14e-08

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 53.10  E-value: 7.14e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3113 LTLVCETSTCDIP-VCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA----GGACSSSI 3177
Cdd:cd00096     1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAsnsaGGSASASV 70
I-set pfam07679
Immunoglobulin I-set domain;
4068-4154 7.90e-08

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 53.42  E-value: 7.90e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4068 PKFKTRLQSLEQETGDIARLCCQLSdAESGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACV----T 4143
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVatnsA 79

                           90
                   ....*....|.
gi 215274225  4144 GGQKTAASLRV 4154
Cdd:pfam07679   80 GEAEASAELTV 90
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
 7656-7868 8.52e-08

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 57.75  E-value: 8.52e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7656 EESQGRSAQPLPSTKTFAFQTQIQRGRFSVVRQ----------CWEKASGRALAAKiipyhpkDKTAVLREYEALKGLRH 7725
Cdd:cd14030    11 EELETKAVG*SPDGRFLKFDIEIGRGSFKTVYKgldtettvevAWCELQDRKLSKS-------ERQRFKEEAGMLKGLQH 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7726 PHLAQLHAAYLSP----RHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMII 7799
Cdd:cd14030    84 PNIVRFYDSWESTvkgkKCIVLVTELMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFI 163

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7800 T-EYNLLKVVDLGNA---QSLSQEKVLPSDKFkdyletMAPELLEgQGAVPQTDIWAIGVTAFIMLSAEYPVS 7868
Cdd:cd14030   164 TgPTGSVKIGDLGLAtlkRASFAKSVIGTPEF------MAPEMYE-EKYDESVDVYAFGMCMLEMATSEYPYS 229
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 109-191 9.10e-08

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 53.33  E-value: 9.10e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  109 APHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgePDGPRVRVE----ELGEA-SALRIRAARPRDGGTYE 183
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPI--PESPRFRVGdyvtSDGDVvSYVNISSVRVEDGGEYT 78


                  ....*...
gi 215274225  184 VRAENPLG 191
Cdd:cd20956    79 CTATNDVG 86
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3804-3885 9.12e-08

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 53.27  E-value: 9.12e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3804 FIEDVKNQEAREGATAVLQCELSkAAPV---EWRKGSETLRGGD-RYSLRQDGTrceLQIHGLSVADTGEYSCVC----G 3875
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQAT-GEPVptiSWLKDGVPLLGKDeRITTLENGS---LQIKGAEKSDTGEYTCVAlnlsG 77

                          90
                  ....*....|
gi 215274225 3876 QERTSATLTV 3885
Cdd:cd20952    78 EATWSAVLDV 87
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 6024-6094 9.12e-08

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 53.40  E-value: 9.12e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 6024 TAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDpDGSCALILDsLTGVDSGQYMCFAASAAG 6094
Cdd:cd05730    14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNE-DGSEMTILD-VDKLDEAEYTCIAENKAG 82
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 6121-6199 9.27e-08

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 52.97  E-value: 9.27e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6121 EGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGLLVLViraasKEDLGLYECELVNRLGSARASAELRI 6199
Cdd:cd05723    11 ESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLV-----KSDEGFYQCIAENDVGNAQASAQLII 84
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3540-3621 9.39e-08

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 53.27  E-value: 9.39e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3540 FIEDVKNQEAREGATAVLQCELnSAAPV---EWRKGSETLRDGD-RYSLRQDGTkceLQIRGLAMADTGEYSCVC----G 3611
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQA-TGEPVptiSWLKDGVPLLGKDeRITTLENGS---LQIKGAEKSDTGEYTCVAlnlsG 77

                          90
                  ....*....|
gi 215274225 3612 QERTSAMLTV 3621
Cdd:cd20952    78 EATWSAVLDV 87
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 5260-5350 9.98e-08

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 53.16  E-value: 9.98e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRLAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKkilHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVED---GTLTIINVQPEDTGYYGCVATNEI 77

                          90
                  ....*....|.
gi 215274225 5340 GAAYSSARLLV 5350
Cdd:cd20978    78 GDIYTETLLHV 88
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 5143-5214 1.05e-07

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 52.57  E-value: 1.05e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 5143 VSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDqqgGHqLIITAVVPADMGVYRCLAENSMGVSSTKAEL 5214
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPE---GY-LAIRDVGVADQGRYECVARNTIGYASVSMVL 68
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 248-327 1.07e-07

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 52.78  E-value: 1.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAqenfvLKILFCKQSDRGLYTCTASNLVGQ-TYSSVLV 326
Cdd:cd05725     8 VVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDHS-----LKIRKVTAGDMGSYTCVAENMVGKiEASATLT 82


                  .
gi 215274225  327 V 327
Cdd:cd05725    83 V 83
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 5127-5216 1.09e-07

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 52.88  E-value: 1.09e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5127 VFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEdQQGGHQLIitAVVPADMGVYRCLAENSMG 5206
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTL-ENGSLQIK--GAEKSDTGEYTCVALNLSG 77

                          90
                  ....*....|
gi 215274225 5207 VSSTKAELRV 5216
Cdd:cd20952    78 EATWSAVLDV 87
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 6121-6197 1.18e-07

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 52.97  E-value: 1.18e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  6121 EGEDAQFTCTI-EGAPYPQIRWYKDGALLTTGNKFQTlSEPRSGLLVLVIRAASKEDLGLYECELVNRLGSARASAEL 6197
Cdd:pfam00047   10 EGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKH-DNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 811-875 1.31e-07

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 52.92  E-value: 1.31e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  811 AGGPAQFECETSEAHVH-VHWYKDGMELGHSGERFLQedvgTRHRLVAATVTRQDEGTYSCRVGED 875
Cdd:cd20957    15 FGRTAVFNCSVTGNPIHtVLWMKDGKPLGHSSRVQIL----SEDVLVIPSVKREDKGMYQCFVRND 76
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3989-4063 1.37e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 52.63  E-value: 1.37e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3989 EVDEGGTAHLCCELSRAGASVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTCDTGHTQSMASLSV 4063
Cdd:cd20967     8 QVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
I-set pfam07679
Immunoglobulin I-set domain;
4248-4336 1.41e-07

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.41e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4248 PEVTIlePLQDVQLSEGQDASFQCrlsRASGQ---EARWALGGVPLQANEMNDITVEQGTlHLLTLHKVTLEDAG----T 4320
Cdd:pfam07679    1 PKFTQ--KPKDVEVQEGESARFTC---TVTGTpdpEVSWFKDGQPLRSSDRFKVTYEGGT-YTLTISNVQPDDSGkytcV 74

                           90
                   ....*....|....*.
gi 215274225  4321 VSFHVGTCSSEAQLKV 4336
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 248-324 1.45e-07

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 52.58  E-value: 1.45e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   248 TVTEGKHARLSC-YVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSV 324
Cdd:pfam00047    7 TVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLST 84
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 5388-5456 1.56e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 51.95  E-value: 1.56e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 5388 ITFSVKVEGRPVPTVHWLREEaerGVLWIGPDTPGYTVASSAqqhSLVLLDVGRQHQGTYTCIASNAAG 5456
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNG---KPLPPSSRDSRRSELGNG---TLTISNVTLEDSGTYTCVASNSAG 63
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 12-99 1.58e-07

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 52.60  E-value: 1.58e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   12 FLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLaQDGDlyrLTILDLALGDSGQYVCRARNAIGEA 91
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV-EAGD---LRITKLSLSDSGMYQCVAENKHGTI 77


                  ....*...
gi 215274225   92 FAAVGLQV 99
Cdd:cd05728    78 YASAELAV 85
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 5260-5350 1.60e-07

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.60e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRLAkFQLKVKGYPAPRLYWFKDGQPLTASAHiRMTDKKILHTLEIISVTREDSGQYAAYISNAM 5339
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFV-AQCSARGKPVPRITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 215274225 5340 GAAYSSARLLV 5350
Cdd:cd20976    80 GQVSCSAWVTV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3724-3797 1.60e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 52.24  E-value: 1.60e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3724 EATEGDTATLWCELSKA-APVEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCVCGQERTSATLTV 3797
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 990-1057 1.62e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 52.18  E-value: 1.62e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   990 SEVQAEAGASATLSCEV-AQAQTEVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEAR 1057
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
I-set pfam07679
Immunoglobulin I-set domain;
2738-2822 1.64e-07

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 52.64  E-value: 1.64e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2738 ITKRLKTMEVLEGESCSFECVLSheSASDP-AMWTVGGKTVGSSSRFQATRQGRKYILVVREAAPSDAGE----VVFSVR 2812
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVT--GTPDPeVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKytcvATNSAG 80

                           90
                   ....*....|
gi 215274225  2813 GLTSKASLIV 2822
Cdd:pfam07679   81 EAEASAELTV 90
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 6369-6447 1.74e-07

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 52.45  E-value: 1.74e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6369 QTGGTAQFEAIIEGDPQPSVTWYKDSVQLVD-STRLSQQQEGTTysLVLRHVASKDAGVYTCLAQNTGGQVLCKAELLVL 6447
Cdd:cd04978    12 SPGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDGRT--LIFSNLQPNDTAVYQCNASNVHGYLLANAFLHVL 89
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 7469-7551 1.74e-07

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 52.51  E-value: 1.74e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7469 LSDETVVLGQSVTLACQVSAQPAAQATWSKDG-APLESSSRVLISAtlkNFQLLTILVVVAEDLGVYTCSVSN-ALGTVT 7546
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGnLIIEFNTRYIVRE---NGTTLTIRNIRRSDMGIYLCIASNgVPGSVE 85


                  ....*
gi 215274225 7547 TTGVL 7551
Cdd:cd20970    86 KRITL 90
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 5382-5466 1.74e-07

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 52.74  E-value: 1.74e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5382 VKKGSSITFSVKVEGRPVPTVHWLREeaerGVLWIGPDTPGYTVASSAQQHSLVLLDVGRQHQGTYTCIASNAAGQALCS 5461
Cdd:cd20974    12 VLEGSTATFEAHVSGKPVPEVSWFRD----GQVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQATST 87


                  ....*
gi 215274225 5462 ASLHV 5466
Cdd:cd20974    88 AELLV 92
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1552-1608 1.90e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 51.56  E-value: 1.90e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1552 ATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA 1608
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 349-412 1.93e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 52.24  E-value: 1.93e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  349 SATFLCEVPQPSTEAAWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYICETPEGSRT 412
Cdd:cd20967    14 KIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCS 77
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1368-1424 1.98e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 51.56  E-value: 1.98e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1368 ATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 10-90 1.99e-07

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 52.41  E-value: 1.99e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFR-LAQDGDLYRLTILDLALGDSGQYVCRARNAI 88
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKmLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                  ..
gi 215274225   89 GE 90
Cdd:cd20990    81 GQ 82
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 6365-6446 1.99e-07

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 52.41  E-value: 1.99e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6365 DVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQL-VDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGGQVLCKAE 6443
Cdd:cd20990     9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQNSFNLE 88


                  ...
gi 215274225 6444 LLV 6446
Cdd:cd20990    89 LVV 91
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 6013-6104 2.02e-07

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 52.25  E-value: 2.02e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6013 PPDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEdpDGSCALILDSLTGVDSGQYMCFAASA 6092
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCE--AGVGELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 215274225 6093 AGNCSTLGKILV 6104
Cdd:cd20976    79 AGQVSCSAWVTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2173-2250 2.11e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 52.12  E-value: 2.11e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2173 QDVVTTEKEKVTLECELS-RPNVDVRWLKDGVE-LRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAH----DAQSSA 2246
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATnssgSASSGT 81


                    ....
gi 215274225   2247 SVKV 2250
Cdd:smart00410   82 TLTV 85
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3284-3357 2.11e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.86  E-value: 2.11e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3284 EATEGATATLRCELSKA-APVEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVCGEERTSASLTI 3357
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1092-1148 2.14e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 51.56  E-value: 2.14e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1092 AMLSCEV-AQAQTEVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
 7680-7858 2.21e-07

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 56.85  E-value: 2.21e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFS-VVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHP------HLAQLHAAYLSPRHLVLILELCSGP- 7751
Cdd:cd14135    10 KGVFSnVVRARDLARGNQEVAIKIIRNNELMHKAGLKELEILKKLNDAdpddkkHCIRLLRHFEHKNHLCLVFESLSMNl 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 -ELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE-YNLLKVVDLGNAQSLSQEKVLPsdkfkd 7829
Cdd:cd14135    90 rEVLKKYGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEkKNTLKLCDFGSASDIGENEITP------ 163

                         170       180       190
                  ....*....|....*....|....*....|..
gi 215274225 7830 YLET---MAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd14135   164 YLVSrfyRAPEIILGLPYDYPIDMWSVGCTLY 195
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
 7654-7854 2.33e-07

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 57.35  E-value: 2.33e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7654 SEEESQGRSAQPLPSTKTFAFQTQ----IQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEAL---KGLRHP 7726
Cdd:cd07876     1 SEEDSQFYSVQVADSTFTVLKRYQqlkpIGSGAQGIVCAAFDTVLGINVAVKKLSRPFQNQTHAKRAYRELvllKCVNHK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7727 HLAQLHAAYLSPRHLVLILELCSGPELLP---CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN 7803
Cdd:cd07876    81 NIISLLNVFTPQKSLEEFQDVYLVMELMDanlCQVIHMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDC 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7804 LLKVVDLGNAQSLSQEKVLPSDKFKDYLEtmAPELLEGQGAVPQTDIWAIG 7854
Cdd:cd07876   161 TLKILDFGLARTACTNFMMTPYVVTRYYR--APEVILGMGYKENVDIWSVG 209
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
 6472-6711 2.33e-07

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 56.09  E-value: 2.33e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6472 EEIGRGVFGFVKRVQHKGNKILCAAKFI--PLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEEL 6549
Cdd:cd05084     2 ERIGRGNFGEVFSGRLRADNTPVAVKSCreTLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6550 LDRLYRKGvvTEAEVKVYIQQL---VEGLHYLHSHGVLHLDIKPSNILMVHpaREDIKICDFGFAQnitpaELQFSQYGS 6626
Cdd:cd05084    82 LTFLRTEG--PRLKVKELIRMVenaAAGMEYLESKHCIHRDLAARNCLVTE--KNVLKISDFGMSR-----EEEDGVYAA 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6627 P--------EFVSPEIIQQNPVSEASDIWAMGVISYLSLTC-SSPFAGESDRATLLNVLEGrvsWSSPMAAHLSEDAKDF 6697
Cdd:cd05084   153 TggmkqipvKWTAPEALNYGRYSSESDVWSFGILLWETFSLgAVPYANLSNQQTREAVEQG---VRLPCPENCPDEVYRL 229

                         250
                  ....*....|....
gi 215274225 6698 IKATLQRAPQARPS 6711
Cdd:cd05084   230 MEQCWEYDPRKRPS 243
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1634-1700 2.47e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 51.80  E-value: 2.47e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1634 REVQAEAGASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEA 1700
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 7681-7862 2.53e-07

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 56.20  E-value: 2.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRF-SVVRQCWEKASGRALAAKIIPYH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRhLVLILELCSGPELLP 7755
Cdd:cd05060     6 GNFgSVRKGVYLMKSGKEVEVAVKTLKqeheKAGKKEFLREASVMAQLDHPCIVRLIGVCKGEP-LMLVMELAPLGPLLK 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDY----- 7830
Cdd:cd05060    85 YLKKRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAG----SDYYRATtagrw 160

                         170       180       190
                  ....*....|....*....|....*....|...
gi 215274225 7831 -LETMAPELLEGQGAVPQTDIWAIGVTAFIMLS 7862
Cdd:cd05060   161 pLKWYAPECINYGKFSSKSDVWSYGVTLWEAFS 193
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 1273-1332 2.54e-07

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 51.95  E-value: 2.54e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 1273 GASATLSCEV-AQAQTEVTWYKDGKKLSSS----SKVRIEAAGcmrqLVVQQAGQADAGEYTCEA 1332
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASvadmSKYRILADG----LLINKVTQDDTGEYTCRA 74
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3548-3621 2.56e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.86  E-value: 2.56e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3548 EAREGATAVLQCELNSA-APVEWRKGSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCVCGQERTSAMLTV 3621
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 6371-6436 2.59e-07

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 51.82  E-value: 2.59e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6371 GGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLsqQQEGTTY--SLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETGRV--QIETTASstSLVIKNAKRSDSGKYTLTLKNSAG 72
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 902-964 2.60e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 51.41  E-value: 2.60e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225   902 AEAGASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:pfam13927   13 VREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 248-330 2.61e-07

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 51.86  E-value: 2.61e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQenfvLKILFCKQSDRGLYTCTASNLVGQTYSSVLVV 327
Cdd:cd20968    10 TIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGS----LRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTI 85


                  ...
gi 215274225  328 VRE 330
Cdd:cd20968    86 EVE 88
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 4907-4981 2.63e-07

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 51.81  E-value: 2.63e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  4907 TEAQVGDALRLEC---VVASKADVRarWLKDGVELTDGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKFGQVT 4981
Cdd:pfam00047    6 VTVLEGDSATLTCsasTGSPGPDVT--WSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 6022-6094 2.75e-07

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 52.13  E-value: 2.75e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6022 DCTAELGETVKLACRVTGTPKPVISWYKDGKAVQ-VDPHHILIEDPDgscALILDSLTGVDSGQYMCFAASAAG 6094
Cdd:cd20970    11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIeFNTRYIVRENGT---TLTIRNIRRSDMGIYLCIASNGVP 81
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2658-2723 2.83e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.47  E-value: 2.83e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2658 AEERGTLALQCEVSDPEAHVVWRKDGVQLGPSDKYDFLHTAGTRGLVVHDVSPEDAGLYTCHVGSE 2723
Cdd:cd20967     9 VSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGE 74
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 2289-2374 3.03e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 51.81  E-value: 3.03e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2289 PVTLVRPLRDKIAMEKHRGVLECQVS-RASAQVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDA---- 2363
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLAtnsv 80

                          90
                  ....*....|.
gi 215274225 2364 GDVKTSAQFFV 2374
Cdd:cd20972    81 GSDTTSAEIFV 91
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
 7652-7860 3.06e-07

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 56.93  E-value: 3.06e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7652 LASEEESQGRSAQPLPSTKtfafQTQIQRGRFSVVRQCWEKASGRALAAK--------IIPYHPKDKTAVlrEYEALKGL 7723
Cdd:PHA03212   67 FADEDESDADASLALCAEA----RAGIEKAGFSILETFTPGAEGFAFACIdnktcehvVIKAGQRGGTAT--EAHILRAI 140

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7724 RHPHLAQLHAAYLSPRHLVLILELCSgPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN 7803
Cdd:PHA03212  141 NHPSIIQLKGTFTYNKFTCLILPRYK-TDLYCYLAAKRNIAICDILAIERSVLRAIQYLHENRIIHRDIKAENIFINHPG 219

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7804 LLKVVDLGNA---QSLSQEKVLpsdKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIM 7860
Cdd:PHA03212  220 DVCLGDFGAAcfpVDINANKYY---GWAGTIATNAPELLARDPYGPAVDIWSAGIVLFEM 276
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 5283-5350 3.09e-07

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 51.69  E-value: 3.09e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5283 KVKGYPAPRLYWFKDGQPLTASAHIRMTDKKilhTLEIISVTREDSGQYAAYISNAMGAAYSSARLLV 5350
Cdd:cd04969    25 KPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 20-99 3.15e-07

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 51.44  E-value: 3.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   20 VVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIGEAFAAVGLQV 99
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 5126-5216 3.16e-07

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 51.97  E-value: 3.16e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5126 PVFLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGH-QLIITAVVPADMGVYRCLAENS 5204
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISFSDGRaKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 215274225 5205 MGVSSTKAELRV 5216
Cdd:cd20974    81 SGQATSTAELLV 92
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 6014-6094 3.22e-07

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 51.69  E-value: 3.22e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHI-LIEDPDGSCALILDSLTGVDSGQYMCFAASA 6092
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRIsLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80


                  ..
gi 215274225 6093 AG 6094
Cdd:cd05892    81 AG 82
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1276-1332 3.32e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 51.18  E-value: 3.32e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1276 ATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3460-3533 3.34e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.47  E-value: 3.34e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3460 EAVEGATAMLWCELSKV-APVEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVCGQERTSATLTI 3533
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1268-1332 3.54e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.35  E-value: 3.54e-07
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   1268 VRTEAGASATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:smart00410    4 VTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
 7674-7858 3.71e-07

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 55.79  E-value: 3.71e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQC----WEKASGRALAAKIIPY----HPKDktaVLREYEALKGLRHPHLAQLHAAYLSP--RHLVL 7743
Cdd:cd14205     8 FLQQLGKGNFGSVEMCrydpLQDNTGEVVAVKKLQHsteeHLRD---FEREIEILKSLQHDNIVKYKGVCYSAgrRNLRL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCSGPELLPCLAE-RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqslsQEKVL 7822
Cdd:cd14205    85 IMEYLPYGSLRDYLQKhKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFG------LTKVL 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 215274225 7823 PSDK----FKDYLET----MAPELLEGQGAVPQTDIWAIGVTAF 7858
Cdd:cd14205   159 PQDKeyykVKEPGESpifwYAPESLTESKFSVASDVWSFGVVLY 202
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 6362-6446 3.80e-07

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 51.45  E-value: 3.80e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6362 TIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLsQQQEGTtysLVLRHVASKDAGVYTCLAQNTGGQVLCK 6441
Cdd:cd05728     5 VISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRI-EVEAGD---LRITKLSLSDSGMYQCVAENKHGTIYAS 80


                  ....*
gi 215274225 6442 AELLV 6446
Cdd:cd05728    81 AELAV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1716-1793 3.80e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 51.03  E-value: 3.80e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1716 PQISERPcrrEPLVVKEHEDIILTATLATPSAATVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:pfam13927    2 PVITVSP---SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
 7713-7861 3.80e-07

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 56.53  E-value: 3.80e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7713 VLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDL 7792
Cdd:PTZ00426   78 VFSERKILNYINHPFCVNLYGSFKDESYLYLVLEFVIGGEFFTFLRRNKRFPNDVGCFYAAQIVLIFEYLQSLNIVYRDL 157

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7793 RSENMIITEYNLLKVVDLGNAqslsqeKVLPSDKFK--DYLETMAPELLEGQGAVPQTDIWAIGVTAFIML 7861
Cdd:PTZ00426  158 KPENLLLDKDGFIKMTDFGFA------KVVDTRTYTlcGTPEYIAPEILLNVGHGKAADWWTLGIFIYEIL 222
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2305-2374 3.90e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 51.09  E-value: 3.90e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2305 HRGVLECQVSRASAQVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDAGDVKTSAQFFV 2374
Cdd:cd20967    13 HKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1084-1148 4.26e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.35  E-value: 4.26e-07
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   1084 VQAEAGASAMLSCEVAQA-QTEVTWYKDG-KKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:smart00410    4 VTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1726-1793 4.26e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 51.35  E-value: 4.26e-07
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   1726 EPLVVKEHEDIILTATLATPSAATVTWLKDGVE-IRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
 7681-7865 4.27e-07

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271038 [Multi-domain]  Cd Length: 320  Bit Score: 56.05  E-value: 4.27e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLR-----HP---HLAQL--HAAYLSP--RHLVLILELC 7748
Cdd:cd14136    21 GHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVReadpkDPgreHVVQLldDFKHTGPngTHVCMVFEVL 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 sGPELLPcLAERASYSE---SEVKDYLWQMLSATQYLHNQ-HILHLDLRSENMIITEYNL-LKVVDLGNAQSLSQekvlp 7823
Cdd:cd14136   101 -GPNLLK-LIKRYNYRGiplPLVKKIARQVLQGLDYLHTKcGIIHTDIKPENVLLCISKIeVKIADLGNACWTDK----- 173

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 7824 sdKFKDYLETM---APELLEGQGAVPQTDIWAIGVTAFIMLSAEY 7865
Cdd:cd14136   174 --HFTEDIQTRqyrSPEVILGAGYGTPADIWSTACMAFELATGDY 216
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1358-1424 4.27e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 51.03  E-value: 4.27e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1358 RKVQAEAGAIATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 7466-7549 4.34e-07

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 51.36  E-value: 4.34e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7466 LRELSDETVVLGQSVTLACQ-VSAQPAAQATWSKDGAPL--ESSSRVLISATLKNFQLlTILVVVAEDLGVYTCSVSNAL 7542
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEaTSENPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSEL-QINKAKLEDSGEYTCVVENIL 81


                  ....*..
gi 215274225 7543 GTVTTTG 7549
Cdd:cd05750    82 GKDTVTG 88
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1906-1973 4.40e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 51.03  E-value: 4.40e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  1906 STVVAEEGGEATFQCVVSPSDVAVV-WFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAE 1973
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPPTItWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 5260-5350 4.49e-07

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 51.58  E-value: 4.49e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQ--PLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISN 5337
Cdd:cd20974     1 PVFTQPLQSVVVLEGST-ATFEAHVSGKPVPEVSWFRDGQviSTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATN 79

                          90
                  ....*....|...
gi 215274225 5338 AMGAAYSSARLLV 5350
Cdd:cd20974    80 GSGQATSTAELLV 92
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 7473-7548 4.52e-07

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 51.05  E-value: 4.52e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7473 TVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATlKNFQLLTILVVVAEDLGVYTCSVSNALGTVTTT 7548
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETT-ASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSAT 77
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 990-1057 4.56e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.97  E-value: 4.56e-07
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    990 SEVQAEAGASATLSCEVAQA-QTEVMWYKDG-KKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEAR 1057
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAT 71
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
4522-4603 4.72e-07

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 56.93  E-value: 4.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4522 LPDPPEDAEVVARSSHTVTLSWAAPmsdGGGGLCGYRVEVKEGATGQWRLCHElVPGPECVVDGLAPGETYRFRVAAVGP 4601
Cdd:COG3401   232 PPSAPTGLTATADTPGSVTLSWDPV---TESDATGYRVYRSNSGDGPFTKVAT-VTTTSYTDTGLTNGTTYYYRVTAVDA 307


                  ..
gi 215274225 4602 VG 4603
Cdd:COG3401   308 AG 309
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 113-191 4.77e-07

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 51.20  E-value: 4.77e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  113 LLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEpdGPRVRVEELGEASALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd05747     7 LTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVS--SQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEG 83
fn3 pfam00041
Fibronectin type III domain;
515-600 4.91e-07

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 50.88  E-value: 4.91e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   515 PPVDPVVKARMESSVILSWSPPPHGERPvtIDGYLVEKKKLGTYT-WIRCHEAEwvATPELTVADVAEEGNFQFRVSALN 593
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGP--ITGYEVEYRPKNSGEpWNEITVPG--TTTSVTLTGLKPGTEYEVRVQAVN 77


                   ....*..
gi 215274225   594 SFGQSPY 600
Cdd:pfam00041   78 GGGEGPP 84
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2297-2375 4.93e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.97  E-value: 4.93e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2297 RDKIAMEKHRGVLECQVS-RASAQVRWFK-GSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDAGDVKTSAQFFV 2374
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    .
gi 215274225   2375 E 2375
Cdd:smart00410   82 T 82
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 7464-7551 4.95e-07

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 51.08  E-value: 4.95e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7464 TFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGA---PLESSSRVLISATLKNFqllTILVVVAEDLGVYTCSVSN 7540
Cdd:cd05763     1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGtdfPAARERRMHVMPEDDVF---FIVDVKIEDTGVYSCTAQN 77

                          90
                  ....*....|.
gi 215274225 7541 ALGTVTTTGVL 7551
Cdd:cd05763    78 SAGSISANATL 88
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 5283-5340 5.06e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 50.41  E-value: 5.06e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5283 KVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMG 5340
Cdd:cd00096     6 SASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2844-2901 5.42e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 50.41  E-value: 5.42e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 2844 VELRCELSRAGTP-VHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVE 2901
Cdd:cd00096     1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
 7668-7866 5.50e-07

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 55.04  E-value: 5.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRF-SVVRQCWEkasGRALAAKIIPYHPKDKTAVL-----REYEALKGLRHPHLAQLHAAYLSPRHL 7741
Cdd:cd14147     1 SFQELRLEEVIGIGGFgKVYRGSWR---GELVAVKAARQDPDEDISVTaesvrQEARLFAMLAHPNIIALKAVCLEEPNL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7742 VLILELCSGPELLPCLAERASYSESEVkDYLWQMLSATQYLHNQHI---LHLDLRSENMIIT--------EYNLLKVVDL 7810
Cdd:cd14147    78 CLVMEYAAGGPLSRALAGRRVPPHVLV-NWAVQIARGMHYLHCEALvpvIHRDLKSNNILLLqpienddmEHKTLKITDF 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7811 GNAQSLSQEKVLPSDKFKDYletMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14147   157 GLAREWHKTTQMSAAGTYAW---MAPEVIKASTFSKGSDVWSFGVLLWELLTGEVP 209
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
 7680-7875 5.57e-07

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 55.52  E-value: 5.57e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIpyH----PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLP 7755
Cdd:cd06615    11 AGNGGVVTKVLHRPSGLIMARKLI--HleikPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQ 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERASYSESEVKDYLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlpSDKFKDYLETM 7834
Cdd:cd06615    89 VLKKAGRIPENILGKISIAVLRGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSM---ANSFVGTRSYM 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 215274225 7835 APELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:cd06615   166 SPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKEL 206
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2468-2542 5.62e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 50.64  E-value: 5.62e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  2468 PVVLTRPLEPKTGRELQSVVLSC--DFRPAPKaVQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA 2542
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCeaTGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6018-6094 5.65e-07

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 50.86  E-value: 5.65e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6018 EELADCTAELGETVKLACRV-TGTPKPVISWYKDGKAVQVDPHHILIEDpDGScaLILDSLTGVDSGQYMCFAASAAG 6094
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVD-DGN--LLIAEARKSDEGTYKCVATNMVG 76
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 7463-7540 5.65e-07

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 51.03  E-value: 5.65e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISA--TlknfqlLTIL-VVVAEDLGVYTCSVS 7539
Cdd:cd20958     1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPngT------LVIEnVQRSSDEGEYTCTAR 74


                  .
gi 215274225 7540 N 7540
Cdd:cd20958    75 N 75
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
 7764-7854 5.97e-07

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 55.87  E-value: 5.97e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7764 SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETM---APE-LL 7839
Cdd:cd07857   103 TDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSENPGENAGFMTEYVATRwyrAPEiML 182

                          90
                  ....*....|....*
gi 215274225 7840 EGQGAVPQTDIWAIG 7854
Cdd:cd07857   183 SFQSYTKAIDVWSVG 197
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1179-1240 6.04e-07

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 50.88  E-value: 6.04e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1179 EAGTTAMLSCEVA-QPQTEVTWYKDGKKLSSSS---KVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd20951    13 WEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1634-1711 6.24e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.58  E-value: 6.24e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1634 REVQAEAGASATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEA----GGQQLSF 1707
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   1708 RLQV 1711
Cdd:smart00410   82 TLTV 85
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 6014-6095 6.53e-07

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 51.01  E-value: 6.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDP-----HHILIedPDGSC---ALILDSLTGVDSGQY 6085
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprsHRIVL--PSGSLfflRVVHGRKGRSDEGVY 78

                          90
                  ....*....|
gi 215274225 6086 MCFAASAAGN 6095
Cdd:cd07693    79 VCVAHNSLGE 88
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 114-191 6.77e-07

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 50.66  E-value: 6.77e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   114 LRPTSIRVREGSEATFRCRV-GGSPRPAVSWSKDGRRLgePDGPRVRVEELGEASA-LRIRAARPRDGGTYEVRAENPLG 191
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTL--IESLKVKHDNGRTTQSsLLISNVTKEDAGTYTCVVNNPGG 78
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 908-964 6.92e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 50.02  E-value: 6.92e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  908 ATLSCEV-AQAQTEVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 6014-6104 7.31e-07

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 50.54  E-value: 7.31e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEE--LADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPH-HILiedPDGScaLILDSLTGVDSGQYMCFAA 6090
Cdd:cd04969     1 PDFELNpvKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRiCIL---PDGS--LKIKNVTKSDEGKYTCFAV 75

                          90
                  ....*....|....
gi 215274225 6091 SAAGNCSTLGKILV 6104
Cdd:cd04969    76 NFFGKANSTGSLSV 89
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 248-328 7.59e-07

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 50.28  E-value: 7.59e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQ-LVTEGRRHVvyEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSVLV 326
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQpLKETGRVQI--ETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80


                  ..
gi 215274225  327 VV 328
Cdd:cd05748    81 KV 82
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
 7667-7880 7.76e-07

