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Conserved domains on  [gi|1937920432|ref|NP_112323|]
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muscle, skeletal receptor tyrosine protein kinase precursor [Rattus norvegicus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
568-857 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk 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: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 616.46  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05050     1 EYPRNNIEYVRDIGQGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCAVG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDlsTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05050    81 KPMCLLFEYMAYGDLNEFLRHRSPRAQCSLSHST--SSARKCGLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLAT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05050   159 RNCLVGENMVVKIADFGLSRNIYSADYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAH 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05050   239 EEVIYYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQR 288
CRD_TK_ROR_related cd07469
Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors; The ...
313-457 1.18e-80

Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors; The cysteine-rich domain (CRD) is an essential part of the tyrosine kinase-like orphan receptor (Ror) proteins, a conserved family of tyrosine kinases that function in various processes, including neuronal and skeletal development, cell polarity, and cell movement. Ror proteins are receptors of Wnt proteins, which are key players in a number of fundamental cellular processes in embryogenesis and postnatal development. In different cellular contexts, Ror proteins can either activate or repress transcription of Wnt target genes, and can modulate Wnt signaling by sequestering Wnt ligands.


:

Pssm-ID: 143578  Cd Length: 147  Bit Score: 256.18  E-value: 1.18e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 313 SKGYCAQYRGEVCDAVLVKDSLVFFNTSYPDPEEAQELLIHTAWNEL-KAVSPLCRPAAEALLCNHLFQECS-SGVLPTP 390
Cdd:cd07469     1 SAGYCATYRGEVCRAYLSNDALVWFNSSYADPEGLNEQLTTGLWEELiKTVSELCRPAAEKLLCNYAFPECHpSGVGPTP 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 391 MPICREYCLAVKELFCAKEWLAMEGKTHRGLYRSGMHFLPVPECSKLPSMHQDPTACTRLPYLDYKK 457
Cdd:cd07469    81 KPLCREDCLAVKELFCYKDWALIEENKQRGIYLKSRGHFTLPECESLPSIHADPPACSHIPLTDLKK 147
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
122-209 5.86e-55

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: 184.37  E-value: 5.86e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 122 KITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYS 201
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

                  ....*...
gi 1937920432 202 KLVKLEVE 209
Cdd:cd20968    81 KPVTIEVE 88
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
28-117 5.50e-42

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: 148.04  E-value: 5.50e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPL--ETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGV 105
Cdd:cd20970     1 PVISTPQpsFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80
                          90
                  ....*....|..
gi 1937920432 106 GGAVESCGALQV 117
Cdd:cd20970    81 PGSVEKRITLQV 92
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
213-296 1.84e-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: 58.04  E-value: 1.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 213 RILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIqenVKDRVIDSRLQLFITK-----PGLYTCIATNK 287
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNvqpddSGKYTCVATNS 78

                  ....*....
gi 1937920432 288 HGEKFSTAK 296
Cdd:pfam07679  79 AGEAEASAE 87
 
Name Accession Description Interval E-value
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
568-857 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk 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: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 616.46  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05050     1 EYPRNNIEYVRDIGQGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCAVG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDlsTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05050    81 KPMCLLFEYMAYGDLNEFLRHRSPRAQCSLSHST--SSARKCGLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLAT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05050   159 RNCLVGENMVVKIADFGLSRNIYSADYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAH 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05050   239 EEVIYYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQR 288
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
574-855 9.30e-133

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: 396.87  E-value: 9.30e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGLlPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGE-GENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIV 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:pfam07714  80 TEYMPGGDLLDFLRKH-----------------------KRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVS 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:pfam07714 137 ENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEF 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:pfam07714 217 LEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
574-855 1.15e-129

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: 388.83  E-value: 1.15e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  574 IEYVRDIGEGAFGRVFQARAPGLLPYEPfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKGDGKE-VEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  654 FEYMAYGDLNEFLRSMSPHTvcsLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:smart00221  80 MEYMPGGDLLDYLRKNRPKE---LSLSDL-------------------LSFALQIARGMEYLESKNFIHRDLAARNCLVG 137
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  734 ENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:smart00221 138 ENLVVKISDFGLSRDLYDDDYYKVKGGK-LPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEY 216
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1937920432  814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:smart00221 217 LKKGYRLPKPPNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
CRD_TK_ROR_related cd07469
Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors; The ...
313-457 1.18e-80

Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors; The cysteine-rich domain (CRD) is an essential part of the tyrosine kinase-like orphan receptor (Ror) proteins, a conserved family of tyrosine kinases that function in various processes, including neuronal and skeletal development, cell polarity, and cell movement. Ror proteins are receptors of Wnt proteins, which are key players in a number of fundamental cellular processes in embryogenesis and postnatal development. In different cellular contexts, Ror proteins can either activate or repress transcription of Wnt target genes, and can modulate Wnt signaling by sequestering Wnt ligands.


Pssm-ID: 143578  Cd Length: 147  Bit Score: 256.18  E-value: 1.18e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 313 SKGYCAQYRGEVCDAVLVKDSLVFFNTSYPDPEEAQELLIHTAWNEL-KAVSPLCRPAAEALLCNHLFQECS-SGVLPTP 390
Cdd:cd07469     1 SAGYCATYRGEVCRAYLSNDALVWFNSSYADPEGLNEQLTTGLWEELiKTVSELCRPAAEKLLCNYAFPECHpSGVGPTP 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 391 MPICREYCLAVKELFCAKEWLAMEGKTHRGLYRSGMHFLPVPECSKLPSMHQDPTACTRLPYLDYKK 457
Cdd:cd07469    81 KPLCREDCLAVKELFCYKDWALIEENKQRGIYLKSRGHFTLPECESLPSIHADPPACSHIPLTDLKK 147
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
122-209 5.86e-55

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: 184.37  E-value: 5.86e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 122 KITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYS 201
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

                  ....*...
gi 1937920432 202 KLVKLEVE 209
Cdd:cd20968    81 KPVTIEVE 88
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
28-117 5.50e-42

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: 148.04  E-value: 5.50e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPL--ETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGV 105
Cdd:cd20970     1 PVISTPQpsFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80
                          90
                  ....*....|..
gi 1937920432 106 GGAVESCGALQV 117
Cdd:cd20970    81 PGSVEKRITLQV 92
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
577-847 1.41e-31

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 129.75  E-value: 1.41e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:COG0515    12 LRLLGRGGMGVVYLARDLRLGRP-----VALKVLRPELAADpeARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVM 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsphtvcslshsdlstrarvssPGPPPLscAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:COG0515    87 EYVEGESLADLLRR----------------------RGPLPP--AEALRILAQLAEALAAAHAAGIVHRDIKPANILLTP 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYV 814
Cdd:COG0515   143 DGRVKLIDFGIARAL-GGATLTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAH 220
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 815 RDGNILACPE---NCPLELYNLMRLCWSKLPADRPS 847
Cdd:COG0515   221 LREPPPPPSElrpDLPPALDAIVLRALAKDPEERYQ 256
I-set pfam07679
Immunoglobulin I-set domain;
121-208 8.68e-28

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 107.34  E-value: 8.68e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAG 80
                          90
                  ....*....|.
gi 1937920432 198 TAYSKlVKLEV 208
Cdd:pfam07679  81 EAEAS-AELTV 90
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
573-797 1.72e-18

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 88.01  E-value: 1.72e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGllpyEPFTMVavkmLKeeasADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:PHA03209   67 GYTVIKTLTPGSEGRVFVATKPG----QPDPVV----LK----IGQKGTTLIEAMLLQNVNHPSVIRMKDTLVSGAITCM 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFeymaygdlneflrsmsPHTVCSLsHSDLSTRARvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:PHA03209  135 VL----------------PHYSSDL-YTYLTKRSR-------PLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFI 190
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 733 GENMVVKIADFGLSR-NIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSY 797
Cdd:PHA03209  191 NDVDQVCIGDLGAAQfPVVAPAFLGLAGT----VETNAPEVLARDKYNSKADIWSAGIVLFEMLAY 252
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
127-208 2.96e-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: 74.46  E-value: 2.96e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIK-GDSALRENSRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLGTAYSK 202
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*.
gi 1937920432  203 lVKLEV 208
Cdd:smart00410  81 -TTLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
28-103 9.30e-16

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 72.98  E-value: 9.30e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTRN-KILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANN 103
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNgEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
317-440 1.08e-13

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.


Pssm-ID: 460190  Cd Length: 116  Bit Score: 68.36  E-value: 1.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 317 CAQYRGEVCDavlvkdSLVFFNTSYP------DPEEAQELLIHTAWNELKAVSPL-CRPAAEALLCNHLFQECS-SGVLP 388
Cdd:pfam01392   1 CEPITLPMCL------GLGYNATVFPnllghqTQEEAELSLAYLVLSEFEPLVDLsCSPSLRLFLCSLYFPPCTlGPSPK 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 389 TPMPICREYCLAVKElFCAKEWLAMEgkthrglyrSGMHFLPVPECSKLPSM 440
Cdd:pfam01392  75 PVCPPCRSLCEEVRY-GCEPLLEEAK---------FGFSWPEFLDCDSLPAD 116
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
605-747 5.10e-13

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 72.52  E-value: 5.10e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVkllGVCAVGK----P---McllfEYMAYGDLNEFLRSmsphtvc 675
Cdd:NF033483   35 VAVKVLRPDLARDpeFVARFRREAQSAASLSHPNIV---SVYDVGEdggiPyivM----EYVDGRTLKDYIRE------- 100
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 676 slsHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSR 747
Cdd:NF033483  101 ---HGPLSPEEAVE--------------IMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIAR 155
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
35-106 7.93e-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: 61.75  E-value: 7.93e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432   35 ETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQL--LTILSVEDSDDGIYCCTANNGVG 106
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSG 75
I-set pfam07679
Immunoglobulin I-set domain;
213-296 1.84e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 58.04  E-value: 1.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 213 RILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIqenVKDRVIDSRLQLFITK-----PGLYTCIATNK 287
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNvqpddSGKYTCVATNS 78

                  ....*....
gi 1937920432 288 HGEKFSTAK 296
Cdd:pfam07679  79 AGEAEASAE 87
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
218-296 2.47e-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: 57.79  E-value: 2.47e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTF--GSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKdrviDSRLQLFITKP---GLYTCIATNKHGEKF 292
Cdd:cd20978     6 KPEKNVVVkgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE----DGTLTIINVQPedtGYYGCVATNEIGDIY 81

                  ....
gi 1937920432 293 STAK 296
Cdd:cd20978    82 TETL 85
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
218-296 6.43e-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: 50.58  E-value: 6.43e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSiqENVKDRVIDSRLQLFITKP-----GLYTCIATNKHGEKF 292
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAES--GRFSVSRSGSTSTLTISNVtpedsGTYTCAATNSSGSAS 78

                   ....
gi 1937920432  293 STAK 296
Cdd:smart00410  79 SGTT 82
 
Name Accession Description Interval E-value
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
568-857 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk 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: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 616.46  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05050     1 EYPRNNIEYVRDIGQGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCAVG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDlsTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05050    81 KPMCLLFEYMAYGDLNEFLRHRSPRAQCSLSHST--SSARKCGLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLAT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05050   159 RNCLVGENMVVKIADFGLSRNIYSADYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAH 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05050   239 EEVIYYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQR 288
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
580-856 2.31e-134

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: 401.15  E-value: 2.31e-134
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd00192     3 LGEGAFGEVYKGKLKGGD--GKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSmsphtvcslshsdlsTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd00192    81 GDLLDFLRK---------------SRPVFPSPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVK 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd00192   146 ISDFGLSRDIYDDDYYRKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYR 225
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1937920432 820 LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd00192   226 LPKPENCPDELYELMLSCWQLDPEDRPTFSELVERLE 262
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
574-855 9.30e-133

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: 396.87  E-value: 9.30e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGLlPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGE-GENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIV 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:pfam07714  80 TEYMPGGDLLDFLRKH-----------------------KRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVS 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:pfam07714 137 ENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEF 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:pfam07714 217 LEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTFSELVEDL 258
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
568-856 1.12e-130

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. 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. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror 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: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 392.51  E-value: 1.12e-130
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05048     1 EIPLSAVRFLEELGEGAFGKVYKGELLGPSSEESAISVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKE 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTRArvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05048    81 QPQCMLFEYMAHGDLHEFLVRHSPHSDVGVSSDDDGTAS--------SLDQSDFLHIAIQIAAGMEYLSSHHYVHRDLAA 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05048   153 RNCLVGDGLTVKISDFGLSRDIYSSDYYRVQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSN 232
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05048   233 QEVIEMIRSRQLLPCPEDCPARVYSLMVECWHEIPSRRPRFKEIHTRLR 281
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
574-855 1.15e-129

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: 388.83  E-value: 1.15e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  574 IEYVRDIGEGAFGRVFQARAPGLLPYEPfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKGDGKE-VEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  654 FEYMAYGDLNEFLRSMSPHTvcsLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:smart00221  80 MEYMPGGDLLDYLRKNRPKE---LSLSDL-------------------LSFALQIARGMEYLESKNFIHRDLAARNCLVG 137
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  734 ENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:smart00221 138 ENLVVKISDFGLSRDLYDDDYYKVKGGK-LPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEY 216
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1937920432  814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:smart00221 217 LKKGYRLPKPPNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
574-855 2.32e-128

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 385.35  E-value: 2.32e-128
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  574 IEYVRDIGEGAFGRVFQARAPGLLPYEPfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGKGGKKK-VEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  654 FEYMAYGDLNEFLRSMSPHtvcsLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:smart00219  80 MEYMEGGDLLSYLRKNRPK----LSLSDL-------------------LSFALQIARGMEYLESKNFIHRDLAARNCLVG 136
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  734 ENMVVKIADFGLSRNIYSADYYKADGnDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:smart00219 137 ENLVVKISDFGLSRDLYDDDYYRKRG-GKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEY 215
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1937920432  814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:smart00219 216 LKNGYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSELVEIL 257
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
568-856 1.63e-120

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk 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: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 366.02  E-value: 1.63e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05049     1 HIKRDTIVLKRELGEGAFGKVFLGECYNLEPEQDKMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCTEG 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVcSLSHSDlstrarvSSPGPppLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05049    81 DPLLMVFEYMEHGDLNKFLRSHGPDAA-FLASED-------SAPGE--LTLSQLLHIAVQIASGMVYLASQHFVHRDLAT 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05049   151 RNCLVGTNLVVKIGDFGMSRDIYSTDYYRVGGHTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSN 230
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05049   231 TEVIECITQGRLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIHKRLQ 279
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
568-857 4.42e-105

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily 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: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 325.84  E-value: 4.42e-105
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05032     2 ELPREKITLIRELGQGSFGMVYEGLAKGVVKGEPETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVSTG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstraRVSSPGPPPLSCAEQLCIarQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05032    82 QPTLVVMELMAKGDLKSYLRSRRPEAE------------NNPGLGPPTLQKFIQMAA--EIADGMAYLAAKKFVHRDLAA 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05032   148 RNCMVAEDLTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSN 227
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05032   228 EEVLKFVIDGGHLDLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLKD 277
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
568-857 1.13e-104

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR 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: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 325.45  E-value: 1.13e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPY-----------EPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPN 636
Cdd:cd05051     1 EFPREKLEFVEKLGEGQFGEVHLCEANGLSDLtsddfigndnkDEPVLVAVKMLRPDASKNAREDFLKEVKIMSQLKDPN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 637 IVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSlshsdlstrarvSSPGPPPLSCAEQLCIARQVAAGMAYLS 716
Cdd:cd05051    81 IVRLLGVCTRDEPLCMIVEYMENGDLNQFLQKHEAETQGA------------SATNSKTLSYGTLLYMATQIASGMKYLE 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 717 ERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd05051   149 SLNFVHRDLATRNCLVGPNYTIKIADFGMSRNLYSGDYYRIEGRAVLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILT 228
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 797 YG-LQPYYGMAHEEVI-----YYVRDGN--ILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05051   229 LCkEQPYEHLTDEQVIenageFFRDDGMevYLSRPPNCPKEIYELMLECWRRDEEDRPTFREIHLFLQR 297
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
571-857 9.65e-104

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA 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: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 322.30  E-value: 9.65e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEeASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd05092     4 RRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKE-ATESARQDFQREAELLTVLQHQHIVRFYGVCTEGEPL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPhtvcslshsDLSTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05092    83 IMVFEYMRHGDLNRFLRSHGP---------DAKILDGGEGQAPGQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNC 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEV 810
Cdd:cd05092   154 LVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEA 233
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 811 IYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05092   234 IECITQGRELERPRTCPPEVYAIMQGCWQREPQQRHSIKDIHSRLQA 280
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
580-856 1.87e-95

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, 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. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros 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: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 300.10  E-value: 1.87e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLL-PYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd05044     3 LGSGAFGEVFEGTAKDILgDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILELME 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRSmsphtvcslshsdlstrARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN--- 735
Cdd:cd05044    83 GGDLLSYLRA-----------------ARPTAFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKdyr 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 -MVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYV 814
Cdd:cd05044   146 eRVVKIGDFGLARDIYKNDYYRKEGEGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFV 225
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 815 RDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05044   226 RAGGRLDQPDNCPDDLYELMLRCWSTDPEERPSFARILEQLQ 267
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
571-860 2.99e-95

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB 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: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 300.42  E-value: 2.99e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEeASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd05093     4 RHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKD-ASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarVSSPGPPP--LSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd05093    83 IMVFEYMKHGDLNKFLRAHGPDAV-------------LMAEGNRPaeLTQSQMLHIAQQIAAGMVYLASQHFVHRDLATR 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05093   150 NCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNN 229
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 809 EVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd05093   230 EVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAK 281
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
568-852 2.14e-94

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. 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 Ror1 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: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 298.08  E-value: 2.14e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARA--PGLlpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCA 645
Cdd:cd05090     1 ELPLSAVRFMEELGECAFGKIYKGHLylPGM---DHAQLVAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGVVT 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 VGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTrarVSSPgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd05090    78 QEQPVCMLFEFMNQGDLHEFLIMRSPHSDVGCSSDEDGT---VKSS----LDHGDFLHIAIQIAAGMEYLSSHFFVHKDL 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGM 805
Cdd:cd05090   151 AARNILVGEQLHVKISDLGLSREIYSSDYYRVQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGF 230
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 806 AHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIH 852
Cdd:cd05090   231 SNQEVIEMVRKRQLLPCSEDCPPRMYSLMTECWQEIPSRRPRFKDIH 277
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
568-858 6.40e-91

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR 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: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 289.32  E-value: 6.40e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGVCA 645
Cdd:cd05053     8 ELPRDRLTLGKPLGEGAFGQVVKAEAVGLDNKPNEVVtVAVKMLKDDATEKDLSDLVSEMEMMKMIgKHKNIINLLGACT 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 VGKPMCLLFEYMAYGDLNEFLRSMSP-HTVCSLSHSDLSTrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRD 724
Cdd:cd05053    88 QDGPLYVVVEYASKGNLREFLRARRPpGEEASPDDPRVPE---------EQLTQKDLVSFAYQVARGMEYLASKKCIHRD 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYG 804
Cdd:cd05053   159 LAARNVLVTEDNVMKIADFGLARDIHHIDYYRKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPG 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 805 MAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05053   239 IPVEELFKLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRI 292
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
574-856 3.33e-90

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: 286.91  E-value: 3.33e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd05091     8 VRFMEELGEDRFGKVYKGHLFGTAPGEQTQAVAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTKEQPMSMI 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTRArvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd05091    88 FSYCSHGDLHEFLVMRSPHSDVGSTDDDKTVKS--------TLEPADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVF 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:cd05091   160 DKLNVKISDLGLFREVYAADYYKLMGNSLLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEM 239
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05091   240 IRNRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRLR 282
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
568-851 2.50e-89

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK 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: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 284.28  E-value: 2.50e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLlPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAV 646
Cdd:cd05036     2 EVPRKNLTLIRALGQGAFGEVYEGTVSGM-PGDPSPLqVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvssPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05036    81 RLPRFILLELMAGGDLKSFLRENRPRP-----------------EQPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIA 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLV---GENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYY 803
Cdd:cd05036   144 ARNCLLtckGPGRVAKIGDFGMARDIYRADYYRKGGKAMLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYP 223
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 804 GMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05036   224 GKSNQEVMEFVTSGGRMDPPKNCPGPVYRIMTQCWQHIPEDRPNFSTI 271
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
571-858 9.12e-89

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC 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: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 283.44  E-value: 9.12e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASAdMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd05094     4 RRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVKTLKDPTLA-ARKDFQREAELLTNLQHDHIVKFYGVCGDGDPL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTRARvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05094    83 IMVFEYMKHGDLNKFLRAHGPDAMILVDGQPRQAKGE--------LGLSQMLHIATQIASGMVYLASQHFVHRDLATRNC 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEV 810
Cdd:cd05094   155 LVGANLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEV 234
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 811 IYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05094   235 IECITQGRVLERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHAL 282
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
568-856 1.09e-87

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR 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: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 280.32  E-value: 1.09e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05061     2 EVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarvSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05061    82 QPTLVVMELMAHGDLKSYLRSLRPEAE--------------NNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAA 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05061   148 RNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSN 227
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05061   228 EQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLK 276
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
569-851 1.93e-85

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 273.96  E-value: 1.93e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 569 YPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd05046     2 FPRSNLQEITTLGRGEFGEVFLAKAKGIEEEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCREAE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLRsmsphtvcslshsdlSTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd05046    82 PHYMILEYTDLGDLKQFLR---------------ATKSKDEKLKPPPLSTKQKVALCTQIALGMDHLSNARFVHRDLAAR 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIYSADYYKADgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05046   147 NCLVSSQREVKVSLLSLSKDVYNSEYYKLR-NALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDE 225
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 809 EVIYYVRDGNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05046   226 EVLNRLQAGKLeLPVPEGCPSRLYKLMTRCWAVNPKDRPSFSEL 269
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
572-858 1.17e-83

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR 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: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 268.86  E-value: 1.17e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARApgLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd05033     4 SYVTIEKVIGGGEFGEVCSGSL--KLPGKKEIDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVTKSRPVM 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSmsphtvcslshsdlsTRARVSspgppplscAEQLC-IARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05033    82 IVTEYMENGSLDKFLRE---------------NDGKFT---------VTQLVgMLRGIASGMKYLSEMNYVHRDLAARNI 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSAD--YYKADGNdaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05033   138 LVNSDLVCKVSDFGLSRRLEDSEatYTTKGGK--IPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQ 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 809 EVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05033   216 DVIKAVEDGYRLPPPMDCPSALYQLMLDCWQKDRNERPTFSQIVSTLDKM 265
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
568-856 2.24e-83

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 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 (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 269.17  E-value: 2.24e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGL------------LPYEPfTMVAVKMLKEEASADMQADFQREAALMAEFDNP 635
Cdd:cd05095     1 EFPRKLLTFKEKLGEGQFGEVHLCEAEGMekfmdkdfalevSENQP-VLVAVKMLRADANKNARNDFLKEIKIMSRLKDP 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 636 NIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTvcslshsdlstrARVSSPGPPPLSCAEQLCIARQVAAGMAYL 715
Cdd:cd05095    80 NIIRLLAVCITDDPLCMITEYMENGDLNQFLSRQQPEG------------QLALPSNALTVSYSDLRFMAAQIASGMKYL 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 716 SERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIF 795
Cdd:cd05095   148 SSLNFVHRDLATRNCLVGKNYTIKIADFGMSRNLYSGDYYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETL 227
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 796 SYGL-QPYYGMAHEEVI----YYVRDGN---ILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05095   228 TFCReQPYSQLSDEQVIentgEFFRDQGrqtYLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHTLLQ 296
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
568-855 4.94e-83

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-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: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 268.38  E-value: 4.94e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPY--EPFT-------MVAVKMLKEEASADMQADFQREAALMAEFDNPNIV 638
Cdd:cd05097     1 EFPRQQLRLKEKLGEGQFGEVHLCEAEGLAEFlgEGAPefdgqpvLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNII 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 639 KLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTvcSLSHSDlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSER 718
Cdd:cd05097    81 RLLGVCVSDDPLCMITEYMENGDLNQFLSQREIES--TFTHAN----------NIPSVSIANLLYMAVQIASGMKYLASL 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 719 KFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSY- 797
Cdd:cd05097   149 NFVHRDLATRNCLVGNHYTIKIADFGMSRNLYSGDYYRIQGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLc 228
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 798 GLQPYYGMAHEEVI----YYVRDGN---ILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05097   229 KEQPYSLLSDEQVIentgEFFRNQGrqiYLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
568-858 1.12e-80

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 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: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 262.59  E-value: 1.12e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTM--VAVKMLKEEASADMQADFQREAALMAEFD-NPNIVKLLGVC 644
Cdd:cd05099     8 EFPRDRLVLGKPLGEGCFGQVVRAEAYGIDKSRPDQTvtVAVKMLKDNATDKDLADLISEMELMKLIGkHKNIINLLGVC 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 AVGKPMCLLFEYMAYGDLNEFLRSMSPHTvcslshSDLSTRARVSSPGPppLSCAEQLCIARQVAAGMAYLSERKFVHRD 724
Cdd:cd05099    88 TQEGPLYVIVEYAAKGNLREFLRARRPPG------PDYTFDITKVPEEQ--LSFKDLVSCAYQVARGMEYLESRRCIHRD 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYG 804
Cdd:cd05099   160 LAARNVLVTEDNVMKIADFGLARGVHDIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPG 239
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 805 MAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05099   240 IPVEELFKLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKV 293
CRD_TK_ROR_related cd07469
Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors; The ...
313-457 1.18e-80

Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors; The cysteine-rich domain (CRD) is an essential part of the tyrosine kinase-like orphan receptor (Ror) proteins, a conserved family of tyrosine kinases that function in various processes, including neuronal and skeletal development, cell polarity, and cell movement. Ror proteins are receptors of Wnt proteins, which are key players in a number of fundamental cellular processes in embryogenesis and postnatal development. In different cellular contexts, Ror proteins can either activate or repress transcription of Wnt target genes, and can modulate Wnt signaling by sequestering Wnt ligands.