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 54.57  E-value: 7.76e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7667 PSTKTFAfqTQIQRGRFSVV-RQCWEKAsgRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLIL 7745
Cdd:cd05112     3 PSELTFV--QEIGSGQFGLVhLGYWLNK--DKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 ELCSGPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPS 7824
Cdd:cd05112    79 EFMEHGCLSDYLrTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSS 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7825 DKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSA-----EYPVSSEGARDLQRGLR 7880
Cdd:cd05112   159 TGTKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEgkipyENRSNSEVVEDINAGFR 219
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1900-1980 7.96e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 50.66  E-value: 7.96e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1900 KFMSGLSTVVAEEGGEATFQCVVSPSDVAVV-WFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEGASSS 1978
Cdd:cd20972     3 QFIQKLRSQEVAEGSKVRLECRVTGNPTPVVrWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVGS 82


                  ..
gi 215274225 1979 AA 1980
Cdd:cd20972    83 DT 84
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1821-1893 8.05e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 50.32  E-value: 8.05e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 1821 ELGGTVTLACELSPACAEVVWRCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVCESRDDHTSAQLTV 1893
Cdd:cd20967    10 SKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 6122-6199 8.31e-07

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 50.70  E-value: 8.31e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6122 GEDAQFTCTIEGAPYPQIRWYKDGallttGNKFQTLSEPRSGLL----VLVIRAASKEDLGLYECELVNRLGSARASAEL 6197
Cdd:cd05763    14 GSTARLECAATGHPTPQIAWQKDG-----GTDFPAARERRMHVMpeddVFFIVDVKIEDTGVYSCTAQNSAGSISANATL 88


                  ..
gi 215274225 6198 RI 6199
Cdd:cd05763    89 TV 90
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 427-505 8.37e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 50.32  E-value: 8.37e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  427 PRKTAVRV--GDTAMFCVELAVPVGPVHWLRNQEEVVAGGRVAISAEGTRHTLTISQCCLEDVGQVAFMAGDCQTSTQFC 504
Cdd:cd20967     2 KAQPAVQVskGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELF 81


                  .
gi 215274225  505 V 505
Cdd:cd20967    82 V 82
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 7473-7548 8.56e-07

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 50.27  E-value: 8.56e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  7473 TVVLGQSVTLACQVSAQ-PAAQATWSKDGAPLESSSRVLISATLKNFQLLTILVVVAEDLGVYTCSVSNALGTVTTT 7548
Cdd:pfam00047    7 TVLEGDSATLTCSASTGsPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLS 83
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
 7716-7868 8.62e-07

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 54.70  E-value: 8.62e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7716 EYEALKGLRHPHLAQLHAAYLSP----RHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILH 7789
Cdd:cd14032    50 EAEMLKGLQHPNIVRFYDFWESCakgkRCIVLVTELMTSGTLKTYLKRFKVMKPKVLRSWCRQILKGLLFLHTRTppIIH 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7790 LDLRSENMIIT-EYNLLKVVDLGNA---QSLSQEKVLPSDKFkdyletMAPELLEgQGAVPQTDIWAIGVTAFIMLSAEY 7865
Cdd:cd14032   130 RDLKCDNIFITgPTGSVKIGDLGLAtlkRASFAKSVIGTPEF------MAPEMYE-EHYDESVDVYAFGMCMLEMATSEY 202


                  ...
gi 215274225 7866 PVS 7868
Cdd:cd14032   203 PYS 205
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 6118-6197 8.88e-07

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 50.19  E-value: 8.88e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6118 PFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSgllvLVIRAASKEDLGLYECELVNRLGSARASAEL 6197
Cdd:cd20952    10 TVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGS----LQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1736-1793 9.01e-07

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 49.64  E-value: 9.01e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1736 IILTATLATPSAATVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRV 1793
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5128-5216 9.05e-07

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 50.72  E-value: 9.05e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5128 FLTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGK--LLeeddhyMINEDQQGGH--------QLIITAVVPADMGVY 5197
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSqnLL------FPYQPPQPSSrfsvsptgDLTITNVQRSDVGYY 75

                          90
                  ....*....|....*....
gi 215274225 5198 RCLAENSMGVSSTKAELRV 5216
Cdd:cd05726    76 ICQALNVAGSILAKAQLEV 94
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 6367-6446 9.15e-07

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 50.54  E-value: 9.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6367 QAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDST-RLSQQQEGTTY-SLVLRHVASKDAGVYTCLAQNTGGQVLCKAEL 6444
Cdd:cd05892    11 KVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTdRISLYQDNCGRiCLLIQNANKKDAGWYTVSAVNEAGVVSCNARL 90


                  ..
gi 215274225 6445 LV 6446
Cdd:cd05892    91 DV 92
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 6021-6097 9.32e-07

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 50.19  E-value: 9.32e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6021 ADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEdPDGScaLILDSLTGVDSGQYMCFAASAAGNCS 6097
Cdd:cd20952     7 QNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTL-ENGS--LQIKGAEKSDTGEYTCVALNLSGEAT 80
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3372-3445 9.50e-07

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 50.32  E-value: 9.50e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3372 ESIEGATATLRCELSKA-APVEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVCGEERTSATLTV 3445
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1990-2069 9.55e-07

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 50.50  E-value: 9.55e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1990 FKKKLEPQTVEERSSVTLEVELT-RPWPELRWTRNATALAP---GKNVEIHAEGARHRLVLHNVGFADRGFFGCETPDDK 2065
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPssiPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIH 82


                  ....
gi 215274225 2066 TQAK 2069
Cdd:cd20951    83 GEAS 86
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3904-3974 9.69e-07

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 50.19  E-value: 9.69e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 3904 GSTATLQCE-LSEPTATVVWSKGGLQLQANGRREPRLQGCTaeLVLQDLQREDTGEYTC----TCGSQATSATLTV 3974
Cdd:cd20952    14 GGTVVLNCQaTGEPVPTISWLKDGVPLLGKDERITTLENGS--LQIKGAEKSDTGEYTCvalnLSGEATWSAVLDV 87
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 247-328 1.01e-06

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 50.33  E-value: 1.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  247 CTVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENfvLKILFCKQSDRGLYTCTASNLVGQTYSSVLV 326
Cdd:cd20976    11 LEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGE--LHIQDVLPEDHGTYTCLAKNAAGQVSCSAWV 88


                  ..
gi 215274225  327 VV 328
Cdd:cd20976    89 TV 90
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 5140-5216 1.02e-06

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 50.32  E-value: 1.02e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5140 GYPVSFDCVVTGQPMPSVRWFKDGKLLE-EDDHYMINEDqqgGHQLIITAVVPADMGVYRCLAENSMGVSSTKAELRV 5216
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIEsGEEKYSFNED---GSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3809-3873 1.03e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 49.87  E-value: 1.03e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  3809 KNQEAREGATAVLQCELSKAAP--VEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCV 3873
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3986-4063 1.04e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.20  E-value: 1.04e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3986 QHQEVDEGGTAHLCCELS-RAGASVEWRKGSLQ-LFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC----DTGHTQSMA 4059
Cdd:smart00410    2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCaatnSSGSASSGT 81


                    ....
gi 215274225   4060 SLSV 4063
Cdd:smart00410   82 TLTV 85
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
 6474-6652 1.04e-06

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 54.56  E-value: 1.04e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGN-KILCAAKFIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDR 6552
Cdd:cd14222     1 LGKGFFGQAIKVTHKATgKVMVMKELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6553 LYRKGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhPAREDIKICDFGFAQNIT------PAEL------- 6619
Cdd:cd14222    81 LRADDPFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLI--KLDKTVVVADFGLSRLIVeekkkpPPDKpttkkrt 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 215274225 6620 --------QFSQYGSPEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd14222   159 lrkndrkkRYTVVGNPYWMAPEMLNGKSYDEKVDIFSFGIV 199
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2918-2987 1.05e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 49.87  E-value: 1.05e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  2918 FTEELTNLQVEEKGTAVFTCKTE-HPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC 2987
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 6103-6199 1.06e-06

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 50.20  E-value: 1.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6103 LVQVPPRFVNKVraspFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEprSGLLvLVIRAASKEDLGLYEC 6182
Cdd:cd20970     2 VISTPQPSFTVT----AREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRE--NGTT-LTIRNIRRSDMGIYLC 74

                          90
                  ....*....|....*..
gi 215274225 6183 ELVNRlgsARASAELRI 6199
Cdd:cd20970    75 IASNG---VPGSVEKRI 88
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
 7678-7866 1.08e-06

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 54.93  E-value: 1.08e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKII---PYHPKDKTAVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL 7753
Cdd:cd05599     9 IGRGAFGEVRLVRKKDTGHVYAMKKLrksEMLEKEQVAHVRaERDILAEADNPWVVKLYYSFQDEENLYLIMEFLPGGDM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSD-KFKDYLe 7832
Cdd:cd05599    89 MTLLMKKDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDFGLCTGLKKSHLAYSTvGTPDYI- 167

                         170       180       190
                  ....*....|....*....|....*....|....
gi 215274225 7833 tmAPELLEGQGAVPQTDIWAIGVTAFIMLsAEYP 7866
Cdd:cd05599   168 --APEVFLQKGYGKECDWWSLGVIMYEML-IGYP 198
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 121-191 1.17e-06

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 50.20  E-value: 1.17e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  121 VREGSEATFRCR-VGGSPRPAVSWSKDGRRLGEPDGPRVRVEELGEASALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd05750    11 VQEGSKLVLKCEaTSENPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILG 82
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 7735-7924 1.23e-06

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 53.82  E-value: 1.23e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7735 YLSPRHLVLILELcsgPE----LLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT-EYNLLKVVD 7809
Cdd:cd14100    74 FERPDSFVLVLER---PEpvqdLFDFITERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILIDlNTGELKLID 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7810 LGNAQSLSQEKVLPSDKFKDYletMAPELLE-----GQGAVpqtdIWAIGVTAFIMLSAEYPVssEGARDLQRGLRKGLV 7884
Cdd:cd14100   151 FGSGALLKDTVYTDFDGTRVY---SPPEWIRfhryhGRSAA----VWSLGILLYDMVCGDIPF--EHDEEIIRGQVFFRQ 221

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 215274225 7885 RLS-RCYaglsggavAFLRSTLCAQPWGRPCASSCLQCPWL 7924
Cdd:cd14100   222 RVSsECQ--------HLIKWCLALRPSDRPSFEDIQNHPWM 254
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 7673-7880 1.23e-06

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 53.99  E-value: 1.23e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7673 AFQTQIQRGRFSVVRQCWEKASgRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPE 7752
Cdd:cd05059     7 TFLKELGSGQFGVVHLGKWRGK-IDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANGC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 LLPCLAERASYSESE-VKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYL 7831
Cdd:cd05059    86 LLNYLRERRGKFQTEqLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVGTKFPV 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLSA---EYP--VSSEGARDLQRGLR 7880
Cdd:cd05059   166 KWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEgkmPYErfSNSEVVEHISQGYR 219
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 3101-3181 1.24e-06

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 49.70  E-value: 1.24e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3101 ELTDATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARcqlsheghraqLLITGATLQDSGRYKCEAG---GACSSS 3176
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPsYTWYKDGSAISSSPN-----------FFTLSVSAEDSGTYTCVARngrGGKVSN 73


                   ....*
gi 215274225  3177 IVRVH 3181
Cdd:pfam13895   74 PVELT 78
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1916-1973 1.24e-06

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 49.25  E-value: 1.24e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1916 ATFQCVVSPSDVAVV-WFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAE 1973
Cdd:cd00096     1 VTLTCSASGNPPPTItWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5151-5216 1.25e-06

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 50.09  E-value: 1.25e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5151 GQPMPSVRWFKDGKLLEEDD-HYMINEDQQgghqLIITAVVPADMGVYRCLAENSMGV-SSTKAELRV 5216
Cdd:cd05724    24 GHPEPTVSWRKDGQPLNLDNeRVRIVDDGN----LLIAEARKSDEGTYKCVATNMVGErESRAARLSV 87
I-set pfam07679
Immunoglobulin I-set domain;
425-489 1.26e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 49.95  E-value: 1.26e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225   425 KLPRKTAVRVGDTAMF-CVELAVPVGPVHWLRNQEEVVAGGRVAISAEGTRHTLTISQCCLEDVGQ 489
Cdd:pfam07679    5 QKPKDVEVQEGESARFtCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGK 70
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 10-99 1.26e-06

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 50.04  E-value: 1.26e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGA--RFRLAQDGDLYRLTILDLALGDSGQYVCRARNA 87
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTlpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 215274225   88 IGEAFAAVGLQV 99
Cdd:cd20974    81 SGQATSTAELLV 92
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
 7709-7866 1.27e-06

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 54.14  E-value: 1.27e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7709 DKTAVLrEYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL---LPCLAERAsYSESEVKDYLWQMLSATQYLHNQ 7785
Cdd:cd05607    46 EKMALL-EKEILEKVNSPFIVSLAYAFETKTHLCLVMSLMNGGDLkyhIYNVGERG-IEMERVIFYSAQITCGILHLHSL 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7786 HILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKvlPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLSAEY 7865
Cdd:cd05607   124 KIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGK--PITQRAGTNGYMAPEILKEESYSYPVDWFAMGCSIYEMVAGRT 201


                  .
gi 215274225 7866 P 7866
Cdd:cd05607   202 P 202
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 114-191 1.27e-06

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 50.09  E-value: 1.27e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  114 LRPTSIRVREGSEATFRC---RvgGSPRPAVSWSKDGRRLGEpDGPRVRVEELGEasaLRIRAARPRDGGTYEVRAENPL 190
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECsppR--GHPEPTVSWRKDGQPLNL-DNERVRIVDDGN---LLIAEARKSDEGTYKCVATNMV 75


                  .
gi 215274225  191 G 191
Cdd:cd05724    76 G 76
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
 6474-6652 1.29e-06

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 54.06  E-value: 1.29e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKRVQHKGNKILCAAKfIPLRSRTRAQAYRERDILAALSHPLVTGLLDQFETRKTLILILELCSSEELLDRL 6553
Cdd:cd14156     1 IGSGFFSKVYKVTHGATGKVMVVK-IYKNDVDQHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6554 YRKGVVTEAEVKVYIQ-QLVEGLHYLHSHGVLHLDIKPSNILM-VHPAREDIKICDFGFAQNI--TPA---ELQFSQYGS 6626
Cdd:cd14156    80 AREELPLSWREKVELAcDISRGMVYLHSKNIYHRDLNSKNCLIrVTPRGREAVVTDFGLAREVgeMPAndpERKLSLVGS 159

                         170       180
                  ....*....|....*....|....*.
gi 215274225 6627 PEFVSPEIIQQNPVSEASDIWAMGVI 6652
Cdd:cd14156   160 AFWMAPEMLRGEPYDRKVDVFSFGIV 185
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 1176-1246 1.30e-06

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 49.71  E-value: 1.30e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1176 VQAEAGTTAMLSCE--VAQPQTEVTWYKDGKKLSSSSKVRMEVKGctRRLVVQQVGKADAGEYSCEAG---GQRVS 1246
Cdd:cd05724     7 TQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLNLDNERVRIVDD--GNLLIAEARKSDEGTYKCVATnmvGERES 80
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1820-1895 1.31e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.81  E-value: 1.31e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   1820 GELGGTVTLACELSPACAEVVW--RCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVCESRDDHTSAQLTVSV 1895
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPEVTwyKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 6121-6197 1.34e-06

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 49.75  E-value: 1.34e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6121 EGEDAQFTCTIEGAPYPQIRWykdgalLTTGNKFQTLSEPRSGLL---VLVIRAASKEDLGLYECELVNRLGSARASAEL 6197
Cdd:cd04978    13 PGETGELICEAEGNPQPTITW------RLNGVPIEPAPEDMRRTVdgrTLIFSNLQPNDTAVYQCNASNVHGYLLANAFL 86
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3545-3609 1.34e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 49.49  E-value: 1.34e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  3545 KNQEAREGATAVLQCELNSAAP--VEWRKGSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCV 3609
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 121-201 1.39e-06

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 49.88  E-value: 1.39e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  121 VREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDgpRVRVEELGEAS-ALRIRAARPRDGGTYEVRAENPLGAASAAAAL 199
Cdd:cd20973     9 VVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESR--RFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86


                  ..
gi 215274225  200 VV 201
Cdd:cd20973    87 TV 88
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 248-315 1.39e-06

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 49.84  E-value: 1.39e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDG-QLVTEGRRHVVYEDaqenfVLKILFCKQSDRGLYTCTASN 315
Cdd:cd20957    12 TVDFGRTAVFNCSVTGNPIHTVLWMKDGkPLGHSSRVQILSED-----VLVIPSVKREDKGMYQCFVRN 75
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 1181-1240 1.40e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 50.02  E-value: 1.40e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 1181 GTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 6469-6711 1.48e-06

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 53.95  E-value: 1.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6469 EVKEEIGRGVFGFVkrvqHKG---NKILCAAKFIPLRSRTRAQAYRERDILAALSHP-LVTglLDQFETRKTLILIL-EL 6543
Cdd:cd05068    11 KLLRKLGSGQFGEV----WEGlwnNTTPVAVKTLKPGTMDPEDFLREAQIMKKLRHPkLIQ--LYAVCTLEEPIYIItEL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEELLDRLYRKGVvteaevKVYIQQLVE-------GLHYLHSHGVLHLDIKPSNILMvhpAREDI-KICDFGFAQNIT 6615
Cdd:cd05068    85 MKHGSLLEYLQGKGR------SLQLPQLIDmaaqvasGMAYLESQNYIHRDLAARNVLV---GENNIcKVADFGLARVIK 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6616 PAELQFSQYGSP---EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSS-PFAGESDRATLLNVLEGrvsWSSPMAAHLS 6691
Cdd:cd05068   156 VEDEYEAREGAKfpiKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRiPYPGMTNAEVLQQVERG---YRMPCPPNCP 232

                         250       260
                  ....*....|....*....|
gi 215274225 6692 EDAKDFIKATLQRAPQARPS 6711
Cdd:cd05068   233 PQLYDIMLECWKADPMERPT 252
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 7465-7551 1.50e-06

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 49.95  E-value: 1.50e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7465 FLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGA--------PLESSSRVLISATLKnfqlLTILVVVAEDLGVYTC 7536
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSqnllfpyqPPQPSSRFSVSPTGD----LTITNVQRSDVGYYIC 77

                          90
                  ....*....|....*
gi 215274225 7537 SVSNALGTVTTTGVL 7551
Cdd:cd05726    78 QALNVAGSILAKAQL 92
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
 7677-7882 1.53e-06

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 53.72  E-value: 1.53e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQcwEKASGRALAAKIIPYhpkDKTA--VLREYEALKGLRHPHLAQLHAAYLSpRHLVLILELCSGPELL 7754
Cdd:cd05083    13 IIGEGEFGAVLQ--GEYMGQKVAVKNIKC---DVTAqaFLEETAVMTKLQHKNLVRLLGVILH-NGLYIVMELMSKGNLV 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAER--ASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLE 7832
Cdd:cd05083    87 NFLRSRgrALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFG----LAKVGSMGVDNSRLPVK 162

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7833 TMAPELLEGQGAVPQTDIWAIGVTAFIMLS---AEYPVSSegARDLQRGLRKG 7882
Cdd:cd05083   163 WTAPEALKNKKFSSKSDVWSYGVLLWEVFSygrAPYPKMS--VKEVKEAVEKG 213
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
 7759-7854 1.54e-06

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 54.34  E-value: 1.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYsesevkdYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLpsdkfKDYLET---MA 7835
Cdd:cd07850   102 ERMSY-------LLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMM-----TPYVVTryyRA 169

                          90
                  ....*....|....*....
gi 215274225 7836 PELLEGQGAVPQTDIWAIG 7854
Cdd:cd07850   170 PEVILGMGYKENVDIWSVG 188
STKc_CDC2L6 cd07867
Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the ...
 7715-7864 1.55e-06

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270850 [Multi-domain]  Cd Length: 318  Bit Score: 54.30  E-value: 1.55e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLS--PRHLVLILELCSGPELLPCLAERASYS--------ESEVKDYLWQMLSATQYLHN 7784
Cdd:cd07867    48 REIALLRELKHPNVIALQKVFLShsDRKVWLLFDYAEHDLWHIIKFHRASKAnkkpmqlpRSMVKSLLYQILDGIHYLHA 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7785 QHILHLDLRSENMIIT----EYNLLKVVDLGNAQsLSQEKVLPSDKFKDYLETM---APELLEG-QGAVPQTDIWAIGVT 7856
Cdd:cd07867   128 NWVLHRDLKPANILVMgegpERGRVKIADMGFAR-LFNSPLKPLADLDPVVVTFwyrAPELLLGaRHYTKAIDIWAIGCI 206


                  ....*...
gi 215274225 7857 AFIMLSAE 7864
Cdd:cd07867   207 FAELLTSE 214
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 331-404 1.56e-06

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 49.81  E-value: 1.56e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  331 PAVPFKKRLQDLEVREKESATFLCEV---PQPstEAAWFKEETRLWASAK-YGIEEEGTErrLTVRNVSADDDAVYIC 404
Cdd:cd20970     1 PVISTPQPSFTVTAREGENATFMCRAegsPEP--EISWTRNGNLIIEFNTrYIVRENGTT--LTIRNIRRSDMGIYLC 74
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 1537-1608 1.56e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 49.64  E-value: 1.56e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1537 EQPASREVQAeaGTSATLSCEV-AQAQTEVTWYKDGKKLSSS----SKVRMEAVGctrrLVVQEAGQADAGEYSCKA 1608
Cdd:cd20949     4 ENAYVTTVKE--GQSATILCEVkGEPQPNVTWHFNGQPISASvadmSKYRILADG----LLINKVTQDDTGEYTCRA 74
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3375-3445 1.56e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.43  E-value: 1.56e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   3375 EGATATLRCELSKAAP--VEWRK-GRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVC----GEERTSATLTV 3445
Cdd:smart00410    8 EGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGTTLTV 85
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 5370-5466 1.60e-06

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 49.94  E-value: 1.60e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5370 PPRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAERGVlwigpdtPGYTVASSAQQHSLVLLDVGRQHQGTYTC 5449
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQY-------AADRSTCEAGVGELHIQDVLPEDHGTYTC 73

                          90
                  ....*....|....*..
gi 215274225 5450 IASNAAGQALCSASLHV 5466
Cdd:cd20976    74 LAKNAAGQVSCSAWVTV 90
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 3805-3885 1.62e-06

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 49.82  E-value: 1.62e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3805 IEDVKNQEAREGATAVLQCELSKAAPV---EWRK-GSETLRGGD-RYSLRQDGTRCELQIHGLSVADTGEYSCVC----G 3875
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEATSENPSpryRWFKdGKELNRKRPkNIKIRNKKKNSELQINKAKLEDSGEYTCVVenilG 82

                          90
                  ....*....|
gi 215274225 3876 QERTSATLTV 3885
Cdd:cd05750    83 KDTVTGNVTV 92
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 4068-4154 1.64e-06

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 49.89  E-value: 1.64e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4068 PKFKTRLQSLEQETGDIARLCCQLSDAESgAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYAC----VT 4143
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPT-PVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSClatnSV 80

                          90
                  ....*....|.
gi 215274225 4144 GGQKTAASLRV 4154
Cdd:cd20972    81 GSDTTSAEIFV 91
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 340-405 1.64e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.43  E-value: 1.64e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225    340 QDLEVREKESATFLCEVPQ-PSTEAAWFKEETR-LWASAKYGIEEEGTERRLTVRNVSADDDAVYICE 405
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGsPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCA 69
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 4911-4983 1.64e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 49.91  E-value: 1.64e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 4911 VGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKFGQVTHS 4983
Cdd:cd05729    18 AANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHT 90
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 5136-5216 1.71e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 49.64  E-value: 1.71e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5136 EVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYM----INEDqqgghQLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:cd20949    10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMskyrILAD-----GLLINKVTQDDTGEYTCRAYQVNSIASDM 84


                  ....*
gi 215274225 5212 AELRV 5216
Cdd:cd20949    85 QERTV 89
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 6014-6104 1.71e-06

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 49.66  E-value: 1.71e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6014 PDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPH-HILIEDPDGSCALILDSLTGVDSGQYMCFAASA 6092
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 215274225 6093 AGNCSTLGKILV 6104
Cdd:cd20974    81 SGQATSTAELLV 92
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 7462-7543 1.73e-06

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 49.66  E-value: 1.73e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7462 APTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATlKNFQLLTILVVVAEDLGVYTCSVSNA 7541
Cdd:cd05747     3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITST-EYKSTFEISKVQMSDEGNYTVVVENS 81


                  ..
gi 215274225 7542 LG 7543
Cdd:cd05747    82 EG 83
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 3895-3962 1.78e-06

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 49.50  E-value: 1.78e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  3895 PLQSLQAEEGSTATLQCELSEPT--ATVVWSKGGLQLQaNGRREPRLQGCT--AELVLQDLQREDTGEYTCT 3962
Cdd:pfam00047    2 APPTVTVLEGDSATLTCSASTGSpgPDVTWSKEGGTLI-ESLKVKHDNGRTtqSSLLISNVTKEDAGTYTCV 72
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 5260-5350 1.83e-06

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 49.71  E-value: 1.83e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGtRLAKFQLKVKGYPAPRLYWFKDGQPLTA-SAHIRMTDKKILHTLEIISVTREDSGQYAAYISNA 5338
Cdd:cd20990     1 PHFLQAPGDLTVQEG-KLCRMDCKVSGLPTPDLSWQLDGKPIRPdSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNR 79

                          90
                  ....*....|..
gi 215274225 5339 MGAAYSSARLLV 5350
Cdd:cd20990    80 AGQNSFNLELVV 91
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 6115-6197 1.92e-06

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 49.38  E-value: 1.92e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6115 RASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFqTLSEPRSgllvLVIRAASKEDLGLYECELVNRLGSARAS 6194
Cdd:cd04969    10 KKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRI-CILPDGS----LKIKNVTKSDEGKYTCFAVNFFGKANST 84


                  ...
gi 215274225 6195 AEL 6197
Cdd:cd04969    85 GSL 87
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 6106-6197 1.94e-06

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 49.66  E-value: 1.94e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6106 VPPRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQ-TLSEPRSGLLVLVIRAAskeDLGLYECEL 6184
Cdd:cd05747     2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQiTSTEYKSTFEISKVQMS---DEGNYTVVV 78

                          90
                  ....*....|...
gi 215274225 6185 VNRLGSARASAEL 6197
Cdd:cd05747    79 ENSEGKQEAQFTL 91
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 7477-7548 2.03e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 49.53  E-value: 2.03e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7477 GQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNFQLLTILVVVAEDLGVYTCSVSNALGTVTTT 7548
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHT 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1358-1424 2.08e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 49.43  E-value: 2.08e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   1358 RKVQAEAGAIATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
STKc_CDK8 cd07868
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs ...
 7715-7864 2.12e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270851 [Multi-domain]  Cd Length: 333  Bit Score: 53.91  E-value: 2.12e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLS--PRHLVLILELCSGPELLPCLAERASYSESE--------VKDYLWQMLSATQYLHN 7784
Cdd:cd07868    63 REIALLRELKHPNVISLQKVFLShaDRKVWLLFDYAEHDLWHIIKFHRASKANKKpvqlprgmVKSLLYQILDGIHYLHA 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7785 QHILHLDLRSENMIIT----EYNLLKVVDLGNAQsLSQEKVLPSDKFKDYLETM---APELLEG-QGAVPQTDIWAIGVT 7856
Cdd:cd07868   143 NWVLHRDLKPANILVMgegpERGRVKIADMGFAR-LFNSPLKPLADLDPVVVTFwyrAPELLLGaRHYTKAIDIWAIGCI 221


                  ....*...
gi 215274225 7857 AFIMLSAE 7864
Cdd:cd07868   222 FAELLTSE 229
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
 7774-7866 2.15e-06

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 54.11  E-value: 2.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7774 QMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSlsqEKVLPSD-KFKDYLETMAPELLEGQGAVPQTDIWA 7852
Cdd:PHA03209  165 QILEGLRYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAAQF---PVVAPAFlGLAGTVETNAPEVLARDKYNSKADIWS 241

                          90
                  ....*....|....
gi 215274225 7853 IGVTAFIMLSaeYP 7866
Cdd:PHA03209  242 AGIVLFEMLA--YP 253
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 7463-7547 2.19e-06

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 49.34  E-value: 2.19e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSS--RVLISATLKNFQLLTILVVVAEDLGVYTCSVSN 7540
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80


                  ....*..
gi 215274225 7541 ALGTVTT 7547
Cdd:cd20951    81 IHGEASS 87
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
 7680-7866 2.20e-06

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 53.91  E-value: 2.20e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIipyHPKDKT-----------AVLREYEALKGLRHPHLAQLHAAY-LSPRHLVLILEL 7747
Cdd:cd14041    16 RGGFSEVYKAFDLTEQRYVAVKI---HQLNKNwrdekkenyhkHACREYRIHKELDHPRIVKLYDYFsLDTDSFCTVLEY 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQH--ILHLDLRSENMI-----------ITEYNLLKVVDLGNAQ 7814
Cdd:cd14041    93 CEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKppIIHYDLKPGNILlvngtacgeikITDFGLSKIMDDDSYN 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7815 SLSQEKvLPSDKFKDYLeTMAPELLEGQGAVP----QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14041   173 SVDGME-LTSQGAGTYW-YLPPECFVVGKEPPkisnKVDVWSVGVIFYQCLYGRKP 226
pknD PRK13184
serine/threonine-protein kinase PknD;
7777-7875 2.22e-06

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 55.16  E-value: 2.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7777 SATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEK-VLPSDKFK-------------------DYletMAP 7836
Cdd:PRK13184  124 ATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIFKKLEEeDLLDIDVDernicyssmtipgkivgtpDY---MAP 200

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 215274225 7837 ELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:PRK13184  201 ERLLGVPASESTDIYALGVILYQMLTLSFPYRRKKGRKI 239
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1644-1700 2.22e-06

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 48.86  E-value: 2.22e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1644 ATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEA 1700
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2165-2240 2.28e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 49.10  E-value: 2.28e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  2165 PVSFSRPLQDVVTTEKEKVTLECE-LSRPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAH 2240
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 6126-6197 2.37e-06

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 48.72  E-value: 2.37e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6126 QFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPrsgllVLVIRAASKEDLGLYECELVNRLGSARASAEL 6197
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEG-----YLAIRDVGVADQGRYECVARNTIGYASVSMVL 68
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 2468-2554 2.43e-06

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 49.34  E-value: 2.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2468 PVVLTRpLEPKTGRELQSVVLSCDFRPAPK-AVQWYKDDTPLSPSE---KFKMSLEGQMAELRILRLMPADAGVYRCQA- 2542
Cdd:cd20951     1 PEFIIR-LQSHTVWEKSDAKLRVEVQGKPDpEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAk 79

                          90
                  ....*....|....*
gi 215274225 2543 ---GSAHSSTEVTVE 2554
Cdd:cd20951    80 nihGEASSSASVVVE 94
I-set pfam07679
Immunoglobulin I-set domain;
737-779 2.45e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 49.18  E-value: 2.45e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 215274225   737 VTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECV 779
Cdd:pfam07679   32 VSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCV 74
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 6108-6199 2.51e-06

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 49.47  E-value: 2.51e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTgNKFQTLSE----PRSGLLVLVIRAA--SKEDLGLYE 6181
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLET-DKDDPRSHrivlPSGSLFFLRVVHGrkGRSDEGVYV 79

                          90
                  ....*....|....*....
gi 215274225 6182 CELVNRLGSAR-ASAELRI 6199
Cdd:cd07693    80 CVAHNSLGEAVsRNASLEV 98
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 6024-6104 2.54e-06

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 49.05  E-value: 2.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6024 TAELGETVKLACRVTG-TPKPVISWYKDGKAV-QVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFAASAAGNCSTLGK 6101
Cdd:cd05750    10 TVQEGSKLVLKCEATSeNPSPRYRWFKDGKELnRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGN 89


                  ...
gi 215274225 6102 ILV 6104
Cdd:cd05750    90 VTV 92
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1735-1804 2.63e-06

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 48.78  E-value: 2.63e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1735 DIILTATLATPSAAtVTWLKDGVEIRRSKRHETASQGDTHTLTVHGAQVLDSAIYSCRVGAEGQDFPVQV 1804
Cdd:cd20967    14 KIRLTVELADPDAE-VKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 905-964 2.67e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 49.25  E-value: 2.67e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  905 GASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 6108-6199 2.76e-06

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 49.27  E-value: 2.76e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 215274225 6188 LGSARASAELRI 6199
Cdd:cd20974    81 SGQATSTAELLV 92
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6122-6199 2.76e-06

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 48.93  E-value: 2.76e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6122 GEDAQFTCTIEGAPYPQIRWYKDGALLTTGnKFQTLSEpRSgllvLVIRAASKEDLGLYECELVNRLGSARASAELRI 6199
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDD-HS----LKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3636-3709 2.79e-06

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 48.78  E-value: 2.79e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3636 EATEGATAVLRCELSKM-APVEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLCMCGKERTSAMLTV 3709
Cdd:cd20967     8 QVSKGHKIRLTVELADPdAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 124-191 2.95e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 49.14  E-value: 2.95e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  124 GSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGPRV-RVEELGeaSALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGtKVEEKG--WSLIIERAIPRDKGKYTCIVENEYG 85
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 20-86 3.05e-06