Pssm-ID: 143578  Cd Length: 147  Bit Score: 256.18  E-value: 1.18e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 313 SKGYCAQYRGEVCDAVLVKDSLVFFNTSYPDPEEAQELLIHTAWNEL-KAVSPLCRPAAEALLCNHLFQECS-SGVLPTP 390
Cdd:cd07469     1 SAGYCATYRGEVCRAYLSNDALVWFNSSYADPEGLNEQLTTGLWEELiKTVSELCRPAAEKLLCNYAFPECHpSGVGPTP 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 391 MPICREYCLAVKELFCAKEWLAMEGKTHRGLYRSGMHFLPVPECSKLPSMHQDPTACTRLPYLDYKK 457
Cdd:cd07469    81 KPLCREDCLAVKELFCYKDWALIEENKQRGIYLKSRGHFTLPECESLPSIHADPPACSHIPLTDLKK 147
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
568-855 2.08e-80

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 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: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 261.79  E-value: 2.08e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVF--QARAPGLLPYE--PFTM-------VAVKMLKEEASADMQADFQREAALMAEFDNPN 636
Cdd:cd05096     1 KFPRGHLLFKEKLGEGQFGEVHlcEVVNPQDLPTLqfPFNVrkgrpllVAVKILRPDANKNARNDFLKEVKILSRLKDPN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 637 IVKLLGVCAVGKPMCLLFEYMAYGDLNEFLrsmsphtvcslSHSDLSTRARVSSPGPPPLSC------AEQLCIARQVAA 710
Cdd:cd05096    81 IIRLLGVCVDEDPLCMITEYMENGDLNQFL-----------SSHHLDDKEENGNDAVPPAHClpaisySSLLHVALQIAS 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 711 GMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVV 790
Cdd:cd05096   150 GMKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLYAGDYYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVT 229
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 791 LWEIFSY-GLQPYYGMAHEEVI----YYVRDGN---ILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05096   230 LWEILMLcKEQPYGELTDEQVIenagEFFRDQGrqvYLFRPPPCPQGLYELMLQCWSRDCRERPSFSDIHAFL 302
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
568-851 4.04e-80

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R 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: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 259.97  E-value: 4.04e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05062     2 EVAREKITMSRELGQGSFGMVYEGIAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSlshsdlstrarvSSPGPPPLSCAEQLciARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05062    82 QPTLVIMELMTRGDLKSYLRSLRPEMENN------------PVQAPPSLKKMIQM--AGEIADGMAYLNANKFVHRDLAA 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05062   148 RNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSN 227
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05062   228 EQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEI 271
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
568-858 1.09e-78

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR 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: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 257.03  E-value: 1.09e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDN-PNIVKLLGVCAV 646
Cdd:cd05055    31 EFPRNNLSFGKTLGAGAFGKVVEATAYGLSKSDAVMKVAVKMLKPTAHSSEREALMSELKIMSHLGNhENIVNLLGACTI 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSMSphtvcslsHSDLSTRarvsspgppplscaEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05055   111 GGPILVITEYCCYGDLLNFLRRKR--------ESFLTLE--------------DLLSFSYQVAKGMAFLASKNCIHRDLA 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05055   169 ARNVLLTHGKIVKICDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMP 248
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 807 HEEVIY-YVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05055   249 VDSKFYkLIKEGYRMAQPEHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIGKQ 301
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
578-856 5.04e-78

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. 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, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases 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 tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 253.14  E-value: 5.04e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARapgllpYEPFTM-VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05041     1 EKIGRGNFGDVYRGV------LKPDNTeVAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMEL 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05041    75 VPGGSLLTFLRKKGAR-----------------------LTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENN 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRD 816
Cdd:cd05041   132 VLKISDFGMSREEEDGEYTVSDGLKQIPIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIES 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 817 GNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05041   212 GYRMPAPELCPEAVYRLMLQCWAYDPENRPSFSEIYNELQ 251
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
578-855 6.35e-78

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They 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). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-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: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 252.97  E-value: 6.35e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGLLPyepftmVAVKMLKEeasADMQ-ADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05034     1 KKLGAGQFGEVWMGVWNGTTK------VAVKTLKP---GTMSpEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTEL 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05034    72 MSKGSLLDYLRTGEGRA----------------------LRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENN 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRD 816
Cdd:cd05034   130 VCKVADFGLARLI-EDDEYTAREGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVER 208
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 817 GNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05034   209 GYRMPKPPGCPDELYDIMLQCWKKEPEERPTFEYLQSFL 247
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
578-857 9.08e-77

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: 249.96  E-value: 9.08e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARApgLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVGKPMCLLFEYM 657
Cdd:cd05060     1 KELGHGNFGSVRKGVY--LMKSGKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGVC-KGEPLMLVMELA 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRsmsphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd05060    78 PLGPLLKYLK------------------------KRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQ 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGLSRNI-YSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRD 816
Cdd:cd05060   134 AKISDFGMSRALgAGSDYYRATTAGRWPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLES 213
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 817 GNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05060   214 GERLPRPEECPQEIYSIMLSCWKYRPEDRPTFSELESTFRR 254
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
568-856 1.11e-76

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: 250.42  E-value: 1.11e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARApgLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVg 647
Cdd:cd05056     2 EIQREDITLGRCIGEGQFGDVYQGVY--MSPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITE- 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPhtvcSLSHSDLstrarvsspgpppLSCAEQLCIArqvaagMAYLSERKFVHRDLAT 727
Cdd:cd05056    79 NPVWIVMELAPLGELRSYLQVNKY----SLDLASL-------------ILYAYQLSTA------LAYLESKRFVHRDIAA 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05056   136 RNVLVSSPDCVKLGDFGLSRYMEDESYYKAS-KGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKN 214
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF----CSIHRILQ 856
Cdd:cd05056   215 NDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSKRPRFtelkAQLSDILQ 267
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
568-848 2.91e-76

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: 249.25  E-value: 2.91e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQarapGLlpYEPFTMVAVKMLKeeaSADMQ-ADFQREAALMAEFDNPNIVKLLGVCAV 646
Cdd:cd05068     4 EIDRKSLKLLRKLGSGQFGEVWE----GL--WNNTTPVAVKTLK---PGTMDpEDFLREAQIMKKLRHPKLIQLYAVCTL 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstRARVsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05068    75 EEPIYIITELMKHGSLLEYLQG----------------KGRS-------LQLPQLIDMAAQVASGMAYLESQNYIHRDLA 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05068   132 ARNVLVGENNICKVADFGLARVIKVEDEYEAREGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMT 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 807 HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05068   212 NAEVLQQVERGYRMPCPPNCPPQLYDIMLECWKADPMERPTF 253
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
573-858 3.38e-76

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET 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: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 249.88  E-value: 3.38e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd05045     1 NLVLGKTLGEGEFGKVVKATAFRLKGRAGYTTVAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRsMSPHTVCSLSHSDLS-TRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd05045    81 IVEYAKYGSLRSFLR-ESRKVGPSYLGSDGNrNSSYLDNPDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVL 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVI 811
Cdd:cd05045   160 VAEGRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLF 239
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 812 YYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05045   240 NLLKTGYRMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKM 286
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
568-858 3.90e-74

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl 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: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 243.48  E-value: 3.90e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARapgllpYEPFTM-VAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAV 646
Cdd:cd05052     2 EIERTDITMKHKLGGGQYGEVYEGV------WKKYNLtVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTR 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarvsspgpPPLSCaeqLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05052    74 EPPFYIITEFMPYGNLLDYLRECNREEL-------------------NAVVL---LYMATQIASAMEYLEKKNFIHRDLA 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05052   132 ARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGID 210
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 807 HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05052   211 LSQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPSDRPSFAEIHQALETM 262
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
569-857 6.47e-73

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: 240.75  E-value: 6.47e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 569 YPRNNIEYVRDIGEGAFGRVFQARapgllpYEP-----FTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGV 643
Cdd:cd05038     1 FEERHLKFIKQLGEGHFGSVELCR------YDPlgdntGEQVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGV 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 C--AVGKPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlsTRARVSSPgppplscaEQLCIARQVAAGMAYLSERKFV 721
Cdd:cd05038    75 CesPGRRSLRLIMEYLPSGSLRDYLQR---------------HRDQIDLK--------RLLLFASQICKGMEYLGSQRYI 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNI-YSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYG-- 798
Cdd:cd05038   132 HRDLAARNILVESEDLVKISDFGLAKVLpEDKEYYYVKEPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGdp 211
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 799 -LQP-----------YYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05038   212 sQSPpalflrmigiaQGQMIVTRLLELLKSGERLPRPPSCPDEVYDLMKECWEYEPQDRPSFSDLILIIDR 282
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
570-857 4.09e-72

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: 237.63  E-value: 4.09e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASADMQadFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd05039     4 NKKDLKLGELIGKGEFGDVMLGDYRG-------QKVAVKCLKDDSTAAQA--FLAEASVMTTLRHPNLVQLLGVVLEGNG 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstRARVSspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05039    75 LYIVTEYMAKGSLVDYLRS----------------RGRAV------ITRKDQLGFALDVCEGMEYLESKKFVHRDLAARN 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRniySADYYKADGNdaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEE 809
Cdd:cd05039   133 VLVSEDNVAKVSDFGLAK---EASSNQDGGK--LPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKD 207
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 810 VIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd05039   208 VVPHVEKGYRMEAPEGCPPEVYKVMKNCWELDPAKRPTFKQLREKLEH 255
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
568-858 6.08e-72

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R 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: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 241.29  E-value: 6.08e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDN-PNIVKLLGVCAV 646
Cdd:cd05106    34 EFPRDNLQFGKTLGAGAFGKVVEATAFGLGKEDNVLRVAVKMLKASAHTDEREALMSELKILSHLGQhKNIVNLLGACTH 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRS---------MSPHTV--------------------------CSLSHSDL---STRARV 688
Cdd:cd05106   114 GGPVLVITEYCCYGDLLNFLRKkaetflnfvMALPEIsetssdyknitlekkyirsdsgfssqGSDTYVEMrpvSSSSSQ 193
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 689 SS--------PGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGN 760
Cdd:cd05106   194 SSdskdeedtEDSWPLDLDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDIMNDSNYVVKGN 273
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 761 DAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIY-YVRDGNILACPENCPLELYNLMRLCWS 839
Cdd:cd05106   274 ARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILVNSKFYkMVKRGYQMSRPDFAPPEIYSIMKMCWN 353
                         330
                  ....*....|....*....
gi 1937920432 840 KLPADRPSFCSIHRILQRM 858
Cdd:cd05106   354 LEPTERPTFSQISQLIQRQ 372
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
580-856 1.17e-71

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: 236.37  E-value: 1.17e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyePFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd05084     4 IGRGNFGEVFSGRLRA-----DNTPVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd05084    79 GDFLTFLRTEGPR-----------------------LKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLK 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd05084   136 ISDFGMSREEEDGVYAATGGMKQIPVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVR 215
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1937920432 820 LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05084   216 LPCPENCPDEVYRLMEQCWEYDPRKRPSFSTVHQDLQ 252
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
568-855 1.23e-71

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR 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: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 237.77  E-value: 1.23e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQAdfqreaALMAEF-------DNPNIVKL 640
Cdd:cd05054     3 EFPRDRLKLGKPLGRGAFGKVIQASAFGIDKSATCRTVAVKMLKEGATASEHK------ALMTELkilihigHHLNVVNL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 641 LGVCAV-GKPMCLLFEYMAYGDLNEFLRSMSPHTVC--SLSHSDLSTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSE 717
Cdd:cd05054    77 LGACTKpGGPLMVIVEFCKFGNLSNYLRSKREEFVPyrDKGARDVEEEEDDDELYKEPLTLEDLICYSFQVARGMEFLAS 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 718 RKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSY 797
Cdd:cd05054   157 RKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSL 236
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 798 GLQPYYGMA-HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05054   237 GASPYPGVQmDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSELVEKL 295
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
568-858 9.47e-71

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 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: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 236.06  E-value: 9.47e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGL---LPYEPFTmVAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGV 643
Cdd:cd05101    20 EFPRDKLTLGKPLGEGCFGQVVMAEAVGIdkdKPKEAVT-VAVKMLKDDATEKDLSDLVSEMEMMKMIgKHKNIINLLGA 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 CAVGKPMCLLFEYMAYGDLNEFLRSMSPhtvCSLSHS-DLstrARVSSPgppPLSCAEQLCIARQVAAGMAYLSERKFVH 722
Cdd:cd05101    99 CTQDGPLYVIVEYASKGNLREYLRARRP---PGMEYSyDI---NRVPEE---QMTFKDLVSCTYQLARGMEYLASQKCIH 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 723 RDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPY 802
Cdd:cd05101   170 RDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPY 249
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 803 YGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05101   250 PGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 305
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
568-858 2.99e-70

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 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: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 234.52  E-value: 2.99e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEP--FTMVAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGVC 644
Cdd:cd05098     9 ELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPnrVTKVAVKMLKSDATEKDLSDLISEMEMMKMIgKHKNIINLLGAC 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 AVGKPMCLLFEYMAYGDLNEFLRSMSPHtvcSLSHSdlstrarvSSPGPPP---LSCAEQLCIARQVAAGMAYLSERKFV 721
Cdd:cd05098    89 TQDGPLYVIVEYASKGNLREYLQARRPP---GMEYC--------YNPSHNPeeqLSSKDLVSCAYQVARGMEYLASKKCI 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQP 801
Cdd:cd05098   158 HRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSP 237
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 802 YYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05098   238 YPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 294
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
568-852 1.16e-69

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: 231.17  E-value: 1.16e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPyepftmVAVKMLKEEaSADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05148     2 ERPREEFTLERKLGSGYFGEVWEGLWKNRVR------VAIKILKSD-DLLKQQDFQKEVQALKRLRHKHLISLFAVCSVG 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstrarvssPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05148    75 EPVYIITELMEKGSLLAFLRS----------------------PEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAA 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRnIYSADYYKADgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05148   133 RNILVGEDLVCKVADFGLAR-LIKEDVYLSS-DKKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNN 210
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIH 852
Cdd:cd05148   211 HEVYDQITAGYRMPCPAKCPQEIYKIMLECWAAEPEDRPSFKALR 255
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
576-848 1.28e-69

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: 230.80  E-value: 1.28e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVRDIGEGAFGRVFQARAPGLLPyepftmVAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd05059     8 FLKELGSGQFGVVHLGKWRGKID------VAIKMIKEGSMS--EDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTE 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSMsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd05059    80 YMANGCLLNYLRER-----------------------RGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQ 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSaDYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVR 815
Cdd:cd05059   137 NVVKVSDFGLARYVLD-DEYTSSVGTKFPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHIS 215
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1937920432 816 DGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05059   216 QGYRLYRPHLAPTEVYTIMYSCWHEKPEERPTF 248
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
568-858 2.34e-69

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 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: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 232.99  E-value: 2.34e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGL---LPYEPFTmVAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGV 643
Cdd:cd05100     8 ELSRTRLTLGKPLGEGCFGQVVMAEAIGIdkdKPNKPVT-VAVKMLKDDATDKDLSDLVSEMEMMKMIgKHKNIINLLGA 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 CAVGKPMCLLFEYMAYGDLNEFLRSMSP------HTVCSLSHSDLSTRARVSSpgppplscaeqlciARQVAAGMAYLSE 717
Cdd:cd05100    87 CTQDGPLYVLVEYASKGNLREYLRARRPpgmdysFDTCKLPEEQLTFKDLVSC--------------AYQVARGMEYLAS 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 718 RKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSY 797
Cdd:cd05100   153 QKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTL 232
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 798 GLQPYYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05100   233 GGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRV 293
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
578-848 5.36e-69

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 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: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 230.19  E-value: 5.36e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQArapgLLPYE--PFTMVAVKMLKEE--ASADMQaDFQREAALMAEFDNPNIVKLLGVC----AVGK- 648
Cdd:cd05074    15 RMLGKGEFGSVREA----QLKSEdgSFQKVAVKMLKADifSSSDIE-EFLREAACMKEFDHPNVIKLIGVSlrsrAKGRl 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 --PMCLLfEYMAYGDLNEFLrsmsphtvcslshsdLSTRArvsspGPPPLSCAEQLCIARQV--AAGMAYLSERKFVHRD 724
Cdd:cd05074    90 piPMVIL-PFMKHGDLHTFL---------------LMSRI-----GEEPFTLPLQTLVRFMIdiASGMEYLSSKNFIHRD 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYG 804
Cdd:cd05074   149 LAARNCMLNENMTVCVADFGLSKKIYSGDYYRQGCASKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAG 228
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 805 MAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05074   229 VENSEIYNYLIKGNRLKQPPDCLEDVYELMCQCWSPEPKCRPSF 272
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
580-855 9.46e-69

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: 228.19  E-value: 9.46e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEA-SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd13999     1 IGSGSFGEVYKGKWRG-------TDVAIKKLKVEDdNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMP 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRSMSPHtvcslshsdLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVV 738
Cdd:cd13999    74 GGSLYDLLHKKKIP---------LSWSLRLK--------------IALDIARGMNYLHSPPIIHRDLKSLNILLDENFTV 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 739 KIADFGLSRNIYSadyyKADGNDAIP--IRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRD 816
Cdd:cd13999   131 KIADFGLSRIKNS----TTEKMTGVVgtPRWMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAVVQ 205
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 817 GNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd13999   206 KGLrPPIPPDCPPELSKLIKRCWNEDPEKRPSFSEIVKRL 245
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
572-858 2.25e-68

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA 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: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 227.83  E-value: 2.25e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd05066     4 SCIKIEKVIGAGEFGEVCSGRLK--LPGKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPVM 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSMSPH-TVCSLshsdlstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05066    82 IVTEYMENGSLDAFLRKHDGQfTVIQL------------------------VGMLRGIASGMKYLSDMGYVHRDLAARNI 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIY---SADYYKADGNdaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05066   138 LVNSNLVCKVSDFGLSRVLEddpEAAYTTRGGK--IPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSN 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05066   216 QDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQKDRNERPKFEQIVSILDKL 266
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
568-855 3.86e-68

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 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: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 229.87  E-value: 3.86e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNP-NIVKLLGVCAV 646
Cdd:cd05102     3 EFPRDRLRLGKVLGHGAFGKVVEASAFGIDKSSSCETVAVKMLKEGATASEHKALMSELKILIHIGNHlNVVNLLGACTK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GK-PMCLLFEYMAYGDLNEFLRSM----------SP-------------------HTVCSLSHSDLSTRARVSSPGP--- 693
Cdd:cd05102    83 PNgPLMVIVEFCKYGNLSNFLRAKregfspyrerSPrtrsqvrsmveavradrrsRQGSDRVASFTESTSSTNQPRQevd 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 694 ----PPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMP 769
Cdd:cd05102   163 dlwqSPLTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGSARLPLKWMA 242
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 770 PESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA-HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05102   243 PESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQiNEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERPTF 322

                  ....*..
gi 1937920432 849 CSIHRIL 855
Cdd:cd05102   323 SDLVEIL 329
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
578-858 6.72e-68

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM 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: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 227.03  E-value: 6.72e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARapglLPYEPFTM--VAVKMLKEEASADMQ-ADFQREAALMAEFDNPNIVKLLGVCAVG------- 647
Cdd:cd05035     5 KILGEGEFGSVMEAQ----LKQDDGSQlkVAVKTMKVDIHTYSEiEEFLSEAACMKDFDHPNVMRLIGVCFTAsdlnkpp 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLfEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05035    81 SPMVIL-PFMKHGDLHSYLLYSRLGG------------------LPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAA 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05035   142 RNCMLDENMTVCVADFGLSRKIYSGDYYRQGRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVEN 221
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05035   222 HEIYDYLRNGNRLKQPEDCLDEVYFLMYFCWTVDPKDRPTFTKLREVLENI 272
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
580-855 2.89e-67

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. 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, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases 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. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 224.50  E-value: 2.89e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQarapGLLPYEpfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd05085     4 LGKGNFGEVYK----GTLKDK--TPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSmsphtvcslSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd05085    78 GDFLSFLRK---------KKDELKTKQLVK--------------FSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALK 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNiYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd05085   135 ISDFGMSRQ-EDDGVYSSSGLKQIPIKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYR 213
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 820 LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05085   214 MSAPQRCPEDIYKIMQRCWDYNPENRPKFSELQKEL 249
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
571-860 4.83e-67

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer 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: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 224.81  E-value: 4.83e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQarapGLLPYEPFT--MVAVKMLKEEASADMQ-ADFQREAALMAEFDNPNIVKLLGVC--- 644
Cdd:cd14204     6 RNLLSLGKVLGEGEFGSVME----GELQQPDGTnhKVAVKTMKLDNFSQREiEEFLSEAACMKDFNHPNVIRLLGVClev 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 ---AVGKPMCLLfEYMAYGDLNEFLrsmsphtvcslshsdLSTRARvSSPGPPPLSCAEQLCIarQVAAGMAYLSERKFV 721
Cdd:cd14204    82 gsqRIPKPMVIL-PFMKYGDLHSFL---------------LRSRLG-SGPQHVPLQTLLKFMI--DIALGMEYLSSRNFL 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQP 801
Cdd:cd14204   143 HRDLAARNCMLRDDMTVCVADFGLSKKIYSGDYYRQGRIAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTP 222
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 802 YYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd14204   223 YPGVQNHEIYDYLLHGHRLKQPEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLEKLLE 281
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
578-860 5.76e-65

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl 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: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 219.11  E-value: 5.76e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQarapGLLPYEPFTM-VAVKMLKEE--ASADMQaDFQREAALMAEFDNPNIVKLLGVCAVG------- 647
Cdd:cd05075     6 KTLGEGEFGSVME----GQLNQDDSVLkVAVKTMKIAicTRSEME-DFLSEAVCMKEFDHPNVMRLIGVCLQNtesegyp 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLfEYMAYGDLNEFLrsmsphtvcslshsdLSTRArvsspGPPPLSCAEQLCIA--RQVAAGMAYLSERKFVHRDL 725
Cdd:cd05075    81 SPVVIL-PFMKHGDLHSFL---------------LYSRL-----GDCPVYLPTQMLVKfmTDIASGMEYLSSKNFIHRDL 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGM 805
Cdd:cd05075   140 AARNCMLNENMNVCVADFGLSKKIYNGDYYRQGRISKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGV 219
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 806 AHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd05075   220 ENSEIYDYLRQGNRLKQPPDCLDGLYELMSSCWLLNPKDRPSFETLRCELEKILK 274
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
580-860 3.60e-64

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie 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: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 216.83  E-value: 3.60e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapglLPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd05047     3 IGEGNFGQVLKAR----IKKDGLRMdAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRS---MSPHTVCSLSHSDLSTrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd05047    79 PHGNLLDFLRKsrvLETDPAFAIANSTAST-----------LSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGE 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRniySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYV 814
Cdd:cd05047   148 NYVAKIADFGLSR---GQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKL 224
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 815 RDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd05047   225 PQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLE 270
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
568-858 6.84e-64

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit 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: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 219.39  E-value: 6.84e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADmqadfQREAaLMAEF-------DNPNIVKL 640
Cdd:cd05104    31 EFPRDRLRFGKTLGAGAFGKVVEATAYGLAKADSAMTVAVKMLKPSAHST-----EREA-LMSELkvlsylgNHINIVNL 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 641 LGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSlSHSDLSTRARVSS-------------------PGP----PP-- 695
Cdd:cd05104   105 LGACTVGGPTLVITEYCCYGDLLNFLRRKRDSFICP-KFEDLAEAALYRNllhqremacdslneymdmkPSVsyvvPTka 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 696 ---------------------------LSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRN 748
Cdd:cd05104   184 dkrrgvrsgsyvdqdvtseileedelaLDTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARD 263
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 749 IYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIY-YVRDGNILACPENCP 827
Cdd:cd05104   264 IRNDSNYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPVDSKFYkMIKEGYRMDSPEFAP 343
                         330       340       350
                  ....*....|....*....|....*....|..
gi 1937920432 828 LELYNLMRLCWSKLPADRPSFCSI-HRILQRM 858
Cdd:cd05104   344 SEMYDIMRSCWDADPLKRPTFKQIvQLIEQQL 375
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
574-859 2.26e-63

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: 214.59  E-value: 2.26e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQA--RAPGllpyEPFTM-VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVGKPM 650
Cdd:cd05057     9 LEKGKVLGSGAFGTVYKGvwIPEG----EKVKIpVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGIC-LSSQV 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSmsphtvcslshsdlsTRARVSSpgppplscAEQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05057    84 QLITQLMPLGCLLDYVRN---------------HRDNIGS--------QLLLNWCVQIAKGMSYLEEKRLVHRDLAARNV 140
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYS-ADYYKADGNdAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEE 809
Cdd:cd05057   141 LVKTPNHVKITDFGLAKLLDVdEKEYHAEGG-KVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVE 219
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 810 VIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMC 859
Cdd:cd05057   220 IPDLLEKGERLPQPPICTIDVYMVLVKCWMIDAESRPTFKELANEFSKMA 269
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
572-848 3.95e-63

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: 213.27  E-value: 3.95e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapgllpYEPFTMVAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd05112     4 SELTFVQEIGSGQFGLVHLGY------WLNKDKVAIKTIREGAMS--EEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPIC 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSmsphtvcslSHSDLSTRARVsspgppplscaeQLCIarQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd05112    76 LVFEFMEHGCLSDYLRT---------QRGLFSAETLL------------GMCL--DVCEGMAYLEEASVIHRDLAARNCL 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVI 811
Cdd:cd05112   133 VGENQVVKVSDFGMTRFVLDDQYTSSTGTK-FPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVV 211
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1937920432 812 YYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05112   212 EDINAGFRLYKPRLASTHVYEIMNHCWKERPEDRPSF 248
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
579-851 6.06e-63

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: 212.90  E-value: 6.06e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 579 DIGEGAFGRVFQARAPGLLPYEPftmVAVKMLKEEAS-ADMQADFQREAALMAEFDNPNIVKLLGVCAvGKPMCLLFEYM 657
Cdd:cd05116     2 ELGSGNFGTVKKGYYQMKKVVKT---VAVKILKNEANdPALKDELLREANVMQQLDNPYIVRMIGICE-AESWMLVMEMA 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFL---RSMSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd05116    78 ELGPLNKFLqknRHVTEKNITELVH---------------------------QVSMGMKYLEESNFVHRDLAARNVLLVT 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYS-ADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY 813
Cdd:cd05116   131 QHYAKISDFGLSKALRAdENYYKAQTHGKWPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQM 210
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05116   211 IEKGERMECPAGCPPEMYDLMKLCWTYDVDERPGFAAV 248
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
580-851 2.42e-62

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: 211.05  E-value: 2.42e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPG--LLPyepftmVAVKMLKEEASADMQA--DFQREAALMAEFDNPNIVKLLGVcAVGKPMCLL 653
Cdd:cd05040     3 LGDGSFGVVRRGewTTPSgkVIQ------VAVKCLKSDVLSQPNAmdDFLKEVNAMHSLDHPNLIRLYGV-VLSSPLMMV 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgppPLScaeQLC-IARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd05040    76 TELAPLGSLLDRLRKDQGHF---------------------LIS---TLCdYAVQIANGMAYLESKRFIHRDLAARNILL 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRNIYSA-DYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVI 811
Cdd:cd05040   132 ASKDKVKIGDFGLMRALPQNeDHYVMQEHRKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQIL 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 812 YYV-RDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05040   212 EKIdKEGERLERPDDCPQDIYNVMLQCWAHKPADRPTFVAL 252
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
568-851 3.49e-62

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 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: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 213.71  E-value: 3.49e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADmqadfqREAALMAEFD-------NPNIVKL 640
Cdd:cd14207     3 EFARERLKLGKSLGRGAFGKVVQASAFGIKKSPTCRVVAVKMLKEGATAS------EYKALMTELKilihighHLNVVNL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 641 LGVCA-VGKPMCLLFEYMAYGDLNEFLRS----MSPHTVCSLSH-------------------SDLSTRARVSSPG---- 692
Cdd:cd14207    77 LGACTkSGGPLMVIVEYCKYGNLSNYLKSkrdfFVTNKDTSLQEelikekkeaeptggkkkrlESVTSSESFASSGfqed 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 693 -----------------PPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYY 755
Cdd:cd14207   157 kslsdveeeeedsgdfyKRPLTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDY 236
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 756 KADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA-HEEVIYYVRDGNILACPENCPLELYNLM 834
Cdd:cd14207   237 VRKGDARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQiDEDFCSKLKEGIRMRAPEFATSEIYQIM 316
                         330
                  ....*....|....*..
gi 1937920432 835 RLCWSKLPADRPSFCSI 851
Cdd:cd14207   317 LDCWQGDPNERPRFSEL 333
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
572-858 4.27e-62

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 210.99  E-value: 4.27e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQarapGLL--PYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd05063     5 SHITKQKVIGAGEFGEVFR----GILkmPGRKEVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKP 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSmsphtvcslSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05063    81 AMIITEYMENGALDKYLRD---------HDGEFSSYQLVG--------------MLRGIAAGMKYLSDMNYVHRDLAARN 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIY---SADYYKADGNdaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05063   138 ILVNSNLECKVSDFGLSRVLEddpEGTYTTSGGK--IPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMS 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 807 HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05063   216 NHEVMKAINDGFRLPAPMDCPSAVYQLMLQCWQQDRARRPRFVDIVNLLDKL 267
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
574-858 2.91e-61

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB 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: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 208.57  E-value: 2.91e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVrdIGEGAFGRVFQARAPglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd05065     8 IEEV--IGAGEFGEVCRGRLK--LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPVMII 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMSPH-TVCSLshsdlstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd05065    84 TEFMENGALDSFLRQNDGQfTVIQL------------------------VGMLRGIAAGMKYLSEMNYVHRDLAARNILV 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSR---NIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEE 809
Cdd:cd05065   140 NSNLVCKVSDFGLSRfleDDTSDPTYTSSLGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQD 219
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 810 VIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05065   220 VINAIEQDYRLPPPMDCPTALHQLMLDCWQKDRNLRPKFGQIVNTLDKM 268
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
568-848 5.24e-61

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 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: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 210.61  E-value: 5.24e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADmqadfqREAALMAEFD-------NPNIVKL 640
Cdd:cd05103     3 EFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHS------EHRALMSELKilihighHLNVVNL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 641 LGVCAV-GKPMCLLFEYMAYGDLNEFLRS----------------MSPHTVCSLShSDLSTRA-RVSSPGPP-------- 694
Cdd:cd05103    77 LGACTKpGGPLMVIVEFCKFGNLSAYLRSkrsefvpyktkgarfrQGKDYVGDIS-VDLKRRLdSITSSQSSassgfvee 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 695 -------------------PLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYY 755
Cdd:cd05103   156 kslsdveeeeagqedlykdFLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDY 235
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 756 KADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA-HEEVIYYVRDGNILACPENCPLELYNLM 834
Cdd:cd05103   236 VRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTM 315
                         330
                  ....*....|....
gi 1937920432 835 RLCWSKLPADRPSF 848
Cdd:cd05103   316 LDCWHGEPSQRPTF 329
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
573-868 1.91e-60

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. 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, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 207.54  E-value: 1.91e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQArapgLLPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGVCAVGKPM 650
Cdd:cd05089     3 DIKFEDVIGEGNFGQVIKA----MIKKDGLKMnAAIKMLKEFASENDHRDFAGELEVLCKLgHHPNIINLLGACENRGYL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRS---MSPHTVCSLSHSDLSTrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05089    79 YIAIEYAPYGNLLDFLRKsrvLETDPAFAKEHGTAST-----------LTSQQLLQFASDVAKGMQYLSEKQFIHRDLAA 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRniySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05089   148 RNVLVGENLVSKIADFGLSR---GEEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTC 224
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCERAEGTVGV 868
Cdd:cd05089   225 AELYEKLPQGYRMEKPRNCDDEVYELMRQCWRDRPYERPPFSQISVQLSRMLEARKAYVNM 285
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
578-851 2.12e-60

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron 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: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 205.79  E-value: 2.12e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARapgLLPYEPF-TMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVC--AVGKPMCLLf 654
Cdd:cd05058     1 EVIGKGHFGCVYHGT---LIDSDGQkIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGIClpSEGSPLVVL- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSMSPH-TVCSLSHSDLstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd05058    77 PYMKHGDLRNFIRSETHNpTVKDLIGFGL------------------------QVAKGMEYLASKKFVHRDLAARNCMLD 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSADYYKADGNDA--IPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVI 811
Cdd:cd05058   133 ESFTVKVADFGLARDIYDKEYYSVHNHTGakLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDIT 212
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 812 YYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05058   213 VYLLQGRRLLQPEYCPDPLYEVMLSCWHPKPEMRPTFSEL 252
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
582-856 2.84e-60

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 206.15  E-value: 2.84e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 582 EGAFGRVFQarapGLLPYEPFTM--VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCA--VGKPMcLLFEYM 657
Cdd:cd05043    16 EGTFGRIFH----GILRDEKGKEeeVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCIedGEKPM-VLYPYM 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSmsphtvCSLShsdlstrarvSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd05043    91 NWGNLKLFLQQ------CRLS----------EANNPQALSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQ 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDG 817
Cdd:cd05043   155 VKITDNALSRDLFPMDYHCLGDNENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDG 234
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 818 NILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05043   235 YRLAQPINCPDELFAVMACCWALDPEERPSFQQLVQCLT 273
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
568-856 3.72e-60

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. 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 Lck/Blk 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: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 205.51  E-value: 3.72e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARapgllpYEPFTMVAVKMLKEeasADMQAD-FQREAALMAEFDNPNIVKLLGVcAV 646
Cdd:cd05067     3 EVPRETLKLVERLGAGQFGEVWMGY------YNGHTKVAIKSLKQ---GSMSPDaFLAEANLMKQLQHQRLVRLYAV-VT 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05067    73 QEPIYIITEYMENGSLVDFLKTPSGIK----------------------LTINKLLDMAAQIAEGMAFIEERNYIHRDLR 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05067   131 AANILVSDTLSCKIADFGLARLIEDNEYTAREGAK-FPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMT 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 807 HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05067   210 NPEVIQNLERGYRMPRPDNCPEELYQLMRLCWKERPEDRPTFEYLRSVLE 259
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
568-858 3.99e-60

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: 209.88  E-value: 3.99e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFD-NPNIVKLLGVCAV 646
Cdd:cd05105    33 EFPRDGLVLGRILGSGAFGKVVEGTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGpHLNIVNLLGACTK 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRS-----MSPH--------TVCSLSHSDLSTRARV------------------------- 688
Cdd:cd05105   113 SGPIYIITEYCFYGDLVNYLHKnrdnfLSRHpekpkkdlDIFGINPADESTRSYVilsfenkgdymdmkqadttqyvpml 192
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 689 ----------------------------------SSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd05105   193 eikeaskysdiqrsnydrpasykgsndsevknllSDDGSEGLTTLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQ 272
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIY-Y 813
Cdd:cd05105   273 GKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMIVDSTFYnK 352
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05105   353 IKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVESL 397
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
568-864 5.17e-60

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: 205.28  E-value: 5.17e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARapgllpYEPFTMVAVKMLKEeASADMQAdFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05072     3 EIPRESIKLVKKLGAGQFGEVWMGY------YNNSTKVAVKTLKP-GTMSVQA-FLEEANLMKTLQHDKLVRLYAVVTKE 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05072    75 EPIYIITEYMAKGSLLDFLKSDEGGKVLLPKLIDFSA----------------------QIAEGMAYIERKNYIHRDLRA 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05072   133 ANVLVSESLMCKIADFGLARVIEDNEYTAREGAK-FPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSN 211
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCERAEG 864
Cdd:cd05072   212 SDVMSALQRGYRMPRMENCPDELYDIMKTCWKEKAEERPTFDYLQSVLDDFYTATEG 268
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
568-858 3.29e-59

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 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: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 202.85  E-value: 3.29e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVfqARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05064     1 ELDNKSIKIERILGTGRFGEL--CRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05064    79 NTMMIVTEYMSNGALDSFLRKHEGQ-----------------------LVAGQLMGMLPGLASGMKYLSEMGYVHKGLAA 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFG-LSRNIYSADYYKADGNDaiPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05064   136 HKVLVNSDLVCKISGFRrLQEDKSEAIYTTMSGKS--PVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMS 213
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 807 HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05064   214 GQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQIHSILSKM 265
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
572-860 8.96e-58

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 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: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 200.22  E-value: 8.96e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapglLPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGVCAVGKP 649
Cdd:cd05088     7 NDIKFQDVIGEGNFGQVLKAR----IKKDGLRMdAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGY 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRS---MSPHTVCSLSHSDLSTrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05088    83 LYLAIEYAPHGNLLDFLRKsrvLETDPAFAIANSTAST-----------LSSQQLLHFAADVARGMDYLSQKQFIHRDLA 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRniySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd05088   152 ARNILVGENYVAKIADFGLSR---GQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMT 228
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 807 HEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd05088   229 CAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLE 282
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
579-859 1.11e-57

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: 198.63  E-value: 1.11e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 579 DIGEGAFGRVFQarapGLLPYEPFTM-VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMcLLFEYM 657
Cdd:cd05115    11 ELGSGNFGCVKK----GVYKMRKKQIdVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALM-LVMEMA 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRS----MSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd05115    86 SGGPLNKFLSGkkdeITVSNVVELMH---------------------------QVSMGMKYLEEKNFVHRDLAARNVLLV 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSAD-YYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIY 812
Cdd:cd05115   139 NQHYAKISDFGLSKALGADDsYYKARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMS 218
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 813 YVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILqRMC 859
Cdd:cd05115   219 FIEQGKRMDCPAECPPEMYALMSDCWIYKWEDRPNFLTVEQRM-RTY 264
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
580-858 2.19e-56

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: 194.71  E-value: 2.19e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASAdmQAdFQREAALMAEFDNPNIVKLLGVCaVGKPMCLLFEYMAY 659
Cdd:cd05083    14 IGEGEFGAVLQGEYMG-------QKVAVKNIKCDVTA--QA-FLEETAVMTKLQHKNLVRLLGVI-LHNGLYIVMELMSK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRsmsphtvcslshsdlsTRARVSSPgPPPLscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd05083    83 GNLVNFLR----------------SRGRALVP-VIQL-----LQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAK 140
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNiysadYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd05083   141 ISDFGLAKV-----GSMGVDNSRLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYR 215
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 820 LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05083   216 MEPPEGCPPDVYSIMTSCWEAEPGKRPSFKKLREKLEKE 254
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
568-858 1.09e-55

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta 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 beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta 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: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 197.54  E-value: 1.09e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFD-NPNIVKLLGVCAV 646
Cdd:cd05107    33 EMPRDNLVLGRTLGSGAFGRVVEATAHGLSHSQSTMKVAVKMLKSTARSSEKQALMSELKIMSHLGpHLNIVNLLGACTK 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSmSPHTV----------------------------CSLS------HSDLSTRARV---- 688
Cdd:cd05107   113 GGPIYIITEYCRYGDLVDYLHR-NKHTFlqyyldknrddgslisggstplsqrkshVSLGsesdggYMDMSKDESAdyvp 191
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 689 ---------------------------SSPG----------PPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd05107   192 mqdmkgtvkyadiessnyespydqylpSAPErtrrdtlineSPALSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVL 271
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVI 811
Cdd:cd05107   272 ICEGKLVKICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYPELPMNEQF 351
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 812 YY-VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05107   352 YNaIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLVHLVGDL 399
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
571-848 2.02e-55

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: 192.02  E-value: 2.02e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPGllPYEpftmVAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd05113     3 PKDLTFLKELGTGQFGVVKYGKWRG--QYD----VAIKMIKEGSMS--EDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPI 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05113    75 FIITEYMANGCLLNYLREMRKR-----------------------FQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNC 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEV 810
Cdd:cd05113   132 LVNDQGVVKVSDFGLSRYVLDDEYTSSVGSK-FPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSET 210
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1937920432 811 IYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05113   211 VEHVSQGLRLYRPHLASEKVYTIMYSCWHEKADERPTF 248
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
122-209 5.86e-55

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: 184.37  E-value: 5.86e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 122 KITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYS 201
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

                  ....*...
gi 1937920432 202 KLVKLEVE 209
Cdd:cd20968    81 KPVTIEVE 88
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
577-848 6.99e-54

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 187.74  E-value: 6.99e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  577 VRDIGEGAFGRVFQAR--APGLLpyepftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:smart00220   4 LEKLGEGSFGKVYLARdkKTGKL-------VAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVM 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  655 EYMAYGDLNEFLRSMSPhtvcsLSHSDLStrarvsspgppplscaeqlCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:smart00220  77 EYCEGGDLFDLLKKRGR-----LSEDEAR-------------------FYLRQILSALEYLHSKGIVHRDLKPENILLDE 132
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  735 NMVVKIADFGLSRNIYSADYYKadgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYV 814
Cdd:smart00220 133 DGHVKLADFGLARQLDPGEKLT---TFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDQLLELFKK 208
                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1937920432  815 ---RDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:smart00220 209 igkPKPPFPPPEWDISPEAKDLIRKLLVKDPEKRLTA 245
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
571-858 6.20e-52

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: 182.49  E-value: 6.20e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASAdmQAdFQREAALMAEFDNPNIVKLLGVCAVGK-P 649
Cdd:cd05082     5 MKELKLLQTIGKGEFGDVMLGDYRG-------NKVAVKCIKNDATA--QA-FLAEASVMTQLRHSNLVQLLGVIVEEKgG 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstRARVSSPGPPPLSCAEQLCiarqvaAGMAYLSERKFVHRDLATRN 729
Cdd:cd05082    75 LYIVTEYMAKGSLVDYLRS----------------RGRSVLGGDCLLKFSLDVC------EAMEYLEGNNFVHRDLAARN 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSA-DYYKadgndaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05082   133 VLVSEDNVAKVSDFGLTKEASSTqDTGK------LPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLK 206
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 809 EVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05082   207 DVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHLDAAMRPSFLQLREQLEHI 256
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
568-856 2.95e-51

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). 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 Hck 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: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 180.61  E-value: 2.95e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQArapgllPYEPFTMVAVKMLKEeASADMQAdFQREAALMAEFDNPNIVKLLGVcAVG 647
Cdd:cd05073     7 EIPRESLKLEKKLGAGQFGEVWMA------TYNKHTKVAVKTMKP-GSMSVEA-FLAEANVMKTLQHDKLVKLHAV-VTK 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSTrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05073    78 EPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSA----------------------QIAEGMAFIEQRNYIHRDLRA 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05073   136 ANILVSASLVCKIADFGLARVIEDNEYTAREGAK-FPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSN 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05073   215 PEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLD 263
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
577-848 5.97e-50

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) 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 for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. 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: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 178.68  E-value: 5.97e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQarapGLLPYEPFTM---VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVGKPMCLL 653
Cdd:cd05108    12 IKVLGSGAFGTVYK----GLWIPEGEKVkipVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGIC-LTSTVQLI 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSmsphtvcslsHSDlstraRVsspgppplsCAEQL---CIarQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05108    87 TQLMPFGCLLDYVRE----------HKD-----NI---------GSQYLlnwCV--QIAKGMNYLEDRRLVHRDLAARNV 140
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRnIYSAD--YYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05108   141 LVKTPQHVKITDFGLAK-LLGAEekEYHAEGGK-VPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPAS 218
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 809 EVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05108   219 EISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKF 258
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
578-856 7.98e-50