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 48.55  E-value: 3.05e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225    20 VVSVGKDATLSCQIVGNPTPQVSWEKDQQPVaagarfrlAQDGDLYRLTIldlALGDSGQYVCRARN 86
Cdd:pfam13895   10 VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI--------SSSPNFFTLSV---SAEDSGTYTCVARN 65
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3192-3256 3.21e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 48.33  E-value: 3.21e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  3192 KDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC 3256
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPPtITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74
I-set pfam07679
Immunoglobulin I-set domain;
807-883 3.23e-06

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 48.79  E-value: 3.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   807 VDAVAGGPAQFECETSEAHV-HVHWYKDGMELgHSGERFLQEDVGTRHRLVAATVTRQDEGTYSCRV----GEDSVDFRL 881
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDpEVSWFKDGQPL-RSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGEAEASAEL 88


                   ..
gi 215274225   882 RV 883
Cdd:pfam07679   89 TV 90
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
 7676-7855 3.30e-06

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 52.97  E-value: 3.30e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQC----WEKASGRALAAKIIPYH-PKDKTAVLREYEALKGLRHPHLAQLHAAYLSP--RHLVLILE-L 7747
Cdd:cd05081    10 SQLGKGNFGSVELCrydpLGDNTGALVAVKQLQHSgPDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrRSLRLVMEyL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGpellpCLAE-----RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqslsqeKVL 7822
Cdd:cd05081    90 PSG-----CLRDflqrhRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLA------KLL 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 215274225 7823 PSDkfKDYLETM----------APELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05081   159 PLD--KDYYVVRepgqspifwyAPESLSDNIFSRQSDVWSFGV 199
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
 7726-7855 3.31e-06

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 52.79  E-value: 3.31e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7726 PHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLL 7805
Cdd:cd05609    60 PFVVSMYCSFETKRHLCMVMEYVEGGDCATLLKNIGPLPVDMARMYFAETVLALEYLHSYGIVHRDLKPDNLLITSMGHI 139

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7806 KVVDLG-------NAQSLSQEKVLPSD--KFKDYL-----ETMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05609   140 KLTDFGlskiglmSLTTNLYEGHIEKDtrEFLDKQvcgtpEYIAPEVILRQGYGKPVDWWAMGI 203
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 5382-5466 3.32e-06

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 48.65  E-value: 3.32e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5382 VKKGSSITFSVKVEGRPVPTVHWLREeaerGVLWIGPDTPgytvASSAQQHSLVLLDVGRQHQGTYTCIASNAAGQALCS 5461
Cdd:cd20952    11 VAVGGTVVLNCQATGEPVPTISWLKD----GVPLLGKDER----ITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWS 82


                  ....*
gi 215274225 5462 ASLHV 5466
Cdd:cd20952    83 AVLDV 87
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
 7764-7960 3.35e-06

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 53.46  E-value: 3.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7764 SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlPSDKFKDYLET---MAPE-LL 7839
Cdd:cd07849   104 SNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARIADPEHD-HTGFLTEYVATrwyRAPEiML 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7840 EGQGAVPQTDIWAIGVTAFIMLSAE---------------------------YPVSSEGARDLQRGL-RKGLVRLSRCYA 7891
Cdd:cd07849   183 NSKGYTKAIDIWSVGCILAEMLSNRplfpgkdylhqlnlilgilgtpsqedlNCIISLKARNYIKSLpFKPKVPWNKLFP 262

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 7892 GLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWLT-----EEGPACSRP-APVTFPTARLrvfvrNREKRRALLYK 7960
Cdd:cd07849   263 NADPKALDLLDKMLTFNPHKRITVEEALAHPYLEqyhdpSDEPVAEEPfPFDMELFDDL-----PKEKLKELIFE 332
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
 7759-7854 3.45e-06

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 53.55  E-value: 3.45e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYsesevkdYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLEtmAPEL 7838
Cdd:cd07874   119 ERMSY-------LLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYR--APEV 189

                          90
                  ....*....|....*.
gi 215274225 7839 LEGQGAVPQTDIWAIG 7854
Cdd:cd07874   190 ILGMGYKENVDIWSVG 205
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1000-1057 3.48e-06

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 48.09  E-value: 3.48e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1000 ATLSCEV-AQAQTEVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEAR 1057
Cdd:cd00096     1 VTLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 3904-3974 3.49e-06

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 48.77  E-value: 3.49e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3904 GSTATLQCELS-EPTATVVWSK-GGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCT----CGSQATSATLTV 3974
Cdd:cd05763    14 GSTARLECAATgHPTPQIAWQKdGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTaqnsAGSISANATLTV 90
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 5129-5206 3.69e-06

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 48.60  E-value: 3.69e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5129 LTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQqgGHQLIITAVVPADMGVYRCLAENSMG 5206
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVD--GRTLIFSNLQPNDTAVYQCNASNVHG 78
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
 6009-6095 3.73e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 48.70  E-value: 3.73e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6009 PVW-RPPDFEEELADCTAelGETVKLACRVTGTPKPVISWYKDGKAVQVDpHHI-LIEDPDGSCALILDSLTGVDSGQYM 6086
Cdd:cd05857     1 PYWtNPEKMEKKLHAVPA--ANTVKFRCPAAGNPTPTMRWLKNGKEFKQE-HRIgGYKVRNQHWSLIMESVVPSDKGNYT 77


                  ....*....
gi 215274225 6087 CFAASAAGN 6095
Cdd:cd05857    78 CVVENEYGS 86
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 6371-6436 3.76e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 48.87  E-value: 3.76e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 6371 GGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd20949    14 GQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNS 79
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 5129-5219 3.89e-06

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 48.89  E-value: 3.89e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5129 LTELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQGGhQLIITAVVPADMGVYRCLAENSMGvs 5208
Cdd:cd05747     7 LTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKS-TFEISKVQMSDEGNYTVVVENSEG-- 83

                          90
                  ....*....|.
gi 215274225 5209 stKAELRVDLT 5219
Cdd:cd05747    84 --KQEAQFTLT 92
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 3189-3269 3.93e-06

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 48.72  E-value: 3.93e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3189 EALKDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAML-ELVVRNLRPQDSGRYSC----SFGDQT 3262
Cdd:cd20973     2 QTLRDKEVVEGSAARFDCKVEGYPDPeVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCkavnSLGEAT 81


                  ....*..
gi 215274225 3263 TSATLTV 3269
Cdd:cd20973    82 CSAELTV 88
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 7465-7552 3.97e-06

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 48.37  E-value: 3.97e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7465 FLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNFQLLTIlvvvaEDLGVYTCSVSNALGT 7544
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSL-----SDSGMYQCVAENKHGT 76


                  ....*...
gi 215274225 7545 VTTTGVLR 7552
Cdd:cd05728    77 IYASAELA 84
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1180-1252 3.99e-06

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 48.72  E-value: 3.99e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1180 AGTTAMLSCEVA-QPQTEVTWYKDGKKLSSSSKVRMEVKGcTrrLVVQQV-GKADAGEYSCEA---GGQRVSFQLHIT 1252
Cdd:cd20958    14 AGQTLRLHCPVAgYPISSITWEKDGRRLPLNHRQRVFPNG-T--LVIENVqRSSDEGEYTCTArnqQGQSASRSVFVK 88
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 5134-5211 4.17e-06

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 48.39  E-value: 4.17e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5134 NQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQgghqLIITAVVPADMGVYRCLAENSMGVSSTK 5211
Cdd:cd20968     8 NVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGS----LRIHNVQKEDAGQYRCVAKNSLGIAYSK 81
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
 7759-7854 4.21e-06

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 53.12  E-value: 4.21e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYsesevkdYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLEtmAPEL 7838
Cdd:cd07875   126 ERMSY-------LLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYR--APEV 196

                          90
                  ....*....|....*.
gi 215274225 7839 LEGQGAVPQTDIWAIG 7854
Cdd:cd07875   197 ILGMGYKENVDIWSVG 212
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 248-318 4.23e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 48.48  E-value: 4.23e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEG----RRHVVYEDAqenfvLKILFCKQSDRGLYTCTASNLVG 318
Cdd:cd20949    10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG-----LLINKVTQDDTGEYTCRAYQVNS 79
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 2830-2911 4.25e-06

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 48.66  E-value: 4.25e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2830 IKPLEDQWVAPGEDVELRCELSrAGTPV---HWLKDRK----------AIRKSQKYdvvcegtmAMLVIRGASLKDAGEY 2896
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEAT-SENPSpryRWFKDGKelnrkrpkniKIRNKKKN--------SELQINKAKLEDSGEY 73

                          90
                  ....*....|....*....
gi 215274225 2897 TCEVEA----SKSTASLHV 2911
Cdd:cd05750    74 TCVVENilgkDTVTGNVTV 92
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2289-2361 4.30e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 47.95  E-value: 4.30e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  2289 PVTLVRPLRDKIAMEKHRGVLECQVSRA-SAQVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTC 2361
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSpPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 4068-4154 4.42e-06

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 48.57  E-value: 4.42e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4068 PKFKTRLQSLEQETGDIARLCCQLSdAESGAVVQWLKEGVEL---HAGPKYEMRSQGATRELLIHQLEAKDTGEYACVT- 4143
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQ-GKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAk 79

                          90
                  ....*....|....
gi 215274225 4144 ---GGQKTAASLRV 4154
Cdd:cd20951    80 nihGEASSSASVVV 93
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
 7768-7854 4.44e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 52.66  E-value: 4.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7768 VKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLpsDKFKDYLETMAPE-LLEGQGAVP 7846
Cdd:cd07863   110 IKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARIYSCQMAL--TPVVVTLWYRAPEvLLQSTYATP 187


                  ....*...
gi 215274225 7847 qTDIWAIG 7854
Cdd:cd07863   188 -VDMWSVG 194
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3721-3785 4.61e-06

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 47.95  E-value: 4.61e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  3721 RNEEATEGDTATLWCELSKAAP--VEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCV 3785
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
 7772-7940 4.68e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 52.95  E-value: 4.68e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7772 LWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQ-EKVLPSDKFKDYLET---MAPELLEGQG---- 7843
Cdd:cd07852   113 MYQLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSLSQlEEDDENPVLTDYVATrwyRAPEILLGSTrytk 192

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7844 AVpqtDIWAIG------------------------VTAFI-MLSAE--YPVSSEGA----RDLQRGLRKGLVRLsrcYAG 7892
Cdd:cd07852   193 GV---DMWSVGcilgemllgkplfpgtstlnqlekIIEVIgRPSAEdiESIQSPFAatmlESLPPSRPKSLDEL---FPK 266

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7893 LSGGAVAFLRSTLCAQPWGRPCASSCLQCPWL-----TEEGPACsrPAPVTFP 7940
Cdd:cd07852   267 ASPDALDLLKKLLVFNPNKRLTAEEALRHPYVaqfhnPADEPSL--PGPIVIP 317
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 3095-3175 4.75e-06

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 48.35  E-value: 4.75e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3095 PSVFSRELTDATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEAGGAC 3173
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPvVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80


                  ..
gi 215274225 3174 SS 3175
Cdd:cd20972    81 GS 82
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 3184-3269 4.80e-06

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 48.35  E-value: 4.80e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3184 PVRFQEALKDLEVLEGGAATLRCVLSSVAAP-VKW-CYGNNVLRPGDkYSLRQEGAMLELVVRNLRPQDSGRYSC----S 3257
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPvVRWfCEGKELQNSPD-IQIHQEGDLHSLIIAEAFEEDTGRYSClatnS 79

                          90
                  ....*....|..
gi 215274225 3258 FGDQTTSATLTV 3269
Cdd:cd20972    80 VGSDTTSAEIFV 91
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 10-89 4.95e-06

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 48.23  E-value: 4.95e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGA-RFRLAQDGDLY-RLTILDLALGDSGQYVCRARNA 87
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTdRISLYQDNCGRiCLLIQNANKKDAGWYTVSAVNE 80


                  ..
gi 215274225   88 IG 89
Cdd:cd05892    81 AG 82
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
 7715-7855 5.03e-06

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 52.32  E-value: 5.03e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSPR-HL-------------VLIlELCSGPELLPCLAERASYSEsEVKDYLWQMLSATQ 7780
Cdd:cd14011    51 RGVKQLTRLRHPRILTVQHPLEESReSLafatepvfaslanVLG-ERDNMPSPPPELQDYKLYDV-EIKYGLLQISEALS 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7781 YLHN-QHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSdKFKDY-----------LETMAPELLEGQGAVPQT 7848
Cdd:cd14011   129 FLHNdVKLVHGNICPESVVINSNGEWKLAGFDFCISSEQATDQFP-YFREYdpnlpplaqpnLNYLAPEYILSKTCDPAS 207


                  ....*..
gi 215274225 7849 DIWAIGV 7855
Cdd:cd14011   208 DMFSLGV 214
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
 7694-7867 5.05e-06

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 52.32  E-value: 5.05e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7694 SGRALAAKIIPYHPKDKTAVLREYEALKGL-RHPHLAQLHAAYL--SP----RHLVLILELCSGPELLPCLAERA--SYS 7764
Cdd:cd06636    40 TGQLAAIKVMDVTEDEEEEIKLEINMLKKYsHHRNIATYYGAFIkkSPpghdDQLWLVMEFCGAGSVTDLVKNTKgnALK 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7765 ESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQeKVLPSDKFKDYLETMAPELL---EG 7841
Cdd:cd06636   120 EDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR-TVGRRNTFIGTPYWMAPEVIacdEN 198

                         170       180
                  ....*....|....*....|....*...
gi 215274225 7842 QGAV--PQTDIWAIGVTAFIMLSAEYPV 7867
Cdd:cd06636   199 PDATydYRSDIWSLGITAIEMAEGAPPL 226
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3457-3533 5.36e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 48.27  E-value: 5.36e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3457 RNEEAVEGATAMLWCELSKVAP--VEWRK-GPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCVC----GQERTSA 3529
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3530 TLTI 3533
Cdd:smart00410   82 TLTV 85
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 6108-6197 5.74e-06

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 48.16  E-value: 5.74e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKV-RASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLtTGNKFQTLSEPRSgllvLVIRAASKEDLGLYECELVN 6186
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPL-QGPMERATVEDGT----LTIINVQPEDTGYYGCVATN 75

                          90
                  ....*....|.
gi 215274225 6187 RLGSARASAEL 6197
Cdd:cd20978    76 EIGDIYTETLL 86
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 7473-7543 5.75e-06

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 48.39  E-value: 5.75e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 7473 TVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNfqLLTILVVVAEDLGVYTCSVSNALG 7543
Cdd:cd05730    14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGS--EMTILDVDKLDEAEYTCIAENKAG 82
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 1365-1424 5.84e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 48.10  E-value: 5.84e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 1365 GAIATLSCEV-AQAQTEVTWYKDGKKLSSS----SKVRMEAVGctrrLVVQQACQADTGEYSCEA 1424
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASvadmSKYRILADG----LLINKVTQDDTGEYTCRA 74
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4630-4695 6.02e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.89  E-value: 6.02e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   4630 PESRQVAAGEDVSLELEVVAEAGEVI-WHK-GMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVtWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTC 68
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
 7708-7874 6.08e-06

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 51.63  E-value: 6.08e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTAVLREyealkgLRHPHLAqLHAAYLSPRHLVLILELCSGPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQH 7786
Cdd:cd14062    37 KNEVAVLRK------TRHVNIL-LFMGYMTKPQLAIVTQWCEGSSLYKHLhVLETKFEMLQLIDIARQTAQGMDYLHAKN 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7787 ILHLDLRSENMIITEYNLLKVVDLGNAQ-----SLSQEKVLPSDKfkdyLETMAPELLEGQGAVP---QTDIWAIGVTAF 7858
Cdd:cd14062   110 IIHRDLKSNNIFLHEDLTVKIGDFGLATvktrwSGSQQFEQPTGS----ILWMAPEVIRMQDENPysfQSDVYAFGIVLY 185

                         170
                  ....*....|....*.
gi 215274225 7859 IMLSAEYPVSSEGARD 7874
Cdd:cd14062   186 ELLTGQLPYSHINNRD 201
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
 6355-6438 6.14e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 48.31  E-value: 6.14e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6355 RPPSMQVTIEDVQAqtGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLS----QQQegtTYSLVLRHVASKDAGVYTCL 6430
Cdd:cd05857     5 NPEKMEKKLHAVPA--ANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGgykvRNQ---HWSLIMESVVPSDKGNYTCV 79


                  ....*...
gi 215274225 6431 AQNTGGQV 6438
Cdd:cd05857    80 VENEYGSI 87
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
 7680-7866 6.25e-06

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 52.37  E-value: 6.25e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIipyHPKDKT-----------AVLREYEALKGLRHPHLAQLHAAY-LSPRHLVLILEL 7747
Cdd:cd14040    16 RGGFSEVYKAFDLYEQRYAAVKI---HQLNKSwrdekkenyhkHACREYRIHKELDHPRIVKLYDYFsLDTDTFCTVLEY 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLH--NQHILHLDLRSENMII---TEYNLLKVVDLGNAQSLSQEKV- 7821
Cdd:cd14040    93 CEGNDLDFYLKQHKLMSEKEARSIVMQIVNALRYLNeiKPPIIHYDLKPGNILLvdgTACGEIKITDFGLSKIMDDDSYg 172

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 215274225 7822 -----LPSDKFKDYLeTMAPELLEGQGAVP----QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14040   173 vdgmdLTSQGAGTYW-YLPPECFVVGKEPPkisnKVDVWSVGVIFFQCLYGRKP 225
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 10-91 6.58e-06

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 47.84  E-value: 6.58e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   10 PRFLTRP--KAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDLYrltILDLALGDSGQYVCRARNA 87
Cdd:cd04969     1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLK---IKNVTKSDEGKYTCFAVNF 77


                  ....
gi 215274225   88 IGEA 91
Cdd:cd04969    78 FGKA 81
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 6108-6199 6.68e-06

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 48.17  E-value: 6.68e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 215274225 6188 LGSARASAELRI 6199
Cdd:cd05893    81 QGRISCTGRLMV 92
PHA03207 PHA03207
serine/threonine kinase US3; Provisional
 7775-7861 6.73e-06

serine/threonine kinase US3; Provisional


Pssm-ID: 165473 [Multi-domain]  Cd Length: 392  Bit Score: 52.54  E-value: 6.73e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7775 MLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDY-----LETMAPELLEGQGAVPQTD 7849
Cdd:PHA03207  194 LLEALAYLHGRGIIHRDVKTENIFLDEPENAVLGDFGAACKLDAH----PDTPQCYgwsgtLETNSPELLALDPYCAKTD 269

                          90
                  ....*....|..
gi 215274225 7850 IWAIGVTAFIML 7861
Cdd:PHA03207  270 IWSAGLVLFEMS 281
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 5284-5351 6.92e-06

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 47.58  E-value: 6.92e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 5284 VKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMGAAysSARLLVR 5351
Cdd:cd05748    16 IKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEK--SATINVK 81
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 898-964 7.04e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.89  E-value: 7.04e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225    898 RKLQAEAGASATLSCEVAQA-QTEVTWYKDG-KKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAA 70
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 6028-6087 7.09e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 47.98  E-value: 7.09e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6028 GETVKLACRVTGTPKPVISWYKDGKavQVDPHHIL--IEDPDGSCALILDSLTGVDSGQYMC 6087
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGK--EFKKEHRIggTKVEEKGWSLIIERAIPRDKGKYTC 78
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 114-191 7.36e-06

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 47.39  E-value: 7.36e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   114 LRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLgePDGPRvrveelgeasaLRIRAARPRDGGTYEVRAENPLG 191
Cdd:pfam13895    4 LTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI--SSSPN-----------FFTLSVSAEDSGTYTCVARNGRG 68
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 248-328 7.49e-06

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 47.89  E-value: 7.49e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGE-PKPETVWKKDGQLVTEGR-RHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQTYSSVL 325
Cdd:cd05750    10 TVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRpKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGN 89


                  ...
gi 215274225  326 VVV 328
Cdd:cd05750    90 VTV 92
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3281-3357 7.61e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.50  E-value: 7.61e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3281 RNKEATEGATATLRCELSKAAP--VEWRK-GSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVC----GEERTSA 3353
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPpeVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3354 SLTI 3357
Cdd:smart00410   82 TLTV 85
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 256-328 7.90e-06

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 47.18  E-value: 7.90e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  256 RLSCYVTGEPKPETVWKKDGQLVTE-GRRHVvyedAQENFvLKILFCKQSDRGLYTCTASNLVGqtYSSVLVVV 328
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDGVQVTEsGKFHI----SPEGY-LAIRDVGVADQGRYECVARNTIG--YASVSMVL 68
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 248-322 7.99e-06

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 47.93  E-value: 7.99e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQ-LVTE---GRRHVVYEDAQENFVLKILFCKQ--SDRGLYTCTASNLVGQTY 321
Cdd:cd07693    11 IVSKGDPATLNCKAEGRPTPTIQWLKNGQpLETDkddPRSHRIVLPSGSLFFLRVVHGRKgrSDEGVYVCVAHNSLGEAV 90


                  .
gi 215274225  322 S 322
Cdd:cd07693    91 S 91
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 6371-6438 8.13e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 47.98  E-value: 8.13e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6371 GGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLS-QQQEGTTYSLVLRHVASKDAGVYTCLAQNTGGQV 6438
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGgTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSI 87
PKc_YAK1 cd14212
Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze ...
 7681-7813 8.16e-06

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271114 [Multi-domain]  Cd Length: 330  Bit Score: 52.25  E-value: 8.16e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIpyhpKDKTAVLR----EYEALKGLR-------HPHLAQLHAAYLSPRHLVLILELCs 7749
Cdd:cd14212    10 GTFGQVVKCQDLKTNKLVAVKVL----KNKPAYFRqamlEIAILTLLNtkydpedKHHIVRLLDHFMHHGHLCIVFELL- 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 7750 GPELLPCLAERA--SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNL--LKVVDLGNA 7813
Cdd:cd14212    85 GVNLYELLKQNQfrGLSLQLIRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDSpeIKLIDFGSA 152
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
 7695-7889 8.46e-06

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 51.62  E-value: 8.46e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7695 GRALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERA-----SYSESEVK 7769
Cdd:cd13992    25 GRTVAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREikmdwMFKSSFIK 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7770 DYLWQMlsatQYLHNQHI-LHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLET--MAPELL----EGQ 7842
Cdd:cd13992   105 DIVKGM----NYLHSSSIgYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNHQLDEDAQHKKLlwTAPELLrgslLEV 180

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 7843 GAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRC 7889
Cdd:cd13992   181 RGTQKGDVYSFAIILYEILFRSDPFALEREVAIVEKVISGGNKPFRP 227
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 3012-3091 8.48e-06

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 47.50  E-value: 8.48e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   3012 EDVDVQEGSSATFRCRISPANYEPVHWFLDKTPLHANELNEIDAQPGGYHVLTLRQLALKDSGTIYFEA----GDQRASA 3087
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   3088 ALRV 3091
Cdd:smart00410   82 TLTV 85
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3187-3269 9.33e-06

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 47.49  E-value: 9.33e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3187 FQEALKDLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDKYS-LRQEGAMLELVVRNLRPQDSGRYSCS----FGD 3260
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPdLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTCIarnrAGE 82


                  ....*....
gi 215274225 3261 QTTSATLTV 3269
Cdd:cd05744    83 NSFNAELVV 91
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 5137-5216 9.35e-06

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 47.45  E-value: 9.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5137 VQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMINEDQQgghqLIITAVVPADMGVYRCLAENSMGVSSTKAELRV 5216
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS----LKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3716-3798 9.71e-06

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 47.46  E-value: 9.71e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3716 FIEGLRNEEATEGDTATLWCELSKAAP--VEWRKGHETLR-DGDRHSLRQDGS-RCELQIRGLAVVDAGEYSCVCGQERT 3791
Cdd:cd05892     3 FIQKPQNKKVLEGDPVRLECQISAIPPpqIFWKKNNEMLQyNTDRISLYQDNCgRICLLIQNANKKDAGWYTVSAVNEAG 82


                  ....*..
gi 215274225 3792 SATLTVR 3798
Cdd:cd05892    83 VVSCNAR 89
PKc_CLK cd14134
Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity ...
 7681-7797 9.79e-06

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271036 [Multi-domain]  Cd Length: 332  Bit Score: 51.80  E-value: 9.79e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRH------PHLAQLHAAYLSPRHLVLILELCsGPELL 7754
Cdd:cd14134    23 GTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEkdpngkSHCVQLRDWFDYRGHMCIVFELL-GPSLY 101

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 215274225 7755 PCLAERA--SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENM 7797
Cdd:cd14134   102 DFLKKNNygPFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENI 146
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 7464-7544 9.90e-06

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 47.33  E-value: 9.90e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7464 TFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSsrvliSATLKNFQL----LTILVVVAEDLGVYTCSVS 7539
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISAS-----VADMSKYRIladgLLINKVTQDDTGEYTCRAY 75


                  ....*
gi 215274225 7540 NALGT 7544
Cdd:cd20949    76 QVNSI 80
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 4898-4988 1.01e-05

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 47.58  E-value: 1.01e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDgTCSLLITGLDRADAGCYTCQVSNKF 4977
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGD-LHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 215274225 4978 GQVTHSACVVV 4988
Cdd:cd20972    81 GSDTTSAEIFV 91
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
 7764-7926 1.02e-05

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 51.91  E-value: 1.02e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7764 SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLsqekvlpSDKFKDYLETM---APELLE 7840
Cdd:cd07851   116 SDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLARHT-------DDEMTGYVATRwyrAPEIML 188

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7841 GQGAVPQT-DIWAIGVTAFIMLSAE--YP-------------------------VSSEGARDLQRGL----RKGLVRLsr 7888
Cdd:cd07851   189 NWMHYNQTvDIWSVGCIMAELLTGKtlFPgsdhidqlkrimnlvgtpdeellkkISSESARNYIQSLpqmpKKDFKEV-- 266

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 215274225 7889 cYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWLTE 7926
Cdd:cd07851   267 -FSGANPLAIDLLEKMLVLDPDKRITAAEALAHPYLAE 303
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1992-2072 1.03e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 47.24  E-value: 1.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1992 KKLEPQT-VEERSSVTLEVELTRPWPELRWTRNATALAPGKNVEIHAEGARHRLVLHNVGFADRGFFGCETPDDKTQAKL 2070
Cdd:cd20967     1 KKAQPAVqVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 2071 TV 2072
Cdd:cd20967    81 FV 82
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6371-6448 1.07e-05

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 47.64  E-value: 1.07e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6371 GGTAQFEAIIEGDPQPSVTWYKDSVQ--------LVDSTRLSQQQEGttySLVLRHVASKDAGVYTCLAQNTGGQVLCKA 6442
Cdd:cd05726    14 GRTVTFQCETKGNPQPAIFWQKEGSQnllfpyqpPQPSSRFSVSPTG---DLTITNVQRSDVGYYICQALNVAGSILAKA 90


                  ....*.
gi 215274225 6443 ELLVLG 6448
Cdd:cd05726    91 QLEVTD 96
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 239-328 1.14e-05

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 47.62  E-value: 1.14e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  239 PPSTGTRTCTVTE----GKHARLSCYVTGEPKPETVWKKDGQLVTEGR-RHVVYEDAQENFVLKIlfcKQSDRGLYTCTA 313
Cdd:cd05730     1 PPTIRARQSEVNAtanlGQSVTLACDADGFPEPTMTWTKDGEPIESGEeKYSFNEDGSEMTILDV---DKLDEAEYTCIA 77

                          90
                  ....*....|....*
gi 215274225  314 SNLVGQTYSSVLVVV 328
Cdd:cd05730    78 ENKAGEQEAEIHLKV 92
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 252-323 1.16e-05

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 47.21  E-value: 1.16e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225  252 GKHARLSCYVTGEPKPETVWKKDGQ-LVTEGRRHVvyedaqENFVLKILFCKQSDRGLYTCTASNLVGQTYSS 323
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQpLASENRIEV------EAGDLRITKLSLSDSGMYQCVAENKHGTIYAS 80
STKc_HIPK cd14211
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs ...
 7680-7870 1.17e-05

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271113 [Multi-domain]  Cd Length: 329  Bit Score: 51.68  E-value: 1.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHP-----HLAQLHAAYLSPRHLVLILELCS----- 7749
Cdd:cd14211     9 RGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILSRLSQEnadefNFVRAYECFQHKNHTCLVFEMLEqnlyd 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7750 -------GPELLPClaerasyseseVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE-----YNlLKVVDLGNAQSLS 7817
Cdd:cd14211    89 flkqnkfSPLPLKY-----------IRPILQQVLTALLKLKSLGLIHADLKPENIMLVDpvrqpYR-VKVIDFGSASHVS 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 7818 qeKVLPSdkfkDYLET---MAPELLEGQGAVPQTDIWAIG-VTAFIMLS-AEYPVSSE 7870
Cdd:cd14211   157 --KAVCS----TYLQSryyRAPEIILGLPFCEAIDMWSLGcVIAELFLGwPLYPGSSE 208
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 256-321 1.20e-05

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 47.60  E-value: 1.20e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  256 RLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQ---TY 321
Cdd:cd05729    23 RLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSinhTY 91
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 4067-4142 1.21e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 46.79  E-value: 1.21e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  4067 RPKFKTRLQSLEQETGDIARLCCQlSDAESGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACV 4142
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCE-ATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6021-6090 1.26e-05

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 47.14  E-value: 1.26e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6021 ADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPdgscALILDSLTGVDSGQYMCFAA 6090
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED----VLVIPSVKREDKGMYQCFVR 74
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 5381-5466 1.29e-05

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 46.81  E-value: 1.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5381 KVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwiGPDTPGYTVASSAQQHSLVLLDVGRQHQGTYTCIASNAAGQAlc 5460
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQP------LKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEK-- 74


                  ....*.
gi 215274225 5461 SASLHV 5466
Cdd:cd05748    75 SATINV 80
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 1178-1240 1.29e-05

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 47.12  E-value: 1.29e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1178 AEAGTTAMLSCEVA--QPQTEVTWYKDGKKL--SSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd05750    11 VQEGSKLVLKCEATseNPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVV 77
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2308-2363 1.31e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 46.55  E-value: 1.31e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 2308 VLECQVS-RASAQVRWFKGSQELQPGPKYELVSDGLYRKLIISDVHAEDEDTYTCDA 2363
Cdd:cd00096     2 TLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 987-1057 1.31e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 47.19  E-value: 1.31e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225   987 VAHSEVQAEAGASATLSCEVAQA--QTEVMWYKDGKKLSSSLKVHVEAKGCRR-RLVVQQAGKTDAGDYSCEAR 1057
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGspGPDVTWSKEGGTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVVN 74
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
 7683-7934 1.31e-05

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 51.70  E-value: 1.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7683 FSVV-RQCwekasGRALAAK-IIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRH--------LVLILELCSGPE 7752
Cdd:cd07854    22 FSAVdSDC-----DKRVAVKkIVLTDPQSVKHALREIKIIRRLDHDNIVKVYEVLGPSGSdltedvgsLTELNSVYIVQE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7753 L----LPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII-TEYNLLKVVDLGNAQSLSQEKvlpsdKF 7827
Cdd:cd07854    97 YmetdLANVLEQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFInTEDLVLKIGDFGLARIVDPHY-----SH 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7828 KDYL-ETM------APELLEGQGAVPQT-DIWAIGVTAFIMLSAE------------------YPVSSEgaRDLQRGLRK 7881
Cdd:cd07854   172 KGYLsEGLvtkwyrSPRLLLSPNNYTKAiDMWAAGCIFAEMLTGKplfagaheleqmqlilesVPVVRE--EDRNELLNV 249

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7882 ---------GLVR--LSRCYAGLSGGAVAFLRSTLCAQPWGRPCASSCLQCPWLT-----EEGPACSRP 7934
Cdd:cd07854   250 ipsfvrndgGEPRrpLRDLLPGVNPEALDFLEQILTFNPMDRLTAEEALMHPYMScyscpFDEPVSLHP 318
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
 7681-7866 1.33e-05

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 50.96  E-value: 1.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALAAKII--PYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLa 7758
Cdd:cd14027     4 GGFGKVSLCFHRTQGLVVLKTVYtgPNCIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVL- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7759 ERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQS-----LSQEKVLPSDKFKD---- 7829
Cdd:cd14027    83 KKVSVPLSVKGRIILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFkmwskLTKEEHNEQREVDGtakk 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 215274225 7830 ---YLETMAPELLEGQGAVP--QTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14027   163 nagTLYYMAPEHLNDVNAKPteKSDVYSFAIVLWAIFANKEP 204
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 737-779 1.39e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 46.55  E-value: 1.39e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 215274225  737 VTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECV 779
Cdd:cd00096    15 ITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
494-633 1.39e-05

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 52.31  E-value: 1.39e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  494 AGDCQTSTQFCVSAPRKPPLqPPVDPVVKARMESSVILSWSPPPHGErpvtIDGYLVEKKK--LGTYTWIrcheAEwVAT 571
Cdd:COG3401   215 GGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVTESD----ATGYRVYRSNsgDGPFTKV----AT-VTT 284

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  572 PELTVADVAEEGNFQFRVSALNSFG----QSPYLEfpGTVHLAPKLAVrTPLKAVqAVEGGEVTFS 633
Cdd:COG3401   285 TSYTDTGLTNGTTYYYRVTAVDAAGnesaPSNVVS--VTTDLTPPAAP-SGLTAT-AVGSSSITLS 346
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
 7670-7855 1.41e-05

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 50.65  E-value: 1.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7670 KTFAFQTQIQRGRFSVVRqcWEKASGR-ALAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELC 7748
Cdd:cd05113     4 KDLTFLKELGTGQFGVVK--YGKWRGQyDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7749 SGPELLPCLAE-RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKF 7827
Cdd:cd05113    82 ANGCLLNYLREmRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGS 161

                         170       180
                  ....*....|....*....|....*...
gi 215274225 7828 KDYLETMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05113   162 KFPVRWSPPEVLMYSKFSSKSDVWAFGV 189
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 6371-6438 1.43e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 46.80  E-value: 1.43e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6371 GGTAQFEA-IIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTT-YSLVLRHVASKDAGVYTCLAQNTGGQV 6438
Cdd:pfam00047   11 GDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVVNNPGGSA 80
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 1641-1700 1.46e-05

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 46.94  E-value: 1.46e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 1641 GASATLSCEV-AQAQTEVTWYKDGKKLSSS----SKVRVEAVGctrrLVVQQAGQAEAGEYSCEA 1700
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASvadmSKYRILADG----LLINKVTQDDTGEYTCRA 74
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
 7671-7937 1.50e-05

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 50.76  E-value: 1.50e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHP----KDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILE 7746
Cdd:cd05631     1 TFRHYRVLGKGGFGEVCACQVRATGKMYACKKLEKKRikkrKGEAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7747 LCSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQekvlpS 7824
Cdd:cd05631    81 IMNGGDLKFHIYNMGNpgFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQIPE-----G 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7825 DKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGAR----DLQRGLRKGLVRLSRCYaglSGGA 7897
Cdd:cd05631   156 ETVRGRVGTvgyMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERvkreEVDRRVKEDQEEYSEKF---SEDA 232

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 215274225 7898 VAFLRSTLCAQPWGRpcasscLQCpwlTEEGPACSRPAPV 7937
Cdd:cd05631   233 KSICRMLLTKNPKER------LGC---RGNGAAGVKQHPI 263
STKc_HIPK2 cd14227
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; ...
 7669-7870 1.51e-05

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271129 [Multi-domain]  Cd Length: 355  Bit Score: 51.63  E-value: 1.51e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHP-----HLAQLHAAYLSPRHLVL 7743
Cdd:cd14227    14 TNTYEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTEsaddyNFVRAYECFQHKNHTCL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCSgpELLPCLAERASYSE---SEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYN----LLKVVDLGNAQSL 7816
Cdd:cd14227    94 VFEMLE--QNLYDFLKQNKFSPlplKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPSrqpyRVKVIDFGSASHV 171

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7817 SQEKVlpsdkfKDYLET---MAPELLEGQGAVPQTDIWAIG-VTAFIMLS-AEYPVSSE 7870
Cdd:cd14227   172 SKAVC------STYLQSryyRAPEIILGLPFCEAIDMWSLGcVIAELFLGwPLYPGASE 224
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 248-328 1.56e-05

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 46.62  E-value: 1.56e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGrrhvvyedaQENFVLKILfckQSDRGLYTCTASN-LVGQTYSSVLV 326
Cdd:pfam13895   10 VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSS---------PNFFTLSVS---AEDSGTYTCVARNgRGGKVSNPVEL 77


                   ..
gi 215274225   327 VV 328
Cdd:pfam13895   78 TV 79
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 249-326 1.58e-05

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 46.96  E-value: 1.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  249 VTEGKHARLSCYVTGEPKPETVWKKDGQ---LVTEGRRHVVYEDAQENFVLKILfcKQSDRGLYTCTASNLVGQ--TYSS 323
Cdd:cd20974    12 VLEGSTATFEAHVSGKPVPEVSWFRDGQvisTSTLPGVQISFSDGRAKLSIPAV--TKANSGRYSLTATNGSGQatSTAE 89


                  ...
gi 215274225  324 VLV 326
Cdd:cd20974    90 LLV 92
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 7465-7551 1.60e-05

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 46.72  E-value: 1.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7465 FLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRvliSATLKNFQLLTILVVVAEDLGVYTCSVSNALGT 7544
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDE---RITTLENGSLQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*..
gi 215274225 7545 VTTTGVL 7551
Cdd:cd20952    79 ATWSAVL 85
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 1089-1148 1.64e-05

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 46.94  E-value: 1.64e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 1089 GASAMLSCEV-AQAQTEVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1078-1155 1.73e-05

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 46.76  E-value: 1.73e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1078 QSVHnevqaeAGASAMLSCEV-AQAQTEVTWYKDGKKLSSSSKVGMEVKGctrRLVLPQAGKADAGEYSCEAGGQRVSF 1155
Cdd:cd20957    11 QTVD------FGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSA 80
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 2472-2553 1.75e-05

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 46.80  E-value: 1.75e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2472 TRPLEPKTGRELQSVVLSC--DFRPAPKaVQWYKDDTPLSPSEKFKMSLEGQ-MAELRILRLMPADAGVYRCQA----GS 2544
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCkvEGYPDPE-VKWMKDDNPIVESRRFQIDQDEDgLCSLIISDVCGDDSGKYTCKAvnslGE 79


                  ....*....
gi 215274225 2545 AHSSTEVTV 2553
Cdd:cd20973    80 ATCSAELTV 88
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 807-872 1.76e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 46.40  E-value: 1.76e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   807 VDAVAGGPAQFECE-TSEAHVHVHWYKDGMELGHSGERFLQEDVGTRhRLVAATVTRQDEGTYSCRV 872
Cdd:pfam13927   11 VTVREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSGSNS-TLTISNVTRSDAGTYTCVA 76
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 4634-4695 1.77e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 46.47  E-value: 1.77e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 4634 QVAAGEDVSLELEVVAEAGEVIWHKGMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:cd20967     8 QVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQC 69
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 7463-7543 1.78e-05

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 47.02  E-value: 1.78e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLISATLKNFQLLTILVVVAEDLGVYTCSVSNAL 7542
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                  .
gi 215274225 7543 G 7543
Cdd:cd20990    81 G 81
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
 7672-7867 1.79e-05

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 50.87  E-value: 1.79e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGL-RHPHLAQLHAAYLSPR------HLVLI 7744
Cdd:cd06637     8 FELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYsHHRNIATYYGAFIKKNppgmddQLWLV 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7745 LELCSGPELLPCLAERA--SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQeKVL 7822
Cdd:cd06637    88 MEFCGAGSVTDLIKNTKgnTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR-TVG 166

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225 7823 PSDKFKDYLETMAPELL---EGQGAVP--QTDIWAIGVTAFIMLSAEYPV 7867
Cdd:cd06637   167 RRNTFIGTPYWMAPEVIacdENPDATYdfKSDLWSLGITAIEMAEGAPPL 216
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 3808-3885 1.82e-05

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 46.68  E-value: 1.82e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3808 VKNQE-AREGATAVLQCElSKAAP---VEWRKGSETLRGGDRYSLRQDGTrceLQIHGLSVADTGEYSCVC----GQERT 3879
Cdd:cd04969     8 VKKKIlAAKGGDVIIECK-PKASPkptISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAvnffGKANS 83


                  ....*.
gi 215274225 3880 SATLTV 3885
Cdd:cd04969    84 TGSLSV 89
PK_TRB2 cd14022
Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein ...
 7765-7924 1.84e-05

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270924 [Multi-domain]  Cd Length: 242  Bit Score: 50.04  E-value: 1.84e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7765 ESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT--EYNLLKVVDLGNAQSLSQEKVLPSDKfKDYLETMAPELLEGQ 7842
Cdd:cd14022    83 EEEAARLFYQIASAVAHCHDGGLVLRDLKLRKFVFKdeERTRVKLESLEDAYILRGHDDSLSDK-HGCPAYVSPEILNTS 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7843 GAVP--QTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSRCyagLSGGAVAFLRSTLCAQPWGRPCASSCLQ 7920
Cdd:cd14022   162 GSYSgkAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFNIPET---LSPKAKCLIRSILRREPSERLTSQEILD 238


                  ....
gi 215274225 7921 CPWL 7924
Cdd:cd14022   239 HPWF 242
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
 7681-7854 1.86e-05

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 50.80  E-value: 1.86e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRALaakiiPYHPKDKTAVLREYEALKglrHPHLAQLHAAYLSPR-----HLVLILELCSgpELLP 7755
Cdd:cd07862    27 GRFVALKRVRVQTGEEGM-----PLSTIREVAVLRHLETFE---HPNVVRLFDVCTVSRtdretKLTLVFEHVD--QDLT 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7756 CLAERA---SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKdyLE 7832
Cdd:cd07862    97 TYLDKVpepGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVVVT--LW 174

                         170       180
                  ....*....|....*....|...
gi 215274225 7833 TMAPE-LLEGQGAVPqTDIWAIG 7854
Cdd:cd07862   175 YRAPEvLLQSSYATP-VDLWSVG 196
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2933-2987 1.90e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 46.17  E-value: 1.90e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2933 AVFTCKTE-HPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTC 2987
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTC 56
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 3890-3974 1.92e-05

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 46.81  E-value: 1.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTC----TCG 3964
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSClatnSVG 81

                          90
                  ....*....|
gi 215274225 3965 SQATSATLTV 3974
Cdd:cd20972    82 SDTTSAEIFV 91
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 116-191 1.97e-05

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 46.47  E-value: 1.97e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  116 PTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEpdGPRVRVEELGeasALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKE--NNRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLG 76
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6356-6438 2.00e-05

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 46.78  E-value: 2.00e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6356 PPSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQ----EGTTYSLV-LRHVASKDAGVYTCL 6430
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDyvtsDGDVVSYVnISSVRVEDGGEYTCT 80


                  ....*...
gi 215274225 6431 AQNTGGQV 6438
Cdd:cd20956    81 ATNDVGSV 88
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
 7707-7855 2.00e-05

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 50.50  E-value: 2.00e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAQLhAAYLSPRHLVLILELCSGPELLPCL-AERASYSESEVKDYLWQMLSATQYLHNQ 7785
Cdd:cd05056    48 PSVREKFLQEAYIMRQFDHPHIVKL-IGVITENPVWIVMELAPLGELRSYLqVNKYSLDLASLILYAYQLSTALAYLESK 126

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7786 HILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05056   127 RFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDESYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGV 196
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3555-3609 2.01e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 46.17  E-value: 2.01e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3555 AVLQCELNSAAP--VEWRKGSETLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSCV 3609
Cdd:cd00096     1 VTLTCSASGNPPptITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 5260-5350 2.02e-05

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 46.78  E-value: 2.02e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRLakfQLK--VKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHT-----LEIISVTREDSGQYA 5332
Cdd:cd20956     2 PVLLETFSEQTLQPGPSV---SLKcvASGNPLPQITWTLDGFPIPESPRFRVGDYVTSDGdvvsyVNISSVRVEDGGEYT 78

                          90
                  ....*....|....*...
gi 215274225 5333 AYISNAMGAAYSSARLLV 5350
Cdd:cd20956    79 CTATNDVGSVSHSARINV 96
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 6108-6199 2.13e-05

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 46.83  E-value: 2.13e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVN----KVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQtLSEPRSGLLVLVIRAASKEDLGLYECE 6183
Cdd:cd05729     1 PRFTDtekmEEREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIG-GTKVEEKGWSLIIERAIPRDKGKYTCI 79

                          90
                  ....*....|....*.
gi 215274225 6184 LVNRLGSARASAELRI 6199
Cdd:cd05729    80 VENEYGSINHTYDVDV 95
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 2826-2912 2.14e-05

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 46.42  E-value: 2.14e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2826 PAAIIKPLEDQWVAPGEDVELRCELSRAGTP-VHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEASK 2904
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPvVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80


                  ....*...
gi 215274225 2905 STASLHVE 2912
Cdd:cd20972    81 GSDTTSAE 88
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 342-416 2.14e-05

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 46.56  E-value: 2.14e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  342 LEVREKESATFLCEV---PQPSTeaAWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYICETPEGSRTVAEL 416
Cdd:cd20949     9 TTVKEGQSATILCEVkgePQPNV--TWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIASDM 84
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
 7771-7854 2.21e-05

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 50.83  E-value: 2.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7771 YLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpSDKFKDYLETM---APELL----EGQG 7843
Cdd:cd07858   113 FLYQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTSEK----GDFMTEYVVTRwyrAPELLlncsEYTT 188

                          90
                  ....*....|.
gi 215274225 7844 AVpqtDIWAIG 7854
Cdd:cd07858   189 AI---DVWSVG 196
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6021-6104 2.29e-05

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 46.23  E-value: 2.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6021 ADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILiedPDGScaLILDSLTGVDSGQYMCFAASAAGNCSTLG 6100
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEIL---DDHS--LKIRKVTAGDMGSYTCVAENMVGKIEASA 79


                  ....
gi 215274225 6101 KILV 6104
Cdd:cd05725    80 TLTV 83
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 7463-7551 2.29e-05

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 46.69  E-value: 2.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLE-SSSRvlISATLKNFQLLTILV--VVAEDLGVYTCSVS 7539
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQyNTDR--ISLYQDNCGRICLLIqnANKKDAGWYTVSAV 78

                          90
                  ....*....|..
gi 215274225 7540 NALGTVTTTGVL 7551
Cdd:cd05892    79 NEAGVVSCNARL 90
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3819-3873 2.31e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 45.78  E-value: 2.31e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3819 AVLQCELS--KAAPVEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSCV 3873
Cdd:cd00096     1 VTLTCSASgnPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
 7668-7869 2.34e-05

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 51.19  E-value: 2.34e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7668 STKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTavlREYEALKGLRHPHLAQLHAAYLSP------RHL 7741
Cdd:PTZ00036   64 PNKSYKLGNIIGNGSFGVVYEAICIDTSEKVAIKKVLQDPQYKN---RELLIMKNLNHINIIFLKDYYYTEcfkkneKNI 140

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7742 VLILELcsgpELLPCLAER--ASYSESE-------VKDYLWQMLSATQYLHNQHILHLDLRSENMIIT-EYNLLKVVDLG 7811
Cdd:PTZ00036  141 FLNVVM----EFIPQTVHKymKHYARNNhalplflVKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDpNTHTLKLCDFG 216

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 7812 NAQSLsqekvLPSDKFKDYLET---MAPELLEGQ-GAVPQTDIWAIG-VTAFIMLSaeYPVSS 7869
Cdd:PTZ00036  217 SAKNL-----LAGQRSVSYICSrfyRAPELMLGAtNYTTHIDLWSLGcIIAEMILG--YPIFS 272
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 3632-3709 2.35e-05

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 46.35  E-value: 2.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3632 LRNEEATEGATAVLRCELSKMAPV---EWWK-GHETLRDGDRH-SLRQDGARCELQIRGLVAEDAGEYLCMC----GKER 3702
Cdd:cd05750     6 MKSQTVQEGSKLVLKCEATSENPSpryRWFKdGKELNRKRPKNiKIRNKKKNSELQINKAKLEDSGEYTCVVenilGKDT 85


                  ....*..
gi 215274225 3703 TSAMLTV 3709
Cdd:cd05750    86 VTGNVTV 92
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 6022-6098 2.36e-05

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 46.46  E-value: 2.36e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6022 DCTAELGETVKLACRVTGTPKPVISWYKDG----KAVQVDPHHILIEDPdgscALILDSLTGVDSGQYMCFAASAAGNCS 6097
Cdd:cd05763     8 DITIRAGSTARLECAATGHPTPQIAWQKDGgtdfPAARERRMHVMPEDD----VFFIVDVKIEDTGVYSCTAQNSAGSIS 83


                  .
gi 215274225 6098 T 6098
Cdd:cd05763    84 A 84
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
 6465-6678 2.37e-05

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 50.13  E-value: 2.37e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6465 HSFYEVKEEIGRGVFGFVKRVQHKGNkILCAAKFIPLRSRTRAQAY-RERDILAALSHplvtglldqfetrKTLILILEL 6543
Cdd:cd05148     5 REEFTLERKLGSGYFGEVWEGLWKNR-VRVAIKILKSDDLLKQQDFqKEVQALKRLRH-------------KHLISLFAV 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6544 CSSEE---LLDRLYRKG------------VVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMvhpaREDI--KIC 6606
Cdd:cd05148    71 CSVGEpvyIITELMEKGsllaflrspegqVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILV----GEDLvcKVA 146

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6607 DFGFAQNITPAELQFSQYGSP-EFVSPEIIQQNPVSEASDIWAMGVISYLSLTCSS-PFAGESDRATLLNVLEG 6678
Cdd:cd05148   147 DFGLARLIKEDVYLSSDKKIPyKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQvPYPGMNNHEVYDQITAG 220
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 124-201 2.40e-05

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 46.44  E-value: 2.40e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  124 GSEATFRCRVGGSPRPAVSWSKDGRRLgePDGPRVRVeelgEASALRIRAARPRDGGTYEVRAENPLGAASAAAALVV 201
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPL--ASENRIEV----EAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
 7671-7920 2.41e-05

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 50.37  E-value: 2.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7671 TFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPK-DKTAVLREYEALKGLRHPHLAQLHAAYLSPR----HLVLIl 7745
Cdd:cd13986     1 RYRIQRLLGEGGFSFVYLVEDLSTGRLYALKKILCHSKeDVKEAMREIENYRLFNHPNILRLLDSQIVKEaggkKEVYL- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7746 elcsgpeLLP-------------CLAERASYSESEVKDYLWQMLSATQYLHnQHIL----HLDLRSENMIITEYNLLKVV 7808
Cdd:cd13986    80 -------LLPyykrgslqdeierRLVKGTFFPEDRILHIFLGICRGLKAMH-EPELvpyaHRDIKPGNVLLSEDDEPILM 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7809 DLG----------NAQSLSQEKVLPSDKfkdylETM---APELLE---GQGAVPQTDIWAIGVTAFIMLSAEYPVSsega 7872
Cdd:cd13986   152 DLGsmnparieieGRREALALQDWAAEH-----CTMpyrAPELFDvksHCTIDEKTDIWSLGCTLYALMYGESPFE---- 222

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 7873 RDLQRGlrkGLVRLSRCYA--------GLSGGAVAFLRSTLCAQPWGRPCASSCLQ 7920
Cdd:cd13986   223 RIFQKG---DSLALAVLSGnysfpdnsRYSEELHQLVKSMLVVNPAERPSIDDLLS 275
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 3541-3621 2.49e-05

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 46.35  E-value: 2.49e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3541 IEDVKNQEAREGATAVLQCELNSAAPV---EWRK-GSETLRDGD-RYSLRQDGTKCELQIRGLAMADTGEYSCVC----G 3611
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEATSENPSpryRWFKdGKELNRKRPkNIKIRNKKKNSELQINKAKLEDSGEYTCVVenilG 82

                          90
                  ....*....|
gi 215274225 3612 QERTSAMLTV 3621
Cdd:cd05750    83 KDTVTGNVTV 92
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 3890-3974 2.54e-05

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 46.23  E-value: 2.54e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3890 PVF-REPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGctaELVLQDLQREDTGEYTCTC---- 3963
Cdd:cd20978     1 PKFiQKPEKNVVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLQGPMERATVEDG---TLTIINVQPEDTGYYGCVAtnei 77

                          90
                  ....*....|.
gi 215274225 3964 GSQATSATLTV 3974
Cdd:cd20978    78 GDIYTETLLHV 88
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 18-84 2.59e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 46.08  E-value: 2.59e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225   18 AFVVSVGKDATLSCQIVGNPTPqVSWEKDQQPVAAGARFRLAQDGDLYRLTILDLALGDSGQYVCRA 84
Cdd:cd20967     6 AVQVSKGHKIRLTVELADPDAE-VKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVA 71
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 811-872 2.62e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 46.03  E-value: 2.62e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225   811 AGGPAQFECETSEAH--VHVHWYKDGMELGHSGERFLQEDVGTRHRLVAATVTRQDEGTYSCRV 872
Cdd:pfam00047   10 EGDSATLTCSASTGSpgPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVV 73
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 5260-5344 2.62e-05

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 46.39  E-value: 2.62e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPL-----TASAHIRMTDKKILHTLEIISVTR--EDSGQYA 5332
Cdd:cd07693     1 PRIVEHPSDLIVSKGDP-ATLNCKAEGRPTPTIQWLKNGQPLetdkdDPRSHRIVLPSGSLFFLRVVHGRKgrSDEGVYV 79

                          90
                  ....*....|..
gi 215274225 5333 AYISNAMGAAYS 5344
Cdd:cd07693    80 CVAHNSLGEAVS 91
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 2649-2718 2.65e-05

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 46.33  E-value: 2.65e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 2649 FLKALDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQLGPSDKYD-FLHTAGTRGLVVHDVSPEDAGLYTC 2718
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSgLPTPDLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTC 74
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1450-1527 2.66e-05

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 45.96  E-value: 2.66e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1450 REVQAQAGASTTLSCEVAQA-QTEVMWYKDG-KKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEA----GSQRLSF 1523
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   1524 HLHV 1527
Cdd:smart00410   82 TLTV 85
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5268-5350 2.67e-05

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 45.85  E-value: 2.67e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5268 DLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTAS-AHIRMTdkkilHTLEIISVTREDSGQYAAYISNAMGAAYSSA 5346
Cdd:cd05725     6 NQVVLVDDS-AEFQCEVGGDPVPTVRWRKEDGELPKGrYEILDD-----HSLKIRKVTAGDMGSYTCVAENMVGKIEASA 79


                  ....
gi 215274225 5347 RLLV 5350
Cdd:cd05725    80 TLTV 83
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 2829-2910 2.68e-05

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 46.26  E-value: 2.68e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2829 IIKPLEDQWVAPGEDVELRCELSraGTP---VHWLKDRKAIRKSQ---KYDVVCEGTMAMLVIRGASLKDAGEYTCEVEA 2902
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQ--GKPdpeVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80


                  ....*...
gi 215274225 2903 SKSTASLH 2910
Cdd:cd20951    81 IHGEASSS 88
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 249-318 2.76e-05

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 46.30  E-value: 2.76e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  249 VTEGKHARLSCYVTGEPKPETVWKKDGQLVTEG-RRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVG 318
Cdd:cd05892    12 VLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCGRICLLIQNANKKDAGWYTVSAVNEAG 82
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2923-2999 2.80e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 46.08  E-value: 2.80e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 2923 TNLQVEEKGTAVFTCKTEHPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTCDIGQaQSRAQLL 2999
Cdd:cd20967     5 PAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGG-EKCSFEL 80
I-set pfam07679
Immunoglobulin I-set domain;
4161-4245 2.88e-05

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 46.10  E-value: 2.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4161 IVRGLVDAEVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRiHTLRLKGVTPEDAG----TVSFHLGN 4236
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGT-YTLTISNVQPDDSGkytcVATNSAGE 81


                   ....*....
gi 215274225  4237 HASSAQLTV 4245
Cdd:pfam07679   82 AEASAELTV 90
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3202-3256 2.89e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 45.40  E-value: 2.89e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 3202 ATLRCVLSSVAAP-VKWCYGNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSC 3256
Cdd:cd00096     1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTC 56
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
 7719-7912 2.91e-05

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270739 [Multi-domain]  Cd Length: 320  Bit Score: 50.47  E-value: 2.91e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7719 ALKGlRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMI 7798
Cdd:cd05587    51 ALSG-KPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGKFKEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVM 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7799 ITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYPVSSEGARDL 7875
Cdd:cd05587   130 LDAEGHIKIADFG----MCKEGIFGGKTTRTFCGTpdyIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDEL 205

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7876 QRGLRKGLVRLSRCyagLSGGAVAFLRSTLCAQPWGR 7912
Cdd:cd05587   206 FQSIMEHNVSYPKS---LSKEAVSICKGLLTKHPAKR 239
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 3188-3269 2.94e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 46.08  E-value: 2.94e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3188 QEALKDLEVLEGGAATLRCVLSSVAAPVKWCYGNNVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSCSFGDQTTSATL 3267
Cdd:cd20967     1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                  ..
gi 215274225 3268 TV 3269
Cdd:cd20967    81 FV 82
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 4906-4988 2.98e-05

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 45.85  E-value: 2.98e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4906 DTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHhidQLGDGtcSLLITGLDRADAGCYTCQVSNKFGQVTHSAC 4985
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYE---ILDDH--SLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80


                  ...
gi 215274225 4986 VVV 4988
Cdd:cd05725    81 LTV 83
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 114-189 3.03e-05

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 45.99  E-value: 3.03e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  114 LRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDgprvRVEELGEaSALRIRAARPRDGGTYEVRAENP 189
Cdd:cd20957     6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSS----RVQILSE-DVLVIPSVKREDKGMYQCFVRND 76
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1900-1984 3.08e-05

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 46.26  E-value: 3.08e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1900 KFMSGLSTVVAEEGGEATFQCVVS--PSDVaVVWFRDGALLQPSE---KFAISQSGASHSLTISDLVLEDAGQITVEAEG 1974
Cdd:cd20951     2 EFIIRLQSHTVWEKSDAKLRVEVQgkPDPE-VKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 215274225 1975 ----ASSSAALRVR 1984
Cdd:cd20951    81 ihgeASSSASVVVE 94
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 6113-6199 3.12e-05

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 45.66  E-value: 3.12e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6113 KVRAspfveGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQ-TLSEPRSgllVLVIRAASKEDLGLYECELVNRLGSA 6191
Cdd:cd05748     3 VVRA-----GESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQiETTASST---SLVIKNAKRSDSGKYTLTLKNSAGEK 74


                  ....*...
gi 215274225 6192 RASAELRI 6199
Cdd:cd05748    75 SATINVKV 82
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 5280-5350 3.22e-05

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 46.24  E-value: 3.22e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 5280 FQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILHT--LEIISVTREDSGQYAAYISNAMGAAYSSARLLV 5350
Cdd:cd05893    20 FTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTcsLHTTASTLDDDGNYTIMAANPQGRISCTGRLMV 92
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 245-328 3.45e-05

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 46.04  E-value: 3.45e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  245 RTCTVTEGKHARLSCYVTGEPKPETVWKKDG---------QLVTEGRRHvvyedaqenfVLKILFCKQSDRGLYTCTASN 315
Cdd:cd20972     9 RSQEVAEGSKVRLECRVTGNPTPVVRWFCEGkelqnspdiQIHQEGDLH----------SLIIAEAFEEDTGRYSCLATN 78

                          90
                  ....*....|...
gi 215274225  316 LVGQTYSSVLVVV 328
Cdd:cd20972    79 SVGSDTTSAEIFV 91
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
 7695-7855 3.46e-05

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 49.59  E-value: 3.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7695 GRALAAKIIPyHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPR-HLVLILELCSGPELLPCLAERAS--YSESEVKDY 7771
Cdd:cd05082    29 GNKVAVKCIK-NDATAQAFLAEASVMTQLRHSNLVQLLGVIVEEKgGLYIVTEYMAKGSLVDYLRSRGRsvLGGDCLLKF 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7772 LWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIW 7851
Cdd:cd05082   108 SLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFG----LTKEASSTQDTGKLPVKWTAPEALREKKFSTKSDVW 183


                  ....
gi 215274225 7852 AIGV 7855
Cdd:cd05082   184 SFGI 187
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 4898-4988 3.52e-05

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 45.86  E-value: 3.52e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNKF 4977
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 215274225 4978 GQVTHSACVVV 4988
Cdd:cd20990    81 GQNSFNLELVV 91
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 7557-7635 3.53e-05

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 45.68  E-value: 3.53e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   7557 PSSSPCPDIGEVYADGVLLVWKPVESYGPVTYIVQCSLE----GGSWTTLASDIFDCCYLTSKLSRGGTYTFRTACVSKA 7632
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEyreeGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 215274225   7633 GMG 7635
Cdd:smart00060   81 GEG 83
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
 7672-7854 3.57e-05

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 49.80  E-value: 3.57e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPY-HPKDK---TAVlREYEALKGLRHPHLAQLHAAYLS---------- 7737
Cdd:cd07864     9 FDIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLdNEKEGfpiTAI-REIKILRQLNHRSVVNLKEIVTDkqdaldfkkd 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7738 PRHLVLILELCSGpELLPCLAER-ASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL 7816
Cdd:cd07864    88 KGAFYLVFEYMDH-DLMGLLESGlVHFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLARLY 166

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 215274225 7817 SQEKVLPSDKFKDYLETMAPELLEGQGAV-PQTDIWAIG 7854
Cdd:cd07864   167 NSEESRPYTNKVITLWYRPPELLLGEERYgPAIDVWSCG 205
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 26-99 3.60e-05

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 45.65  E-value: 3.60e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225   26 DATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDlyrLTILDLALGDSGQYVCRARNAIGEAFAAVGLQV 99
Cdd:cd05723    14 DIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHN---LQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
 7657-7864 3.60e-05

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 50.29  E-value: 3.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7657 ESQGRSAQPLPstKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKII--PYHPK--DKTAvLREYEALKGLRH------- 7725
Cdd:cd07879     4 EEVNKTVWELP--ERYTSLKQVGSGAYGSVCSAIDKRTGEKVAIKKLsrPFQSEifAKRA-YRELTLLKHMQHenvigll 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7726 ------PHLAQLHAAYLSPRHLVLILELCSGPELlpclaerasySESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII 7799
Cdd:cd07879    81 dvftsaVSGDEFQDFYLVMPYMQTDLQKIMGHPL----------SEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAV 150

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7800 TEYNLLKVVDLGNAQSLSQEkvlpsdkFKDYLET---MAPELLEGQGAVPQT-DIWAIGVTAFIMLSAE 7864
Cdd:cd07879   151 NEDCELKILDFGLARHADAE-------MTGYVVTrwyRAPEVILNWMHYNQTvDIWSVGCIMAEMLTGK 212
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 6368-6436 3.71e-05

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 45.91  E-value: 3.71e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6368 AQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEGTtysLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAVNFFG 79
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 3275-3358 3.74e-05

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 45.87  E-value: 3.74e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3275 QFIGKLRNKEATEGATATLRCELS-KAAP-VEWRKGSETL---RDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCVC--- 3346
Cdd:cd20951     2 EFIIRLQSHTVWEKSDAKLRVEVQgKPDPeVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAkni 81

                          90
                  ....*....|...
gi 215274225 3347 -GEERTSASLTIR 3358
Cdd:cd20951    82 hGEASSSASVVVE 94
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3890-3974 3.84e-05

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 45.95  E-value: 3.84e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQ-GCTAELVLQDLQREDTGEYTCTC---- 3963
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSgLPTPDLFWQLNGKPVRPDSAHKMLVReNGRHSLIIEPVTKRDAGIYTCIArnra 80

                          90
                  ....*....|.
gi 215274225 3964 GSQATSATLTV 3974
Cdd:cd05744    81 GENSFNAELVV 91
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
 7708-7862 3.89e-05

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 49.63  E-value: 3.89e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7708 KDKTAV-LRE---YEAL--KGLRHPHLAQLHAAYLSPRHLVLILELCSGPELLPCLAERASYSES-------------EV 7768
Cdd:cd05091    45 KDKAEGpLREefrHEAMlrSRLQHPNIVCLLGVVTKEQPMSMIFSYCSHGDLHEFLVMRSPHSDVgstdddktvkstlEP 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7769 KDYLW---QMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGnaqsLSQEkVLPSDKFKDY------LETMAPE-L 7838
Cdd:cd05091   125 ADFLHivtQIAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDLG----LFRE-VYAADYYKLMgnsllpIRWMSPEaI 199

                         170       180
                  ....*....|....*....|....
gi 215274225 7839 LEGQGAVpQTDIWAIGVTAFIMLS 7862
Cdd:cd05091   200 MYGKFSI-DSDIWSYGVVLWEVFS 222
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 5261-5350 3.95e-05

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 45.67  E-value: 3.95e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5261 QVVEELRDLQVAPGTRLaKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKilhtLEIISVTREDSGQYAAYISNAMG 5340
Cdd:cd05728     1 EWLKVISDTEADIGSSL-RWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD----LRITKLSLSDSGMYQCVAENKHG 75