Catalytic domain of a subset of 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 includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They 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). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-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: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 176.26  E-value: 7.98e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGLlpyepfTMVAVKMLKeeaSADMQAD-FQREAALMAEFDNPNIVKLLGVCAvGKPMCLLFEY 656
Cdd:cd14203     1 VKLGQGCFGEVWMGTWNGT------TKVAIKTLK---PGTMSPEaFLEEAQIMKKLRHDKLVQLYAVVS-EEPIYIVTEF 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd14203    71 MSKGSLLDFLKDGEGKY----------------------LKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNL 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRD 816
Cdd:cd14203   129 VCKIADFGLARLIEDNEYTARQGAK-FPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVER 207
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 817 GNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd14203   208 GYRMPCPPGCPESLHELMCQCWRKDPEERPTFEYLQSFLE 247
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
580-858 2.47e-49

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: 173.61  E-value: 2.47e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd00180     1 LGKGSFGKVYKARDKETGKK-----VAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEG 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSPhtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd00180    76 GSLKDLLKENKG-----------------------PLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVK 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFsyglqpyygmaheeviyyvrdgni 819
Cdd:cd00180   133 LADFGLAKDLDSDDSLLKTTGGTTPPYYAPPELLGGRYYGPKVDIWSLGVILYELE------------------------ 188
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 820 lacpencplELYNLMRLCWSKLPADRPSFcsiHRILQRM 858
Cdd:cd00180   189 ---------ELKDLIRRMLQYDPKKRPSA---KELLEHL 215
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
568-856 1.65e-48

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. 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 Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 173.33  E-value: 1.65e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGllpyepFTMVAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAvG 647
Cdd:cd05070     5 EIPRESLQLIKRLGNGQFGEVWMGTWNG------NTKVAIKTLKPGTMS--PESFLEEAQIMKKLKHDKLVQLYAVVS-E 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRsmsphtvcslshsDLSTRArvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05070    76 EPIYIVTEYMSKGSLLDFLK-------------DGEGRA---------LKLPNLVDMAAQVAAGMAYIERMNYIHRDLRS 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05070   134 ANILVGNGLICKIADFGLARLIEDNEYTARQGAK-FPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNN 212
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05070   213 REVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQGFLE 261
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
576-860 2.51e-48

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: 172.35  E-value: 2.51e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVRDIGEGAFGRVFqarapgLLPYEPFTMVAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd05114     8 FMKELGSGLFGVVR------LGKWRAQYKVAIKAIREGAMS--EEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTE 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd05114    80 FMENGCLLNYLRQRRGK-----------------------LSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDT 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVR 815
Cdd:cd05114   137 GVVKVSDFGMTRYVLDDQYTSSSGAK-FPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVS 215
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 816 DGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd05114   216 RGHRLYRPKLASKSVYEVMYSCWHEKPEGRPTFADLLRTITEIAE 260
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
568-856 3.37e-48

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. 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 Yes 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 (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 172.56  E-value: 3.37e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLlpyepfTMVAVKMLKeeASADMQADFQREAALMAEFDNPNIVKLLGVCAvG 647
Cdd:cd05069     8 EIPRESLRLDVKLGQGCFGEVWMGTWNGT------TKVAIKTLK--PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVS-E 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05069    79 EPIYIVTEFMGKGSLLDFLKEGDGKY----------------------LKLPQLVDMAAQIADGMAYIERMNYIHRDLRA 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05069   137 ANILVGDNLVCKIADFGLARLIEDNEYTARQGAK-FPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVN 215
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05069   216 REVLEQVERGYRMPCPQGCPESLHELMKLCWKKDPDERPTFEYIQSFLE 264
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
569-848 2.74e-47

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: 170.07  E-value: 2.74e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 569 YPRNNIEYVRDIGEGAFGRVFQARapgllpYEPF-----TMVAVKMLKEEaSADMQADFQREAALMAEFDNPNIVKLLGV 643
Cdd:cd05081     1 FEERHLKYISQLGKGNFGSVELCR------YDPLgdntgALVAVKQLQHS-GPDQQRDFQREIQILKALHSDFIVKYRGV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 C-AVGKP-MCLLFEYMAYGDLNEFLrsmsPHTVCSLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFV 721
Cdd:cd05081    74 SyGPGRRsLRLVMEYLPSGCLRDFL----QRHRARLDASRL-------------------LLYSSQICKGMEYLGSRRCV 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNI-YSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQ 800
Cdd:cd05081   131 HRDLAARNILVESEAHVKIADFGLAKLLpLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDK 210
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 801 P------YYGMAHEE--------VIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd05081   211 ScspsaeFLRMMGCErdvpalcrLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSF 272
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
577-858 4.40e-47

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) 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. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 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: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 169.43  E-value: 4.40e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQA---------RAPgllpyepftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVG 647
Cdd:cd05109    12 VKVLGSGAFGTVYKGiwipdgenvKIP----------VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGIC-LT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlsTRARVSSpgppplscAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05109    81 STVQLVTQLMPYGCLLDYVRE---------------NKDRIGS--------QDLLNWCVQIAKGMSYLEEVRLVHRDLAA 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSR--NIYSADYYkADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGM 805
Cdd:cd05109   138 RNVLVKSPNHVKITDFGLARllDIDETEYH-ADGGK-VPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGI 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 806 AHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05109   216 PAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVDEFSRM 268
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
577-851 2.23e-46

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 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 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 Jak1 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: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 167.80  E-value: 2.23e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARapgllpYEPF-----TMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCA--VGKP 649
Cdd:cd05079     9 IRDLGEGHFGKVELCR------YDPEgdntgEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTedGGNG 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLrsmsPHTVcslSHSDLSTrarvsspgppplscaeQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05079    83 IKLIMEFLPSGSLKEYL----PRNK---NKINLKQ----------------QLKYAVQICKGMDYLGSRQYVHRDLAARN 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYS-ADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYG---------- 798
Cdd:cd05079   140 VLVESEHQVKIGDFGLTKAIETdKEYYTVKDDLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCdsesspmtlf 219
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 799 ---LQPYYG-MAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd05079   220 lkmIGPTHGqMTVTRLVRVLEEGKRLPRPPNCPEEVYQLMRKCWEFQPSKRTTFQNL 276
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
568-856 2.48e-46

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing 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 with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src 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: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 167.17  E-value: 2.48e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGLlpyepfTMVAVKMLKEEASAdmQADFQREAALMAEFDNPNIVKLLGVCAvG 647
Cdd:cd05071     5 EIPRESLRLEVKLGQGCFGEVWMGTWNGT------TRVAIKTLKPGTMS--PEAFLQEAQVMKKLRHEKLVQLYAVVS-E 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSmsphtvcslshsDLSTRARVsspgpPPLscaeqLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05071    76 EPIYIVTEYMSKGSLLDFLKG------------EMGKYLRL-----PQL-----VDMAAQIASGMAYVERMNYVHRDLRA 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05071   134 ANILVGENLVCKVADFGLARLIEDNEYTARQGAK-FPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVN 212
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd05071   213 REVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLE 261
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
577-860 3.53e-46

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: 167.00  E-value: 3.53e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVfqarapGLLPYEPFT-----MVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG--KP 649
Cdd:cd05080     9 IRDLGEGHFGKV------SLYCYDPTNdgtgeMVAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQggKS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSphtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05080    83 LQLIMEYVPLGSLRDYLPKHS-------------------------IGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARN 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSA-DYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEI-------------F 795
Cdd:cd05080   138 VLLDNDRLVKIGDFGLAKAVPEGhEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELlthcdssqspptkF 217
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 796 SYGLQPYYG-MAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd05080   218 LEMIGIAQGqMTVVRLIELLERGERLPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTVHE 283
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
576-855 4.71e-46

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 166.28  E-value: 4.71e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVRDIGEGAFGRVFQARApgLLPYEPfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14206     1 YLQEIGNGWFGKVILGEI--FSDYTP-AQVVVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIME 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRS------MSPhtvcSLSHSDLSTRARvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd14206    78 FCQLGDLKRYLRAqrkadgMTP----DLPTRDLRTLQR----------------MAYEITLGLLHLHKNNYIHSDLALRN 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPE-------SIFYNRYTTESDVWAYGVVLWEIFSYGLQPY 802
Cdd:cd14206   138 CLLTSDLTVRIGDYGLSHNNYKEDYYLTPDRLWIPLRWVAPElldelhgNLIVVDQSKESNVWSLGVTIWELFEFGAQPY 217
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 803 YGMAHEEVIYYV-RDGNI-LACPEncpLEL------YNLMRLCWSKlPADRPSFCSIHRIL 855
Cdd:cd14206   218 RHLSDEEVLTFVvREQQMkLAKPR---LKLpyadywYEIMQSCWLP-PSQRPSVEELHLQL 274
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
578-855 9.15e-46

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk 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: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 165.45  E-value: 9.15e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARA-PGLLPYEpftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05042     1 QEIGNGWFGKVLLGEIySGTSVAQ----VVVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEF 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSPHtvcSLSHSDLSTRARvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05042    77 CDLGDLKAYLRSEREH---ERGDSDTRTLQR----------------MACEVAAGLAHLHKLNFVHSDLALRNCLLTSDL 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESI--FYNRY-----TTESDVWAYGVVLWEIFSYGLQPYYGMAHEE 809
Cdd:cd05042   138 TVKIGDYGLAHSRYKEDYIETDDKLWFPLRWTAPELVteFHDRLlvvdqTKYSNIWSLGVTLWELFENGAQPYSNLSDLD 217
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 810 VI-YYVRDGNI-LACPEncpLEL------YNLMRLCWSKlPADRPSFCSIHRIL 855
Cdd:cd05042   218 VLaQVVREQDTkLPKPQ---LELpysdrwYEVLQFCWLS-PEQRPAAEDVHLLL 267
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
580-858 4.08e-45

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: 162.95  E-value: 4.08e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLpyepftmVAVKMLKEEASADMQ---ADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14061     2 IGVGGFGKVYRGIWRGEE-------VAVKAARQDPDEDISvtlENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEY 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFL--RSMSPHTVcslshsdlstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFV---HRDLATRNCL 731
Cdd:cd14061    75 ARGGALNRVLagRKIPPHVL---------------------------VDWAIQIARGMNYLHNEAPVpiiHRDLKSSNIL 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGE--------NMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY 803
Cdd:cd14061   128 ILEaienedleNKTLKITDFGLAREWHKTTRMSAAGTYA----WMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYK 202
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 804 GMAHEEVIYYVRDGNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14061   203 GIDGLAVAYGVAVNKLtLPIPSTCPEPFAQLMKDCWQPDPHDRPSFADILKQLENI 258
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
569-863 9.37e-45

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: 162.88  E-value: 9.37e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 569 YPRNNIEYVRDIGEGAFGRVFQARapgllpYEPFT-----MVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGV 643
Cdd:cd14205     1 FEERHLKFLQQLGKGNFGSVEMCR------YDPLQdntgeVVAVKKL-QHSTEEHLRDFEREIEILKSLQHDNIVKYKGV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 C--AVGKPMCLLFEYMAYGDLNEFLRSMSPHtvcsLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFV 721
Cdd:cd14205    74 CysAGRRNLRLIMEYLPYGSLRDYLQKHKER----IDHIKL-------------------LQYTSQICKGMEYLGTKRYI 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNI-YSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSY--- 797
Cdd:cd14205   131 HRDLATRNILVENENRVKIGDFGLTKVLpQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYiek 210
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 798 ------------GLQPYYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFcsihRILQRMCERAE 863
Cdd:cd14205   211 sksppaefmrmiGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSF----RDLALRVDQIR 284
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
574-858 5.62e-44

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: 161.39  E-value: 5.62e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQarapGLLPYEPFTM---VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVGKPM 650
Cdd:cd05110     9 LKRVKVLGSGAFGTVYK----GIWVPEGETVkipVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVC-LSPTI 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSmsphtvcslsHSDlstrarvsspgppplSCAEQLCI--ARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd05110    84 QLVTQLMPHGCLLDYVHE----------HKD---------------NIGSQLLLnwCVQIAKGMMYLEERRLVHRDLAAR 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIYSADY-YKADGNDaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAH 807
Cdd:cd05110   139 NVLVKSPNHVKITDFGLARLLEGDEKeYNADGGK-MPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPT 217
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05110   218 REIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFSRM 268
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
576-855 6.20e-43

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 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: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 157.46  E-value: 6.20e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVRDIGEGAFGRVFQARAPGLLPYepfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd05087     1 YLKEIGHGWFGKVFLGEVNSGLSS---TQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVME 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSmsphtvCSLShsdlstrarvSSPGPPPLSCAEQLCiarQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd05087    78 FCPLGDLKGYLRS------CRAA----------ESMAPDPLTLQRMAC---EVACGLLHLHRNNFVHSDLALRNCLLTAD 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPE-------SIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05087   139 LTVKIGDYGLSHCKYKEDYFVTADQLWVPLRWIAPElvdevhgNLLVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDR 218
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 809 EVIYYVRDGNILACPE-NCPLEL----YNLMRLCWSKlPADRPSFCSIHRIL 855
Cdd:cd05087   219 QVLTYTVREQQLKLPKpQLKLSLaerwYEVMQFCWLQ-PEQRPTAEEVHLLL 269
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
28-117 5.50e-42

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: 148.04  E-value: 5.50e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPL--ETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGV 105
Cdd:cd20970     1 PVISTPQpsFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80
                          90
                  ....*....|..
gi 1937920432 106 GGAVESCGALQV 117
Cdd:cd20970    81 PGSVEKRITLQV 92
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
580-848 3.45e-41

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: 152.22  E-value: 3.45e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgllpYEPFTMVAVKMLK-EEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd13978     1 LGSGGFGTVSKARH-----VSWFGMVAIKCLHsSPNCIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYME 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRSMSPhtvcslshsdlstrarvssPGPPPLScaeqLCIARQVAAGMAYL--SERKFVHRDLATRNCLVGENM 736
Cdd:cd13978    76 NGSLKSLLEREIQ-------------------DVPWSLR----FRIIHEIALGMNFLhnMDPPLLHHDLKPENILLDNHF 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSR---NIYSADYYKADGNDAIPIRWMPPESI--FYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd13978   133 HVKISDFGLSKlgmKSISANRRRGTENLGGTPIYMAPEAFddFNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLI 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 812 YY-VRDGN-------ILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd13978   212 MQiVSKGDrpslddiGRLKQIENVQELISLMIRCWDGNPDARPTF 256
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
580-858 7.43e-41

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: 151.65  E-value: 7.43e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQarapGLLPYEPFTM---VAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAvGKPMCLLFEY 656
Cdd:cd05111    15 LGSGVFGTVHK----GIWIPEGDSIkipVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICP-GASLQLVTQL 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSmsphtvcslsHSDlstrarvsSPGPPPLScaeQLCIarQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05111    90 LPLGSLLDHVRQ----------HRG--------SLGPQLLL---NWCV--QIAKGMYYLEEHRMVHRNLAARNVLLKSPS 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRD 816
Cdd:cd05111   147 QVQVADFGVADLLYPDDKKYFYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEK 226
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 817 GNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd05111   227 GERLAQPQICTIDVYMVMVKCWMIDENIRPTFKELANEFTRM 268
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
580-851 2.84e-40

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: 149.80  E-value: 2.84e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASADMQA---DFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14146     2 IGVGGFGKVYRATWKG-------QEVAVKAARQDPDEDIKAtaeSVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEF 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEflrsmsphtvcSLSHSDLSTRARVSSPGPPPLscaeQLCIARQVAAGMAYLSERKFV---HRDLATRNCLVG 733
Cdd:cd14146    75 ARGGTLNR-----------ALAAANAAPGPRRARRIPPHI----LVNWAVQIARGMLYLHEEAVVpilHRDLKSSNILLL 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENM--------VVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGM 805
Cdd:cd14146   140 EKIehddicnkTLKITDFGLAREWHRTTKMSAAGTYA----WMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGI 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 806 AHEEVIYYVRDGNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14146   215 DGLAVAYGVAVNKLtLPIPSTCPEPFAKLMKECWEQDPHIRPSFALI 261
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
580-851 4.66e-40

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: 148.03  E-value: 4.66e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyEPftmVAVKMLKEEASADMQAdfqreaalMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14059     1 LGSGAQGAVFLGKFRG----EE---VAVKKVRDEKETDIKH--------LRKLNHPNIIKFKGVCTQAPCYCILMEYCPY 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRS---MSPHTVCSLShsdlstrarvsspgppplscaeqlciaRQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd14059    66 GQLYEVLRAgreITPSLLVDWS---------------------------KQIASGMNYLHLHKIIHRDLKSPNVLVTYND 118
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNiYSADYYKAdgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRD 816
Cdd:cd14059   119 VLKISDFGTSKE-LSEKSTKM--SFAGTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVGS 194
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 817 GNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14059   195 NSLqLPVPSTCPDGFKLLMKQCWNSKPRNRPSFRQI 230
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
580-855 3.90e-39

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: 145.66  E-value: 3.90e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLpyepftmVAVKMLKEEASadmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14058     1 VGRGSFGVVCKARWRNQI-------VAVKIIESESE---KKAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEG 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSPHTVCSLSHSdlstrarvsspgppplscaeqLCIARQVAAGMAYL---SERKFVHRDLATRNCLVGEN- 735
Cdd:cd14058    71 GSLYNVLHGKEPKPIYTAAHA---------------------MSWALQCAKGVAYLhsmKPKALIHRDLKPPNLLLTNGg 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLsrniySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGlQPYYGMAHEEVIY--Y 813
Cdd:cd14058   130 TVLKICDFGT-----ACDISTHMTNNKGSAAWMAPEVFEGSKYSEKCDVFSWGIILWEVITRR-KPFDHIGGPAFRImwA 203
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd14058   204 VHNGERPPLIKNCPKPIESLMTRCWSKDPEKRPSMKEIVKIM 245
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
580-847 3.15e-38

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: 143.43  E-value: 3.15e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGllpyepfTMVAVKM--LKEEASADMQAdFQREAALMAEFDNPNIVKLLGvCAVGKPMCLLF- 654
Cdd:cd06606     8 LGKGSFGSVYLAlnLDTG-------ELMAVKEveLSGDSEEELEA-LEREIRILSSLKHPNIVRYLG-TERTENTLNIFl 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLR---SMSPHTVCSLshsdlstrarvsspgppplscaeqlciARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd06606    79 EYVPGGSLASLLKkfgKLPEPVVRKY---------------------------TRQILEGLEYLHSNGIVHRDIKGANIL 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHE-EV 810
Cdd:cd06606   132 VDSDGVVKLADFGCAKRLAEIATGEGTKSLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWSELGNPvAA 210
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1937920432 811 IYYV-RDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06606   211 LFKIgSSGEPPPIPEHLSEEAKDFLRKCLQRDPKKRPT 248
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
577-847 3.17e-38

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: 143.50  E-value: 3.17e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd14014     5 VRLLGRGGMGEVYRARDTLLGRP-----VAIKVLRPELAEDeeFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVM 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSMSphtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd14014    80 EYVEGGSLADLLRERG------------------------PLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTE 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKAD---GNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd14014   136 DGRVKLTDFGIARALGDSGLTQTGsvlGTPA----YMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGDSPAAVL 210
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 812 YYVRDGNILACPE---NCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14014   211 AKHLQEAPPPPSPlnpDVPPALDAIILRALAKDPEERPQ 249
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
576-855 2.88e-37

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 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: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 141.16  E-value: 2.88e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVRDIGEGAFGRVFQARapgLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd05086     1 YIQEIGNGWFGKVLLGE---IYTGTSVARVVVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFE 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSMSPHTvcsLSHSDLSTRARvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd05086    78 FCDLGDLKTYLANQQEKL---RGDSQIMLLQR----------------MACEIAAGLAHMHKHNFLHSDLALRNCYLTSD 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESI--FYNRY-----TTESDVWAYGVVLWEIFSYGLQPYYGMAHE 808
Cdd:cd05086   139 LTVKVGDYGIGFSRYKEDYIETDDKKYAPLRWTAPELVtsFQDGLlaaeqTKYSNIWSLGVTLWELFENAAQPYSDLSDR 218
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 809 EVIYYV-RDGNI-LACPEncpLEL------YNLMRLCWSKlPADRPSFCSIHRIL 855
Cdd:cd05086   219 EVLNHViKERQVkLFKPH---LEQpysdrwYEVLQFCWLS-PEKRPTAEEVHRLL 269
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
580-851 2.14e-36

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: 138.64  E-value: 2.14e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASADMQA---DFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14145    14 IGIGGFGKVYRAIWIG-------DEVAVKAARHDPDEDISQtieNVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEF 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFL--RSMSPHTVCSLshsdlstrarvsspgppplscaeqlciARQVAAGMAYLSERKFV---HRDLATRNCL 731
Cdd:cd14145    87 ARGGPLNRVLsgKRIPPDILVNW---------------------------AVQIARGMNYLHCEAIVpviHRDLKSSNIL 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGE--------NMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY 803
Cdd:cd14145   140 ILEkvengdlsNKILKITDFGLAREWHRTTKMSAAGTYA----WMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFR 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 804 GMAHEEVIYYVRDGNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14145   215 GIDGLAVAYGVAMNKLsLPIPSTCPEPFARLMEDCWNPDPHSRPPFTNI 263
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
580-858 2.83e-35

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: 135.11  E-value: 2.83e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQarapGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14148     2 IGVGGFGKVYK----GLWRGEEVAVKAARQDPDEDIAVTAENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFL--RSMSPHTVCSLshsdlstrarvsspgppplscaeqlciARQVAAGMAYLSERKFV---HRDLATRNCLVGE 734
Cdd:cd14148    78 GALNRALagKKVPPHVLVNW---------------------------AVQIARGMNYLHNEAIVpiiHRDLKSSNILILE 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 --------NMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMA 806
Cdd:cd14148   131 pienddlsGKTLKITDFGLAREWHKTTKMSAAGTYA----WMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREID 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 807 HEEVIYYVRDGNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSihrILQRM 858
Cdd:cd14148   206 ALAVAYGVAMNKLtLPIPSTCPEPFARLLEECWDPDPHGRPDFGS---ILKRL 255
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
580-851 3.08e-35

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: 135.16  E-value: 3.08e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLpyepftmVAVKMLKEEASADMQADFQ---REAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14147    11 IGIGGFGKVYRGSWRGEL-------VAVKAARQDPDEDISVTAEsvrQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEY 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFL--RSMSPHTVCSLshsdlstrarvsspgppplscaeqlciARQVAAGMAYLSERKFV---HRDLATRNCL 731
Cdd:cd14147    84 AAGGPLSRALagRRVPPHVLVNW---------------------------AVQIARGMHYLHCEALVpviHRDLKSNNIL 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 -----VGENM---VVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY 803
Cdd:cd14147   137 llqpiENDDMehkTLKITDFGLAREWHKTTQMSAAGTYA----WMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYR 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 804 GMAHEEVIYYVRDGNI-LACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14147   212 GIDCLAVAYGVAVNKLtLPIPSTCPEPFAQLMADCWAQDPHRRPDFASI 260
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
580-858 6.31e-35

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: 134.32  E-value: 6.31e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14066     1 IGSGGFGTVYKGV------LENGTVVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPN 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRsmsphtvCSLSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYL---SERKFVHRDLATRNCLVGENM 736
Cdd:cd14066    75 GSLEDRLH-------CHKGSPPLPWPQRLK--------------IAKGIARGLEYLheeCPPPIIHGDIKSSNILLDEDF 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNI-YSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY--------GMAH 807
Cdd:cd14066   134 EPKLTDFGLARLIpPSESVSKTSAVKGTIG-YLAPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAVDenrenasrKDLV 211
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 808 EEV----------IYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14066   212 EWVeskgkeeledILDKRLVDDDGVEEEEVEALLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
CRD_TK_ROR_like cd07459
Cysteine-rich domain of tyrosine kinase-like orphan receptors; The cysteine-rich domain (CRD) ...
315-452 1.27e-34

Cysteine-rich domain of tyrosine kinase-like orphan receptors; The cysteine-rich domain (CRD) is an essential part of the tyrosine kinase-like orphan receptor (Ror) proteins, a conserved family of tyrosine kinases that function in various processes, including neuronal and skeletal development, cell polarity, and cell movement. Ror proteins are receptors of Wnt proteins, which are key players in a number of fundamental cellular processes in embryogenesis and postnatal development. In different cellular contexts, Ror proteins can either activate or repress transcription of Wnt target genes, and can modulate Wnt signaling by sequestering Wnt ligands. In addition, a number of Wnt-independent functions have been proposed for both Ror1 and Ror2.


Pssm-ID: 143568  Cd Length: 135  Bit Score: 128.67  E-value: 1.27e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 315 GYCAQYRGEVCDAVLVKDSlvFFNTSYPDPE--EAQELLIHTAWNELKAVSPLCRPAAEALLCNHLFQECSSGVL-PTPM 391
Cdd:cd07459     1 GYCQPYRGSVCAKYLGNKS--VYVTSKQTQEdiEEQLSAAFTVISTSSDVSPKCQQYALPSLCYYAFPLCDEGSStPKPR 78
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 392 PICREYCLAVKELFCAKEWLAMEGKTHRGlyrsgmHFLPVPECSKLPSMH-QDPTACTRLPY 452
Cdd:cd07459    79 RICRDECELLENDLCKKEYAIAKRHPLIG------HQLLLPDCSSLPSPGsPESSNCIRLGI 134
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
603-855 7.19e-34

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They 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. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. 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 serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 131.06  E-value: 7.19e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 603 TMVAVKMLKEEASADMQAdFQREAALMAEFDNPNIVKLLGVCaVGKPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdl 682
Cdd:cd05037    31 VEVLLKVLDSDHRDISES-FFETASLMSQISHKHLVKLYGVC-VADENIMVQEYVRYGPLDKYLRRM------------- 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 683 strarvssPGPPPLSCaeQLCIARQVAAGMAYLSERKFVHRDLATRNCLV------GENMVVKIADFGLSRNIYSADYYK 756
Cdd:cd05037    96 --------GNNVPLSW--KLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldGYPPFIKLSDPGVPITVLSREERV 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 757 ADgndaIPirWMPPE--SIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYYVRDGNILACPEnCPlELYNLM 834
Cdd:cd05037   166 DR----IP--WIAPEclRNLQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAPD-CA-ELAELI 237
                         250       260
                  ....*....|....*....|.
gi 1937920432 835 RLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05037   238 MQCWTYEPTKRPSFRAILRDL 258
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
580-859 2.85e-33

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 129.55  E-value: 2.85e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGllpyepftmvAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14154     1 LGKGFFGQAIKVthRETG----------EVMVMKELIRFDeeAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITE 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSMSPhtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14154    71 YIPGGTLKDVLKDMAR-----------------------PLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVRED 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKADGNDAIPIR------------------WMPPESIFYNRYTTESDVWAYGVVLWEIFS- 796
Cdd:cd14154   128 KTVVVADFGLARLIVEERLPSGNMSPSETLRhlkspdrkkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEIIGr 207
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 797 YGLQPYYGMAHEEVIYYVRDGNILACPEnCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMC 859
Cdd:cd14154   208 VEADPDYLPRTKDFGLNVDSFREKFCAG-CPPPFFKLAFLCCDLDPEKRPPFETLEEWLEALY 269
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
575-847 2.72e-32

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: 126.16  E-value: 2.72e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgllpYEPF-TMVAVKMLKEEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd05122     3 EILEKIGKGGFGVVYKAR------HKKTgQIVAIKKINLESKEKKE-SILNEIAILKKCKHPNIVKYYGSYLKKDELWIV 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRsmspHTVCSLSHSDLStrarvsspgppplscaeqlCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd05122    76 MEFCSGGSLKDLLK----NTNKTLTEQQIA-------------------YVCKEVLKGLEYLHSHGIIHRDIKAANILLT 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIysadyykADGNDAI-----PIrWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHE 808
Cdd:cd05122   133 SDGEVKLIDFGLSAQL-------SDGKTRNtfvgtPY-WMAPEVIQGKPYGFKADIWSLGITAIEMA-EGKPPYSELPPM 203
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 809 EVIYYVRDGNI--LACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd05122   204 KALFLIATNGPpgLRNPKKWSKEFKDFLKKCLQKDPEKRPT 244
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
580-851 1.10e-31

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: 124.53  E-value: 1.10e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyepfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14065     1 LGKGFFGEVYKVTHR--------ETGKVMVMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNG 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSphtvcslshsdlstrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV-----GE 734
Cdd:cd14065    73 GTLEELLKSMD-----------------------EQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVreanrGR 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVkiADFGLSRNIysADYYKADGNDAIPIR------WMPPESIFYNRYTTESDVWAYGVVLWEIFSYGL-QPYYGMAH 807
Cdd:cd14065   130 NAVV--ADFGLAREM--PDEKTKKPDRKKRLTvvgspyWMAPEMLRGESYDEKVDVFSFGIVLCEIIGRVPaDPDYLPRT 205
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 808 EEVIYYVRDGNILAcPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14065   206 MDFGLDVRAFRTLY-VPDCPPSFLPLAIRCCQLDPEKRPSFVEL 248
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
577-847 1.41e-31

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 129.75  E-value: 1.41e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:COG0515    12 LRLLGRGGMGVVYLARDLRLGRP-----VALKVLRPELAADpeARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVM 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsphtvcslshsdlstrarvssPGPPPLscAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:COG0515    87 EYVEGESLADLLRR----------------------RGPLPP--AEALRILAQLAEALAAAHAAGIVHRDIKPANILLTP 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYV 814
Cdd:COG0515   143 DGRVKLIDFGIARAL-GGATLTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAH 220
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 815 RDGNILACPE---NCPLELYNLMRLCWSKLPADRPS 847
Cdd:COG0515   221 LREPPPPPSElrpDLPPALDAIVLRALAKDPEERYQ 256
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
581-858 4.43e-31

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: 122.37  E-value: 4.43e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 581 GEGAFGRVFQARapgLLPYEpfTMVAVKMLKEeasadmqadFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYG 660
Cdd:cd14060     2 GGGSFGSVYRAI---WVSQD--KEVAVKKLLK---------IEKEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYG 67
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 661 DLNEFLrsmsphtvcslshsdlstrarvSSPGPPPLSCAEQLCIARQVAAGMAYLSER---KFVHRDLATRNCLVGENMV 737
Cdd:cd14060    68 SLFDYL----------------------NSNESEEMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAADGV 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGLSRNIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLqPYYGMAHEEVIYYV-RD 816
Cdd:cd14060   126 LKICDFGASRFHSHTTHMSLVGT----FPWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREV-PFKGLEGLQVAWLVvEK 200
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 817 GNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14060   201 NERPTIPSSCPRSFAELMRRCWEADVKERPSFKQIIGILESM 242
Pkinase pfam00069
Protein kinase domain;
575-851 1.11e-29

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 117.34  E-value: 1.11e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQA--RAPGLLpyepftmVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:pfam00069   2 EVLRKLGSGSFGTVYKAkhRDTGKI-------VAIKKIkKEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLY 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSMsphtvCSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERK-FVhrdlATRNc 730
Cdd:pfam00069  75 LVLEYVEGGSLFDLLSEK-----GAFSEREAKF-------------------IMKQILEGLESGSSLTtFV----GTPW- 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 lvgenmvvkiadfglsrniysadyykadgndaipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEV 810
Cdd:pfam00069 126 ------------------------------------YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEI 168
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1937920432 811 IYYVRDG--NILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:pfam00069 169 YELIIDQpyAFPELPSNLSEEAKDLLKKLLKKDPSKRLTATQA 211
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
624-858 1.16e-29

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: 119.03  E-value: 1.16e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 624 REAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSmsphtvcslshSDLstrarvsspgppPLSCAEQLC 703
Cdd:cd13992    45 QELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLN-----------REI------------KMDWMFKSS 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 704 IARQVAAGMAYL-SERKFVHRDLATRNCLVGENMVVKIADFGLsRNIYSADYYKADGNDAIPIR--WMPPESIFYN---- 776
Cdd:cd13992   102 FIKDIVKGMNYLhSSSIGYHGRLKSSNCLVDSRWVVKLTDFGL-RNLLEEQTNHQLDEDAQHKKllWTAPELLRGSllev 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 777 RYTTESDVWAYGVVLWEIFSYgLQPYY-GMAHEEVIYYVRDGNILACPE------NCPLELYNLMRLCWSKLPADRPSFC 849
Cdd:cd13992   181 RGTQKGDVYSFAIILYEILFR-SDPFAlEREVAIVEKVISGGNKPFRPElavlldEFPPRLVLLVKQCWAENPEKRPSFK 259

                  ....*....
gi 1937920432 850 SIHRILQRM 858
Cdd:cd13992   260 QIKKTLTEN 268
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
575-794 2.23e-29

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: 118.35  E-value: 2.23e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgllpyEPFT--MVAVKMLKEEASAD-MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd07829     2 EKLEKLGEGTYGVVYKAK-------DKKTgeIVALKKIRLDNEEEgIPSTALREISLLKELKHPNIVKLLDVIHTENKLY 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYgDLNEFLRSMsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd07829    75 LVFEYCDQ-DLKKYLDKR-----------------------PGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLL 130
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 732 VGENMVVKIADFGLSRnIYSadyykadgndaIPIR---------WM-PPESIF-YNRYTTESDVWAYGVVLWEI 794
Cdd:cd07829   131 INRDGVLKLADFGLAR-AFG-----------IPLRtythevvtlWYrAPEILLgSKHYSTAVDIWSVGCIFAEL 192
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
580-847 2.52e-29

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: 117.71  E-value: 2.52e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLKEE--ASADMQADfQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd06627     8 IGRGAFGSVYKG-----LNLNTGEFVAIKQISLEkiPKSDLKSV-MGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPhtvcslshsdlstrarvsspgppplsCAEQLCIA--RQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd06627    82 ENGSLASIIKKFGK--------------------------FPESLVAVyiYQVLEGLAYLHEQGVIHRDIKGANILTTKD 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSadyykADGNDAIPI---RWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIY 812
Cdd:cd06627   136 GLVKLADFGVATKLNE-----VEKDENSVVgtpYWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPYYDLQPMAALF 209
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 813 -YVRDGNiLACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06627   210 rIVQDDH-PPLPENISPELRDFLLQCFQKDPTLRPS 244
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
619-851 2.34e-28

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: 115.29  E-value: 2.34e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 619 QADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSphtvcslshSDLSTRARvsspgppplsc 698
Cdd:cd14027    35 NEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVLKKVS---------VPLSVKGR----------- 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 699 aeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGL-SRNIYS----------ADYYKADGNDAIPIRW 767
Cdd:cd14027    95 -----IILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLaSFKMWSkltkeehneqREVDGTAKKNAGTLYY 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 768 MPPESI--FYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYY-VRDGN---ILACPENCPLELYNLMRLCWSKL 841
Cdd:cd14027   170 MAPEHLndVNAKPTEKSDVYSFAIVLWAIFA-NKEPYENAINEDQIIMcIKSGNrpdVDDITEYCPREIIDLMKLCWEAN 248
                         250
                  ....*....|
gi 1937920432 842 PADRPSFCSI 851
Cdd:cd14027   249 PEARPTFPGI 258
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
580-856 2.56e-28

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: 114.80  E-value: 2.56e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepftMVAVKMLK--EEASADMQAdFQREAALMAEFDNPNIVKLLGVCAvgKPMCLLFEYM 657
Cdd:cd14062     1 IGSGSFGTVYKGRWHG--------DVAVKKLNvtDPTPSQLQA-FKNEVAVLRKTRHVNILLFMGYMT--KPQLAIVTQW 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDlneflrSMSPHTVCSLSHSDLSTrarvsspgppplscaeQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd14062    70 CEGS------SLYKHLHVLETKFEMLQ----------------LIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLT 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGL----SRNIYSADYYKADGNdaipIRWMPPESIFY---NRYTTESDVWAYGVVLWEIFSYGLqPYYG-MAHEE 809
Cdd:cd14062   128 VKIGDFGLatvkTRWSGSQQFEQPTGS----ILWMAPEVIRMqdeNPYSFQSDVYAFGIVLYELLTGQL-PYSHiNNRDQ 202
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 810 VIYYVRDG----NILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd14062   203 ILFMVGRGylrpDLSKVRSDTPKALRRLMEDCIKFQRDERPLFPQILASLE 253
I-set pfam07679
Immunoglobulin I-set domain;
121-208 8.68e-28

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 107.34  E-value: 8.68e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAG 80
                          90
                  ....*....|.
gi 1937920432 198 TAYSKlVKLEV 208
Cdd:pfam07679  81 EAEAS-AELTV 90
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
580-858 1.28e-26

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. 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 LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 110.05  E-value: 1.28e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGllpyEPFTMVAVKMLKEEAsadmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14221     1 LGKGCFGQAIKVthRETG----EVMVMKELIRFDEET----QRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYI 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHtvCSLSHsdlstraRVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd14221    73 KGGTLRGIIKSMDSH--YPWSQ-------RVS--------------FAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKS 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGLSRNIY-SADYYKADGNDAIPIR-----------WMPPESIFYNRYTTESDVWAYGVVLWEIFS-YGLQPYYG 804
Cdd:cd14221   130 VVVADFGLARLMVdEKTQPEGLRSLKKPDRkkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEIIGrVNADPDYL 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 805 MAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14221   210 PRTMDFGLNVRGFLDRYCPPNCPPSFFPIAVLCCDLDPEKRPSFSKLEHWLETL 263
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
580-856 2.15e-26

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. 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 STK_BAK1-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: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 109.51  E-value: 2.15e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14664     1 IGRGGAGTVYKGVMPN------GTLVAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPN 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSPHTVcslsHSDLSTRARvsspgppplscaeqlcIARQVAAGMAYLSER---KFVHRDLATRNCLVGENM 736
Cdd:cd14664    75 GSLGELLHSRPESQP----PLDWETRQR----------------IALGSARGLAYLHHDcspLIIHRDVKSNNILLDEEF 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIysaDYYKADGNDAI--PIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY---YGMAHEEVI 811
Cdd:cd14664   135 EAHVADFGLAKLM---DDKDSHVMSSVagSYGYIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFdeaFLDDGVDIV 210
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 812 YYVRDGNILACPENC-------------PLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd14664   211 DWVRGLLEEKKVEALvdpdlqgvykleeVEQVFQVALLCTQSSPMERPTMREVVRMLE 268
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
578-801 1.32e-25

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: 107.59  E-value: 1.32e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASA---DMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd14158    21 NKLGEGGFGVVFKGYIND-------KNVAVKKLAAMVDIsteDLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVY 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLrSMSPHTvcslshsdlstrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd14158    94 TYMPNGSLLDRL-ACLNDT--------------------PPLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDE 152
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 735 NMVVKIADFGLSRniysadyykADGNDAIPIR---------WMPPESiFYNRYTTESDVWAYGVVLWEIFSyGLQP 801
Cdd:cd14158   153 TFVPKISDFGLAR---------ASEKFSQTIMterivgttaYMAPEA-LRGEITPKSDIFSFGVVLLEIIT-GLPP 217
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
580-845 1.32e-25

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: 107.25  E-value: 1.32e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQAR--APGLLpyepftmVAVKMLK-------------EEASADMQADFQREAALMAEFDNPNIVKLLGVC 644
Cdd:cd14008     1 LGRGSFGKVKLALdtETGQL-------YAIKIFNksrlrkrregkndRGKIKNALDDVRREIAIMKKLDHPNIVRLYEVI 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 --AVGKPMCLLFEYMAYGDLNEFLrsmsphtvcslshsdlstrarvSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVH 722
Cdd:cd14008    74 ddPESDKLYLVLEYCEGGPVMELD----------------------SGDRVPPLPEETARKYFRDLVLGLEYLHENGIVH 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 723 RDLATRNCLVGENMVVKIADFGLSRNIYSADYY--KADGNDAipirWMPPEsIFYNRYTTES----DVWAYGVVLWeIFS 796
Cdd:cd14008   132 RDIKPENLLLTADGTVKISDFGVSEMFEDGNDTlqKTAGTPA----FLAPE-LCDGDSKTYSgkaaDIWALGVTLY-CLV 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 797 YGLQPYYGMahEEVIYYVrdgNILAC------PENCPLELYNLMRLCWSKLPADR 845
Cdd:cd14008   206 FGRLPFNGD--NILELYE---AIQNQndefpiPPELSPELKDLLRRMLEKDPEKR 255
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
580-855 3.61e-25

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: 106.16  E-value: 3.61e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyEPftmVAVKML-------KEEASADMQAD-------------FQREAALMAEFDNPNIVK 639
Cdd:cd14000     2 LGDGGFGSVYRASYKG----EP---VAVKIFnkhtssnFANVPADTMLRhlratdamknfrlLRQELTVLSHLHHPSIVY 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 640 LLGVCAvgKPMCLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERK 719
Cdd:cd14000    75 LLGIGI--HPLMLVLELAPLGSLDHLLQQDSRSFA--------------------SLGRTLQQRIALQVADGLRYLHSAM 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 720 FVHRDLATRNCLV-----GENMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYN-RYTTESDVWAYGVVLWE 793
Cdd:cd14000   133 IIYRDLKSHNVLVwtlypNSAIIIKIADYGISRQCCRMGAKGSEGTPG----FRAPEIARGNvIYNEKVDVFSFGMLLYE 208
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 794 IFSyGLQPYYG--MAHEEVIYYVRDGNILACPENCPL-ELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd14000   209 ILS-GGAPMVGhlKFPNEFDIHGGLRPPLKQYECAPWpEVEVLMKKCWKENPQQRPTAVTVVSIL 272
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
580-852 7.93e-25

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: 105.03  E-value: 7.93e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGllpyepftmvAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14222     1 LGKGFFGQAIKVthKATG----------KVMVMKELIRCDeeTQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTE 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSMSPHTvcslshsdlsTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14222    71 FIEGGTLKDFLRADDPFP----------WQQKVS--------------FAKGIASGMAYLHSMSIIHRDLNSHNCLIKLD 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYS----------------------ADYYKADGNDaipiRWMPPESIFYNRYTTESDVWAYGVVLWE 793
Cdd:cd14222   127 KTVVVADFGLSRLIVEekkkpppdkpttkkrtlrkndrKKRYTVVGNP----YWMAPEMLNGKSYDEKVDIFSFGIVLCE 202
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 794 IFSyglQPYygmAHEEVIYYVRDGNILA-------CPENCPLELYNLMRLCWSKLPADRPSFCSIH 852
Cdd:cd14222   203 IIG---QVY---ADPDCLPRTLDFGLNVrlfwekfVPKDCPPAFFPLAAICCRLEPDSRPAFSKLE 262
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
575-857 8.78e-25

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: 104.47  E-value: 8.78e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQAR--APGLLpyepftmVAVKMLK-EEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd08215     3 EKIRVIGKGSFGSAYLVRrkSDGKL-------YVLKEIDlSNMSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLC 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRsmsphtvcslshsdlstrARVSSPGPPPlscAEQLC-IARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd08215    76 IVMEYADGGDLAQKIK------------------KQKKKGQPFP---EEQILdWFVQICLALKYLHSRKILHRDLKTQNI 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRnIYSAD-----------YYkadgndaipirwMPPEsIFYNR-YTTESDVWAYGVVLWEIFSyg 798
Cdd:cd08215   135 FLTKDGVVKLGDFGISK-VLESTtdlaktvvgtpYY------------LSPE-LCENKpYNYKSDIWALGCVLYELCT-- 198
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 799 LQ-PYYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPsfcSIHRILQR 857
Cdd:cd08215   199 LKhPFEANNLPALVYKIVKGQYPPIPSQYSSELRDLVNSMLQKDPEKRP---SANEILSS 255
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
580-861 1.14e-24

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: 104.35  E-value: 1.14e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepftMVAVKMLKEEASADMQ-ADFQREAALMAEFDNPNIVKLLGVCavgkpmcllfeyma 658
Cdd:cd14063     8 IGKGRFGRVHRGRWHG--------DVAIKLLNIDYLNEEQlEAFKEEVAAYKNTRHDNLVLFMGAC-------------- 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 ygdlneflrsMSPHT---VCSL-SHSDLSTRARVsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd14063    66 ----------MDPPHlaiVTSLcKGRTLYSLIHE---RKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLEN 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVkIADFGLSRNIYSADYYKADGNDAIPIRWMP---PE-----SIFYNR-----YTTESDVWAYGVVLWEIFSYGLqP 801
Cdd:cd14063   133 GRVV-ITDFGLFSLSGLLQPGRREDTLVIPNGWLCylaPEiiralSPDLDFeeslpFTKASDVYAFGTVWYELLAGRW-P 210
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 802 YYGMAHEEVIYYVRDG-----NILACPEncplELYNLMRLCWSKLPADRPSFCSIHRILQRMCER 861
Cdd:cd14063   211 FKEQPAESIIWQVGCGkkqslSQLDIGR----EVKDILMQCWAYDPEKRPTFSDLLRMLERLPKK 271
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
580-847 2.99e-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: 103.23  E-value: 2.99e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEA-SADMQADFQREAALmAEFDNPNIVKLLGVCAVGKPMCLLFEYMa 658
Cdd:cd13979    11 LGSGGFGSVYKATYKG-------ETVAVKIVRRRRkNRASRQSFWAELNA-ARLRHENIVRVLAAETGTDFASLGLIIM- 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 ygdlnEFLRSMSPHtvcslshsdlstraRVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVV 738
Cdd:cd13979    82 -----EYCGNGTLQ--------------QLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVC 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 739 KIADFGLSR-----NIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMaHEEVIYY 813
Cdd:cd13979   143 KLCDFGCSVklgegNEVGTPRSHIGGT----YTYRAPELLKGERVTPKADIYSFGITLWQMLT-RELPYAGL-RQHVLYA 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 814 VRDGNILacPENCPLE-------LYNLMRLCWSKLPADRPS 847
Cdd:cd13979   217 VVAKDLR--PDLSGLEdsefgqrLRSLISRCWSAQPAERPN 255
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
577-854 4.45e-24