                          90
                  ....*....|
gi 215274225 5341 AAYSSARLLV 5350
Cdd:cd05728    76 TIYASAELAV 85
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 5382-5464 3.95e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 45.65  E-value: 3.95e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5382 VKKGSSITFSVKV-EGRPVPTVHWLRE-EAERGVLWIGPDTPGYTvassaqQHSLVLLDVGRQHQGTYTCIASNAAGQAL 5459
Cdd:pfam00047    8 VLEGDSATLTCSAsTGSPGPDVTWSKEgGTLIESLKVKHDNGRTT------QSSLLISNVTKEDAGTYTCVVNNPGGSAT 81


                   ....*
gi 215274225  5460 CSASL 5464
Cdd:pfam00047   82 LSTSL 86
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 263-324 4.08e-05

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 45.47  E-value: 4.08e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  263 GEPKPETVWKKDGQLVTEG--RRHVVyEDAQenfvLKILFCKQSDRGLYTCTASNLVGQTYSSV 324
Cdd:cd05724    24 GHPEPTVSWRKDGQPLNLDneRVRIV-DDGN----LLIAEARKSDEGTYKCVATNMVGERESRA 82
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 2564-2642 4.16e-05

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 45.56  E-value: 4.16e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2564 LQDAEATEEGWASFSCELS-HEDEEVEWSLNGMPLYNDSFHE-ISHKGRRHTLVLKSIQRADAGIVRASSL----KVSTS 2637
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKVSgLPTPDLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTCIARnragENSFN 86


                  ....*
gi 215274225 2638 ARLEV 2642
Cdd:cd05744    87 AELVV 91
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 5137-5217 4.31e-05

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 45.27  E-value: 4.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5137 VQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEDDHYMI--NEDQQgghQLIITAVVPADMGVYRCLAENSMGvsSTKAEL 5214
Cdd:cd05748     4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIetTASST---SLVIKNAKRSDSGKYTLTLKNSAG--EKSATI 78


                  ...
gi 215274225 5215 RVD 5217
Cdd:cd05748    79 NVK 81
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
 7672-7855 4.34e-05

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 49.09  E-value: 4.34e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7672 FAFQTQIQRGRFSVVRQCWEKASGRaLAAKIIPYHPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd05114     6 LTFMKELGSGLFGVVRLGKWRAQYK-VAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLAERASYSESEVKDYLWQ-MLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDY 7830
Cdd:cd05114    85 CLLNYLRQRRGKLSRDMLLSMCQdVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSGAKFP 164

                         170       180
                  ....*....|....*....|....*
gi 215274225 7831 LETMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05114   165 VKWSPPEVFNYSKFSSKSDVWSFGV 189
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 1263-1332 4.49e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 45.65  E-value: 4.49e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225  1263 LVHNEVRTEAGASATLSCEVAQA--QTEVTWYKDGKKLSSSSKVRIEAAGCMR-QLVVQQAGQADAGEYTCEA 1332
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGspGPDVTWSKEGGTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVV 73
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 3890-3975 4.50e-05

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 45.81  E-value: 4.50e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANgrREPRLQGCT----AELVLQDLQREDTGEY----T 3960
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSgKPVPEVSWFRDGQVISTS--TLPGVQISFsdgrAKLSIPAVTKANSGRYsltaT 78

                          90
                  ....*....|....*
gi 215274225 3961 CTCGSQATSATLTVT 3975
Cdd:cd20974    79 NGSGQATSTAELLVL 93
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 737-779 4.64e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 45.25  E-value: 4.64e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 215274225   737 VTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECV 779
Cdd:pfam13927   33 ITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 110-201 4.69e-05

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 45.53  E-value: 4.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPT--SIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEpdGPRVRVEELGeasALRIRAARPRDGGTYEVRAE 187
Cdd:cd04969     1 PDFELNPVkkKILAAKGGDVIIECKPKASPKPTISWSKGTELLTN--SSRICILPDG---SLKIKNVTKSDEGKYTCFAV 75

                          90
                  ....*....|....
gi 215274225  188 NPLGAASAAAALVV 201
Cdd:cd04969    76 NFFGKANSTGSLSV 89
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 2664-2718 4.71e-05

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 44.87  E-value: 4.71e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2664 LALQCEVS-DPEAHVVWRKDGVQLGPSDKYdflHTAGTRGLVVHDVSPEDAGLYTC 2718
Cdd:cd05746     1 VQIPCSAQgDPEPTITWNKDGVQVTESGKF---HISPEGYLAIRDVGVADQGRYEC 53
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 1536-1608 4.73e-05

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 45.47  E-value: 4.73e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1536 KEQPasREVQAEAGTSATLSCE--VAQAQTEVTWYKDGKKL-SSSSKVRMEAVGctrRLVVQEAGQADAGEYSCKA 1608
Cdd:cd05724     1 RVEP--SDTQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLnLDNERVRIVDDG---NLLIAEARKSDEGTYKCVA 71
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1535-1615 4.74e-05

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 45.60  E-value: 4.74e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1535 AKEQPASREVqaEAGTSATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRMEAVGctrRLVVQEAGQADAGEYSCKAGDQRL 1613
Cdd:cd20957     4 ATIDPPVQTV--DFGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGD 78


                  ..
gi 215274225 1614 SF 1615
Cdd:cd20957    79 SA 80
STKc_HIPK1 cd14228
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; ...
 7669-7870 4.92e-05

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271130 [Multi-domain]  Cd Length: 355  Bit Score: 49.70  E-value: 4.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7669 TKTFAFQTQIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKTAVLREYEALKGLRHP-----HLAQLHAAYLSPRHLVL 7743
Cdd:cd14228    14 TNSYEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSSEnadeyNFVRSYECFQHKNHTCL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7744 ILELCSgpELLPCLAERASYSE---SEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITE-----YNlLKVVDLGNAQS 7815
Cdd:cd14228    94 VFEMLE--QNLYDFLKQNKFSPlplKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDpvrqpYR-VKVIDFGSASH 170

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7816 LSQEKVlpsdkfKDYLET---MAPELLEGQGAVPQTDIWAIG-VTAFIMLS-AEYPVSSE 7870
Cdd:cd14228   171 VSKAVC------STYLQSryyRAPEIILGLPFCEAIDMWSLGcVIAELFLGwPLYPGASE 224
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2649-2732 4.95e-05

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 45.25  E-value: 4.95e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2649 FLKALDDLSAEERGTLALQCEVSD-PEAHVVWRKDGVQLgPSDKYDFLHTAGTrgLVVHDVSP-EDAGLYTCHVGSEE-T 2725
Cdd:cd20958     3 FIRPMGNLTAVAGQTLRLHCPVAGyPISSITWEKDGRRL-PLNHRQRVFPNGT--LVIENVQRsSDEGEYTCTARNQQgQ 79


                  ....*..
gi 215274225 2726 RARVRVH 2732
Cdd:cd20958    80 SASRSVF 86
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1269-1332 5.06e-05

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 45.49  E-value: 5.06e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1269 RTEAGASATLSCEVA-QAQTEVTWYKDGKKLSSSS---KVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:cd20951    11 TVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
 7715-7854 5.13e-05

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 49.65  E-value: 5.13e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSPRHL-----VLILELCSGPEL---LPClaerASYSESEVKDYLWQMLSATQYLHNQH 7786
Cdd:cd07877    65 RELRLLKHMKHENVIGLLDVFTPARSLeefndVYLVTHLMGADLnniVKC----QKLTDDHVQFLIYQILRGLKYIHSAD 140

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 7787 ILHLDLRSENMIITEYNLLKVVDLGNAQSlsqekvlPSDKFKDYLET---MAPELLEGQGAVPQT-DIWAIG 7854
Cdd:cd07877   141 IIHRDLKPSNLAVNEDCELKILDFGLARH-------TDDEMTGYVATrwyRAPEIMLNWMHYNQTvDIWSVG 205
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 1908-1983 5.29e-05

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 45.31  E-value: 5.29e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1908 VVAEEGGEATFQCVVSPSDVAVVWFRDGALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEGASSSAALRV 1983
Cdd:cd20967     7 VQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 5286-5344 5.45e-05

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 45.31  E-value: 5.45e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 5286 GYPAPRLYWFKDGQPLTASAHIRMTDKKilhTLEIISVTREDSGQYAAYISNAMGAAYS 5344
Cdd:cd20968    25 GNPKPSVSWIKGDDLIKENNRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLGIAYS 80
STKc_Cdc7 cd14019
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze ...
 7762-7866 5.49e-05

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270921 [Multi-domain]  Cd Length: 252  Bit Score: 48.76  E-value: 5.49e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7762 SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII---TEYNLLkvVDLGNAQSLSQEKVLPSDK-----FKdylet 7833
Cdd:cd14019    97 KMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYnreTGKGVL--VDFGLAQREEDRPEQRAPRagtrgFR----- 169

                          90       100       110
                  ....*....|....*....|....*....|....
gi 215274225 7834 mAPE-LLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14019   170 -APEvLFKCPHQTTAIDIWSAGVILLSILSGRFP 202
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 2651-2726 5.96e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 45.26  E-value: 5.96e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2651 KALDDLSAEERGTLALQCEVS--DPEAHVVWRKDGVQLGPSDKYdFLHTAGTRGLVVH--DVSPEDAGLYTC---HVGSE 2723
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAStgSPGPDVTWSKEGGTLIESLKV-KHDNGRTTQSSLLisNVTKEDAGTYTCvvnNPGGS 79


                   ...
gi 215274225  2724 ETR 2726
Cdd:pfam00047   80 ATL 82
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 3981-4064 6.52e-05

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 45.10  E-value: 6.52e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3981 FLRELQHQEVDEGGTAHLCCELS-RAGASVEWRKGSLQLFPCA---KYQMVQDGAAAELLVRGVEQEDAGDYTC----DT 4052
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAvaknIH 82

                          90
                  ....*....|..
gi 215274225 4053 GHTQSMASLSVR 4064
Cdd:cd20951    83 GEASSSASVVVE 94
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 113-201 6.60e-05

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 44.88  E-value: 6.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  113 LLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLGEPDGPRVrVEElgeaSALRIRAARPRDGGTYEVRAENPLGA 192
Cdd:cd05723     1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKI-VKE----HNLQVLGLVKSDEGFYQCIAENDVGN 75


                  ....*....
gi 215274225  193 ASAAAALVV 201
Cdd:cd05723    76 AQASAQLII 84
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 3544-3621 6.66e-05

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 45.14  E-value: 6.66e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3544 VKNQE-AREGATAVLQCELNSA--APVEWRKGSETLRDGDRYSLRQDGTkceLQIRGLAMADTGEYSCVC----GQERTS 3616
Cdd:cd04969     8 VKKKIlAAKGGDVIIECKPKASpkPTISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAvnffGKANST 84


                  ....*
gi 215274225 3617 AMLTV 3621
Cdd:cd04969    85 GSLSV 89
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 112-201 6.72e-05

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 45.30  E-value: 6.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  112 FLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGrrlGE--PDGPRVRVEELGEASALRIRAARPRDGGTYEVRAENP 189
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDG---GTdfPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNS 78

                          90
                  ....*....|..
gi 215274225  190 LGAASAAAALVV 201
Cdd:cd05763    79 AGSISANATLTV 90
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3643-3697 6.92e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 44.63  E-value: 6.92e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3643 AVLRCELS--KMAPVEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLCM 3697
Cdd:cd00096     1 VTLTCSASgnPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 4897-4981 6.95e-05

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 45.15  E-value: 6.95e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4897 GPMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQLGDGTCSLLITGLD-RADAGCYTCQVSN 4975
Cdd:cd20971     1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATN 80


                  ....*.
gi 215274225 4976 KFGQVT 4981
Cdd:cd20971    81 QGGSVS 86
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
 7689-7878 6.97e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 50.12  E-value: 6.97e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7689 CWEKASGRALAAKiipyhpkDKTAVLREYEALKGLRHPHLAQLHAAYLSP--RHLVLILELCSGPEL----LPCLAERAS 7762
Cdd:PTZ00266   42 CWKAISYRGLKER-------EKSQLVIEVNVMRELKHKNIVRYIDRFLNKanQKLYILMEFCDAGDLsrniQKCYKMFGK 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7763 YSESEVKDYLWQMLSATQYLHN-------QHILHLDLRSENM-----------IITEYNLL------KVVDLGNAQSLSQ 7818
Cdd:PTZ00266  115 IEEHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIflstgirhigkITAQANNLngrpiaKIGDFGLSKNIGI 194

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 7819 EKVLPSDKFKDYLetMAPELL--EGQGAVPQTDIWAIGVTAFIMLSAEYPVS-----SEGARDLQRG 7878
Cdd:PTZ00266  195 ESMAHSCVGTPYY--WSPELLlhETKSYDDKSDMWALGCIIYELCSGKTPFHkannfSQLISELKRG 259
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 340-405 7.01e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 44.86  E-value: 7.01e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225   340 QDLEVREKESATFLCEV---PQPSTEaaWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYICE 405
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtgsPPPTIT--WYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
 7715-7862 7.25e-05

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 48.92  E-value: 7.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSP--RHLVLILE-LCSGP--ELLPCLAERASysESEVKDYLWQMLSATQYLHNQHILH 7789
Cdd:cd05038    55 REIEILRTLDHEYIVKYKGVCESPgrRSLRLIMEyLPSGSlrDYLQRHRDQID--LKRLLLFASQICKGMEYLGSQRYIH 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7790 LDLRSENMIITEYNLLKVVDLGNAqslsqeKVLPSDKfkDYLET----------MAPELLEGQGAVPQTDIWAIGVTAFI 7859
Cdd:cd05038   133 RDLAARNILVESEDLVKISDFGLA------KVLPEDK--EYYYVkepgespifwYAPECLRESRFSSASDVWSFGVTLYE 204


                  ...
gi 215274225 7860 MLS 7862
Cdd:cd05038   205 LFT 207
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6109-6199 7.27e-05

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 45.33  E-value: 7.27e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6109 RFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGA--LLTTGNKFQtlsePRSGLLV-----LVIRAASKEDLGLYE 6181
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSqnLLFPYQPPQ----PSSRFSVsptgdLTITNVQRSDVGYYI 76

                          90
                  ....*....|....*...
gi 215274225 6182 CELVNRLGSARASAELRI 6199
Cdd:cd05726    77 CQALNVAGSILAKAQLEV 94
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 5380-5466 7.29e-05

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 45.08  E-value: 7.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5380 KKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDTPGYTVassaQQHSLVLLDVGRQHQGTYTCIASNAAGQAL 5459
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGVPQPKITWLHNGKP-----LQGPMERATV----EDGTLTIINVQPEDTGYYGCVATNEIGDIY 81


                  ....*..
gi 215274225 5460 CSASLHV 5466
Cdd:cd20978    82 TETLLHV 88
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 4898-4984 7.52e-05

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 45.24  E-value: 7.52e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELTDGRH----HHIDQLGDGTCSLLITGLDRADAGCYTCQV 4973
Cdd:cd20956     2 PVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgDYVTSDGDVVSYVNISSVRVEDGGEYTCTA 81

                          90
                  ....*....|.
gi 215274225 4974 SNKFGQVTHSA 4984
Cdd:cd20956    82 TNDVGSVSHSA 92
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 131-191 7.61e-05

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 44.48  E-value: 7.61e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  131 CRVGGSPRPAVSWSKDGrrlgepdgprVRVEELG-----EASALRIRAARPRDGGTYEVRAENPLG 191
Cdd:cd05746     5 CSAQGDPEPTITWNKDG----------VQVTESGkfhisPEGYLAIRDVGVADQGRYECVARNTIG 60
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
 7678-7855 7.64e-05

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 48.24  E-value: 7.64e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIPYhPKDKTAVLREYEALKGLRHP----------HLAQLHAaylsprhlvlILEL 7747
Cdd:cd14155     1 IGSGFFSEVYKVRHRTSGQVMALKMNTL-SSNRANMLREVQLMNRLSHPnilrfmgvcvHQGQLHA----------LTEY 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7748 CSGPELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMII--TEYNLLKVV-DLGNAqslsqEKVLPS 7824
Cdd:cd14155    70 INGGNLEQLLDSNEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrDENGYTAVVgDFGLA-----EKIPDY 144

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7825 DKFKDYLET------MAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd14155   145 SDGKEKLAVvgspywMAPEVLRGEPYNEKADVFSYGI 181
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1627-1698 7.73e-05

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 44.83  E-value: 7.73e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 1627 AKEQPAHREVqaEAGASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRVEAVGctrRLVVQQAGQAEAGEYSC 1698
Cdd:cd20957     4 ATIDPPVQTV--DFGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQC 71
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1537-1608 7.75e-05

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 44.88  E-value: 7.75e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 1537 EQPASREVqAEaGTSATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKA 1608
Cdd:cd20972     6 QKLRSQEV-AE-GSKVRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 2838-2900 7.83e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 44.88  E-value: 7.83e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  2838 VAPGEDVELRCELSRA--GTPVHWLKDRKAIRKSQKYDVVCEGTM-AMLVIRGASLKDAGEYTCEV 2900
Cdd:pfam00047    8 VLEGDSATLTCSASTGspGPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVV 73
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 3889-3974 8.03e-05

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 44.93  E-value: 8.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3889 QPVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREpRLQGCTAELVLQDLQREDTGEYTCTCGSQA 3967
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARgKPVPRITWIRNAQPLQYAADRS-TCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79


                  ....*..
gi 215274225 3968 TSATLTV 3974
Cdd:cd20976    80 GQVSCSA 86
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 259-328 8.11e-05

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 44.88  E-value: 8.11e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  259 CYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQenfvLKILFCKQSDRGLYTCTASNLVGQTYSSVLVVV 328
Cdd:cd05723    19 CEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHN----LQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 1171-1240 8.22e-05

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 44.88  E-value: 8.22e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  1171 SVHNEVQAEAGTTAMLSCEV--AQPQTEVTWYKDGKKLSSSSKVrMEVKGCTRR--LVVQQVGKADAGEYSCEA 1240
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAstGSPGPDVTWSKEGGTLIESLKV-KHDNGRTTQssLLISNVTKEDAGTYTCVV 73
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
 6355-6437 8.66e-05

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 45.04  E-value: 8.66e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6355 RPPSMQVTiedvqaqTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTR--LSQQQEGTTYSLVLrhVASKDAGVYTCLAQ 6432
Cdd:cd05747     9 KPRSLTVS-------EGESARFSCDVDGEPAPTVTWMREGQIIVSSQRhqITSTEYKSTFEISK--VQMSDEGNYTVVVE 79


                  ....*
gi 215274225 6433 NTGGQ 6437
Cdd:cd05747    80 NSEGK 84
PK_TRB3 cd14024
Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein ...
 7760-7924 8.74e-05

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270926 [Multi-domain]  Cd Length: 242  Bit Score: 47.95  E-value: 8.74e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7760 RASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDL---------GNAQSLSQEKVLPSdkfkdy 7830
Cdd:cd14024    78 RRRLSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVLVnledscplnGDDDSLTDKHGCPA------ 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 leTMAPELLEGQGAVP--QTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGLVRLSrcyAGLSGGAVAFLRSTLCAQ 7908
Cdd:cd14024   152 --YVGPEILSSRRSYSgkAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFSLP---AWLSPGARCLVSCMLRRS 226

                         170
                  ....*....|....*.
gi 215274225 7909 PWGRPCASSCLQCPWL 7924
Cdd:cd14024   227 PAERLKASEILLHPWL 242
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3731-3785 8.76e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 44.24  E-value: 8.76e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3731 ATLWCELS--KAAPVEWRKGHETLRDGDRHSLRQDGSRCELQIRGLAVVDAGEYSCV 3785
Cdd:cd00096     1 VTLTCSASgnPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 4085-4142 8.85e-05

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 44.24  E-value: 8.85e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 4085 ARLCCQLSDAESgAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYACV 4142
Cdd:cd00096     1 VTLTCSASGNPP-PTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1987-2072 9.61e-05

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 44.88  E-value: 9.61e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1987 PVLFKKKLEPQTVEERSSVTLEVELT-RPWPELRWTRNATALAPGKNVEIHAEGARHRLVLHNVGFADRGFFGCETPD-- 2063
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNsv 80

                          90
                  ....*....|.
gi 215274225 2064 --DKTQAKLTV 2072
Cdd:cd20972    81 gsDTTSAEIFV 91
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1087-1148 9.64e-05

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 44.72  E-value: 9.64e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1087 EAGASAMLSCEVA-QAQTEVTWYKDGKKLSSSS---KVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:cd20951    13 WEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
 7680-7866 9.70e-05

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270756 [Multi-domain]  Cd Length: 285  Bit Score: 48.51  E-value: 9.70e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7680 RGRFSVVRQCWEKASGRALAAKIIPY----HPKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPEL-- 7753
Cdd:cd05605    10 KGGFGEVCACQVRATGKMYACKKLEKkrikKRKGEAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDLkf 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7754 -LPCLAErASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAqslsqEKVLPSDKFKDYLE 7832
Cdd:cd05605    90 hIYNMGN-PGFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLA-----VEIPEGETIRGRVG 163

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 215274225 7833 T---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd05605   164 TvgyMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAP 200
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 5260-5350 1.00e-04

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 44.76  E-value: 1.00e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5260 PQVVEELRDLQVAPGTRlAKFQLKVKGYPAPRLYWFKDGQPLTASA-HIRM-TDKKILHTLEIISVTREDSGQYAAYISN 5337
Cdd:cd05892     1 PMFIQKPQNKKVLEGDP-VRLECQISAIPPPQIFWKKNNEMLQYNTdRISLyQDNCGRICLLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 215274225 5338 AMGAAYSSARLLV 5350
Cdd:cd05892    80 EAGVVSCNARLDV 92
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4082-4154 1.01e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 44.42  E-value: 1.01e-04
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225   4082 GDIARLCCQLSDAESgAVVQWLKEGVELHA-GPKYEMRSQGATRELLIHQLEAKDTGEYACV---TGGQKTA-ASLRV 4154
Cdd:smart00410    9 GESVTLSCEASGSPP-PEVTWYKQGGKLLAeSGRFSVSRSGSTSTLTISNVTPEDSGTYTCAatnSSGSASSgTTLTV 85
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3379-3433 1.05e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 43.86  E-value: 1.05e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3379 ATLRCELS--KAAPVEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCV 3433
Cdd:cd00096     1 VTLTCSASgnPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
I-set pfam07679
Immunoglobulin I-set domain;
4630-4695 1.09e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 44.56  E-value: 1.09e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  4630 PESRQVAAGEDVSLELEVVAE-AGEVIWHKGMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTpDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTC 73
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 4899-4988 1.13e-04

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 44.72  E-value: 1.13e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4899 MFSHTFGDTEaqvgDAlRLECVVASKADVRARWLKDGVELT---DGRHHHIdQLGDGTCSLLITGLDRADAGCYTCQVSN 4975
Cdd:cd20951     7 LQSHTVWEKS----DA-KLRVEVQGKPDPEVKWYKNGVPIDpssIPGKYKI-ESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 215274225 4976 KFGQVTHSACVVV 4988
Cdd:cd20951    81 IHGEASSSASVVV 93
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
 7768-7854 1.18e-04

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270830 [Multi-domain]  Cd Length: 294  Bit Score: 48.29  E-value: 1.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7768 VKDYLWQMLSATQYLHNQHILHLDLRSENMII-TEYNLLKVVDLGnaqsLSQEKVLPSDKFKDYLETM---APELLEG-- 7841
Cdd:cd07837   111 IQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVdKQKGLLKIADLG----LGRAFTIPIKSYTHEIVTLwyrAPEVLLGst 186

                          90
                  ....*....|...
gi 215274225 7842 QGAVPqTDIWAIG 7854
Cdd:cd07837   187 HYSTP-VDMWSVG 198
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
 7764-7864 1.21e-04

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 48.41  E-value: 1.21e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7764 SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEkvlpsdkFKDYLET---MAPELLE 7840
Cdd:cd07880   116 SEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQTDSE-------MTGYVVTrwyRAPEVIL 188

                          90       100
                  ....*....|....*....|....*
gi 215274225 7841 GQGAVPQT-DIWAIGVTAFIMLSAE 7864
Cdd:cd07880   189 NWMHYTQTvDIWSVGCIMAEMLTGK 213
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 4912-4979 1.22e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 44.48  E-value: 1.22e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 4912 GDALRLECVVASKADVRARWLKDGVELTDGRHHHIDQlgDGTcsLLITGLDRA-DAGCYTCQVSNKFGQ 4979
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFP--NGT--LVIENVQRSsDEGEYTCTARNQQGQ 79
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 2170-2250 1.25e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 44.42  E-value: 1.25e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2170 RPLQDVVTTEKEKVTLECELS--RPNVDVRWLKDGVELRAGKTMAIAAQGACRS--LTIYRCEFADQGVYVCDAHDAQSS 2245
Cdd:cd05750     4 KEMKSQTVQEGSKLVLKCEATseNPSPRYRWFKDGKELNRKRPKNIKIRNKKKNseLQINKAKLEDSGEYTCVVENILGK 83


                  ....*
gi 215274225 2246 ASVKV 2250
Cdd:cd05750    84 DTVTG 88
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 1271-1332 1.25e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 44.42  E-value: 1.25e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1271 EAGASATLSCEVA--QAQTEVTWYKDGKKL--SSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:cd05750    12 QEGSKLVLKCEATseNPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVV 77
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1273-1332 1.25e-04

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 44.50  E-value: 1.25e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 1273 GASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYTCEA 1332
Cdd:cd20972    16 GSKVRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 3367-3445 1.27e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 44.42  E-value: 1.27e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3367 RLRHQESIEGATATLRCELSKAAPV---EWRK-GRESLRDGDRH-SLRQDGAVCELQICGLAVADAGEYSCVC----GEE 3437
Cdd:cd05750     5 EMKSQTVQEGSKLVLKCEATSENPSpryRWFKdGKELNRKRPKNiKIRNKKKNSELQINKAKLEDSGEYTCVVenilGKD 84


                  ....*...
gi 215274225 3438 RTSATLTV 3445
Cdd:cd05750    85 TVTGNVTV 92
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
7757-7866 1.29e-04

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 49.02  E-value: 1.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 LAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQ------EKVLPSdkfKDY 7830
Cdd:NF033483   98 IREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSttmtqtNSVLGT---VHY 174

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 215274225 7831 LetmAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:NF033483  175 L---SPEQARGGTVDARSDIYSLGIVLYEMLTGRPP 207
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 5388-5464 1.30e-04

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 44.11  E-value: 1.30e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 5388 ITFSVKVEGRPVPTVHWLREeaerGVLWIGPDtpgytVASSAQQHSLVLLDVGRQHQGTYTCIASNAAGQALCSASL 5464
Cdd:cd05723    15 IVFECEVTGKPTPTVKWVKN----GDVVIPSD-----YFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6382-6437 1.30e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 44.10  E-value: 1.30e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 6382 GDPQPSVTWYKDSVQLVDSTRLSQQQEGTtysLVLRHV-ASKDAGVYTCLAQNTGGQ 6437
Cdd:cd20958    26 GYPISSITWEKDGRRLPLNHRQRVFPNGT---LVIENVqRSSDEGEYTCTARNQQGQ 79
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
 7684-7862 1.30e-04

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 47.64  E-value: 1.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7684 SVVRQCWEkasGRALAAKIIPYHPKDKtaVLR-EYEALKGLRHPHLAQLHAAYLSPRHLVliLELCSGPELLPCLA-ERA 7761
Cdd:cd14068     9 SVYRAVYR---GEDVAVKIFNKHTSFR--LLRqELVVLSHLHHPSLVALLAAGTAPRMLV--MELAPKGSLDALLQqDNA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7762 SYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIteYNL-------LKVVDLGNAQSLSQEKVLPSDKFKDYletM 7834
Cdd:cd14068    82 SLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLL--FTLypncaiiAKIADYGIAQYCCRMGIKTSEGTPGF---R 156

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7835 APELLEGQGAV-PQTDIWAIGVTAFIMLS 7862
Cdd:cd14068   157 APEVARGNVIYnQQADVYSFGLLLYDILT 185
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 2663-2731 1.34e-04

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 43.92  E-value: 1.34e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 2663 TLALQCEVS-DPEAHVVWRKDGVQLgPSDKYDFLHTagtRGLVVHDVSPEDAGLYTCH----VGSEETRARVRV 2731
Cdd:cd05725    14 SAEFQCEVGgDPVPTVRWRKEDGEL-PKGRYEILDD---HSLKIRKVTAGDMGSYTCVaenmVGKIEASATLTV 83
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3890-3973 1.36e-04

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 44.37  E-value: 1.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGCTAE--LVLQDLQREDTGEYTCTCGSQ 3966
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISaIPPPQIFWKKNNEMLQYNTDRISLYQDNCGRicLLIQNANKKDAGWYTVSAVNE 80


                  ....*..
gi 215274225 3967 ATSATLT 3973
Cdd:cd05892    81 AGVVSCN 87
I-set pfam07679
Immunoglobulin I-set domain;
3011-3091 1.36e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 44.17  E-value: 1.36e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3011 LEDVDVQEGSSATFRCRISpANYEP-VHWFLDKTPLHANELNEIDAQpGGYHVLTLRQLALKDSGtIYF-----EAGDQR 3084
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVT-GTPDPeVSWFKDGQPLRSSDRFKVTYE-GGTYTLTISNVQPDDSG-KYTcvatnSAGEAE 83


                   ....*..
gi 215274225  3085 ASAALRV 3091
Cdd:pfam07679   84 ASAELTV 90
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
 6474-6669 1.36e-04

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 48.14  E-value: 1.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6474 IGRGVFGFVKR----VQHKGNKILCAAKFIPLRSRTRAQA--YRERDILAALSHPLVTGLLDQFETrKTLILILELCSSE 6547
Cdd:cd05110    15 LGSGAFGTVYKgiwvPEGETVKIPVAIKILNETTGPKANVefMDEALIMASMDHPHLVRLLGVCLS-PTIQLVTQLMPHG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6548 ELLDRLYR-KGVVTEAEVKVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHParEDIKICDFGFAQNITPAELQFSQYGS 6626
Cdd:cd05110    94 CLLDYVHEhKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSP--NHVKITDFGLARLLEGDEKEYNADGG 171

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 215274225 6627 P---EFVSPEIIQQNPVSEASDIWAMGVISYLSLTC-SSPFAGESDR 6669
Cdd:cd05110   172 KmpiKWMALECIHYRKFTHQSDVWSYGVTIWELMTFgGKPYDGIPTR 218
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 1169-1240 1.39e-04

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 44.31  E-value: 1.39e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 1169 EQSVHNEVQAEAGTTAMLSCEVA-QPQTEVTWYKDGKKLSSSSKVRMEVKGctrRLVVQQVGKADAGEYSCEA 1240
Cdd:cd20978     4 IQKPEKNVVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLQGPMERATVEDG---TLTIINVQPEDTGYYGCVA 73
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 7674-7866 1.41e-04

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 47.95  E-value: 1.41e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7674 FQTQIQRGRFSVVRQCWEKASGRALAAKIIPYH--PKDKTAVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGP 7751
Cdd:cd06619     5 YQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDitVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELlpclAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVlpsdkfKDYL 7831
Cdd:cd06619    85 SL----DVYRKIPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSIA------KTYV 154

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 215274225 7832 ET---MAPELLEGQGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd06619   155 GTnayMAPERISGEQYGIHSDVWSLGISFMELALGRFP 192
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 3193-3257 1.45e-04

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 44.42  E-value: 1.45e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3193 DLEVLEGGAATLRCVLSSVAAP-VKWCYGNNVLRPGDK-YSLRQEGAMLElvVRNLRPQDSGRYSCS 3257
Cdd:cd20970    11 TVTAREGENATFMCRAEGSPEPeISWTRNGNLIIEFNTrYIVRENGTTLT--IRNIRRSDMGIYLCI 75
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 2649-2718 1.45e-04

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 44.32  E-value: 1.45e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 2649 FLKALDDLSAEERGTLALQCEVSD-PEAHVVWRKDGVQLGPSDKYDFL-HTAGTRGLVVHDVSPEDAGLYTC 2718
Cdd:cd20990     3 FLQAPGDLTVQEGKLCRMDCKVSGlPTPDLSWQLDGKPIRPDSAHKMLvRENGVHSLIIEPVTSRDAGIYTC 74
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 2289-2375 1.45e-04

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 44.33  E-value: 1.45e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2289 PVTLVRPLRDKIAmEKHRGVLECQVS-RASAQVRWFKGSQELQP---GPKYELVSDGLYRKLIISDVHAEDEDTYTCDA- 2363
Cdd:cd20951     1 PEFIIRLQSHTVW-EKSDAKLRVEVQgKPDPEVKWYKNGVPIDPssiPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAk 79

                          90
                  ....*....|....*
gi 215274225 2364 ---GDVKTSAQFFVE 2375
Cdd:cd20951    80 nihGEASSSASVVVE 94
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3802-3886 1.48e-04

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 44.37  E-value: 1.48e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3802 ARFIEDVKNQEAREGATAVLQCELSKAAP--VEWRKGSETLR-GGDRYSLRQDGT-RCELQIHGLSVADTGEYSCVCGQE 3877
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPpqIFWKKNNEMLQyNTDRISLYQDNCgRICLLIQNANKKDAGWYTVSAVNE 80


                  ....*....
gi 215274225 3878 RTSATLTVR 3886
Cdd:cd05892    81 AGVVSCNAR 89
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3716-3797 1.49e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 44.02  E-value: 1.49e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3716 FIEGLRNEEATEGDTATLWCELSKAAP--VEWRKGHETLRDGDRHSLRQD-GSRCELQIRGLAVVDAGEYSCVC----GQ 3788
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTpdLFWQLNGKPVRPDSAHKMLVReNGRHSLIIEPVTKRDAGIYTCIArnraGE 82


                  ....*....
gi 215274225 3789 ERTSATLTV 3797
Cdd:cd05744    83 NSFNAELVV 91
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 6116-6190 1.50e-04

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 43.92  E-value: 1.50e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  6116 ASPFVEGEDAQFTCTIEGAPYPQIRWYKDG-ALLTTGNKFqtlseprsgllvlvIRAASKEDLGLYECELVNRLGS 6190
Cdd:pfam13895    8 PTVVTEGEPVTLTCSAPGNPPPSYTWYKDGsAISSSPNFF--------------TLSVSAEDSGTYTCVARNGRGG 69
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 6109-6199 1.53e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 44.24  E-value: 1.53e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6109 RFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFqtLSEPRSGLLVLVIRAASKEDLGLYECELVNRL 6188
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVAD--MSKYRILADGLLINKVTQDDTGEYTCRAYQVN 78

                          90
                  ....*....|.
gi 215274225 6189 GSARASAELRI 6199
Cdd:cd20949    79 SIASDMQERTV 89
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 815-872 1.53e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 43.47  E-value: 1.53e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  815 AQFECETSEAH-VHVHWYKDGMELGHSgERFLQEDVGTRHRLVAATVTRQDEGTYSCRV 872
Cdd:cd00096     1 VTLTCSASGNPpPTITWYKNGKPLPPS-SRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 6016-6099 1.54e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 44.24  E-value: 1.54e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6016 FEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVD-----PHHILiedPDGscaLILDSLTGVDSGQYMCFAA 6090
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmsKYRIL---ADG---LLINKVTQDDTGEYTCRAY 75


                  ....*....
gi 215274225 6091 SAAGNCSTL 6099
Cdd:cd20949    76 QVNSIASDM 84
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6013-6094 1.55e-04

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 44.09  E-value: 1.55e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6013 PPDFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQvDPHHILIED---PDGSCA--LILDSLTGVDSGQYMC 6087
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIP-ESPRFRVGDyvtSDGDVVsyVNISSVRVEDGGEYTC 79


                  ....*..
gi 215274225 6088 FAASAAG 6094
Cdd:cd20956    80 TATNDVG 86
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 3187-3269 1.57e-04

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 44.33  E-value: 1.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3187 FQEALKDLEVLEGGAATLRCVLSSVAAP-VKWcYGN----NVLRPGDKYSLRQEGAMLELVVRNLRPQDSGRYSCS---- 3257
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPeVKW-YKNgvpiDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVakni 81

                          90
                  ....*....|..
gi 215274225 3258 FGDQTTSATLTV 3269
Cdd:cd20951    82 HGEASSSASVVV 93
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 2485-2553 1.58e-04

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 43.77  E-value: 1.58e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 2485 SVVLSCDFRPAPKAVQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQAGSAHSSTEVTV 2553
Cdd:cd20967    14 KIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 3892-3961 1.62e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 43.86  E-value: 1.62e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 3892 FREPLQSLQAEEGSTATLQCEL-SEPTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTC 3961
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVkGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTC 72
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1450-1516 1.63e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 43.71  E-value: 1.63e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  1450 REVQAQAGASTTLSCEV-AQAQTEVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEA 1516
Cdd:pfam13927    9 SSVTVREGETVTLTCEAtGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 1539-1608 1.63e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 44.11  E-value: 1.63e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  1539 PASREVQAEAGTSATLSCEVAQA--QTEVTWYKDGKKLSSSSKVrMEAVGCTRR--LVVQEAGQADAGEYSCKA 1608
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGspGPDVTWSKEGGTLIESLKV-KHDNGRTTQssLLISNVTKEDAGTYTCVV 73
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 2165-2247 1.64e-04

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 44.11  E-value: 1.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2165 PVSFSRPLQDVVTTEKEKVTLECELS-RPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAHDAQ 2243
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80


                  ....
gi 215274225 2244 SSAS 2247
Cdd:cd20972    81 GSDT 84
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 3895-3973 1.66e-04

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 44.06  E-value: 1.66e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3895 PLQSLQAeeGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQgctAELVLQDLQREDTGEYTCTCGSQATSATLT 3973
Cdd:cd20957     9 PVQTVDF--GRTAVFNCSVTgNPIHTVLWMKDGKPLGHSSRVQILSE---DVLVIPSVKREDKGMYQCFVRNDGDSAQAT 83
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 111-191 1.68e-04

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 44.18  E-value: 1.68e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  111 HFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRR-LGEPDGP-----RVRVEELGEasaLRIRAARPRDGGTYEV 184
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnLLFPYQPpqpssRFSVSPTGD---LTITNVQRSDVGYYIC 77


                  ....*..
gi 215274225  185 RAENPLG 191
Cdd:cd05726    78 QALNVAG 84
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 6028-6085 1.71e-04

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 43.73  E-value: 1.71e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6028 GETVKLACRVTGTPKPVISWYKDGKAVQVDPhHILIEDPDGSCALILDSLTGVDSGQY 6085
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETG-RVQIETTASSTSLVIKNAKRSDSGKY 63
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 3890-3962 1.73e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 43.71  E-value: 1.73e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3890 PVFRePLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREPRLQGctaELVLQDLQR-EDTGEYTCT 3962
Cdd:cd20958     2 PFIR-PMGNLTAVAGQTLRLHCPVAgYPISSITWEKDGRRLPLNHRQRVFPNG---TLVIENVQRsSDEGEYTCT 72
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 6365-6446 1.74e-04

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 43.92  E-value: 1.74e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6365 DVQAQTGGTAQFEAIIEGDPQPSVTWykdsvqLVDSTRLSQQQEGTTY---SLVLRHVASKDAGVYTCLAQNTGGQVLCK 6441
Cdd:cd20978    10 NVVVKGGQDVTLPCQVTGVPQPKITW------LHNGKPLQGPMERATVedgTLTIINVQPEDTGYYGCVATNEIGDIYTE 83


                  ....*
gi 215274225 6442 AELLV 6446
Cdd:cd20978    84 TLLHV 88
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 3188-3269 1.74e-04

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 43.92  E-value: 1.74e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3188 QEALKDLEVLEGGAATLRCVLSSVAAP-VKWCY-GNNVLRPGDKYSLRQEGamleLVVRNLRPQDSGRYSC----SFGDQ 3261
Cdd:cd20978     5 QKPEKNVVVKGGQDVTLPCQVTGVPQPkITWLHnGKPLQGPMERATVEDGT----LTIINVQPEDTGYYGCvatnEIGDI 80


                  ....*...
gi 215274225 3262 TTSATLTV 3269
Cdd:cd20978    81 YTETLLHV 88
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 6355-6441 1.80e-04

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 43.77  E-value: 1.80e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6355 RPPSMQVTIEDVQAQTGGTAQfeaiieGDPQPSVTWYKDSVQLVDSTRLSQQQEGttySLVLRHVASKDAGVYTCLAQNT 6434
Cdd:cd20968     4 RPPTNVTIIEGLKAVLPCTTM------GNPKPSVSWIKGDDLIKENNRIAVLESG---SLRIHNVQKEDAGQYRCVAKNS 74


                  ....*..
gi 215274225 6435 GGQVLCK 6441
Cdd:cd20968    75 LGIAYSK 81
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3986-4050 1.85e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 43.32  E-value: 1.85e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  3986 QHQEVDEGGTAHLCCELSRAG-ASVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC 4050
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPpPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74
I-set pfam07679
Immunoglobulin I-set domain;
617-673 1.86e-04

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 43.79  E-value: 1.86e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225   617 TPLKAVQAVEGGEVTFSV------DLTVasagEWFLDGQALKASSVYEIHCDRTRHTLTIREV 673
Cdd:pfam07679    5 QKPKDVEVQEGESARFTCtvtgtpDPEV----SWFKDGQPLRSSDRFKVTYEGGTYTLTISNV 63
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 3090-3169 1.87e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 43.86  E-value: 1.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3090 RVTEKPSVfsreltdATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCE 3168
Cdd:cd20949     1 TFTENAYV-------TTVKEGQSATILCEVKGEPQPnVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCR 73


                  .
gi 215274225 3169 A 3169
Cdd:cd20949    74 A 74
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 5280-5350 1.92e-04

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 43.72  E-value: 1.92e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 5280 FQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKkilHTLEIISVTREDSGQYAAYISNAMGAAYSSARLLV 5350
Cdd:cd05723    17 FECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKE---HNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
 7715-7883 1.94e-04

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 47.22  E-value: 1.94e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7715 REYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGpelLPCLAERASYSESEVKDYLWQML-----SATQYLHNQHILH 7789
Cdd:cd14000    59 QELTVLSHLHHPSIVYLLGIGIHPLMLVLELAPLGS---LDHLLQQDSRSFASLGRTLQQRIalqvaDGLRYLHSAMIIY 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7790 LDLRSENMII-----TEYNLLKVVDLGNAQSLSQEKVLPSDKFKDYletMAPELLEGQGAV-PQTDIWAIGVTAFIMLSA 7863
Cdd:cd14000   136 RDLKSHNVLVwtlypNSAIIIKIADYGISRQCCRMGAKGSEGTPGF---RAPEIARGNVIYnEKVDVFSFGMLLYEILSG 212

                         170       180
                  ....*....|....*....|....
gi 215274225 7864 EYPV----SSEGARDLQRGLRKGL 7883
Cdd:cd14000   213 GAPMvghlKFPNEFDIHGGLRPPL 236
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 1461-1516 1.98e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 43.09  E-value: 1.98e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1461 TLSCEV-AQAQTEVMWYKDGKKLSFSSKVRMEAVGCTRRLVVQQAGQAVAGEYSCEA 1516
Cdd:cd00096     2 TLTCSAsGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 4069-4141 2.05e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 43.86  E-value: 2.05e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 4069 KFKTRLQSLEQETGDIARLCCQLSdAESGAVVQWLKEGVELHAGPKYEMRSQGATRELLIHQLEAKDTGEYAC 4141
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVK-GEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTC 72
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
 7707-7862 2.11e-04

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 47.20  E-value: 2.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRHPHLAQLHA--AYLSPRHLVLILE---LCSGPELLPclaeRASYSESEVKDYLWQMLSATQY 7781
Cdd:cd05080    47 PQHRSGWKQEIDILKTLYHENIVKYKGccSEQGGKSLQLIMEyvpLGSLRDYLP----KHSIGLAQLLLFAQQICEGMAY 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7782 LHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSL--SQEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFI 7859
Cdd:cd05080   123 LHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVpeGHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYE 202


                  ...
gi 215274225 7860 MLS 7862
Cdd:cd05080   203 LLT 205
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 7462-7547 2.24e-04

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 43.61  E-value: 2.24e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7462 APTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSSRVLIS-ATLKNFQLLTILVVVAEDLGVYTCSVSN 7540
Cdd:cd20971     1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIqEFKGGYHQLIIASVTDDDATVYQVRATN 80


                  ....*..
gi 215274225 7541 ALGTVTT 7547
Cdd:cd20971    81 QGGSVSG 87
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 995-1063 2.24e-04

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 43.67  E-value: 2.24e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  995 EAGASATLSCEV-AQAQTEVMWYKDGKKLSSSLKVHVEAkgcRRRLVVQQAGKTDAGDYSCEARGQRVSF 1063
Cdd:cd20957    14 DFGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILS---EDVLVIPSVKREDKGMYQCFVRNDGDSA 80
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 6357-6446 2.40e-04

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 43.55  E-value: 2.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6357 PSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQL---VDSTRLSQQQEGTTySLVLRHVASKDAGVYTCLAQN 6433
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQIspkSDHYTIQRDLDGTC-SLHTTASTLDDDGNYTIMAAN 79

                          90
                  ....*....|...
gi 215274225 6434 TGGQVLCKAELLV 6446
Cdd:cd05893    80 PQGRISCTGRLMV 92
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 4-90 2.45e-04

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 43.75  E-value: 2.45e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    4 PQFSGAPRFLTRPKAfvVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGDL-YRLTILDLALGDSGQYVC 82
Cdd:cd05729     1 PRFTDTEKMEEREHA--LPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKgWSLIIERAIPRDKGKYTC 78


                  ....*...
gi 215274225   83 RARNAIGE 90
Cdd:cd05729    79 IVENEYGS 86
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2183-2240 2.53e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 42.70  E-value: 2.53e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 2183 VTLECELS-RPNVDVRWLKDGVELRAGKTMAIAAQGACRSLTIYRCEFADQGVYVCDAH 2240
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3633-3696 2.55e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 42.94  E-value: 2.55e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  3633 RNEEATEGATAVLRCELSKMAP--VEWWKGHETLRDGDRHSLRQDGARCELQIRGLVAEDAGEYLC 3696
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3369-3433 2.63e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 42.94  E-value: 2.63e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  3369 RHQESIEGATATLRCELSKAAP--VEWRKGRESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCV 3433
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6120-6199 2.66e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 43.32  E-value: 2.66e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6120 VEGEDAQFTCTIEGAPYPQIRWYKDGALLTTgNKFQTLSEPRSgllvLVIRAASK-EDLGLYECELVNRLG-SARASAEL 6197
Cdd:cd20958    13 VAGQTLRLHCPVAGYPISSITWEKDGRRLPL-NHRQRVFPNGT----LVIENVQRsSDEGEYTCTARNQQGqSASRSVFV 87


                  ..
gi 215274225 6198 RI 6199
Cdd:cd20958    88 KV 89
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 986-1062 2.67e-04

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 43.16  E-value: 2.67e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  986 QVAHSEVQAEAGASATLSCE--VAQAQTEVMWYKDGKKL-SSSLKVHVEAKGcrrRLVVQQAGKTDAGDYSCEAR---GQ 1059
Cdd:cd05724     1 RVEPSDTQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLnLDNERVRIVDDG---NLLIAEARKSDEGTYKCVATnmvGE 77


                  ...
gi 215274225 1060 RVS 1062
Cdd:cd05724    78 RES 80
PHA03211 PHA03211
serine/threonine kinase US3; Provisional
 7774-7858 2.70e-04

serine/threonine kinase US3; Provisional


Pssm-ID: 223009 [Multi-domain]  Cd Length: 461  Bit Score: 47.97  E-value: 2.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7774 QMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSD-KFKDYLETMAPELLEGQGAVPQTDIWA 7852
Cdd:PHA03211  268 QLLSAIDYIHGEGIIHRDIKTENVLVNGPEDICLGDFGAACFARGSWSTPFHyGIAGTVDTNAPEVLAGDPYTPSVDIWS 347


                  ....*.
gi 215274225 7853 IGVTAF 7858
Cdd:PHA03211  348 AGLVIF 353
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
 6565-6652 2.70e-04

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270879 [Multi-domain]  Cd Length: 322  Bit Score: 47.17  E-value: 2.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6565 KVYIQQLVEGLHYLHSHGVLHLDIKPSNILMVHPAREDI-KICDFGFAQ-------------NITPAELQfSQYGSPEFV 6630
Cdd:cd13977   137 TSFMLQLSSALAFLHRNQIVHRDLKPDNILISHKRGEPIlKVADFGLSKvcsgsglnpeepaNVNKHFLS-SACGSDFYM 215

                          90       100
                  ....*....|....*....|..
gi 215274225 6631 SPEIIQQNPVSEAsDIWAMGVI 6652
Cdd:cd13977   216 APEVWEGHYTAKA-DIFALGII 236
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6365-6436 2.75e-04

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 43.16  E-value: 2.75e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6365 DVQAQTGGTAQFE-AIIEGDPQPSVTWYKDSVQLV-DSTRLSQQQEGttySLVLRHVASKDAGVYTCLAQNTGG 6436
Cdd:cd05724     6 DTQVAVGEMAVLEcSPPRGHPEPTVSWRKDGQPLNlDNERVRIVDDG---NLLIAEARKSDEGTYKCVATNMVG 76
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 4898-4988 2.83e-04

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 43.39  E-value: 2.83e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELT-DGRHHHIDQlgdGTCSLLITGLDRADAGCYTCQVSNK 4976
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEA---GVGELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 215274225 4977 FGQVTHSACVVV 4988
Cdd:cd20976    79 AGQVSCSAWVTV 90
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 1070-1148 2.86e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 43.27  E-value: 2.86e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1070 PKMMFAKEQSVhnevqaEAGASAMLSCEVA--QAQTEVTWYKDGKKL--SSSSKVGMEVKGCTRRLVLPQAGKADAGEYS 1145
Cdd:cd05750     1 PKLKEMKSQTV------QEGSKLVLKCEATseNPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYT 74


                  ...
gi 215274225 1146 CEA 1148
Cdd:cd05750    75 CVV 77
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
 7764-7854 2.91e-04

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 47.35  E-value: 2.91e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7764 SESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSlsqekvlPSDKFKDYLET---MAPELLE 7840
Cdd:cd07878   116 SDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQ-------ADDEMTGYVATrwyRAPEIML 188

                          90
                  ....*....|....*
gi 215274225 7841 GQGAVPQT-DIWAIG 7854
Cdd:cd07878   189 NWMHYNQTvDIWSVG 203
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 3280-3356 3.03e-04

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 43.22  E-value: 3.03e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3280 LRNKE-ATEGATATLRCElSKAAP---VEWRKGSETLRDGDRYCLRQDGAmceLQIRGLAMVDAAEYSCVCGEERTSASL 3355
Cdd:cd04969     8 VKKKIlAAKGGDVIIECK-PKASPkptISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAVNFFGKANS 83


                  .
gi 215274225 3356 T 3356
Cdd:cd04969    84 T 84
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
 7681-7862 3.14e-04

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 46.86  E-value: 3.14e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7681 GRFSVVRQCWEKASGRAL--AAKIIPYHPK--DKTAVLREYEALKGLRHPHLAQLhAAYLSPRHLVLILELCSGPELLPC 7756
Cdd:cd05115    15 GNFGCVKKGVYKMRKKQIdvAIKVLKQGNEkaVRDEMMREAQIMHQLDNPYIVRM-IGVCEAEALMLVMEMASGGPLNKF 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7757 L-AERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQE----KVLPSDKFKdyL 7831
Cdd:cd05115    94 LsGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADdsyyKARSAGKWP--L 171

                         170       180       190
                  ....*....|....*....|....*....|.
gi 215274225 7832 ETMAPELLEGQGAVPQTDIWAIGVTAFIMLS 7862
Cdd:cd05115   172 KWYAPECINFRKFSSRSDVWSYGVTMWEAFS 202
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 3720-3797 3.18e-04

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 43.22  E-value: 3.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3720 LRNEEATEGDTATLWCElSKAAP---VEWRKGHETLRDGDRHSLRQDGSrceLQIRGLAVVDAGEYSCVC----GQERTS 3792
Cdd:cd04969     9 KKKILAAKGGDVIIECK-PKASPkptISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAvnffGKANST 84


                  ....*
gi 215274225 3793 ATLTV 3797
Cdd:cd04969    85 GSLSV 89
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 997-1057 3.21e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 43.09  E-value: 3.21e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  997 GASATLSCEV-AQAQTEVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEAR 1057
Cdd:cd20949    14 GQSATILCEVkGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAY 75
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 248-320 3.45e-04

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 43.32  E-value: 3.45e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  248 TVTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRR----HVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVGQT 320
Cdd:cd20956    12 TLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgDYVTSDGDVVSYVNISSVRVEDGGEYTCTATNDVGSV 88
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 6022-6106 3.46e-04

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 43.41  E-value: 3.46e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6022 DCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILieDPDGSCA------LILDSLTGVDSGQYMCFAASAAGn 6095
Cdd:cd05726     8 DQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPP--QPSSRFSvsptgdLTITNVQRSDVGYYICQALNVAG- 84

                          90
                  ....*....|.
gi 215274225 6096 cSTLGKILVQV 6106
Cdd:cd05726    85 -SILAKAQLEV 94
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5261-5352 3.49e-04

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 43.41  E-value: 3.49e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5261 QVVEELRDLQVAPGtRLAKFQLKVKGYPAPRLYWFKDG--------QPLTASAHIRMTDKKilhTLEIISVTREDSGQYA 5332
Cdd:cd05726     1 QFVVKPRDQVVALG-RTVTFQCETKGNPQPAIFWQKEGsqnllfpyQPPQPSSRFSVSPTG---DLTITNVQRSDVGYYI 76

                          90       100
                  ....*....|....*....|
gi 215274225 5333 AYISNAMGAAYSSARLLVRG 5352
Cdd:cd05726    77 CQALNVAGSILAKAQLEVTD 96
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
 7676-7855 3.50e-04

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 46.49  E-value: 3.50e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7676 TQIQRGRFSVVRQCW--EKASGRALAAKIIPYHPKD---KTAVLREYEALKGLRHPHLAQLhAAYLSPRHLVLILELCSG 7750
Cdd:cd05116     1 GELGSGNFGTVKKGYyqMKKVVKTVAVKILKNEANDpalKDELLREANVMQQLDNPYIVRM-IGICEAESWMLVMEMAEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7751 PELLPCLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQE----KVLPSDK 7826
Cdd:cd05116    80 GPLNKFLQKNRHVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADenyyKAQTHGK 159

                         170       180
                  ....*....|....*....|....*....
gi 215274225 7827 FKdyLETMAPELLEGQGAVPQTDIWAIGV 7855
Cdd:cd05116   160 WP--VKWYAPECMNYYKFSSKSDVWSFGV 186
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3457-3521 3.53e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 42.55  E-value: 3.53e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  3457 RNEEAVEGATAMLWCELSKVAP--VEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCV 3521
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 350-405 3.53e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 42.32  E-value: 3.53e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  350 ATFLCEVP-QPSTEAAWFKEETRLWASAKYGIEEEGTERRLTVRNVSADDDAVYICE 405
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 3387-3445 3.68e-04

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 42.83  E-value: 3.68e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 3387 KAAP---VEWRKGRESLRDGDRHSLRQDGAvceLQICGLAVADAGEYSCVC----GEERTSATLTV 3445
Cdd:cd04969    27 KASPkptISWSKGTELLTNSSRICILPDGS---LKIKNVTKSDEGKYTCFAvnffGKANSTGSLSV 89
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2931-2998 3.73e-04

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 42.90  E-value: 3.73e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 2931 GTAVFTCK-TEHPAATVTWRKGLLELRASGKHQPSQEGltlRLTISALEKADSDTYTC----DIGQAQSRAQL 2998
Cdd:cd20957    17 RTAVFNCSvTGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCfvrnDGDSAQATAEL 86
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 5371-5466 3.81e-04

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 43.17  E-value: 3.81e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDTPGYTVASSAQQHSLVLLDVGRQHQGTYTCI 5450
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKP-----IRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCI 75

                          90
                  ....*....|....*.
gi 215274225 5451 ASNAAGQALCSASLHV 5466
Cdd:cd20990    76 ATNRAGQNSFNLELVV 91
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 6120-6191 4.00e-04

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 43.00  E-value: 4.00e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 6120 VEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSeprSGllVLVIRAASKEDLGLYECELVNRLGSA 6191
Cdd:cd20968    12 IEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLE---SG--SLRIHNVQKEDAGQYRCVAKNSLGIA 78
IgI_C2_MyBP-C-like cd20967
Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set ...
 6366-6446 4.02e-04

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409559  Cd Length: 82  Bit Score: 42.61  E-value: 4.02e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6366 VQAQTGGTAQFEAIIeGDPQPSVTWYKDSVQLVDSTRLSQQQEGTTYSLVLRHVASKDAGVYTCLAqntgGQVLCKAELL 6445
Cdd:cd20967     7 VQVSKGHKIRLTVEL-ADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVA----GGEKCSFELF 81


                  .
gi 215274225 6446 V 6446
Cdd:cd20967    82 V 82
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6009-6106 4.05e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 42.94  E-value: 4.05e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6009 PVWRPpdfeeeLADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILieDPDGScaLILDSLTG-VDSGQYMC 6087
Cdd:cd20958     2 PFIRP------MGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRV--FPNGT--LVIENVQRsSDEGEYTC 71

                          90
                  ....*....|....*....
gi 215274225 6088 FAASAAGNCSTlGKILVQV 6106
Cdd:cd20958    72 TARNQQGQSAS-RSVFVKV 89
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 5140-5216 4.09e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 42.94  E-value: 4.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5140 GYPVSFDCVVTGQPMPSVRWFKDGKLLEeddhymINEDQQ---GGhQLIITAVVPA-DMGVYRCLAENSMGVSST-KAEL 5214
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRLP------LNHRQRvfpNG-TLVIENVQRSsDEGEYTCTARNQQGQSASrSVFV 87


                  ..
gi 215274225 5215 RV 5216
Cdd:cd20958    88 KV 89
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 4162-4245 4.17e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.87  E-value: 4.17e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4162 VRGLVDAEVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRIHTLRLKGVTPEDAGTVSFHLGNHAS-- 4239
Cdd:cd05744     4 LQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGen 83


                  ....*...
gi 215274225 4240 --SAQLTV 4245
Cdd:cd05744    84 sfNAELVV 91
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 3097-3180 4.24e-04

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 43.11  E-value: 4.24e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3097 VFSRELTDATITEGEDLTLVCETSTCDIP-VCWTKDGK--TLRGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA---- 3169
Cdd:cd20974     2 VFTQPLQSVVVLEGSTATFEAHVSGKPVPeVSWFRDGQviSTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTAtngs 81

                          90
                  ....*....|.
gi 215274225 3170 GGACSSSIVRV 3180
Cdd:cd20974    82 GQATSTAELLV 92
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1547-1608 4.33e-04

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 42.79  E-value: 4.33e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1547 EAGTSATLSCEVA-QAQTEVTWYKDGKKLSSSS---KVRMEAVGCTRRLVVQEAGQADAGEYSCKA 1608
Cdd:cd20951    13 WEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3628-3709 4.36e-04

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 42.87  E-value: 4.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3628 FTEGLRNEEATEGATAVLRC--ELSKMAPVEWWK-GHETLRDGDRHSLRQDGArceLQIRGLVAEDAGEYLCMC----GK 3700
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCqaTGEPVPTISWLKdGVPLLGKDERITTLENGS---LQIKGAEKSDTGEYTCVAlnlsGE 78


                  ....*....
gi 215274225 3701 ERTSAMLTV 3709
Cdd:cd20952    79 ATWSAVLDV 87
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1363-1431 4.40e-04

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 42.90  E-value: 4.40e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1363 EAGAIATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRMEAVGctrRLVVQQACQADTGEYSCEAGGQRLSF 1431
Cdd:cd20957    14 DFGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSA 80
PK_TRB1 cd14023
Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein ...
 7765-7924 4.56e-04

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270925 [Multi-domain]  Cd Length: 242  Bit Score: 45.81  E-value: 4.56e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7765 ESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT--EYNLLKVVDLGNAQSLSQEKVLPSDKF--KDYLetmAPELLE 7840
Cdd:cd14023    83 EEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSdeERTQLRLESLEDTHIMKGEDDALSDKHgcPAYV---SPEILN 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7841 GQGAVP--QTDIWAIGVTAFIMLSAEYPVSSEGARDLQRGLRKGlvrlSRCYAG-LSGGAVAFLRSTLCAQPWGRPCASS 7917
Cdd:cd14023   160 TTGTYSgkSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRG----QFCIPDhVSPKARCLIRSLLRREPSERLTAPE 235


                  ....*..
gi 215274225 7918 CLQCPWL 7924
Cdd:cd14023   236 ILLHPWF 242
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 6108-6199 4.63e-04

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 42.78  E-value: 4.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6108 PRFVNKVRASPFVEGEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEpRSGLLVLVIRAASKEDLGLYECELVNR 6187
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVR-ENGVHSLIIEPVTSRDAGIYTCIATNR 79

                          90
                  ....*....|..
gi 215274225 6188 LGSARASAELRI 6199
Cdd:cd20990    80 AGQNSFNLELVV 91
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 6031-6104 4.81e-04

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 42.57  E-value: 4.81e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 6031 VKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEDPDgscaLILDSLTGVDSGQYMCFAASAAGNCSTLGKILV 6104
Cdd:cd05723    15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHN----LQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 1631-1709 4.83e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 42.57  E-value: 4.83e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1631 PAHREVQAEAGASATLSCEVAQA--QTEVTWYKDGKKLSSSSKVRVEAVGCTR-RLVVQQAGQAEAGEYSCEA----GGQ 1703
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGspGPDVTWSKEGGTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVVnnpgGSA 80


                   ....*.
gi 215274225  1704 QLSFRL 1709
Cdd:pfam00047   81 TLSTSL 86
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 1912-1983 5.11e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.48  E-value: 5.11e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1912 EGGEATFQCVVS--PSDvAVVWFRDGALLQP-SEKFAISQSGASHSLTISDLVLEDAGQITV----EAEGASSSAALRV 1983
Cdd:cd05744    14 EGRLCRFDCKVSglPTP-DLFWQLNGKPVRPdSAHKMLVRENGRHSLIIEPVTKRDAGIYTCiarnRAGENSFNAELVV 91
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 904-964 5.22e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 42.57  E-value: 5.22e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225   904 AGASATLSCEVAQA--QTEVTWYKDGKKLSSSSKVcMEATGCTRR--LVVQQAGQADAGEYSCEA 964
Cdd:pfam00047   10 EGDSATLTCSASTGspGPDVTWSKEGGTLIESLKV-KHDNGRTTQssLLISNVTKEDAGTYTCVV 73
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 5382-5466 5.34e-04

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 42.45  E-value: 5.34e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5382 VKKGSSITFSVKVEGRPVPTVHWLR-----EEAERGVLWigPDTpgytvassaqqhSLVLLDVGRQHQGTYTCIASNAAG 5456
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKgtellTNSSRICIL--PDG------------SLKIKNVTKSDEGKYTCFAVNFFG 79

                          90
                  ....*....|
gi 215274225 5457 QALCSASLHV 5466
Cdd:cd04969    80 KANSTGSLSV 89
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3364-3431 5.42e-04

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 42.45  E-value: 5.42e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 3364 FIGRLRHQESIEGATATLRCELSKAAP--VEWRKGRESLR-DGDRHSLRQD--GAVCeLQICGLAVADAGEYS 3431
Cdd:cd05892     3 FIQKPQNKKVLEGDPVRLECQISAIPPpqIFWKKNNEMLQyNTDRISLYQDncGRIC-LLIQNANKKDAGWYT 74
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 6024-6089 5.48e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 42.57  E-value: 5.48e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  6024 TAELGETVKLACRV-TGTPKPVISWYKDGKAVQVDPHHILIEDPDGSCALILDSLTGVDSGQYMCFA 6089
Cdd:pfam00047    7 TVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVV 73
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 110-191 5.53e-04

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 42.45  E-value: 5.53e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  110 PHFLLRPTSIRVREGSEATFRCRVGGSPRPAVSWSKDGRRLG-EPDGPRVRVEELGEASALrIRAARPRDGGTYEVRAEN 188
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQyNTDRISLYQDNCGRICLL-IQNANKKDAGWYTVSAVN 79


                  ...
gi 215274225  189 PLG 191
Cdd:cd05892    80 EAG 82
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3276-3358 5.58e-04

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 42.45  E-value: 5.58e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3276 FIGKLRNKEATEGATATLRCELSKAAP--VEWRKGSETLR-DGDRYCLRQD--GAMCeLQIRGLAMVDAAEYSCVCGEER 3350
Cdd:cd05892     3 FIQKPQNKKVLEGDPVRLECQISAIPPpqIFWKKNNEMLQyNTDRISLYQDncGRIC-LLIQNANKKDAGWYTVSAVNEA 81


                  ....*...
gi 215274225 3351 TSASLTIR 3358
Cdd:cd05892    82 GVVSCNAR 89
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 13-99 5.72e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 42.50  E-value: 5.72e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   13 LTRPKAFVVSVGKDATLSCQIVG-NPTPQVSWEKDQQPVAAGA--RFRLAQDGDLYRLTILDLALGDSGQYVCRARNAIG 89
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRpkNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILG 82

                          90
                  ....*....|
gi 215274225   90 EAFAAVGLQV 99
Cdd:cd05750    83 KDTVTGNVTV 92
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
 7707-7854 5.73e-04