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: 102.50  E-value: 4.45e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVF-----QARAPGLLpyepftmvavKMLKEEASADMQ----ADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd08222     5 VRKLGSGNFGTVYlvsdlKATADEEL----------KVLKEISVGELQpdetVDANREAKLLSKLDHPAIVKFHDSFVEK 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLneflrsmsphtvcslshsDLSTRARVSSPGPPPlscaEQLCIAR--QVAAGMAYLSERKFVHRDL 725
Cdd:cd08222    75 ESFCIVTEYCEGGDL------------------DDKISEYKKSGTTID----ENQILDWfiQLLLAVQYMHERRILHRDL 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENmVVKIADFGLSRnIYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEI--FSYGLQPYY 803
Cdd:cd08222   133 KAKNIFLKNN-VIKVGDFGISR-ILMGTSDLATTFTGTPY-YMSPEVLKHEGYNSKSDIWSLGCILYEMccLKHAFDGQN 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 804 GMAheeVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHRI 854
Cdd:cd08222   210 LLS---VMYKIVEGETPSLPDKYSKELNAIYSRMLNKDPALRPSAAEILKI 257
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
580-861 5.70e-24

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: 102.17  E-value: 5.70e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF--QARAPGllpyepftmvAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14155     1 IGSGFFSEVYkvRHRTSG----------QVMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYI 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSmsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV----- 732
Cdd:cd14155    71 NGGNLEQLLDS------------------------NEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrden 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVkiADFGLSRNIYSADYykadGNDAIPI----RWMPPESIFYNRYTTESDVWAYGVVLWEIF------------- 795
Cdd:cd14155   127 GYTAVV--GDFGLAEKIPDYSD----GKEKLAVvgspYWMAPEVLRGEPYNEKADVFSYGIILCEIIariqadpdylprt 200
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 796 -SYGLQpYYGMAHeeviyyvrdgnilACPEnCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCER 861
Cdd:cd14155   201 eDFGLD-YDAFQH-------------MVGD-CPPDFLQLAFNCCNMDPKSRPSFHDIVKTLEEILEK 252
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
573-856 6.31e-24

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: 101.83  E-value: 6.31e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd14003     1 NYELGKTLGEGSFGKVKLARhkLTG-------EKVAIKIIdKSKLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENK 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPhtvcsLSHSDlstrARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd14003    74 IYLVMEYASGGELFDYIVNNGR-----LSEDE----ARR---------------FFQQLISAVDYCHSNGIVHRDLKLEN 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIY----------SADYykadgndaipirwMPPESIFYNRY-TTESDVWAYGVVLWEIFsYG 798
Cdd:cd14003   130 ILLDKNGNLKIIDFGLSNEFRggsllktfcgTPAY-------------AAPEVLLGRKYdGPKADVWSLGVILYAML-TG 195
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 799 LQPYYGMAHEEVIYYVRDGNILaCPENCPLELYNLMRLCWSKLPADRPsfcSIHRILQ 856
Cdd:cd14003   196 YLPFDDDNDSKLFRKILKGKYP-IPSHLSPDARDLIRRMLVVDPSKRI---TIEEILN 249
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
575-856 7.67e-24

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: 101.40  E-value: 7.67e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgllpyEPFT--MVAVKMLKEE--ASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14007     3 EIGKPLGKGKFGNVYLAR-------EKKSgfIVALKVISKSqlQKSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRI 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRS---MSPHTVCSlshsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd14007    76 YLILEYAPNGELYKELKKqkrFDEKEAAK---------------------------YIYQLALALDYLHSKNIIHRDIKP 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSA---------DYykadgndaipirwMPPESIFYNRYTTESDVWAYGVVLWEiFSYG 798
Cdd:cd14007   129 ENILLGSNGELKLADFGWSVHAPSNrrktfcgtlDY-------------LPPEMVEGKEYDYKVDIWSLGVLCYE-LLVG 194
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 799 LQPYYGMAHEEVIyyvrdGNILAC----PENCPLELYNLMRLCWSKLPADRPsfcSIHRILQ 856
Cdd:cd14007   195 KPPFESKSHQETY-----KRIQNVdikfPSSVSPEAKDLISKLLQKDPSKRL---SLEQVLN 248
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
575-796 9.26e-24

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: 102.26  E-value: 9.26e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEasaDMQADFQ----REAALMAEFDNPNIVKLLGVCaVGKPM 650
Cdd:cd07840     2 EKIAQIGEGTYGQVYKARN-----KKTGELVALKKIRME---NEKEGFPitaiREIKLLQKLDHPNVVRLKEIV-TSKGS 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 C-------LLFEYMAYgDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHR 723
Cdd:cd07840    73 AkykgsiyMVFEYMDH-DLTGLLDNPEVK-----------------------FTESQIKCYMKQLLEGLQYLHSNGILHR 128
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSRNI---YSADYykadGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd07840   129 DIKGSNILINNDGVLKLADFGLARPYtkeNNADY----TNRVITLWYRPPELLLgATRYGPEVDMWSVGCILAELFT 201
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
568-851 9.70e-24

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: 102.06  E-value: 9.70e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPGllpyepftMVAVKMLKEEASADMQAD-FQREAALMAEFDNPNIVKLLGVCAv 646
Cdd:cd14151     4 EIPDGQITVGQRIGSGSFGTVYKGKWHG--------DVAVKMLNVTAPTPQQLQaFKNEVGVLRKTRHVNILLFMGYST- 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 gKPMCLLFEYMAYGDlneflrsmsphtvcSLSHSDLSTRARvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd14151    75 -KPQLAIVTQWCEGS--------------SLYHHLHIIETK--------FEMIKLIDIARQTAQGMDYLHAKSIIHRDLK 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGL----SRNIYSADYYKADGNdaipIRWMPPESIFY---NRYTTESDVWAYGVVLWEIFSyGL 799
Cdd:cd14151   132 SNNIFLHEDLTVKIGDFGLatvkSRWSGSHQFEQLSGS----ILWMAPEVIRMqdkNPYSFQSDVYAFGIVLYELMT-GQ 206
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 800 QPYYGMAH-EEVIYYVRDG----NILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14151   207 LPYSNINNrDQIIFMVGRGylspDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQI 263
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
580-794 1.45e-23

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: 101.64  E-value: 1.45e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQAR--APGllpyepfTMVAVKML---KEEASADMQAdfQREAALMAEF-DNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd07832     8 IGEGAHGIVFKAKdrETG-------ETVALKKValrKLEGGIPNQA--LREIKALQACqGHPYVVKLRDVFPHGTGFVLV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAyGDLNEFLRsmsphtvcslsHSDlstrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd07832    79 FEYML-SSLSEVLR-----------DEE------------RPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLIS 134
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 734 ENMVVKIADFGLSRnIYSAD----YYKADGNdaipiRW-MPPESIFYNR-YTTESDVWAYGVVLWEI 794
Cdd:cd07832   135 STGVLKIADFGLAR-LFSEEdprlYSHQVAT-----RWyRAPELLYGSRkYDEGVDLWAVGCIFAEL 195
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
570-861 2.08e-23

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: 100.92  E-value: 2.08e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06641     2 PEELFTKLEKIGKGSFGEVFKG-----IDNRTQKVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRsmsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06641    77 LWIIMEYLGGGSALDLLE-------------------------PGPLDETQIATILREILKGLDYLHSEKKIHRDIKAAN 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSADyYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIfSYGLQPYYGMAHEE 809
Cdd:cd06641   132 VLLSEHGEVKLADFGVAGQLTDTQ-IKRN*FVGTPF-WMAPEVIKQSAYDSKADIWSLGITAIEL-ARGEPPHSELHPMK 208
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 810 VIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI--HRILQRMCER 861
Cdd:cd06641   209 VLFLIPKNNPPTLEGNYSKPLKEFVEACLNKEPSFRPTAKELlkHKFILRNAKK 262
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
580-819 2.65e-23

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: 100.24  E-value: 2.65e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGLLpyepftmVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05117     8 LGRGSFGVVRLAvhKKTGEE-------YAVKIIdKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMEL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLrsmspHTVCSLSHSDlstrARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV---G 733
Cdd:cd05117    81 CTGGELFDRI-----VKKGSFSERE----AAK---------------IMKQILSAVAYLHSQGIVHRDLKPENILLaskD 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNI----------YSADYykadgndaipirwMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY 803
Cdd:cd05117   137 PDSPIKIIDFGLAKIFeegeklktvcGTPYY-------------VAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFY 202
                         250
                  ....*....|....*.
gi 1937920432 804 GMAHEEVIYYVRDGNI 819
Cdd:cd05117   203 GETEQELFEKILKGKY 218
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
580-803 2.70e-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: 100.02  E-value: 2.70e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpyEPFT--MVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14002     9 IGEGSFGKVYKGR-------RKYTgqVVALKFIpKRGKSEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEY 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 mAYGDLNEFLrsmsphtvcslshSDLSTrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd14002    82 -AQGELFQIL-------------EDDGT-----------LPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGG 136
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 737 VVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYY 803
Cdd:cd14002   137 VVKLCDFGFARAM-SCNTLVLTSIKGTPL-YMAPELVQEQPYDHTADLWSLGCILYELF-VGQPPFY 200
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
580-847 3.16e-23

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: 99.98  E-value: 3.16e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGLLpyepftmVAVKMLKEEaSADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd06614     8 IGEGASGEVYKAtdRATGKE-------VAIKKMRLR-KQNKELIIN-EILIMKECKHPNIVDYYDSYLVGDELWVVMEYM 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRsmspHTVCSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd06614    79 DGGSLTDIIT----QNPVRMNESQIAY-------------------VCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGS 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGlsrniysadyYKADGNDAIPIR--------WMPPESIFYNRYTTESDVWAYGVVLWEIfSYGLQPYYGMAHEE 809
Cdd:cd06614   136 VKLADFG----------FAAQLTKEKSKRnsvvgtpyWMAPEVIKRKDYGPKVDIWSLGIMCIEM-AEGEPPYLEEPPLR 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 810 VIYYVRDGNI--LACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06614   205 ALFLITTKGIppLKNPEKWSPEFKDFLNKCLVKDPEKRPS 244
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
575-795 3.89e-23

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: 100.42  E-value: 3.89e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASAD-MQADFQREAALM---AEFDNPNIVKLLGVCAVGK-- 648
Cdd:cd07863     3 EPVAEIGVGAYGTVYKARDP-----HSGHFVALKSVRVQTNEDgLPLSTVREVALLkrlEAFDHPNIVRLMDVCATSRtd 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 ---PMCLLFEymaygdlneflrsmsphtvcslsHSDLSTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd07863    78 retKVTLVFE-----------------------HVDQDLRTYLDKVPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDL 134
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRnIYSadYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIF 795
Cdd:cd07863   135 KPENILVTSGGQVKLADFGLAR-IYS--CQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMF 201
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
580-848 4.95e-23

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: 99.22  E-value: 4.95e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVK-MLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd14009     1 IGRGSFATVWKGRHK-----QTGEVVAIKeISRKKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCA 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRsmsphtvcslshsdlsTRARVSSpgppplscAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV---GEN 735
Cdd:cd14009    76 GGDLSQYIR----------------KRGRLPE--------AVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLstsGDD 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADYykADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYyvr 815
Cdd:cd14009   132 PVLKIADFGFARSLQPASM--AETLCGSPL-YMAPEILQFQKYDAKADLWSVGAILFEMLV-GKPPFRGSNHVQLLR--- 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 816 dgNILACPENCPLELY-----NLMRLCWSKL---PADRPSF 848
Cdd:cd14009   205 --NIERSDAVIPFPIAaqlspDCKDLLRRLLrrdPAERISF 243
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
572-847 6.12e-23

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: 99.20  E-value: 6.12e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapgllpYEPfT--MVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06623     1 SDLERVKVLGQGSSGVVYKVR------HKP-TgkIYALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGE 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstrarvsSPGPPPLSCAeqlCIARQVAAGMAYL-SERKFVHRDLATR 728
Cdd:cd06623    74 ISIVLEYMDGGSLADLLKK---------------------VGKIPEPVLA---YIARQILKGLDYLhTKRHIIHRDIKPS 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIYSADYYKAD--GNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEiFSYGLQPY---- 802
Cdd:cd06623   130 NLLINSKGEVKIADFGISKVLENTLDQCNTfvGTVT----YMSPERIQGESYSYAADIWSLGLTLLE-CALGKFPFlppg 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 803 -YGMAheEVIYYVRDGNILACPEN-CPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06623   205 qPSFF--ELMQAICDGPPPSLPAEeFSPEFRDFISACLQKDPKKRPS 249
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
580-796 8.14e-23

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; 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. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 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: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 99.90  E-value: 8.14e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASAD---MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14159     1 IGEGGFGCVYQAVMRN-------TEYAVKRLKEDSELDwsvVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVY 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRsmsPHTVCslshsdlstrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERK--FVHRDLATRNCLVGE 734
Cdd:cd14159    74 LPNGSLEDRLH---CQVSC------------------PCLSWSQRLHVLLGTARAIQYLHSDSpsLIHGDVKSSNILLDA 132
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 735 NMVVKIADFGLSRniySADYYKADGNDAIPIR---------WMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd14159   133 ALNPKLGDFGLAR---FSRRPKQPGMSSTLARtqtvrgtlaYLPEEYVKTGTLSVEIDVYSFGVVLLELLT 200
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
574-851 9.24e-23

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: 98.94  E-value: 9.24e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGllpyepftMVAVKMLK--EEASADMQAdFQREAALMAEFDNPNIVKLLGVcaVGKPmc 651
Cdd:cd14150     2 VSMLKRIGTGSFGTVFRGKWHG--------DVAVKILKvtEPTPEQLQA-FKNEMQVLRKTRHVNILLFMGF--MTRP-- 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 llfeymAYGDLNEFLRSMSPHTVCSLSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd14150    69 ------NFAIITQWCEGSSLYRHLHVTETRFDTMQLID--------------VARQTAQGMDYLHAKNIIHRDLKSNNIF 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGL----SRNIYSADYYKADGNdaipIRWMPPESIFY---NRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14150   129 LHEGLTVKIGDFGLatvkTRWSGSQQVEQPSGS----ILWMAPEVIRMqdtNPYSFQSDVYAYGVVLYELMS-GTLPYSN 203
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 805 MAH-EEVIYYVRDG----NILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14150   204 INNrDQIIFMVGRGylspDLSKLSSNCPKAMKRLLIDCLKFKREERPLFPQI 255
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
580-851 1.08e-22

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting 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. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K 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: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 98.37  E-value: 1.08e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEA-----SADMqadFQREAALMAEFDNPNIVKLLGVCaVGKP--MCL 652
Cdd:cd14064     1 IGSGSFGKVYKGRCRN-------KIVAIKRYRANTycsksDVDM---FCREVSILCRLNHPCVIQFVGAC-LDDPsqFAI 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLneflrsmsphtvcslsHSDLSTRARVSSPgppplscAEQLCIARQVAAGMAYLSE--RKFVHRDLATRNC 730
Cdd:cd14064    70 VTQYVSGGSL----------------FSLLHEQKRVIDL-------QSKLIIAVDVAKGMEYLHNltQPIIHRDLNSHNI 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSAD---YYKADGNdaipIRWMPPESIFYN-RYTTESDVWAYGVVLWEIFSyGLQPYYGM- 805
Cdd:cd14064   127 LLYEDGHAVVADFGESRFLQSLDednMTKQPGN----LRWMAPEVFTQCtRYSIKADVFSYALCLWELLT-GEIPFAHLk 201
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 806 ---AHEEVIYYVRDGNIlacPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14064   202 paaAAADMAYHHIRPPI---GYSIPKPISSLLMRGWNAEPESRPSFVEI 247
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
570-847 1.58e-22

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: 97.72  E-value: 1.58e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLkeEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06612     1 PEEVFDILEKLGEGSYGSVYKAIHK-----ETGQVVAIKVV--PVEEDLQ-EIIKEISILKQCDSPYIVKYYGSYFKNTD 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPhtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06612    73 LWIVMEYCGAGSVSDIMKITNK-----------------------TLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGN 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSAdyyKADGNDAI--PIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAH 807
Cdd:cd06612   130 ILLNEEGQAKLADFGVSGQLTDT---MAKRNTVIgtPF-WMAPEVIQEIGYNNKADIWSLGITAIEMAE-GKPPYSDIHP 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 808 EEVIYYV--RDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06612   205 MRAIFMIpnKPPPTLSDPEKWSPEFNDFVKKCLVKDPEERPS 246
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
577-796 2.13e-22

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: 97.31  E-value: 2.13e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEASADMQAdfQREAALMAEFDN----PNIVKLLGVC--AVGKPM 650
Cdd:cd05118     4 LRKIGEGAFGTVWLARD-----KVTGEKVAIKKIKNDFRHPKAA--LREIKLLKHLNDveghPNIVKLLDVFehRGGNHL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYgDLNEFLRsmsphtvcslshsdlstraRVSSPGPPPLSCAeqlcIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05118    77 CLVFELMGM-NLYELIK-------------------DYPRGLPLDLIKS----YLYQLLQALDFLHSNGIIHRDLKPENI 132
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 731 LV-GENMVVKIADFGLSRnIYSADYYkadgNDAIPIRW-MPPESIF-YNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd05118   133 LInLELGQLKLADFGLAR-SFTSPPY----TPYVATRWyRAPEVLLgAKPYGSSIDIWSLGCILAELLT 196
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
580-847 4.65e-22

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: 96.70  E-value: 4.65e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLK----EEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd06632     8 LGSGSFGSVYEG-----FNGDTGDFFAVKEVSlvddDKKSRESVKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLE 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSMSPHT--VCSLshsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd06632    83 YVPGGSIHKLLQRYGAFEepVIRL--------------------------YTRQILSGLAYLHSRNTVHRDIKGANILVD 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSADYYKADGNDAIpirWMPPESI--FYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd06632   137 TNGVVKLADFGMAKHVEAFSFAKSFKGSPY---WMAPEVImqKNSGYGLAVDIWSLGCTVLEMAT-GKPPWSQYEGVAAI 212
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1937920432 812 YYV-RDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06632   213 FKIgNSGELPPIPDHLSPDAKDFIRLCLQRDPEDRPT 249
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
605-858 5.55e-22

Pseudokinase domain of the unknown subfamily 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: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 96.47  E-value: 5.55e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKMLKEEASAdMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSmsphtvcslshSDLst 684
Cdd:cd14045    33 VAIKKIAKKSFT-LSKRIRKEVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLN-----------EDI-- 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 685 rarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLS--RNIYSADYYKADGNDA 762
Cdd:cd14045    99 ----------PLNWGFRFSFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTtyRKEDGSENASGYQQRL 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 763 IPIrWMPPE--SIFYNRYTTESDVWAYGVVLWEIFS---------YGLQPYYGMAHEEVIYYVRDGnilACPenCPLELY 831
Cdd:cd14045   169 MQV-YLPPEnhSNTDTEPTQATDVYSYAIILLEIATrndpvpeddYSLDEAWCPPLPELISGKTEN---SCP--CPADYV 242
                         250       260
                  ....*....|....*....|....*..
gi 1937920432 832 NLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14045   243 ELIRRCRKNNPAQRPTFEQIKKTLHKI 269
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
575-801 7.18e-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: 96.58  E-value: 7.18e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASAD-MQADFQREAALMAE---FDNPNIVKLLGVCAV---- 646
Cdd:cd07838     2 EEVAEIGEGAYGTVYKARDL-----QDGRFVALKKVRVPLSEEgIPLSTIREIALLKQlesFEHPNVVRLLDVCHGprtd 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 -GKPMCLLFEYMAYgDLNEFLRsmsphtvcslshsdlstraRVSSPGPPPlscaEQLC-IARQVAAGMAYLSERKFVHRD 724
Cdd:cd07838    77 rELKLTLVFEHVDQ-DLATYLD-------------------KCPKPGLPP----ETIKdLMRQLLRGLDFLHSHRIVHRD 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRnIYSAD----------YYKAdgndaipirwmpPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd07838   133 LKPQNILVTSDGQVKLADFGLAR-IYSFEmaltsvvvtlWYRA------------PEVLLQSSYATPVDMWSVGCIFAEL 199

                  ....*..
gi 1937920432 795 FSygLQP 801
Cdd:cd07838   200 FN--RRP 204
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
575-795 1.50e-21

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: 95.87  E-value: 1.50e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapGLLPYEPFtmVAVKMLKEEASAD-MQADFQREAALMAE---FDNPNIVKLLGVCAVGK-- 648
Cdd:cd07862     4 ECVAEIGEGAYGKVFKAR--DLKNGGRF--VALKRVRVQTGEEgMPLSTIREVAVLRHletFEHPNVVRLFDVCTVSRtd 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 ---PMCLLFEYMAYgDLNEFLRsmsphtvcslshsdlstraRVSSPGPPPLSCAEQLCiarQVAAGMAYLSERKFVHRDL 725
Cdd:cd07862    80 retKLTLVFEHVDQ-DLTTYLD-------------------KVPEPGVPTETIKDMMF---QLLRGLDFLHSHRVVHRDL 136
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRnIYSadYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIF 795
Cdd:cd07862   137 KPQNILVTSSGQIKLADFGLAR-IYS--FQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMF 203
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
575-793 2.56e-21

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: 95.33  E-value: 2.56e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLK--EEASADMQADFQ--REAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd07841     3 EKGKKLGEGTYAVVYKARdkETG-------RIVAIKKIKlgERKEAKDGINFTalREIKLLQELKHPNIIGLLDVFGHKS 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAyGDLNEFLRSMSPhtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd07841    76 NINLVFEFME-TDLEKVIKDKSI-----------------------VLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPN 131
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIYSADY---YKadgndaIPIRWM-PPESIFYNR-YTTESDVWAYGVVLWE 793
Cdd:cd07841   132 NLLIASDGVLKLADFGLARSFGSPNRkmtHQ------VVTRWYrAPELLFGARhYGVGVDMWSVGCIFAE 195
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
571-847 1.24e-20

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: 92.74  E-value: 1.24e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQAR-APGLLPYepftmvAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGvCAVGKP 649
Cdd:cd13996     5 LNDFEEIELLGSGGFGSVYKVRnKVDGVTY------AIKKIRLTEKSSASEKVLREVKALAKLNHPNIVRYYT-AWVEEP 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 -MCLLFEYMAYGDLNEFLRsmsphtvCSLSHSDLStrarvsspgppplscaEQLC--IARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd13996    78 pLYIQMELCEGGTLRDWID-------RRNSSSKND----------------RKLAleLFKQILKGVSYIHSKGIVHRDLK 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLV-GENMVVKIADFGLSRNI---------YSADYYKADGNDAIPI---RWMPPESIFYNRYTTESDVWAYGVVLWE 793
Cdd:cd13996   135 PSNIFLdNDDLQVKIGDFGLATSIgnqkrelnnLNNNNNGNTSNNSVGIgtpLYASPEQLDGENYNEKADIYSLGIILFE 214
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 794 IFSyglQPYYGMAHEEVIYYVRDGNIlacPENCPLELYN---LMRLCWSKLPADRPS 847
Cdd:cd13996   215 MLH---PFKTAMERSTILTDLRNGIL---PESFKAKHPKeadLIQSLLSKNPEERPS 265
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
580-847 1.32e-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: 92.44  E-value: 1.32e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQAD---------FQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd06629     9 IGKGTYGRVYLA-----MNATTGEMLAVKQVELPKTSSDRADsrqktvvdaLKSEIDTLKDLDHPNIVQYLGFEETEDYF 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgppplscaEQLC--IARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd06629    84 SIFLEYVPGGSIGSCLRKYGKFE--------------------------EDLVrfFTRQILDGLAYLHSKGILHRDLKAD 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNiySADYYKADGNDAI--PIRWMPPESIFYNR--YTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd06629   138 NILVDLEGICKISDFGISKK--SDDIYGNNGATSMqgSVFWMAPEVIHSQGqgYSAKVDIWSLGCVVLEMLA-GRRPWSD 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 805 MAHEEVIYYVrdGNILACP---ENCPL--ELYNLMRLCWSKLPADRPS 847
Cdd:cd06629   215 DEAIAAMFKL--GNKRSAPpvpEDVNLspEALDFLNACFAIDPRDRPT 260
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
577-848 2.21e-20