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 46.05  E-value: 5.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7707 PKDKTAVLREYEALKGLRH-PHLAQLHAA-YLSPRHLVLILELCSGPELLPCLAERAS--YSESEVKDYLWQMLSATQYL 7782
Cdd:cd14131    40 EQTLQSYKNEIELLKKLKGsDRIIQLYDYeVTDEDDYLYMVMECGEIDLATILKKKRPkpIDPNFIRYYWKQMLEAVHTI 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7783 HNQHILHLDLRSENMIITEyNLLKVVDLGNAqslsqeKVLPSDKFKDYLET-------MAPELL------EGQGAV---- 7845
Cdd:cd14131   120 HEEGIVHSDLKPANFLLVK-GRLKLIDFGIA------KAIQNDTTSIVRDSqvgtlnyMSPEAIkdtsasGEGKPKskig 192


                  ....*....
gi 215274225 7846 PQTDIWAIG 7854
Cdd:cd14131   193 RPSDVWSLG 201
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 1546-1611 6.01e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 42.50  E-value: 6.01e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1546 AEAGTSATLSCEVA--QAQTEVTWYKDGKKL--SSSSKVRMEAVGCTRRLVVQEAGQADAGEYSCKAGDQ 1611
Cdd:cd05750    11 VQEGSKLVLKCEATseNPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENI 80
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 5381-5466 6.08e-04

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 42.39  E-value: 6.08e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5381 KVKKGSSITFSVKVEGRPVPTVHWLREEAErgvlwIGPDTPGYTV-----ASSAQQHSLVLLDvgrqHQGTYTCIASNAA 5455
Cdd:cd05893    11 KIFEGMPVTFTCRVAGNPKPKIYWFKDGKQ-----ISPKSDHYTIqrdldGTCSLHTTASTLD----DDGNYTIMAANPQ 81

                          90
                  ....*....|.
gi 215274225 5456 GQALCSASLHV 5466
Cdd:cd05893    82 GRISCTGRLMV 92
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 6028-6087 6.09e-04

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 42.00  E-value: 6.09e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  6028 GETVKLACRVTGTPKPVISWYKDGKAVQvdphhiliedpdGSCALILDSLTGVDSGQYMC 6087
Cdd:pfam13895   14 GEPVTLTCSAPGNPPPSYTWYKDGSAIS------------SSPNFFTLSVSAEDSGTYTC 61
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 6031-6098 6.10e-04

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 41.78  E-value: 6.10e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6031 VKLACRVTGTPKPVISWYKDGkaVQVDPHHILIEDPDGScaLILDSLTGVDSGQYMCFAASAAGNCST 6098
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDG--VQVTESGKFHISPEGY--LAIRDVGVADQGRYECVARNTIGYASV 64
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 427-488 6.27e-04

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 42.11  E-value: 6.27e-04
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225    427 PRKTAVRVGDTAMF-CVELAVPVGPVHWLRN-QEEVVAGGRVAISAEGTRHTLTISQCCLEDVG 488
Cdd:smart00410    1 PPSVTVKEGESVTLsCEASGSPPPEVTWYKQgGKLLAESGRFSVSRSGSTSTLTISNVTPEDSG 64
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 3190-3256 6.35e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 42.18  E-value: 6.35e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  3190 ALKDLEVLEGGAATLRC--VLSSVAAPVKWCYGNNVLRPGDKYSLRQEGAM-LELVVRNLRPQDSGRYSC 3256
Cdd:pfam00047    2 APPTVTVLEGDSATLTCsaSTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTC 71
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 5385-5466 6.40e-04

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 42.61  E-value: 6.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5385 GSSITFSVKVEGRPVPTVHWLREeaergvlwigpdtpGYTVASSAQQHS-------LVLLDVGRQHQGTYTCIASNAAGQ 5457
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKD--------------GEPIESGEEKYSfnedgseMTILDVDKLDEAEYTCIAENKAGE 83


                  ....*....
gi 215274225 5458 ALCSASLHV 5466
Cdd:cd05730    84 QEAEIHLKV 92
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3006-3091 6.59e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.48  E-value: 6.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3006 HIIEDLEDVDVQEGSSATFRCRISPANYEPVHWFLDKTPLHANELNEIDAQPGGYHVLTLRQLALKDSGtIYF-----EA 3080
Cdd:cd05744     2 HFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAG-IYTciarnRA 80

                          90
                  ....*....|.
gi 215274225 3081 GDQRASAALRV 3091
Cdd:cd05744    81 GENSFNAELVV 91
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
 6122-6199 6.66e-04

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 42.61  E-value: 6.66e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6122 GEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEPRSGllvLVIRAASKEDLGLYECELVNRLGSARASAELRI 6199
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSE---MTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 4907-4988 6.70e-04

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 42.10  E-value: 6.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4907 TEAQVGDALrLECVVASKADVRARWLKDGVELTdGRHHHIDQLGDGtcSLLITGLDRADAGCYTCQVSNKFGQVTHSACV 4986
Cdd:cd20952    10 TVAVGGTVV-LNCQATGEPVPTISWLKDGVPLL-GKDERITTLENG--SLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85


                  ..
gi 215274225 4987 VV 4988
Cdd:cd20952    86 DV 87
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 5131-5216 6.92e-04

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 42.00  E-value: 6.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  5131 ELQNQEVQDGYPVSFDCVVTGQPMPSVRWFKDGKLLEEddhyminedqqgGHQLIITAVVPADMGVYRCLAENSMGV-SS 5209
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISS------------SPNFFTLSVSAEDSGTYTCVARNGRGGkVS 72


                   ....*..
gi 215274225  5210 TKAELRV 5216
Cdd:pfam13895   73 NPVELTV 79
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
 5267-5340 7.08e-04

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 42.21  E-value: 7.08e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 5267 RDLQVAPGTRLAKFQLKVKGYPAPRLYWFKDGQPLTASAHIRMTDKKILH-TLEIISVTREDSGQYAAYISNAMG 5340
Cdd:cd05729    11 EREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVENEYG 85
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 3545-3621 7.45e-04

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 42.00  E-value: 7.45e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3545 KNQEAREGATAVLQCELNSAAP--VEWRKGSETLRDGdRYSLRQDGTkceLQIRGLAMADTGEYSCVC----GQERTSAM 3618
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVptVRWRKEDGELPKG-RYEILDDHS---LKIRKVTAGDMGSYTCVAenmvGKIEASAT 80


                  ...
gi 215274225 3619 LTV 3621
Cdd:cd05725    81 LTV 83
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3728-3797 7.46e-04

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 42.10  E-value: 7.46e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 3728 GDTATLWCELSkAAPV---EWRK-GHETLRDGDRHSLRQDGSrceLQIRGLAVVDAGEYSCVC----GQERTSATLTV 3797
Cdd:cd20952    14 GGTVVLNCQAT-GEPVptiSWLKdGVPLLGKDERITTLENGS---LQIKGAEKSDTGEYTCVAlnlsGEATWSAVLDV 87
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 4909-4988 7.51e-04

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 41.81  E-value: 7.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4909 AQVGDALRLECVVASKADVRARWLKDGVELTDGRHHHIDqLGDGTCSLLITGLDRADAGCYTCQVSNKFGQVTHSACVVV 4988
Cdd:cd05748     4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIE-TTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 3364-3446 7.55e-04

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 42.41  E-value: 7.55e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3364 FIGRLRHQESIEGATATLRCELS-KAAP-VEWRKGR---ESLRDGDRHSLRQDGAVCELQICGLAVADAGEYSCVC---- 3434
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPeVKWYKNGvpiDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAknih 82

                          90
                  ....*....|..
gi 215274225 3435 GEERTSATLTVK 3446
Cdd:cd20951    83 GEASSSASVVVE 94
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 1903-1983 7.57e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 42.18  E-value: 7.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  1903 SGLSTVVAEEGGEATFQCVVSPSDVA--VVWFRDG-ALLQPSEKFAISQSGASHSLTISDLVLEDAGQITVEAEGASSSA 1979
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGpdVTWSKEGgTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....
gi 215274225  1980 ALRV 1983
Cdd:pfam00047   81 TLST 84
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3628-3709 7.63e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.10  E-value: 7.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3628 FTEGLRNEEATEGATAVLRCELSKMAP--VEWWKGHETLRDGDRHSLRQD-GARCELQIRGLVAEDAGEYLCMC----GK 3700
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTpdLFWQLNGKPVRPDSAHKMLVReNGRHSLIIEPVTKRDAGIYTCIArnraGE 82


                  ....*....
gi 215274225 3701 ERTSAMLTV 3709
Cdd:cd05744    83 NSFNAELVV 91
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 5278-5339 8.04e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 41.93  E-value: 8.04e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 5278 AKFQLKVKGYPAPRLYWFKDGQPLTASAHiRMTDKKIL-HTLEIISVTREDSGQYA--AYISNAM 5339
Cdd:cd20949    17 ATILCEVKGEPQPNVTWHFNGQPISASVA-DMSKYRILaDGLLINKVTQDDTGEYTcrAYQVNSI 80
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 3539-3608 8.28e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 41.93  E-value: 8.28e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 3539 RFIEDVKNQEAREGATAVLQCELNSAAP--VEWRKG----SETLRDGDRYSLRQDGtkceLQIRGLAMADTGEYSC 3608
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQpnVTWHFNgqpiSASVADMSKYRILADG----LLINKVTQDDTGEYTC 72
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 3890-3962 8.31e-04

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 42.11  E-value: 8.31e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 3890 PVFREPLQS--LQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRREpRLQGCTAELVLQDLQREDTGEYTCT 3962
Cdd:cd20970     1 PVISTPQPSftVTAREGENATFMCRAEgSPEPEISWTRNGNLIIEFNTRY-IVRENGTTLTIRNIRRSDMGIYLCI 75
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 3275-3345 8.36e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.78  E-value: 8.36e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225  3275 QFIGKLRNKEATEGATATLRCELSKAAP--VEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCV 3345
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPptITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3098-3169 8.67e-04

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 42.10  E-value: 8.67e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 3098 FSRELTDATITEGEDLTLVCETSTCDIP-VCWTKDGKTLRGSARCQ-LSHEGHRAQLLITGATLQDSGRYKCEA 3169
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPdLFWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIYTCIA 76
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1995-2060 9.31e-04

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.40  E-value: 9.31e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  1995 EPQTVEERSSVTLEVELT-RPWPELRWTRNATALAPGKNVEIHAEGARHRLVLHNVGFADRGFFGCE 2060
Cdd:pfam13927    9 SSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 4906-4978 9.42e-04

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 41.62  E-value: 9.42e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4906 DTEAQVGDALRLEC---------VVAskadvrarWLKDGVELT-DGRHHHIdqLGDGtcSLLITGLDRADAGCYTCQVSN 4975
Cdd:cd05724     6 DTQVAVGEMAVLECspprghpepTVS--------WRKDGQPLNlDNERVRI--VDDG--NLLIAEARKSDEGTYKCVATN 73


                  ...
gi 215274225 4976 KFG 4978
Cdd:cd05724    74 MVG 76
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 4898-4988 9.62e-04

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 42.01  E-value: 9.62e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDGVELT-DGRHHHIDQLGDGTCSLLITGLDRADAGCYTCQVSNK 4976
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISpKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 215274225 4977 FGQVTHSACVVV 4988
Cdd:cd05893    81 QGRISCTGRLMV 92
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 1288-1329 9.69e-04

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 41.42  E-value: 9.69e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 215274225 1288 EVTWYKDGKKLSSSSKVRIEAAGCMRQLVVQQAGQADAGEYT 1329
Cdd:cd05748    23 TVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYT 64
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3376-3445 1.03e-03

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 41.71  E-value: 1.03e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3376 GATATLRCELSkAAPV---EWRKGRESLRDGDRHSLRQDGAVceLQICGLAVADAGEYSCVC----GEERTSATLTV 3445
Cdd:cd20952    14 GGTVVLNCQAT-GEPVptiSWLKDGVPLLGKDERITTLENGS--LQIKGAEKSDTGEYTCVAlnlsGEATWSAVLDV 87
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 2833-2911 1.03e-03

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 41.23  E-value: 1.03e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2833 LEDQWVAPGEDVELRCELSRAGTP-VHWLKDRKAIRKSQKYdvvcegtmamlVIRGASLKDAGEYTCEVEA---SKSTAS 2908
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPsYTWYKDGSAISSSPNF-----------FTLSVSAEDSGTYTCVARNgrgGKVSNP 74


                   ...
gi 215274225  2909 LHV 2911
Cdd:pfam13895   75 VEL 77
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 903-971 1.07e-03

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 41.75  E-value: 1.07e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  903 EAGASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVCMEATGctrRLVVQQAGQADAGEYSCEAGGQRLSF 971
Cdd:cd20957    14 DFGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSA 80
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 898-964 1.07e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 41.64  E-value: 1.07e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  898 RKLQAEAGASATLSCEVA-QAQTEVTWYKDGKKLSSSS---KVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:cd20951     8 QSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 997-1056 1.08e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 41.80  E-value: 1.08e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225  997 GASATLSCEVAQAQT-EVMWYKDGKKLSSSLKVHVEAKGCRRRLVVQQAGKTDAGDYSCEA 1056
Cdd:cd20972    16 GSKVRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 124-191 1.09e-03

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 41.78  E-value: 1.09e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  124 GSEATFRCRVGGSPRPAVSWSKDGRRLgePDGPRVRVEELGeasALRIRAA-RPRDGGTYEVRAENPLG 191
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRL--PLNHRQRVFPNG---TLVIENVqRSSDEGEYTCTARNQQG 78
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1272-1343 1.10e-03

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 41.78  E-value: 1.10e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1272 AGASATLSCEVAQAQ-TEVTWYKDGKKLSSSSKVRIEAAGcmrQLVVQQA-GQADAGEYTCEAGGQ-----RLSFHLDV 1343
Cdd:cd20958    14 AGQTLRLHCPVAGYPiSSITWEKDGRRLPLNHRQRVFPNG---TLVIENVqRSSDEGEYTCTARNQqgqsaSRSVFVKV 89
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 1084-1154 1.10e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 41.62  E-value: 1.10e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1084 VQAEAGASAMLSCE--VAQAQTEVTWYKDGKKLSSSSKVGMEVKGctRRLVLPQAGKADAGEYSCEAG---GQRVS 1154
Cdd:cd05724     7 TQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLNLDNERVRIVDD--GNLLIAEARKSDEGTYKCVATnmvGERES 80
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2575-2642 1.11e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 41.34  E-value: 1.11e-03
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225   2575 ASFSCELS-HEDEEVEWSLNG--MPLYNDSFHeISHKGRRHTLVLKSIQRADAGI----VRASSLKVSTSARLEV 2642
Cdd:smart00410   12 VTLSCEASgSPPPEVTWYKQGgkLLAESGRFS-VSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGTTLTV 85
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 5267-5350 1.13e-03

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 41.84  E-value: 1.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5267 RDLQVAPGTrLAKFQLKVKGYPAPRLYWFKD-GQPLTASAHIRMTDKKILHTLEIISVTREDSGQYAAYISNAMGAAYSS 5345
Cdd:cd05763     7 HDITIRAGS-TARLECAATGHPTPQIAWQKDgGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                  ....*
gi 215274225 5346 ARLLV 5350
Cdd:cd05763    86 ATLTV 90
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 2170-2249 1.13e-03

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 41.23  E-value: 1.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2170 RPLQDVVTTEKEKVTLECELS-RPNVDVRWLKDGVELRAGKtmaiAAQGACRSLTIYRCEFADQGVYVCDAHDAQSSASV 2248
Cdd:cd05725     2 KRPQNQVVLVDDSAEFQCEVGgDPVPTVRWRKEDGELPKGR----YEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEA 77


                  .
gi 215274225 2249 K 2249
Cdd:cd05725    78 S 78
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
 2295-2370 1.17e-03

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 41.68  E-value: 1.17e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 2295 PLRDKIAMEKHRGVL-ECQvSRAS--AQVRWFKGSQELQPGPKYELVSDGlyrKLIISDVHAEDEDTYTCDAGDVKTSA 2370
Cdd:cd04969     7 PVKKKILAAKGGDVIiECK-PKASpkPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKA 81
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 978-1056 1.18e-03

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 41.73  E-value: 1.18e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  978 PKVVFAKDQVAhsevqaEAGASATLSCEVA--QAQTEVMWYKDGKKLSSSLKVHVEAKGCRR--RLVVQQAGKTDAGDYS 1053
Cdd:cd05750     1 PKLKEMKSQTV------QEGSKLVLKCEATseNPSPRYRWFKDGKELNRKRPKNIKIRNKKKnsELQINKAKLEDSGEYT 74


                  ...
gi 215274225 1054 CEA 1056
Cdd:cd05750    75 CVV 77
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 3916-3974 1.21e-03

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 41.42  E-value: 1.21e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 3916 PTATVVWSKGGLQLQANGRREPRLQGCTAELVLQDLQREDTGEYTCT----CGSqaTSATLTV 3974
Cdd:cd05748    20 PTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTlknsAGE--KSATINV 80
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 3363-3445 1.24e-03

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 41.71  E-value: 1.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3363 HFIGRLRHQESIEGATATLRCELSKAAP--VEWRKGRESLRDGDRHSLRQD-GAVCELQICGLAVADAGEYSCVC----G 3435
Cdd:cd05744     2 HFLQAPGDLEVQEGRLCRFDCKVSGLPTpdLFWQLNGKPVRPDSAHKMLVReNGRHSLIIEPVTKRDAGIYTCIArnraG 81

                          90
                  ....*....|
gi 215274225 3436 EERTSATLTV 3445
Cdd:cd05744    82 ENSFNAELVV 91
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1358-1424 1.25e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 41.41  E-value: 1.25e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1358 RKVQAEAGAIATLSCEVAQAQT-EVTWYKDGKKLSSSSKVRMEAVGCTRRLVVQQACQADTGEYSCEA 1424
Cdd:cd20972     9 RSQEVAEGSKVRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 996-1068 1.30e-03

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 41.40  E-value: 1.30e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  996 AGASATLSCEVAQAQ-TEVMWYKDGKKLSSSLKVHVEAKGCrrrLVVQQA-GKTDAGDYSCEAR---GQRVSFRLHIT 1068
Cdd:cd20958    14 AGQTLRLHCPVAGYPiSSITWEKDGRRLPLNHRQRVFPNGT---LVIENVqRSSDEGEYTCTARnqqGQSASRSVFVK 88
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 4630-4695 1.30e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.01  E-value: 1.30e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225  4630 PESRQVAAGEDVSLELEVVAE-AGEVIWHKGMERIQPGGRFEVVSQGRQQMLVIKGFTAEDQGEYHC 4695
Cdd:pfam13927    8 PSSVTVREGETVTLTCEATGSpPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 5371-5466 1.31e-03

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 41.68  E-value: 1.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5371 PRMLERFTPKKVKKGSSITFSVKVEGRPVPTVHW------LREEAERGVLWigPDTPGYtvassaqqHSLVLLDVGRQHQ 5444
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWkknnemLQYNTDRISLY--QDNCGR--------ICLLIQNANKKDA 70

                          90       100
                  ....*....|....*....|..
gi 215274225 5445 GTYTCIASNAAGQALCSASLHV 5466
Cdd:cd05892    71 GWYTVSAVNEAGVVSCNARLDV 92
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3628-3694 1.31e-03

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 41.68  E-value: 1.31e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 3628 FTEGLRNEEATEGATAVLRCELSKMAP--VEWWKGHETLR-DGDRHSLRQDG-ARCELQIRGLVAEDAGEY 3694
Cdd:cd05892     3 FIQKPQNKKVLEGDPVRLECQISAIPPpqIFWKKNNEMLQyNTDRISLYQDNcGRICLLIQNANKKDAGWY 73
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 2918-3001 1.31e-03

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 41.55  E-value: 1.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2918 FTEELTNLQVEEKGTAVFTCKTE-HPAATVTWRKGLLELRASGKHQPSQEGLTLRLTISALEKADSDTYTCDIGQAQSRA 2996
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKgEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIA 81


                  ....*
gi 215274225 2997 QLLVQ 3001
Cdd:cd20949    82 SDMQE 86
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 3801-3885 1.32e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 41.41  E-value: 1.32e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3801 PARFIEDVKNQEAREGATAVLQCELSKAAP--VEW-RKGSEtLRGGDRYSLRQDGtrcelQIHGLSVA-----DTGEYSC 3872
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTpvVRWfCEGKE-LQNSPDIQIHQEG-----DLHSLIIAeafeeDTGRYSC 74

                          90
                  ....*....|....*..
gi 215274225 3873 ----VCGQERTSATLTV 3885
Cdd:cd20972    75 latnSVGSDTTSAEIFV 91
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 1268-1338 1.33e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 41.23  E-value: 1.33e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1268 VRTEAGASATLSCE--VAQAQTEVTWYKDGKKL-SSSSKVRIEAAGcmrQLVVQQAGQADAGEYTCEAG---GQRLS 1338
Cdd:cd05724     7 TQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLnLDNERVRIVDDG---NLLIAEARKSDEGTYKCVATnmvGERES 80
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2662-2723 1.36e-03

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 41.36  E-value: 1.36e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225 2662 GTLALQCEVSDPEAH-VVWRKDGVQLGPSDKydfLHTAGTRGLVVHDVSPEDAGLYTCHVGSE 2723
Cdd:cd20957    17 RTAVFNCSVTGNPIHtVLWMKDGKPLGHSSR---VQILSEDVLVIPSVKREDKGMYQCFVRND 76
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 3537-3621 1.37e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 41.41  E-value: 1.37e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3537 PARFIEDVKNQEAREGATAVLQCELNSAAP--VEW-RKGSEtLRDGDRYSLRQDGTKCELQIRGLAMADTGEYSC----V 3609
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTpvVRWfCEGKE-LQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSClatnS 79

                          90
                  ....*....|..
gi 215274225 3610 CGQERTSAMLTV 3621
Cdd:cd20972    80 VGSDTTSAEIFV 91
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 995-1056 1.45e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 41.64  E-value: 1.45e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  995 EAGASATLSCEVA-QAQTEVMWYKDGKKLSSSL---KVHVEAKGCRRRLVVQQAGKTDAGDYSCEA 1056
Cdd:cd20951    13 WEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1271-1339 1.47e-03

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 41.36  E-value: 1.47e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1271 EAGASATLSCEV-AQAQTEVTWYKDGKKLSSSSKVRIEAAGcmrQLVVQQAGQADAGEYTCEAGGQRLSF 1339
Cdd:cd20957    14 DFGRTAVFNCSVtGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSA 80
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 1628-1700 1.51e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 41.23  E-value: 1.51e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1628 KEQPahREVQAEAGASATLSCE--VAQAQTEVTWYKDGKKL-SSSSKVRVEAVGctrRLVVQQAGQAEAGEYSCEA 1700
Cdd:cd05724     1 RVEP--SDTQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLnLDNERVRIVDDG---NLLIAEARKSDEGTYKCVA 71
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 4257-4336 1.51e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 40.95  E-value: 1.51e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   4257 QDVQLSEGQDASFQCRLSRASGQEARWALGGVPLQANEMNDITVEQGTLHLLTLHKVTLEDAGT----VSFHVGTCSSEA 4332
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTytcaATNSSGSASSGT 81


                    ....
gi 215274225   4333 QLKV 4336
Cdd:smart00410   82 TLTV 85
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 2468-2553 1.52e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 41.41  E-value: 1.52e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2468 PVVLTRPLEPKTGRELQSVVLSCDFR--PAPKaVQWYKDDTPLSPSEKFKMSLEGQMAELRILRLMPADAGVYRCQA--- 2542
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTgnPTPV-VRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLAtns 79

                          90
                  ....*....|..
gi 215274225 2543 -GSAHSSTEVTV 2553
Cdd:cd20972    80 vGSDTTSAEIFV 91
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 3803-3872 1.53e-03

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 41.16  E-value: 1.53e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 3803 RFIEDVKNQEAREGATAVLQCELSKAAP--VEWRKGSETLRGGDRYSLRQDGTRCELQIHGLSVADTGEYSC 3872
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQpnVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTC 72
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
 4256-4336 1.54e-03

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 41.33  E-value: 1.54e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4256 LQDVQLSEGQDASFQCRLSRASGQEARWALGGVPLQANEMNDITVEQGTLHLLTLHKVTLEDAGTVSF----HVGTCSSE 4331
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCiarnRAGENSFN 86


                  ....*
gi 215274225 4332 AQLKV 4336
Cdd:cd05744    87 AELVV 91
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 3893-3974 1.55e-03

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 40.84  E-value: 1.55e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3893 REPlQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLqANGRREPRLQgctAELVLQDLQREDTGEYTCTC----GSQA 3967
Cdd:cd05725     2 KRP-QNQVVLVDDSAEFQCEVGgDPVPTVRWRKEDGEL-PKGRYEILDD---HSLKIRKVTAGDMGSYTCVAenmvGKIE 76


                  ....*..
gi 215274225 3968 TSATLTV 3974
Cdd:cd05725    77 ASATLTV 83
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 2166-2239 1.57e-03

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 41.34  E-value: 1.57e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 2166 VSFSRPLQDVVTTEKEKVTLECELS-RPNVDVRWLKDGVELRAGKTMAIAaQGACRSLTIYRCEFADQGVYVCDA 2239
Cdd:cd20970     3 ISTPQPSFTVTAREGENATFMCRAEgSPEPEISWTRNGNLIIEFNTRYIV-RENGTTLTIRNIRRSDMGIYLCIA 76
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 6357-6446 1.58e-03

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 41.30  E-value: 1.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6357 PSMQVTIEDVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTR--LSQQQEGTTYSLVLRHVASKDAGVYTCLAQNT 6434
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLkyRIQEFKGGYHQLIIASVTDDDATVYQVRATNQ 81

                          90
                  ....*....|..
gi 215274225 6435 GGQVLCKAELLV 6446
Cdd:cd20971    82 GGSVSGTASLEV 93
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 894-964 1.59e-03

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 41.34  E-value: 1.59e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  894 QLARRKLQ-AEAGASATLSCEVA--QAQTEVTWYKDGKKL--SSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:cd05750     2 KLKEMKSQtVQEGSKLVLKCEATseNPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVV 77
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 2482-2553 1.60e-03

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 41.08  E-value: 1.60e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 2482 ELQSVVLSCDFR--PAPKaVQWYKDDTPLSPSEKfKMSLEGQMAELRILRLMPADAGVYRC----QAGSAHSSTEVTV 2553
Cdd:cd20976    15 EGQDFVAQCSARgkPVPR-ITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLPEDHGTYTClaknAAGQVSCSAWVTV 90
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 20-100 1.61e-03

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 41.01  E-value: 1.61e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   20 VVSvGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLAQDGdlyRLTILDLALG-DSGQYVCRARNAIGEaFAAVGLQ 98
Cdd:cd20958    12 AVA-GQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNG---TLVIENVQRSsDEGEYTCTARNQQGQ-SASRSVF 86


                  ..
gi 215274225   99 VD 100
Cdd:cd20958    87 VK 88
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 1192-1249 1.61e-03

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 40.63  E-value: 1.61e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225 1192 QPQTEVTWYKDGKKLSSSSKVRMEVKGctrRLVVQQVGKADAGEYSCEA----GGQRVSFQL 1249
Cdd:cd05746    10 DPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVArntiGYASVSMVL 68
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 1821-1881 1.61e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 41.01  E-value: 1.61e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225  1821 ELGGTVTLACELS--PAcAEVVWRCGNTQLRVGKRFQMVAEGPVRSLTVLGLRAEDAGEYVCE 1881
Cdd:pfam13927   14 REGETVTLTCEATgsPP-PTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 6028-6094 1.67e-03

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 41.28  E-value: 1.67e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 6028 GETVKLACRVTGTPKPVISWYKDGKAVQVDP-HHILIEDPDgscALILDSLTGVDSGQYMCFAASAAG 6094
Cdd:cd04978    14 GETGELICEAEGNPQPTITWRLNGVPIEPAPeDMRRTVDGR---TLIFSNLQPNDTAVYQCNASNVHG 78
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
505-659 1.69e-03

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 45.38  E-value: 1.69e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  505 VSA-PRKPPLQPPVDPVVKARMESSVILSWSPPPhgerPVTIDGYLVEKKK--LGTYTWIrcheAEWVATPELTVADVAE 581
Cdd:COG3401   318 VSVtTDLTPPAAPSGLTATAVGSSSITLSWTASS----DADVTGYNVYRSTsgGGTYTKI----AETVTTTSYTDTGLTP 389

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  582 EGNFQFRVSALNSFGQSPYLEFPGTVHlapKLAVRTPLKAVQAVEGGEVTFSVDLTVASAGEWFLDGQALKASSVYEI 659
Cdd:COG3401   390 GTTYYYKVTAVDAAGNESAPSEEVSAT---TASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDT 464
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 3100-3169 1.72e-03

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 41.34  E-value: 1.72e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3100 RELTDATITEGEDLTLVCETsTCDIPVC---WTKDGKTL--RGSARCQLSHEGHRAQLLITGATLQDSGRYKCEA 3169
Cdd:cd05750     4 KEMKSQTVQEGSKLVLKCEA-TSENPSPryrWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVV 77
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 7677-7930 1.77e-03

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 44.45  E-value: 1.77e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7677 QIQRGRFSVVRQCWEKASGRALAAKIIPYHPKDKT--AVLREYEALKGLRHPHLAQLHAAYLSPRHLVLILELCSGPELL 7754
Cdd:cd06622     8 ELGKGNYGSVYKVLHRPTGVTMAMKEIRLELDESKfnQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAGSLD 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7755 PCLAERASYS---ESEVKDYLWQMLSATQYLHNQH-ILHLDLRSENMIITEYNLLKVVDLGNAQSLSQEKVLPSDKFKDY 7830
Cdd:cd06622    88 KLYAGGVATEgipEDVLRRITYAVVKGLKFLKEEHnIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASLAKTNIGCQSY 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7831 letMAPELLEGQGAVP------QTDIWAIGVTAFIMLSAEYPVSSEGARDLqrglrkgLVRLS--------RCYAGLSGG 7896
Cdd:cd06622   168 ---MAPERIKSGGPNQnptytvQSDVWSLGLSILEMALGRYPYPPETYANI-------FAQLSaivdgdppTLPSGYSDD 237

                         250       260       270
                  ....*....|....*....|....*....|....
gi 215274225 7897 AVAFLRSTLCAQPWGRPCASSCLQCPWLTEEGPA 7930
Cdd:cd06622   238 AQDFVAKCLNKIPNRRPTYAQLLEHPWLVKYKNA 271
I-set pfam07679
Immunoglobulin I-set domain;
2078-2161 1.77e-03

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 41.09  E-value: 1.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2078 RLVRGLQAVEAREQGTATMEVQlshadVDG------SWTRDGLRFQQGPTCHLAVRGPMHTLTLSGLRPEDSGLMVFKAE 2151
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCT-----VTGtpdpevSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 215274225  2152 G----VHTSARLVV 2161
Cdd:pfam07679   77 NsageAEASAELTV 90
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 2743-2822 1.79e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 40.95  E-value: 1.79e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   2743 KTMEVLEGESCSFECVLSheSASDPAMW--TVGGKTVGSSSRFQATRQGRKYILVVREAAPSDAG----EVVFSVRGLTS 2816
Cdd:smart00410    2 PSVTVKEGESVTLSCEAS--GSPPPEVTwyKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGtytcAATNSSGSASS 79


                    ....*.
gi 215274225   2817 KASLIV 2822
Cdd:smart00410   80 GTTLTV 85
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 1537-1619 1.83e-03

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 40.84  E-value: 1.83e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1537 EQPASREVQAEAGTSATLSCEVA-QAQTEVTWYKDGKKLSSsskvRMEAVGCTR-RLVVQEAGQADAGEYSCKA----GD 1610
Cdd:cd20978     4 IQKPEKNVVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLQG----PMERATVEDgTLTIINVQPEDTGYYGCVAtneiGD 79


                  ....*....
gi 215274225 1611 QRLSFHLHV 1619
Cdd:cd20978    80 IYTETLLHV 88
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 1176-1247 1.84e-03

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 41.18  E-value: 1.84e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1176 VQAEAGTTAMLSCEVA-QPQTEVTWYKDGK--KLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA---GGQRVSF 1247
Cdd:cd20974    10 VVVLEGSTATFEAHVSgKPVPEVSWFRDGQviSTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTAtngSGQATST 87
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 7463-7547 1.84e-03

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 41.38  E-value: 1.84e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLES------SSRVLISATlknfqLLTILVVV-----AEDL 7531
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETdkddprSHRIVLPSG-----SLFFLRVVhgrkgRSDE 75

                          90
                  ....*....|....*.
gi 215274225 7532 GVYTCSVSNALGTVTT 7547
Cdd:cd07693    76 GVYVCVAHNSLGEAVS 91
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5382-5468 1.87e-03

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 41.48  E-value: 1.87e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5382 VKKGSSITFSVKVEGRPVPTVHWLREEAERGVLWIGPDTPGYTVASSaQQHSLVLLDVGRQHQGTYTCIASNAAGQALCS 5461
Cdd:cd05726    11 VALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSRFSVS-PTGDLTITNVQRSDVGYYICQALNVAGSILAK 89


                  ....*..
gi 215274225 5462 ASLHVSG 5468
Cdd:cd05726    90 AQLEVTD 96
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3288-3357 1.93e-03