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 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: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 92.29  E-value: 2.21e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASA--DMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd14026     2 LRYLSRGAFGTVSRARHA-----DWRVTVAIKCLKLDSPVgdSERNCLLKEAEILHKARFSYILPILGICNEPEFLGIVT 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERK--FVHRDLATRNCLV 732
Cdd:cd14026    77 EYMTNGSLNELLHEKDIY---------------------PDVAWPLRLRILYEIALGVNYLHNMSppLLHHDLKTQNILL 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSR-NIYSADyyKADGNDAIP----IRWMPPESifYN-----RYTTESDVWAYGVVLWEIFSYGlQPY 802
Cdd:cd14026   136 DGEFHVKIADFGLSKwRQLSIS--QSRSSKSAPeggtIIYMPPEE--YEpsqkrRASVKHDIYSYAIIMWEVLSRK-IPF 210
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 803 YGMAHE-EVIYYVRDG-----NILACPENCPLE--LYNLMRLCWSKLPADRPSF 848
Cdd:cd14026   211 EEVTNPlQIMYSVSQGhrpdtGEDSLPVDIPHRatLINLIESGWAQNPDERPSF 264
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
574-855 3.38e-20

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It 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 cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 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: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 91.16  E-value: 3.38e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGLLPYEPF--TMVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd05078     1 LIFNESLGQGTFTKIFKGIRREVGDYGQLheTEVLLKVL-DKAHRNYSESFFEAASMMSQLSHKHLVLNYGVCVCGDENI 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRsmsphtvcslshsdlstRARVSspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd05078    80 LVQEYVKFGSLDTYLK-----------------KNKNC------INILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNIL 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 V--------GENMVVKIADFGLSRNIYSADYYKadgnDAIPirWMPPESIFYNRYTT-ESDVWAYGVVLWEIFSYGLQPY 802
Cdd:cd05078   137 LireedrktGNPPFIKLSDPGISITVLPKDILL----ERIP--WVPPECIENPKNLSlATDKWSFGTTLWEICSGGDKPL 210
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 803 YGMAHEEVIYYVRDGNILACPEncPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd05078   211 SALDSQRKLQFYEDRHQLPAPK--WTELANLINNCMDYEPDHRPSFRAIIRDL 261
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
121-201 9.23e-20

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: 84.43  E-value: 9.23e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKII--EGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd04969     1 PDFELNPVKKKILaaKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80

                  ...
gi 1937920432 199 AYS 201
Cdd:cd04969    81 ANS 83
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
120-194 1.16e-19

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 83.77  E-value: 1.16e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 120 KPKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENS---RIAVLESGSLRIHNVQKEDAGQYRCVAKN 194
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGStrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
580-861 1.31e-19

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: 89.73  E-value: 1.31e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd06642    12 IGKGSFGEVYKG-----IDNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGG 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRsmsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd06642    87 GSALDLLK-------------------------PGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVK 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNIYSADyYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIfSYGLQPYYGMAHEEVIYYVrdgni 819
Cdd:cd06642   142 LADFGVAGQLTDTQ-IKRNTFVGTPF-WMAPEVIKQSAYDFKADIWSLGITAIEL-AKGEPPNSDLHPMRVLFLI----- 213
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 820 lacPENCPLELY--------NLMRLCWSKLPADRPSFCSI--HRILQRMCER 861
Cdd:cd06642   214 ---PKNSPPTLEgqhskpfkEFVEACLNKDPRFRPTAKELlkHKFITRYTKK 262
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
572-795 1.56e-19

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: 90.45  E-value: 1.56e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVK---MLKEEASADMQAdfQREAALMAEFDNPNIVKLLGVcAV 646
Cdd:cd07866     8 RDYEILGKLGEGTFGEVYKARqiKTG-------RVVALKkilMHNEKDGFPITA--LREIKILKKLKHPNVVPLIDM-AV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKP---------MCLLFEYMAYgDLNEFLRSMSPHtvcsLSHSDLStrarvsspgppplscaeqlCIARQVAAGMAYLSE 717
Cdd:cd07866    78 ERPdkskrkrgsVYMVTPYMDH-DLSGLLENPSVK----LTESQIK-------------------CYMLQLLEGINYLHE 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 718 RKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADY---YKADGNDA-----IPIRWM-PPESIF-YNRYTTESDVWAY 787
Cdd:cd07866   134 NHILHRDIKAANILIDNQGILKIADFGLARPYDGPPPnpkGGGGGGTRkytnlVVTRWYrPPELLLgERRYTTAVDIWGI 213

                  ....*...
gi 1937920432 788 GVVLWEIF 795
Cdd:cd07866   214 GCVFAEMF 221
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
573-795 1.69e-19

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: 1.69e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASAD-MQADFQREAALMAEFDNPNIVKLLGVcAVGKPMC 651
Cdd:cd07845     8 EFEKLNRIGEGTYGIVYRARDT-----TSGEIVALKKVRMDNERDgIPISSLREITLLLNLRHPNIVELKEV-VVGKHLD 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAY--GDLNEFLRSMsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd07845    82 SIFLVMEYceQDLASLLDNM-----------------------PTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSN 138
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 730 CLVGENMVVKIADFGLSRNIysADYYKADGNDAIPIRWMPPESIFYNR-YTTESDVWAYGVVLWEIF 795
Cdd:cd07845   139 LLLTDKGCLKIADFGLARTY--GLPAKPMTPKVVTLWYRAPELLLGCTtYTTAIDMWAVGCILAELL 203
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
571-817 1.74e-19

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: 88.86  E-value: 1.74e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARApgllpyEPFTMVAVKMLKEEASADMQ--ADFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd14161     2 KHRYEFLETLGKGTYGRVKKARD------SSGRLVAIKSIRKDRIKDEQdlLHIRREIEIMSSLNHPHIISVYEVFENSS 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLrsmsphtvcslshsdlSTRARvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd14161    76 KIVIVMEYASRGDLYDYI----------------SERQR--------LSELEARHFFRQIVSAVHYCHANGIVHRDLKLE 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSrNIYSADYYKADGNDAiPIrWMPPESIFYNRYT-TESDVWAYGVVLWeIFSYGLQPYYGMAH 807
Cdd:cd14161   132 NILLDANGNIKIADFGLS-NLYNQDKFLQTYCGS-PL-YASPEIVNGRPYIgPEVDSWSLGVLLY-ILVHGTMPFDGHDY 207
                         250
                  ....*....|
gi 1937920432 808 EEVIYYVRDG 817
Cdd:cd14161   208 KILVKQISSG 217
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
580-847 1.88e-19

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: 88.90  E-value: 1.88e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFG--RVFQARAPGLLPYepftmVAVKMLKEEASADMQADFqrEAALMAEFD------NPNIVKLLGVCAVGKP-M 650
Cdd:cd13994     1 IGKGATSvvRIVTKKNPRSGVL-----YAVKEYRRRDDESKRKDY--VKRLTSEYIissklhHPNIVKVLDLCQDLHGkW 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLrsmsphtvcslshsdlsTRARVSSPGppplscaEQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd13994    74 CLVMEYCPGGDLFTLI-----------------EKADSLSLE-------EKDCFFKQILRGVAYLHSHGIAHRDLKPENI 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNI-YSADYYKADGNDAI-PIRWMPPESIFYNRYTTES-DVWAYGVVLWEIFSyGLQPyYGMAH 807
Cdd:cd13994   130 LLDEDGVLKLTDFGTAEVFgMPAEKESPMSAGLCgSEPYMAPEVFTSGSYDGRAvDVWSCGIVLFALFT-GRFP-WRSAK 207
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 808 -EEVIYYV----RDGNILACPENCPLELYNLMRLCWSKL---PADRPS 847
Cdd:cd13994   208 kSDSAYKAyeksGDFTNGPYEPIENLLPSECRRLIYRMLhpdPEKRIT 255
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
572-796 2.85e-19

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: 88.91  E-value: 2.85e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEEASADM-QADFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd07833     1 NKYEVLGVVGEGAYGVVLKCRnkATG-------EIVAIKKFKESEDDEDvKKTALREVKVLRQLRHENIVNLKEAFRRKG 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYG---DLNEFLRSMSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDL 725
Cdd:cd07833    74 RLYLVFEYVERTlleLLEASPGGLPPDAVRSYIW---------------------------QLLQAIAYCHSHNIIHRDI 126
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIY--SADYYkadgNDAIPIRWM-PPESIF-YNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd07833   127 KPENILVSESGVLKLCDFGFARALTarPASPL----TDYVATRWYrAPELLVgDTNYGKPVDVWAIGCIMAELLD 197
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
580-847 3.05e-19

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: 88.57  E-value: 3.05e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpYEPFTM-VAVKMLK-EEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd06610     9 IGSGATAVVYAAY------CLPKKEkVAIKRIDlEKCQTSMD-ELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHTVcslshsdlstrarvsspgppplscAEQLCIA---RQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd06610    82 SGGSLLDIMKSSYPRGG------------------------LDEAIIAtvlKEVLKGLEYLHSNGQIHRDVKAGNILLGE 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSadyykaDGNDAIPIR--------WMPPESIFYNR-YTTESDVWAYGVVLWEIfSYGLQPYYGM 805
Cdd:cd06610   138 DGSVKIADFGVSASLAT------GGDRTRKVRktfvgtpcWMAPEVMEQVRgYDFKADIWSFGITAIEL-ATGAAPYSKY 210
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 806 AHEEVIYYVRDGNILACPENCPLELY-----NLMRLCWSKLPADRPS 847
Cdd:cd06610   211 PPMKVLMLTLQNDPPSLETGADYKKYsksfrKMISLCLQKDPSKRPT 257
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
575-847 4.20e-19

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: 87.75  E-value: 4.20e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEEASADMqADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd06613     3 ELIQRIGSGTYGDVYKARniATG-------ELAAVKVIKLEPGDDF-EIIQQEISMLKECRHPNIVAYFGSYLRRDKLWI 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLrsmspHTVCSLShsdlstrarvsspgppplscaeQLCIA---RQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06613    75 VMEYCGGGSLQDIY-----QVTGPLS----------------------ELQIAyvcRETLKGLAYLHSTGKIHRDIKGAN 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNR---YTTESDVWAYGVVLWEIfSYGLQPYYGMA 806
Cdd:cd06613   128 ILLTEDGDVKLADFGVSAQL-TATIAKRKSFIGTPY-WMAPEVAAVERkggYDGKCDIWALGITAIEL-AELQPPMFDLH 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 807 HEEVIYYV-RDGNI---LACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06613   205 PMRALFLIpKSNFDppkLKDKEKWSPDFHDFIKKCLTKNPKKRPT 249
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
573-853 4.30e-19

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: 87.71  E-value: 4.30e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPG-----LLPYEPFTMVAVKmlKEEASadmqadfQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd08225     1 RYEIIKKIGEGSFGKIYLAKAKSdsehcVIKEIDLTKMPVK--EKEAS-------KKEVILLAKMKHPNIVTFFASFQEN 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEflrsmsphtvcslshsdlstraRVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd08225    72 GRLFIVMEYCDGGDLMK----------------------RINRQRGVLFSEDQILSWFVQISLGLKHIHDRKILHRDIKS 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGEN-MVVKIADFGLSRNIysadyykadgNDAIPIR--------WMPPEsIFYNR-YTTESDVWAYGVVLWEIFSY 797
Cdd:cd08225   130 QNIFLSKNgMVAKLGDFGIARQL----------NDSMELAytcvgtpyYLSPE-ICQNRpYNNKTDIWSLGCVLYELCTL 198
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 798 GlQPYYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHR 853
Cdd:cd08225   199 K-HPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSLISQLFKVSPRDRPSITSILK 253
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
580-851 4.55e-19

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: 88.55  E-value: 4.55e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepftMVAVKMLK--EEASADMQAdFQREAALMAEFDNPNIVKLLGvcavgkpmcllfeYM 657
Cdd:cd14149    20 IGSGSFGTVYKGKWHG--------DVAVKILKvvDPTPEQFQA-FRNEVAVLRKTRHVNILLFMG-------------YM 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHTVCSLSHSdLSTRARVsspgppplscAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd14149    78 TKDNLAIVTQWCEGSSLYKHLHV-QETKFQM----------FQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLT 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGL----SRNIYSADYYKADGNdaipIRWMPPESIFY---NRYTTESDVWAYGVVLWEIFSyGLQPYYGMAH-EE 809
Cdd:cd14149   147 VKIGDFGLatvkSRWSGSQQVEQPTGS----ILWMAPEVIRMqdnNPFSFQSDVYSYGIVLYELMT-GELPYSHINNrDQ 221
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 810 VIYYVRDG----NILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14149   222 IIFMVGRGyaspDLSKLYKNCPKAMKRLVADCIKKVKEERPLFPQI 267
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
580-847 4.98e-19

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: 4.98e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF---QARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd06628     8 IGSGSFGSVYlgmNASSGELMAVKQVELPSVSAENKDRKKSMLDALQREIALLRELQHENIVQYLGSSSDANHLNIFLEY 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGdlneflrsmsphtvcslshsdlSTRARVSSPGPPPLSCAEQLciARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd06628    88 VPGG----------------------SVATLLNNYGAFEESLVRNF--VRQILKGLNYLHNRGIIHRDIKGANILVDNKG 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIySADYYKADGNDAIP-----IRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd06628   144 GIKISDFGISKKL-EANSLSTKNNGARPslqgsVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAI 221
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 812 YYVRDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06628   222 FKIGENASPTIPSNISSEARDFLEKTFEIDHNKRPT 257
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
577-801 5.52e-19

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: 87.97  E-value: 5.52e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLKEE-ASAD--MQAdfqREA-ALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd07830     4 IKQLGDGTFGSVYLARN-----KETGELVAIKKMKKKfYSWEecMNL---REVkSLRKLNEHPNIVKLKEVFRENDELYF 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAyGDLNEFLRS-----MSPHTVCSlshsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd07830    76 VFEYME-GNLYQLMKDrkgkpFSESVIRS---------------------------IIYQILQGLAHIHKHGFFHRDLKP 127
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYkadgNDAIPIRWM-PPE----SIFYNrytTESDVWAYGVVLWEIFSygLQP 801
Cdd:cd07830   128 ENLLVSGPEVVKIADFGLAREIRSRPPY----TDYVSTRWYrAPEillrSTSYS---SPVDIWALGCIMAELYT--LRP 197
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
580-845 5.97e-19

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: 87.19  E-value: 5.97e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLlgVCAV--GKPMCLL 653
Cdd:cd05123     1 LGKGSFGKVLLVRkkDTG-------KLYAMKVLRKKEiiKRKEVEHTLNERNILERVNHPFIVKL--HYAFqtEEKLYLV 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLneflrsmsphtvcslsHSDLSTRARVsspgppPLSCAeQLCIArQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd05123    72 LDYVPGGEL----------------FSHLSKEGRF------PEERA-RFYAA-EIVLALEYLHSLGIIYRDLKPENILLD 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSaDYYKADGnDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHEEvIYy 813
Cdd:cd05123   128 SDGHIKLTDFGLAKELSS-DGDRTYT-FCGTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEML-TGKPPFYAENRKE-IY- 202
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1937920432 814 vrdGNIL----ACPENCPLELYNLMRLCWSKLPADR 845
Cdd:cd05123   203 ---EKILksplKFPEYVSPEAKSLISGLLQKDPTKR 235
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
580-861 6.29e-19

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: 87.80  E-value: 6.29e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd06640    12 IGKGSFGEVFKG-----IDNRTQQVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGG 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSmsphtvcslshsdlstrarvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd06640    87 GSALDLLRA-------------------------GPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVK 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNIYSADyYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIfSYGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd06640   142 LADFGVAGQLTDTQ-IKRNTFVGTPF-WMAPEVIQQSAYDSKADIWSLGITAIEL-AKGEPPNSDMHPMRVLFLIPKNNP 218
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 820 LACPENCPLELYNLMRLCWSKLPADRPSFCSI--HRILQRMCER 861
Cdd:cd06640   219 PTLVGDFSKPFKEFIDACLNKDPSFRPTAKELlkHKFIVKNAKK 262
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
577-810 6.68e-19

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: 87.54  E-value: 6.68e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEeasADMQADFQ------REAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd05611     1 LKPISKGAFGSVYLAKKRSTGDY-----FAIKVLKK---SDMIAKNQvtnvkaERAIMMIQGESPYVAKLYYSFQSKDYL 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEQLciARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd05611    73 YLVMEYLNGGDCASLIKTL----------------------GGLPEDWAKQY--IAEVVLGVEDLHQRGIIHRDIKPENL 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIY----------SADYykadgndaipirwMPPESIFYNRYTTESDVWAYGVVLWEiFSYGLQ 800
Cdd:cd05611   129 LIDQTGHLKLTDFGLSRNGLekrhnkkfvgTPDY-------------LAPETILGVGDDKMSDWWSLGCVIFE-FLFGYP 194
                         250
                  ....*....|
gi 1937920432 801 PYYGMAHEEV 810
Cdd:cd05611   195 PFHAETPDAV 204
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
575-807 8.52e-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: 87.06  E-value: 8.52e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgllpyEPFT--MVAVKMLKE---EASADMqADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd14073     4 ELLETLGKGTYGKVKLAI-------ERATgrEVAIKSIKKdkiEDEQDM-VRIRREIEIMSSLNHPHIIRIYEVFENKDK 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLrsmsphtvcslshsdlSTRARVSSpgppplscAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd14073    76 IVIVMEYASGGELYDYI----------------SERRRLPE--------REARRIFRQIVSAVHYCHKNGVVHRDLKLEN 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSrNIYSADYYKAD--GNdaiPIrWMPPESIFYNRYT-TESDVWAYGVVLWeIFSYGLQPYYGMA 806
Cdd:cd14073   132 ILLDQNGNAKIADFGLS-NLYSKDKLLQTfcGS---PL-YASPEIVNGTPYQgPEVDCWSLGVLLY-TLVYGTMPFDGSD 205

                  .
gi 1937920432 807 H 807
Cdd:cd14073   206 F 206
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
580-851 1.07e-18

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. 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 LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 87.33  E-value: 1.07e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRV-FQARAPGllpyEPftmVAVK-----------------MLKEEASADMQ---ADFQREAALMAEFDNPNIV 638
Cdd:cd14067     1 LGQGGSGTViYRARYQG----QP---VAVKrfhikkckkrtdgsadtMLKHLRAADAMknfSEFRQEASMLHSLQHPCIV 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 639 KLLGVCAvgKPMCLLFEYMAYGDLNeflrsmsphTVCSLSHSDLSTRarvsspgppPLSCAEQLCIARQVAAGMAYLSER 718
Cdd:cd14067    74 YLIGISI--HPLCFALELAPLGSLN---------TVLEENHKGSSFM---------PLGHMLTFKIAYQIAAGLAYLHKK 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 719 KFVHRDLATRNCLV-----GENMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWE 793
Cdd:cd14067   134 NIIFCDLKSDNILVwsldvQEHINIKLSDYGISRQSFHEGALGVEGTPG----YQAPEIRPRIVYDEKVDMFSYGMVLYE 209
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 794 IFSyGLQPYYGMAHEEVIYYVRDG--NILACPENCPL-ELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14067   210 LLS-GQRPSLGHHQLQIAKKLSKGirPVLGQPEEVQFfRLQALMMECWDTKPEKRPLACSV 269
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
572-847 1.41e-18

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: 86.63  E-value: 1.41e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapgllpYEPFTMV-AVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd06605     1 DDLEYLGELGEGNGGVVSKVR------HRPSGQImAVKVIRLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEGDI 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLscaEQLC-IARQVAAGMAYLSE-RKFVHRDLATR 728
Cdd:cd06605    75 SICMEYMDGGSLDKILKEV----------------------GRIPE---RILGkIAVAVVKGLIYLHEkHKIIHRDVKPS 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIySADYYKAD-GNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIfSYGLQPY----- 802
Cdd:cd06605   130 NILVNSRGQVKLCDFGVSGQL-VDSLAKTFvGTRS----YMAPERISGGKYTVKSDIWSLGLSLVEL-ATGRFPYpppna 203
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 803 -YGMAHEEVIYYVRDGNILACP-ENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06605   204 kPSMMIFELLSYIVDEPPPLLPsGKFSPDFQDFVSQCLQKDPTERPS 250
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
711-858 1.51e-18

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. 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 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-2D 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: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 86.31  E-value: 1.51e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 711 GMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPIRWMPPESI----FYNRYTTESDVWA 786
Cdd:cd14043   109 GMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNE-ILEAQNLPLPEPAPEELLWTAPELLrdprLERRGTFPGDVFS 187
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 787 YGVVLWEIFSYGLqPY--YGMAHEEVIYYVRDGNILACP----ENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14043   188 FAIIMQEVIVRGA-PYcmLGLSPEEIIEKVRSPPPLCRPsvsmDQAPLECIQLMKQCWSEAPERRPTFDQIFDQFKSI 264
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
573-797 1.72e-18

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 88.01  E-value: 1.72e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGllpyEPFTMVavkmLKeeasADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:PHA03209   67 GYTVIKTLTPGSEGRVFVATKPG----QPDPVV----LK----IGQKGTTLIEAMLLQNVNHPSVIRMKDTLVSGAITCM 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFeymaygdlneflrsmsPHTVCSLsHSDLSTRARvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:PHA03209  135 VL----------------PHYSSDL-YTYLTKRSR-------PLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFI 190
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 733 GENMVVKIADFGLSR-NIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSY 797
Cdd:PHA03209  191 NDVDQVCIGDLGAAQfPVVAPAFLGLAGT----VETNAPEVLARDKYNSKADIWSAGIVLFEMLAY 252
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
570-847 1.73e-18

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: 87.01  E-value: 1.73e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06644    10 PNEVWEIIGELGDGAFGKVYKAKNK-----ETGALAAAKVIETKSEEELE-DYMVEIEILATCNHPYIVKLLGAFYWDGK 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPhtvcSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06644    84 LWIMIEFCPGGAVDAIMLELDR----GLTEPQIQV-------------------ICRQMLEALQYLHSMKIIHRDLKAGN 140
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLS-RNIYSADyyKADGNDAIPIrWMPPESIFYNR-----YTTESDVWAYGVVLWEIFSYGlQPYY 803
Cdd:cd06644   141 VLLTLDGDIKLADFGVSaKNVKTLQ--RRDSFIGTPY-WMAPEVVMCETmkdtpYDYKADIWSLGITLIEMAQIE-PPHH 216
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 804 GMAHEEVIYYV--RDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06644   217 ELNPMRVLLKIakSEPPTLSQPSKWSMEFRDFLKTALDKHPETRPS 262
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
574-855 2.11e-18