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 40.94  E-value: 1.93e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 3288 GATATLRCELSkAAPV---EWRKGSETLRDGD-RYCLRQDGAmceLQIRGLAMVDAAEYSCVC----GEERTSASLTI 3357
Cdd:cd20952    14 GGTVVLNCQAT-GEPVptiSWLKDGVPLLGKDeRITTLENGS---LQIKGAEKSDTGEYTCVAlnlsGEATWSAVLDV 87
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 7459-7545 1.99e-03

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 40.89  E-value: 1.99e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7459 WDRAPtflrelSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLE----SSSRVLisatlkNFQLLTILVVVAEDLGVY 7534
Cdd:cd04978     2 WIIEP------PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEpapeDMRRTV------DGRTLIFSNLQPNDTAVY 69

                          90
                  ....*....|.
gi 215274225 7535 TCSVSNALGTV 7545
Cdd:cd04978    70 QCNASNVHGYL 80
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3996-4050 2.01e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 40.39  E-value: 2.01e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 3996 AHLCCELS-RAGASVEWRKGSLQLFPCAKYQMVQDGAAAELLVRGVEQEDAGDYTC 4050
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTC 56
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 732-781 2.02e-03

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 40.24  E-value: 2.02e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 215274225  732 DQAAAVTWLKDGRTLSPGPKYEVQASAgrrVLLVRDVARDDAGLYECVSR 781
Cdd:cd05746    10 DPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVAR 56
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
 1278-1332 2.06e-03

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 40.24  E-value: 2.06e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1278 LSCEvAQAQTE--VTWYKDGKKLSSSSKVRIEAAGcmrQLVVQQAGQADAGEYTCEA 1332
Cdd:cd05746     3 IPCS-AQGDPEptITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVA 55
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 1181-1240 2.13e-03

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 40.64  E-value: 2.13e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225 1181 GTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKVRMEVKG---CTrrLVVQQVGKADAGEYSCEA 1240
Cdd:cd20973    12 GSAARFDCKVeGYPDPEVKWMKDDNPIVESRRFQIDQDEdglCS--LIISDVCGDDSGKYTCKA 73
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
 1175-1240 2.26e-03

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 40.68  E-value: 2.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225 1175 EVQAEAGTTAMLSCE-VAQPQTEVTWYKDG-KKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd05763     8 DITIRAGSTARLECAaTGHPTPQIAWQKDGgTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTA 75
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 5285-5350 2.27e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 40.85  E-value: 2.27e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 5285 KGYPAPRLYWFKDGQPLtASAHIRMTdkkILH--TLEIISVTREDSGQYAAYISNAMGAAYSS-ARLLV 5350
Cdd:cd05724    23 RGHPEPTVSWRKDGQPL-NLDNERVR---IVDdgNLLIAEARKSDEGTYKCVATNMVGERESRaARLSV 87
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
 7740-7882 2.28e-03

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 44.18  E-value: 2.28e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7740 HLVLILELCSGP------ELLP-------CLAERASYSESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLK 7806
Cdd:cd05111    70 YIVRLLGICPGAslqlvtQLLPlgslldhVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQ 149

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7807 VVDLGNAQSL-SQEKVLPSDKFKDYLETMAPELLEGQGAVPQTDIWAIGVTAFIMLS--AEyPVSSEGARDLQRGLRKG 7882
Cdd:cd05111   150 VADFGVADLLyPDDKKYFYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTfgAE-PYAGMRLAEVPDLLEKG 227
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 5385-5466 2.31e-03

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 40.89  E-value: 2.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 5385 GSSITFSVKVEGRPVPTVHW------LREEAERGVLWIGPDTpgytvassaqqhsLVLLDVGRQHQGTYTCIASNAAGQA 5458
Cdd:cd04978    14 GETGELICEAEGNPQPTITWrlngvpIEPAPEDMRRTVDGRT-------------LIFSNLQPNDTAVYQCNASNVHGYL 80


                  ....*...
gi 215274225 5459 LCSASLHV 5466
Cdd:cd04978    81 LANAFLHV 88
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 1079-1148 2.31e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 40.64  E-value: 2.31e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  1079 SVHNEVQAEAGASAMLSCEVAQA--QTEVTWYKDGKKLSSSSKVgMEVKGCTRR--LVLPQAGKADAGEYSCEA 1148
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGspGPDVTWSKEGGTLIESLKV-KHDNGRTTQssLLISNVTKEDAGTYTCVV 73
IgI_VEGFR cd04976
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member ...
 7472-7540 2.33e-03

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409365  Cd Length: 90  Bit Score: 40.66  E-value: 2.33e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7472 ETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESssrvliSATLKNFQLLTILVVVAEDLGVYTCSVSN 7540
Cdd:cd04976    13 EATAGKRSVRLPMKVKAYPPPEVVWYKDGLPLTE------KARYLTRHSLIIKEVTEEDTGNYTILLSN 75
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 2830-2911 2.33e-03

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 40.63  E-value: 2.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2830 IKPLEDQWVAPGEDVELRCELsrAGTPVH---WLKDRKAIRKSQKYDVVCEGTmamLVIRGASLK-DAGEYTCEVEASK- 2904
Cdd:cd20958     4 IRPMGNLTAVAGQTLRLHCPV--AGYPISsitWEKDGRRLPLNHRQRVFPNGT---LVIENVQRSsDEGEYTCTARNQQg 78


                  ....*....
gi 215274225 2905 --STASLHV 2911
Cdd:cd20958    79 qsASRSVFV 87
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
 2838-2912 2.33e-03

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 40.78  E-value: 2.33e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 2838 VAPGEDVELRCELSRAGTP-VHWLKDRKAIRKSQKYDVVCEGTMAMLVIRGASLKDAGEYTCEVEASKSTASLHVE 2912
Cdd:cd20949    11 VKEGQSATILCEVKGEPQPnVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIASDMQE 86
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 2649-2731 2.38e-03

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 40.70  E-value: 2.38e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2649 FLKALDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQLgpsdKYDFLHT---AGTRGLVVHDVSPEDAGLYTC----HV 2720
Cdd:cd20976     4 FSSVPKDLEAVEGQDFVAQCSARgKPVPRITWIRNAQPL----QYAADRStceAGVGELHIQDVLPEDHGTYTClaknAA 79

                          90
                  ....*....|.
gi 215274225 2721 GSEETRARVRV 2731
Cdd:cd20976    80 GQVSCSAWVTV 90
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 7468-7544 2.41e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 40.46  E-value: 2.41e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 7468 ELSDETVVLGQSVTLACQVS-AQPAAQATWSKDGAPL-ESSSRVLIsatLKNFQLLtILVVVAEDLGVYTCSVSNALGT 7544
Cdd:cd05724     3 EPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLnLDNERVRI---VDDGNLL-IAEARKSDEGTYKCVATNMVGE 77
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 7463-7551 2.44e-03

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 40.80  E-value: 2.44e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLESSS--RVLISaTLKNFQLLTILVVVAEDLGVYTCSVSN 7540
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTlpGVQIS-FSDGRAKLSIPAVTKANSGRYSLTATN 79

                          90
                  ....*....|.
gi 215274225 7541 ALGTVTTTGVL 7551
Cdd:cd20974    80 GSGQATSTAEL 90
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
 6015-6094 2.50e-03

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 40.66  E-value: 2.50e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6015 DFEEELADCTAELGETVKLACRVTGTPKPVISWYKDGkavQVDPHHILIEDPDGScaLILDSLTGVDSGQYMCFAASAAG 6094
Cdd:cd05728     1 EWLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNG---QPLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHG 75
IgI_1_Titin-A168_like cd20971
First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and ...
 9-91 2.53e-03

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409563  Cd Length: 93  Bit Score: 40.92  E-value: 2.53e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    9 APRFLTRPKAFVVSVGKDATLSCQIVGNPTPQVSWEKDQQPVAAGARFRLA--QDGDLYRLTILDLALGDSGQYVCRARN 86
Cdd:cd20971     1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIqeFKGGYHQLIIASVTDDDATVYQVRATN 80


                  ....*
gi 215274225   87 AIGEA 91
Cdd:cd20971    81 QGGSV 85
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 2295-2370 2.53e-03

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 40.45  E-value: 2.53e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2295 PLRDKIAMEKHRGVLECQVSRA-SAQVRWFKGSQELQPGPKYELVSDGlyrKLIISDVHAEDEDTYTCDA----GDVKTS 2369
Cdd:cd20978     7 PEKNVVVKGGQDVTLPCQVTGVpQPKITWLHNGKPLQGPMERATVEDG---TLTIINVQPEDTGYYGCVAtneiGDIYTE 83


                  .
gi 215274225 2370 A 2370
Cdd:cd20978    84 T 84
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
 3538-3607 2.54e-03

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 40.52  E-value: 2.54e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 3538 ARFIEDVKNQEAREGATAVLQCELnSAAP---VEWRKGSETLR-DGDRYSLRQDGT-KCELQIRGLAMADTGEYS 3607
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQI-SAIPppqIFWKKNNEMLQyNTDRISLYQDNCgRICLLIQNANKKDAGWYT 74
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
 3893-3961 2.55e-03

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 40.51  E-value: 2.55e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3893 REPlQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGRrEPRLQGCTAELVLQDLQREDTGEYTC 3961
Cdd:cd04978     4 IEP-PSLVLSPGETGELICEAEgNPQPTITWRLNGVPIEPAPE-DMRRTVDGRTLIFSNLQPNDTAVYQC 71
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 3890-3974 2.58e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 40.87  E-value: 2.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3890 PVFREPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQ--ANGRR---EPRLQGCTaeLVLQDLQREDTGEYTCTC 3963
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDpsSIPGKykiESEYGVHV--LHIRRVTVEDSAVYSAVA 78

                          90
                  ....*....|....*
gi 215274225 3964 ----GSQATSATLTV 3974
Cdd:cd20951    79 knihGEASSSASVVV 93
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 1716-1799 2.68e-03

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 40.57  E-value: 2.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1716 PQISErPCRREPLVVKEHEDIILTATLATPSAATVTWLKDGVEIRR-SKRHETASQGDthTLTVHGAQVLDSAIYSCRV- 1793
Cdd:cd20970     1 PVIST-PQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGT--TLTIRNIRRSDMGIYLCIAs 77


                  ....*..
gi 215274225 1794 -GAEGQD 1799
Cdd:cd20970    78 nGVPGSV 84
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 2575-2628 2.69e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 40.01  E-value: 2.69e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 2575 ASFSCELS-HEDEEVEWSLNGMPLYNDSFHEISHKGRRHTLVLKSIQRADAGIVR 2628
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYT 55
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 3452-3533 2.74e-03

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 40.56  E-value: 2.74e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3452 FTEGLRNEEAVEGATAMLWC--ELSKVAPVEWRKGPENLRDGD-RYILRQEGTrceLQICGLAMADAGEYLCVC----GQ 3524
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCqaTGEPVPTISWLKDGVPLLGKDeRITTLENGS---LQIKGAEKSDTGEYTCVAlnlsGE 78


                  ....*....
gi 215274225 3525 ERTSATLTI 3533
Cdd:cd20952    79 ATWSAVLDV 87
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 4176-4231 2.83e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 40.01  E-value: 2.83e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 4176 VEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDGRiHTLRLKGVTPEDAGTVS 4231
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGN-GTLTISNVTLEDSGTYT 55
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 5277-5350 2.84e-03

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 40.57  E-value: 2.84e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 5277 LAKFQLKVKGYPAPRLYWFKDGQPLTASA--HIRMTDKKilhTLEIISVTREDSGQYAAYISNAMGAAYSSARLLV 5350
Cdd:cd20970    19 NATFMCRAEGSPEPEISWTRNGNLIIEFNtrYIVRENGT---TLTIRNIRRSDMGIYLCIASNGVPGSVEKRITLQ 91
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
 4898-4988 2.88e-03

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 40.80  E-value: 2.88e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4898 PMFSHTFGDTEAQVGDALRLECVVASKADVRARWLKDG--VELTDGRHHHIDqLGDGTCSLLITGLDRADAGCYTCQVSN 4975
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqvISTSTLPGVQIS-FSDGRAKLSIPAVTKANSGRYSLTATN 79

                          90
                  ....*....|...
gi 215274225 4976 KFGQVTHSACVVV 4988
Cdd:cd20974    80 GSGQATSTAELLV 92
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 2646-2718 2.93e-03

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 40.45  E-value: 2.93e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 2646 PVVFLKALDDLSAEERGTLALQCEVS-DPEAHVVWRKDGVQL-GPSDKYDFlhTAGTrgLVVHDVSPEDAGLYTC 2718
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTgVPQPKITWLHNGKPLqGPMERATV--EDGT--LTIINVQPEDTGYYGC 71
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
 1638-1700 3.01e-03

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 40.57  E-value: 3.01e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 1638 AEAGASATLSCEVA--QAQTEVTWYKDGKKL--SSSSKVRVEAVGCTRRLVVQQAGQAEAGEYSCEA 1700
Cdd:cd05750    11 VQEGSKLVLKCEATseNPSPRYRWFKDGKELnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVV 77
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
 7692-7857 3.02e-03

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 43.82  E-value: 3.02e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7692 KASGRALAAKIIPYHPKDKTAVLR---EYEALKGLRHPHLAQLHAAYLSPRHLVLILELC---SGPELLpclaeRASYS- 7764
Cdd:cd08216    22 KPTNTLVAVKKINLESDSKEDLKFlqqEILTSRQLQHPNILPYVTSFVVDNDLYVVTPLMaygSCRDLL-----KTHFPe 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7765 ---ESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIITEYNLLKVVDLGNAQSLSQE--KVLPSDKFKDY----LETMA 7835
Cdd:cd08216    97 glpELAIAFILRDVLNALEYIHSKGYIHRSVKASHILISGDGKVVLSGLRYAYSMVKHgkRQRVVHDFPKSseknLPWLS 176

                         170       180
                  ....*....|....*....|....
gi 215274225 7836 PELLEG--QGAVPQTDIWAIGVTA 7857
Cdd:cd08216   177 PEVLQQnlLGYNEKSDIYSVGITA 200
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 3101-3169 3.10e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 40.26  E-value: 3.10e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  3101 ELTDATITEGEDLTLVCETSTCD--IPVCWTKDGKTLRGSARCQLSHEGHR-AQLLITGATLQDSGRYKCEA 3169
Cdd:pfam00047    2 APPTVTVLEGDSATLTCSASTGSpgPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVV 73
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
 249-321 3.13e-03

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 40.61  E-value: 3.13e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  249 VTEGKHARLSCYVTGEPKPETVWKKDGQLVTEGRRHVVYEDAQENFVLKILFCKQSDRGLYTCTASNLVG---QTY 321
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGsinHTY 91
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1181-1240 3.14e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 40.26  E-value: 3.14e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 1181 GTTAMLSCEVA-QPQTEVTWYKDGKKLSSSSKVRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd20972    16 GSKVRLECRVTgNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
 6365-6436 3.20e-03

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 40.61  E-value: 3.20e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 6365 DVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQ-----EGTTYSLVLRH--VASKDAGVYTCLAQNTGG 6436
Cdd:cd07693     9 DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHrivlpSGSLFFLRVVHgrKGRSDEGVYVCVAHNSLG 87
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 3804-3886 3.33e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 40.48  E-value: 3.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3804 FIEDVKNQEAREGATAVLQCELS-KAAP-VEWRKGSETLRG---GDRYSLRQDGTRCELQIHGLSVADTGEYSCVC---- 3874
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQgKPDPeVKWYKNGVPIDPssiPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAknih 82

                          90
                  ....*....|..
gi 215274225 3875 GQERTSATLTVR 3886
Cdd:cd20951    83 GEASSSASVVVE 94
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 1995-2072 3.48e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 40.18  E-value: 3.48e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225   1995 EPQTVEERSSVTLEVELTRPW-PELRWTRNA-TALAPGKNVEIHAEGARHRLVLHNVGFADRGFFGCET----PDDKTQA 2068
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPpPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 215274225   2069 KLTV 2072
Cdd:smart00410   82 TLTV 85
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1639-1700 3.74e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 40.10  E-value: 3.74e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1639 EAGASATLSCEVA-QAQTEVTWYKDGKKLSSSS---KVRVEAVGCTRRLVVQQAGQAEAGEYSCEA 1700
Cdd:cd20951    13 WEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 2921-2998 3.77e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 39.87  E-value: 3.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  2921 ELTNLQVEEKGTAVFTCKTEH--PAATVTWRKGLLELRASGKHQPSQEGLT-LRLTISALEKADSDTYTCD----IGQAQ 2993
Cdd:pfam00047    2 APPTVTVLEGDSATLTCSASTgsPGPDVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCVvnnpGGSAT 81


                   ....*
gi 215274225  2994 SRAQL 2998
Cdd:pfam00047   82 LSTSL 86
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1346-1424 3.78e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 40.10  E-value: 3.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 1346 PKAVFAKEQlahrkvqaeagaiATLSCEVA-QAQTEVTWYKDGKKLSSSS---KVRMEAVGCTRRLVVQQACQADTGEYS 1421
Cdd:cd20951     9 SHTVWEKSD-------------AKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYS 75


                  ...
gi 215274225 1422 CEA 1424
Cdd:cd20951    76 AVA 78
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 2830-2911 3.78e-03

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 40.07  E-value: 3.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2830 IKPLEDQWVAPGEDVELRCELSraGTP---VHWLKDRKAIRKSqKYDVVCEGTmamLVIRGASLKDAGEYTCEVE----A 2902
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVG--GDPvptVRWRKEDGELPKG-RYEILDDHS---LKIRKVTAGDMGSYTCVAEnmvgK 74


                  ....*....
gi 215274225 2903 SKSTASLHV 2911
Cdd:cd05725    75 IEASATLTV 83
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 2835-2911 3.82e-03

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 40.17  E-value: 3.82e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2835 DQWVAPGEDVELRCelSRAGTPV---HWLKDRKAIR-KSQKYDVVCEGTmamLVIRGASLKDAGEYTCEVEASKSTASLH 2910
Cdd:cd20952     8 NQTVAVGGTVVLNC--QATGEPVptiSWLKDGVPLLgKDERITTLENGS---LQIKGAEKSDTGEYTCVALNLSGEATWS 82


                  .
gi 215274225 2911 V 2911
Cdd:cd20952    83 A 83
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
 736-777 3.89e-03

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 39.88  E-value: 3.89e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 215274225  736 AVTWLKDGRTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYE 777
Cdd:cd05748    23 TVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYT 64
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 5286-5348 3.96e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 39.87  E-value: 3.96e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 215274225  5286 GYPAPRLYWFKDGQPLTASAHI-RMTDKKILHTLEIISVTREDSGQYAAYISNAMGAAYSSARL 5348
Cdd:pfam00047   23 GSPGPDVTWSKEGGTLIESLKVkHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 2484-2553 3.96e-03

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 39.69  E-value: 3.96e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225  2484 QSVVLSCDF-RPAPKAVQWYKDDTPLSPSEKFKmslegqmaelrILRLMPADAGVYRCQAGSAH-----SSTEVTV 2553
Cdd:pfam13895   15 EPVTLTCSApGNPPPSYTWYKDGSAISSSPNFF-----------TLSVSAEDSGTYTCVARNGRggkvsNPVELTV 79
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
 4252-4336 4.17e-03

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 40.07  E-value: 4.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 4252 ILEPLQDVQLSEGQDASFQCRLSRASGQEARWALGGVPLQANeMNDITVEQGTLHLLTLHKvtlEDAGT-----VSFHvG 4326
Cdd:cd20978     4 IQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGP-MERATVEDGTLTIINVQP---EDTGYygcvaTNEI-G 78

                          90
                  ....*....|
gi 215274225 4327 TCSSEAQLKV 4336
Cdd:cd20978    79 DIYTETLLHV 88
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
 1716-1791 4.21e-03

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 40.10  E-value: 4.21e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1716 PQISERPcrrEPLVVKEHEDIILTATLATPSAATVTWLKDGVEIRRSK---RHETASQGDTHTLTVHGAQVLDSAIYSC 1791
Cdd:cd20951     1 PEFIIRL---QSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSA 76
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
 6365-6446 4.31e-03

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409388  Cd Length: 84  Bit Score: 39.87  E-value: 4.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6365 DVQAQTGGTAQFEAIIEGDPQPSVTWYKDSVQLVDSTRLSQQQEgttYSLVLRHVASKDAGVYTCLAQNTGGQVLCKAEL 6444
Cdd:cd05723     6 NIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKE---HNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82


                  ..
gi 215274225 6445 LV 6446
Cdd:cd05723    83 II 84
IgI_1_Palladin_C cd05893
First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
 7463-7551 4.46e-03

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409474  Cd Length: 92  Bit Score: 40.08  E-value: 4.46e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7463 PTFLRELSDETVVLGQSVTLACQVSAQPAAQATWSKDGAPLE-SSSRVLISATLKNFQLLTILVVVAEDLGVYTCSVSNA 7541
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISpKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|
gi 215274225 7542 LGTVTTTGVL 7551
Cdd:cd05893    81 QGRISCTGRL 90
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 6122-6199 4.61e-03

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 40.24  E-value: 4.61e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6122 GEDAQFTCTIEGAPYPQIRWYKDGALLTTGNKFQTLSEP-RSGLLV--LVIRAASKEDLGLYECELVNRLGSARASAELR 6198
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVtSDGDVVsyVNISSVRVEDGGEYTCTATNDVGSVSHSARIN 95


                  .
gi 215274225 6199 I 6199
Cdd:cd20956    96 V 96
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
 1176-1240 4.73e-03

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 39.80  E-value: 4.73e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 1176 VQAEAGTTAMLSCEV-AQPQTEVTWYKDGKKLSSSSKvRMEVKGCTRRLVVQQVGKADAGEYSCEA 1240
Cdd:cd20970    12 VTAREGENATFMCRAeGSPEPEISWTRNGNLIIEFNT-RYIVRENGTTLTIRNIRRSDMGIYLCIA 76
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 898-964 4.78e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 39.87  E-value: 4.78e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 215274225  898 RKLQAEAGASATLSCEVAQAQT-EVTWYKDGKKLSSSSKVCMEATGCTRRLVVQQAGQADAGEYSCEA 964
Cdd:cd20972     9 RSQEVAEGSKVRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 3633-3697 4.96e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 39.87  E-value: 4.96e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  3633 RNEEATEGATAVLRCELS---KMAPVEWWKGHETLRDGDRHSLRQDG-ARCELQIRGLVAEDAGEYLCM 3697
Cdd:pfam00047    4 PTVTVLEGDSATLTCSAStgsPGPDVTWSKEGGTLIESLKVKHDNGRtTQSSLLISNVTKEDAGTYTCV 72
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
 3809-3873 5.15e-03

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 39.49  E-value: 5.15e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  3809 KNQEAREGATAVLQCELSKAAP---VEWRKGSETLRGGDRYSLRQDGTR-CELQIHGLSVADTGEYSCV 3873
Cdd:pfam00047    4 PTVTVLEGDSATLTCSASTGSPgpdVTWSKEGGTLIESLKVKHDNGRTTqSSLLISNVTKEDAGTYTCV 72
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 1640-1711 5.19e-03

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 39.86  E-value: 5.19e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1640 AGASATLSCEVAQAQ-TEVTWYKDGKKLSSSSKVRVEAVGcTrrLVVQQAGQAE-AGEYSCEAGGQQ-----LSFRLQV 1711
Cdd:cd20958    14 AGQTLRLHCPVAGYPiSSITWEKDGRRLPLNHRQRVFPNG-T--LVIENVQRSSdEGEYTCTARNQQgqsasRSVFVKV 89
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3467-3521 5.31e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 39.23  E-value: 5.31e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3467 AMLWCELS--KVAPVEWRKGPENLRDGDRYILRQEGTRCELQICGLAMADAGEYLCV 3521
Cdd:cd00096     1 VTLTCSASgnPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 1358-1430 5.32e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 39.69  E-value: 5.32e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225 1358 RKVQAEAGAIATLSCE--VAQAQTEVTWYKDGKKL-SSSSKVRMEAVGctrRLVVQQACQADTGEYSCEAG---GQRLS 1430
Cdd:cd05724     5 SDTQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLnLDNERVRIVDDG---NLLIAEARKSDEGTYKCVATnmvGERES 80
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
 6012-6105 5.45e-03

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 39.53  E-value: 5.45e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 6012 RPPdfeeelADCTAELGETVKLACRVTGTPKPVISWYKDGKAVQVDPHHILIEdpdgSCALILDSLTGVDSGQYMCFAAS 6091
Cdd:cd20968     4 RPP------TNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLE----SGSLRIHNVQKEDAGQYRCVAKN 73

                          90
                  ....*....|....*
gi 215274225 6092 AAGNC-STLGKILVQ 6105
Cdd:cd20968    74 SLGIAySKPVTIEVE 88
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 714-792 6.07e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 39.41  E-value: 6.07e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225    714 REVLARLHEEAQLLAELSDQAAA-VTWLKDG-RTLSPGPKYEVQASAGRRVLLVRDVARDDAGLYECVSRGGRIAYQLSV 791
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPeVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    .
gi 215274225    792 Q 792
Cdd:smart00410   82 T 82
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
 3809-3885 6.24e-03

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 39.30  E-value: 6.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3809 KNQEAREGATAVLQCELSKAAP--VEWRKGSETLRGGdRYSLRQDGTrceLQIHGLSVADTGEYSCVC----GQERTSAT 3882
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVptVRWRKEDGELPKG-RYEILDDHS---LKIRKVTAGDMGSYTCVAenmvGKIEASAT 80


                  ...
gi 215274225 3883 LTV 3885
Cdd:cd05725    81 LTV 83
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
 4170-4244 6.36e-03

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 39.44  E-value: 6.36e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 215274225 4170 VTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEVTEVAVRDgrihTLRLKGVTPEDAGTVSFHLGNHASSAQLT 4244
Cdd:cd20957    13 VDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED----VLVIPSVKREDKGMYQCFVRNDGDSAQAT 83
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 3184-3269 6.59e-03

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 39.54  E-value: 6.59e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3184 PVRFQEALKDLEVLEGGAATLRCVLSSVAAP-VKWCY-GNNVLRPGDKYSLrqEGAMLELVVRNLRPQDSGRYSC----S 3257
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPrITWIRnAQPLQYAADRSTC--EAGVGELHIQDVLPEDHGTYTClaknA 78

                          90
                  ....*....|..
gi 215274225 3258 FGDQTTSATLTV 3269
Cdd:cd20976    79 AGQVSCSAWVTV 90
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 337-404 6.61e-03

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 39.48  E-value: 6.61e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  337 KRLQDLEVREKESATFLCEV---PQPstEAAWFKEETRLWASAKYGIEEEGTER-RLTVRNVSADDDAVYIC 404
Cdd:cd20973     2 QTLRDKEVVEGSAARFDCKVegyPDP--EVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTC 71
PKc_DYRK cd14210
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
 7774-7854 7.20e-03

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.


Pssm-ID: 271112 [Multi-domain]  Cd Length: 311  Bit Score: 42.53  E-value: 7.20e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7774 QMLSATQYLHNQHILHLDLRSENMIITEYNL--LKVVDLGNAqSLSQEKVLpsdkfkDYLET---MAPELLEGQGAVPQT 7848
Cdd:cd14210   124 QILQALQFLHKLNIIHCDLKPENILLKQPSKssIKVIDFGSS-CFEGEKVY------TYIQSrfyRAPEVILGLPYDTAI 196


                  ....*.
gi 215274225 7849 DIWAIG 7854
Cdd:cd14210   197 DMWSLG 202
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
 2826-2912 7.26e-03

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 39.54  E-value: 7.26e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 2826 PAAIIKPLEDQWVAPGEDVELRCELSraGTPV---HWLKDRKAIRKSQKYdVVCEGTMAMLVIRGASLKDAGEYTCEVEA 2902
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSAR--GKPVpriTWIRNAQPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKN 77

                          90
                  ....*....|
gi 215274225 2903 SKSTASLHVE 2912
Cdd:cd20976    78 AAGQVSCSAW 87
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 4157-4229 7.37e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 39.09  E-value: 7.37e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 215274225  4157 PEVTIVRGLVdaEVTADEDVEFSCEVSRAGATGVQWCLQGLPLQSNEvTEVAVRDGRIHTLRLKGVTPEDAGT 4229
Cdd:pfam13927    2 PVITVSPSSV--TVREGETVTLTCEATGSPPPTITWYKNGEPISSGS-TRSRSLSGSNSTLTISNVTRSDAGT 71
STKc_CK2_alpha cd14132
Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the ...
 7678-7866 7.40e-03

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271034 [Multi-domain]  Cd Length: 306  Bit Score: 42.53  E-value: 7.40e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7678 IQRGRFSVVRQCWEKASGRALAAKIIpyHPKDKTAVLREYEALKGLR-HPHLAQLHAAYLSP--RHLVLILEL--CSGP- 7751
Cdd:cd14132    26 IGRGKYSEVFEGINIGNNEKVVIKVL--KPVKKKKIKREIKILQNLRgGPNIVKLLDVVKDPqsKTPSLIFEYvnNTDFk 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 7752 ELLPCLaerasySESEVKDYLWQMLSATQYLHNQHILHLDLRSENMIIT-EYNLLKVVDLGNAqslsqEKVLP------- 7823
Cdd:cd14132   104 TLYPTL------TDYDIRYYMYELLKALDYCHSKGIMHRDVKPHNIMIDhEKRKLRLIDWGLA-----EFYHPgqeynvr 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 215274225 7824 --SDKFKdyletmAPELLEG-QGAVPQTDIWAIGVTAFIMLSAEYP 7866
Cdd:cd14132   173 vaSRYYK------GPELLVDyQYYDYSLDMWSLGCMLASMIFRKEP 212
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
 3893-3974 7.96e-03

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 39.09  E-value: 7.96e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225 3893 REPLQSLQAEEGSTATLQCELS-EPTATVVWSKGGLQLQANGR-----REPRLqgCTaeLVLQDLQREDTGEYTC----T 3962
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEgYPDPEVKWMKDDNPIVESRRfqidqDEDGL--CS--LIISDVCGDDSGKYTCkavnS 76

                          90
                  ....*....|..
gi 215274225 3963 CGSQATSATLTV 3974
Cdd:cd20973    77 LGEATCSAELTV 88
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
 5286-5350 8.12e-03

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 39.02  E-value: 8.12e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 215274225 5286 GYPAPRLYWFKDGQPL-TASAHIRMTDkkiLHTLEIISVTREDSGQYAAYISNAMGAAYSSARLLV 5350
Cdd:cd20952    25 GEPVPTISWLKDGVPLlGKDERITTLE---NGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 6382-6436 8.18e-03

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 38.92  E-value: 8.18e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 215274225  6382 GDPQPSVTWYKdsvqlvDSTRLSQQQEGTTYSLVLRhvaskDAGVYTCLAQNTGG 6436
Cdd:pfam13895   25 GNPPPSYTWYK------DGSAISSSPNFFTLSVSAE-----DSGTYTCVARNGRG 68
I-set pfam07679
Immunoglobulin I-set domain;
4342-4427 9.17e-03

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 39.16  E-value: 9.17e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 215274225  4342 VVRGLENVEALEGGEALFECQLS---QPEVaahTWLLDDEPVHTSEnaEVVFFENGLRHLLLLKNLRPQDS----CRVTF 4414
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTgtpDPEV---SWFKDGQPLRSSD--RFKVTYEGGTYTLTISNVQPDDSgkytCVATN 77

                           90
                   ....*....|...
gi 215274225  4415 LAGDMVTSAFLTV 4427
Cdd:pfam07679   78 SAGEAEASAELTV 90
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
 1181-1248 9.21e-03

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 38.53  E-value: 9.21e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 215274225  1181 GTTAMLSCEV-AQPQTEVTWYKDGKKLSSSskvrmevkgctRRLVVQQVGKADAGEYSCEAGGQRVSFQ 1248
Cdd:pfam13895   14 GEPVTLTCSApGNPPPSYTWYKDGSAISSS-----------PNFFTLSVSAEDSGTYTCVARNGRGGKV 71
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
 3291-3345 9.30e-03

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 38.46  E-value: 9.30e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 215274225 3291 ATLRCELS--KAAPVEWRKGSETLRDGDRYCLRQDGAMCELQIRGLAMVDAAEYSCV 3345
Cdd:cd00096     1 VTLTCSASgnPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
 1089-1148 9.76e-03

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 39.10  E-value: 9.76e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 215274225 1089 GASAMLSCEVAQAQT-EVTWYKDGKKLSSSSKVGMEVKGCTRRLVLPQAGKADAGEYSCEA 1148
Cdd:cd20972    16 GSKVRLECRVTGNPTpVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLA 76
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 2738-2806 9.90e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 38.70  E-value: 9.90e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 215274225  2738 ITKRLKTMEVLEGESCSFECvlshESASDPA---MWTVGGKTVGSSSRFQATRQGRKYILVVREAAPSDAGE 2806
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTC----EATGSPPptiTWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGT 71
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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