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; 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 cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks 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 Jak3 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: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 86.11  E-value: 2.11e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGLLPYEPF-TMVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVGKPMCL 652
Cdd:cd14208     1 LTFMESLGKGSFTKIYRGLRTDEEDDERCeTEVLLKVM-DPTHGNCQESFLEAASIMSQISHKHLVLLHGVC-VGKDSIM 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRsmsphtvcslshsdlstraRVSSPGPPPLSCaeQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14208    79 VQEFVCHGALDLYLK-------------------KQQQKGPVAISW--KLQVVKQLAYALNYLEDKQLVHGNVSAKKVLL 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 ------GENMVVKIADFGLSRNIYSADYYKadgnDAIPirWMPPESIF-YNRYTTESDVWAYGVVLWEIFSYGLQPYYGM 805
Cdd:cd14208   138 sregdkGSPPFIKLSDPGVSIKVLDEELLA----ERIP--WVAPECLSdPQNLALEADKWGFGATLWEIFSGGHMPLSAL 211
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 806 AHEEVIYYVRDGNILACPEncPLELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd14208   212 DPSKKLQFYNDRKQLPAPH--WIELASLIQQCMSYNPLLRPSFRAIIRDL 259
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
568-819 3.77e-18

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: 85.45  E-value: 3.77e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIeyvrdIGEGAFGRVFQARAPGLLPYEpftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd14202     3 EFSRKDL-----IGHGAFAVVFKGRHKEKHDLE----VAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEIA 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLrsmspHTVCSLSHSDLstraRVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd14202    74 NSVYLVMEYCNGGDLADYL-----HTMRTLSEDTI----RL---------------FLQQIAGAMKMLHSKGIIHRDLKP 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVG---------ENMVVKIADFGLSRniYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyG 798
Cdd:cd14202   130 QNILLSysggrksnpNNIRIKIADFGFAR--YLQNNMMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-G 205
                         250       260
                  ....*....|....*....|..
gi 1937920432 799 LQPYYGMAHEEV-IYYVRDGNI 819
Cdd:cd14202   206 KAPFQASSPQDLrLFYEKNKSL 227
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
570-794 3.81e-18

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: 85.85  E-value: 3.81e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06643     3 PEDFWEIVGELGDGAFGKVYKAQNK-----ETGILAAAKVIDTKSEEELE-DYMVEIDILASCDHPNIVKLLDAFYYENN 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPhtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06643    77 LWILIEFCAGGAVDAVMLELER-----------------------PLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGN 133
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 730 CLVGENMVVKIADFGLS-RNIYSADyyKADGNDAIPIrWMPPESIFYNR-----YTTESDVWAYGVVLWEI 794
Cdd:cd06643   134 ILFTLDGDIKLADFGVSaKNTRTLQ--RRDSFIGTPY-WMAPEVVMCETskdrpYDYKADVWSLGVTLIEM 201
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
570-847 4.33e-18

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: 85.56  E-value: 4.33e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQA--RAPGLLpyepftmVAVKMLKEEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd06611     3 PNDIWEIIGELGDGAFGKVYKAqhKETGLF-------AAAKIIQIESEEELE-DFMVEIDILSECKHPNIVGLYEAYFYE 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFlrsmsphtVCSLSHsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd06611    75 NKLWILIEFCDGGALDSI--------MLELER---------------GLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKA 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADyYKADGNDAIPiRWMPPESIFY-----NRYTTESDVWAYGVVLWEIfSYGLQPY 802
Cdd:cd06611   132 GNILLTLDGDVKLADFGVSAKNKSTL-QKRDTFIGTP-YWMAPEVVACetfkdNPYDYKADIWSLGITLIEL-AQMEPPH 208
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 803 YGMAHEEVIYYVRDGN--ILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06611   209 HELNPMRVLLKILKSEppTLDQPSKWSSSFNDFLKSCLVKDPDDRPT 255
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
580-847 4.50e-18

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: 85.37  E-value: 4.50e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd06609     9 IGKGSFGEVYKGIDK-----RTNQVVAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCGG 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRsmsphtvcslshsdlstrarvssPGPPPlscaEQL--CIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd06609    84 GSVLDLLK-----------------------PGPLD----ETYiaFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGD 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VKIADFGLS---------RNIYSADYYkadgndaipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHE 808
Cdd:cd06609   137 VKLADFGVSgqltstmskRNTFVGTPF-----------WMAPEVIKQSGYDEKADIWSLGITAIELAK-GEPPLSDLHPM 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 809 EVIyyvrdgnILACPENCPL--------ELYNLMRLCWSKLPADRPS 847
Cdd:cd06609   205 RVL-------FLIPKNNPPSlegnkfskPFKDFVELCLNKDPKERPS 244
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
580-856 6.07e-18

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: 84.37  E-value: 6.07e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgllpYEPFTMVAVKmlkeEASADMQADFQREAA-----LMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd08530     8 LGKGSYGSVYKVKR-----LSDNQVYALK----EVNLGSLSQKEREDSvneirLLASVNHPNIIRYKEAFLDGNRLCIVM 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsphtvcslshsdlstRARVSSPGPpplscaEQLC--IARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd08530    79 EYAPFGDLSKLISK----------------RKKKRRLFP------EDDIwrIFIQMLRGLKALHDQKILHRDLKSANILL 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRNIYSADYYKADGNdaiPIrWMPPEsIFYNR-YTTESDVWAYGVVLWEIFSYGLqPYYGMAHEEVI 811
Cdd:cd08530   137 SAGDLVKIGDLGISKVLKKNLAKTQIGT---PL-YAAPE-VWKGRpYDYKSDIWSLGCLLYEMATFRP-PFEARTMQELR 210
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 812 YYVRDGNILACPENCPLELYNLMRLCWSKLPADRPsfcSIHRILQ 856
Cdd:cd08530   211 YKVCRGKFPPIPPVYSQDLQQIIRSLLQVNPKKRP---SCDKLLQ 252
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
580-860 7.38e-18

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: 84.11  E-value: 7.38e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyEPFTMVaVKMLKEEASadmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14156     1 IGSGFFSKVYKVTHGA----TGKVMV-VKIYKNDVD---QHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSG 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLrsmsphtvcslshsdlsTRARVsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd14156    73 GCLEELL-----------------AREEL------PLSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIRVTPRGR 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 ---IADFGLSRNIysADYYKADGNDAIPIR----WMPPESIFYNRYTTESDVWAYGVVLWEIFsyGLQPyygmAHEEVIY 812
Cdd:cd14156   130 eavVTDFGLAREV--GEMPANDPERKLSLVgsafWMAPEMLRGEPYDRKVDVFSFGIVLCEIL--ARIP----ADPEVLP 201
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 813 YVRD-GNILA-----CPEnCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCE 860
Cdd:cd14156   202 RTGDfGLDVQafkemVPG-CPEPFLDLAASCCRMDAFKRPSFAELLDELEDIAE 254
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
575-801 8.74e-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: 85.41  E-value: 8.74e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgLLPYEPFTMVAVKMLKeeASADMQADFQ----REAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd07842     3 EIEGCIGRGTYGRVYKAK---RKNGKDGKEYAIKKFK--GDKEQYTGISqsacREIALLRELKHENVVSLVEVFLEHADK 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 C--LLFEYMAYgDLNEFLRSMSPHTVCSLShsdlstRARVSSpgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd07842    78 SvyLLFDYAEH-DLWQIIKFHRQAKRVSIP------PSMVKS-------------LLWQILNGIHYLHSNWVLHRDLKPA 137
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 729 NCLV----GENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWM-PPESIFYNR-YTTESDVWAYGVVLWEIFSygLQP 801
Cdd:cd07842   138 NILVmgegPERGVVKIGDLGLARLFNAPLKPLADLDPVVVTIWYrAPELLLGARhYTKAIDIWAIGCIFAELLT--LEP 214
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
580-796 1.35e-17

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 85.20  E-value: 1.35e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLlpyepFTMVAVKMLK-EEASADMQADFQ------------REAALMAEFDNPNIVKLLGVCAV 646
Cdd:PTZ00024   17 LGEGTYGKVEKAYDTLT-----GKIVAIKKVKiIEISNDVTKDRQlvgmcgihfttlRELKIMNEIKHENIMGLVDVYVE 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYgDLNEFLRSmsphtvcslshsdlstRARvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:PTZ00024   92 GDFINLVMDIMAS-DLKKVVDR----------------KIR--------LTESQVKCILLQILNGLNVLHKWYFMHRDLS 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSR----NIYSADYYKADGN--------DAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWE 793
Cdd:PTZ00024  147 PANIFINSKGICKIADFGLARrygyPPYSDTLSKDETMqrreemtsKVVTLWYRAPELLMgAEKYHFAVDMWSVGCIFAE 226

                  ...
gi 1937920432 794 IFS 796
Cdd:PTZ00024  227 LLT 229
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
572-805 1.62e-17

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: 83.80  E-value: 1.62e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKML------KEEAsadmQADFQREAALMAEFDNPNIVKLLgvCA 645
Cdd:cd05581     1 NDFKFGKPLGEGSYSTVVLAKE-----KETGKEYAIKVLdkrhiiKEKK----VKYVTIEKEVLSRLAHPGIVKLY--YT 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 VGKPMCLLF--EYMAYGDLNEFLRSMSphtvcslSHSDLSTRarvsspgpppLSCAEQLCIarqvaagMAYLSERKFVHR 723
Cdd:cd05581    70 FQDESKLYFvlEYAPNGDLLEYIRKYG-------SLDEKCTR----------FYTAEIVLA-------LEYLHSKGIIHR 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGlSRNIYSADY------YKADGNDAIPIR----------WMPPESIFYNRYTTESDVWAY 787
Cdd:cd05581   126 DLKPENILLDEDMHIKITDFG-TAKVLGPDSspestkGDADSQIAYNQAraasfvgtaeYVSPELLNEKPAGKSSDLWAL 204
                         250
                  ....*....|....*...
gi 1937920432 788 GVVLWEIFsYGLQPYYGM 805
Cdd:cd05581   205 GCIIYQML-TGKPPFRGS 221
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
573-794 1.65e-17

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: 83.71  E-value: 1.65e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASAD-MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd07860     1 NFQKVEKIGEGTYGVVYKARNK-----LTGEVVALKKIRLDTETEgVPSTAIREISLLKELNHPNIVKLLDVIHTENKLY 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMaygdlneflrsmsphtvcslsHSDLSTRARVSSPGPPPLSCAEQLCIarQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd07860    76 LVFEFL---------------------HQDLKKFMDASALTGIPLPLIKSYLF--QLLQGLAFCHSHRVLHRDLKPQNLL 132
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 732 VGENMVVKIADFGLSRNIysadyykadgndAIPIR----------WMPPESIFYNR-YTTESDVWAYGVVLWEI 794
Cdd:cd07860   133 INTEGAIKLADFGLARAF------------GVPVRtythevvtlwYRAPEILLGCKyYSTAVDIWSLGCIFAEM 194
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
578-791 2.05e-17

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: 83.00  E-value: 2.05e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQA--RAPGLLpyepfTMVAVKML-KEEASADMQADF-QREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd14080     6 KTIGEGSYSKVKLAeyTKSGLK-----EKVACKIIdKKKAPKDFLEKFlPRELEILRKLRHPNIIQVYSIFERGSKVFIF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSmsphtvcslsHSDLS-TRARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14080    81 MEYAEHGDLLEYIQK----------RGALSeSQARI---------------WFRQLALAVQYLHSLDIAHRDLKCENILL 135
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 733 GENMVVKIADFGLSRNI-----------Y--SADYykadgndaipirwMPPE---SIFYNryTTESDVWAYGVVL 791
Cdd:cd14080   136 DSNNNVKLSDFGFARLCpdddgdvlsktFcgSAAY-------------AAPEilqGIPYD--PKKYDIWSLGVIL 195
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
575-859 2.05e-17

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: 83.10  E-value: 2.05e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARApgLLPYEPFTMVAVKMLKeeASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd08219     3 NVLRVVGEGSFGRALLVQH--VNSDQKYAMKEIRLPK--SSSAVE-DSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVM 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRsmsphtvcsLSHSDLSTRARVsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd08219    78 EYCDGGDLMQKIK---------LQRGKLFPEDTI-------------LQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQ 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYkADGNDAIPIrWMPPEsIFYNR-YTTESDVWAYGVVLWEIFSYGlQPYYGMAHEEVIYY 813
Cdd:cd08219   136 NGKVKLGDFGSARLLTSPGAY-ACTYVGTPY-YVPPE-IWENMpYNNKSDIWSLGCILYELCTLK-HPFQANSWKNLILK 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 814 VRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSihrILQRMC 859
Cdd:cd08219   212 VCQGSYKPLPSHYSYELRSLIKQMFKRNPRSRPSATT---ILSRGS 254
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
578-851 2.37e-17

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: 82.93  E-value: 2.37e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQAR------------APGLLPYEPftmvAVKMLKEEASADMQADFQreaalmaefdnpNIVKLLGVCA 645
Cdd:cd14025     2 EKVGSGGFGQVYKVRhkhwktwlaikcPPSLHVDDS----ERMELLEEAKKMEMAKFR------------HILPVYGICS 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 vgKPMCLLFEYMAYGDLNEFLRSmspHTVCSlshsDLSTRarvsspgppplscaeqlcIARQVAAGMAYLSERK--FVHR 723
Cdd:cd14025    66 --EPVGLVMEYMETGSLEKLLAS---EPLPW----ELRFR------------------IIHETAVGMNFLHCMKppLLHL 118
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSR--NIYSADYYKADGNDAIpIRWMPPESIF-YNR-YTTESDVWAYGVVLWEIFSYGl 799
Cdd:cd14025   119 DLKPANILLDAHYHVKISDFGLAKwnGLSHSHDLSRDGLRGT-IAYLPPERFKeKNRcPDTKHDVYSFAIVIWGILTQK- 196
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 800 QPYYG---MAHeeVIYYVRDG---NILACPENCPLE---LYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14025   197 KPFAGennILH--IMVKVVKGhrpSLSPIPRQRPSEcqqMICLMKRCWDQDPRKRPTFQDI 255
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
571-795 2.38e-17

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: 83.32  E-value: 2.38e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEY--VRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLkeeasadmqadFQ------REAALMAEFDNPNIVKLLG 642
Cdd:cd14137     1 PVEISYtiEKVIGSGSFGVVYQAKL-----LETGEVVAIKKV-----------LQdkryknRELQIMRRLKHPNIVKLKY 64
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 643 VC--AVGKP----MCLLFEYMaygdlneflrsmsPHTVCSLSHSdlSTRARVSSPgppplscaeqLCIAR----QVAAGM 712
Cdd:cd14137    65 FFysSGEKKdevyLNLVMEYM-------------PETLYRVIRH--YSKNKQTIP----------IIYVKlysyQLFRGL 119
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 713 AYLSERKFVHRDLATRNCLV-GENMVVKIADFG----LSRN------IYSAdYYKAdgndaipirwmpPESIF-YNRYTT 780
Cdd:cd14137   120 AYLHSLGICHRDIKPQNLLVdPETGVLKLCDFGsakrLVPGepnvsyICSR-YYRA------------PELIFgATDYTT 186
                         250
                  ....*....|....*
gi 1937920432 781 ESDVWAYGVVLWEIF 795
Cdd:cd14137   187 AIDIWSAGCVLAELL 201
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
573-858 2.51e-17

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: 82.77  E-value: 2.51e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFqaRAPGLLPYEPFTMVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd08228     3 NFQIEKKIGRGQFSEVY--RATCLLDRKPVALKKVQIF-EMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNI 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSphtvcslshsdlstRARVSSPGPPPLSCAEQLCIArqvaagMAYLSERKFVHRDLATRNCLV 732
Cdd:cd08228    80 VLELADAGDLSQMIKYFK--------------KQKRLIPERTVWKYFVQLCSA------VEHMHSRRVMHRDIKPANVFI 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRnIYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSygLQ-PYYG--MAHEE 809
Cdd:cd08228   140 TATGVVKLGDLGLGR-FFSSKTTAAHSLVGTPY-YMSPERIHENGYNFKSDIWSLGCLLYEMAA--LQsPFYGdkMNLFS 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 810 VIYYVRDGNILACP-ENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd08228   216 LCQKIEQCDYPPLPtEHYSEKLRELVSMCIYPDPDQRPDIGYVHQIAKQM 265
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
570-845 2.57e-17

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: 82.88  E-value: 2.57e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLkeeasaDMQADFQRE-----AALMAEFDNPNIVKLLGVC 644
Cdd:cd06648     5 PRSDLDNFVKIGEGSTGIVCIATD-----KSTGRQVAVKKM------DLRKQQRREllfneVVIMRDYQHPNIVEMYSSY 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 AVGKPMCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRARVSSpgppplscaEQL-CIARQVAAGMAYLSERKFVHR 723
Cdd:cd06648    74 LVGDELWVVMEFLEGGAL-----------------TDIVTHTRMNE---------EQIaTVCRAVLKALSFLHSQGVIHR 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSRNIysadyykadgNDAIPIR--------WMPPESIFYNRYTTESDVWAYGVVLWEIF 795
Cdd:cd06648   128 DIKSDSILLTSDGRVKLSDFGFCAQV----------SKEVPRRkslvgtpyWMAPEVISRLPYGTEVDIWSLGIMVIEMV 197
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 796 SyGLQPYYGMAHEEVIYYVRDGN--ILACPENCPLELYNLMRLCWSKLPADR 845
Cdd:cd06648   198 D-GEPPYFNEPPLQAMKRIRDNEppKLKNLHKVSPRLRSFLDRMLVRDPAQR 248
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
121-208 3.97e-17

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: 77.05  E-value: 3.97e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PK-ITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd20978     1 PKfIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDI 80

                  ....*....
gi 1937920432 200 YSKlVKLEV 208
Cdd:cd20978    81 YTE-TLLHV 88
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
127-208 5.18e-17

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: 76.67  E-value: 5.18e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 127 PINVKIIEGLKAVLPCTT-MGNPKPSVSWIKGDSALRE-NSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKLV 204
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLdNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRAA 83

                  ....
gi 1937920432 205 KLEV 208
Cdd:cd05724    84 RLSV 87
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
123-199 5.56e-17

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: 76.77  E-value: 5.56e-17
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 123 ITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIK-GDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKdGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEA 79
IgI_7_Dscam cd20954
Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar ...
121-208 7.17e-17

Seventh 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 seventh 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: 409546 [Multi-domain]  Cd Length: 96  Bit Score: 76.58  E-value: 7.17e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIK--GDSA-----LRENSRIAVLESGSLRIHNVQKEDAGQYRCVAK 193
Cdd:cd20954     2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTPgeykdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAK 81
                          90
                  ....*....|....*
gi 1937920432 194 NSLGTAYSKLVKLEV 208
Cdd:cd20954    82 NGIGSGLSKVIFLKV 96
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
580-819 9.04e-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: 81.49  E-value: 9.04e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEeasADMQADFQREAAL-----MAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd05579     1 ISRGAYGRVYLAKkkSTG-------DLYAIKVIKK---RDMIRKNQVDSVLaerniLSQAQNPFVVKLYYSFQGKKNLYL 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSphtvcSLSHSdlstRARVsspgppplscaeqlCIArQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd05579    71 VMEYLPGGDLYSLLENVG-----ALDED----VARI--------------YIA-EIVLALEYLHSHGIIHRDLKPDNILI 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLS------RNIYSADYYKADGNDAIPIR-------WMPPESIFYNRYTTESDVWAYGVVLWEIFSyGL 799
Cdd:cd05579   127 DANGHLKLTDFGLSkvglvrRQIKLSIQKKSNGAPEKEDRrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLV-GI 205
                         250       260
                  ....*....|....*....|
gi 1937920432 800 QPYYGMAHEEVIYYVRDGNI 819
Cdd:cd05579   206 PPFHAETPEEIFQNILNGKI 225
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
580-796 1.42e-16

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: 80.99  E-value: 1.42e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAy 659
Cdd:cd07836     8 LGEGTYATVYKGRN-----RTTGEIVALKEIHLDAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMD- 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFlrsMSPHTVcslshsdlstrarvssPGPPPLSCAEQLciARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd07836    82 KDLKKY---MDTHGV----------------RGALDPNTVKSF--TYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELK 140
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 740 IADFGLSR------NIYSadyykadgNDAIPIRWMPPESIFYNR-YTTESDVWAYGVVLWEIFS 796
Cdd:cd07836   141 LADFGLARafgipvNTFS--------NEVVTLWYRAPDVLLGSRtYSTSIDIWSVGCIMAEMIT 196
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
576-794 2.01e-16

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: 80.82  E-value: 2.01e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVR--DIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd07871     7 YVKldKLGEGTYATVFKGRSK-----LTENLVALKEIRLEHEEGAPCTAIREVSLLKNLKHANIVTLHDIIHTERCLTLV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAyGDLNEFLRS----MSPHTVcslshsdlstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd07871    82 FEYLD-SDLKQYLDNcgnlMSMHNV---------------------------KIFMFQLLRGLSYCHKRKILHRDLKPQN 133
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 730 CLVGENMVVKIADFGLSR--NIYSADYykadGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEI 794
Cdd:cd07871   134 LLINEKGELKLADFGLARakSVPTKTY----SNEVVTLWYRPPDVLLgSTEYSTPIDMWGVGCILYEM 197
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
573-804 2.19e-16

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: 79.87  E-value: 2.19e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARApglLPYEpfTMVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd14072     1 NYRLLKTIGKGNFAKVKLARH---VLTG--REVAIKIIdKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLY 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLrsmsphtvcsLSHSDLSTR-ARVSspgppplscaeqlciARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd14072    76 LVMEYASGGEVFDYL----------VAHGRMKEKeARAK---------------FRQIVSAVQYCHQKRIVHRDLKAENL 130
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADyyKADGNDAIPiRWMPPESIFYNRYT-TESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14072   131 LLDADMNIKIADFGFSNEFTPGN--KLDTFCGSP-PYAAPELFQGKKYDgPEVDVWSLGVILYTLVS-GSLPFDG 201
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
127-208 2.96e-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: 74.46  E-value: 2.96e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIK-GDSALRENSRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLGTAYSK 202
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*.
gi 1937920432  203 lVKLEV 208
Cdd:smart00410  81 -TTLTV 85
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
580-798 3.43e-16

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: 79.78  E-value: 3.43e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgllpYEPFTMVAVKMLK-EEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd07839     8 IGEGTYGTVFKAKN-----RETHEIVALKRVRlDDDDEGVPSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYCD 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YgDLNEFLRS----MSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd07839    83 Q-DLKKYFDScngdIDPEIVKSFMF---------------------------QLLKGLAFCHSHNVLHRDLKPQNLLINK 134
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 735 NMVVKIADFGLSRNI------YSAdyykadgnDAIPIRWMPPESIFYNR-YTTESDVWAYGVVLWEIFSYG 798
Cdd:cd07839   135 NGELKLADFGLARAFgipvrcYSA--------EVVTLWYRPPDVLFGAKlYSTSIDMWSAGCIFAELANAG 197
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
573-792 3.66e-16

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: 79.41  E-value: 3.66e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQAR--------APGLLPYEP---FTMVAVKMLKEEASADMQAdfQREAALMAEFDNPNIVKLL 641
Cdd:cd14077     2 NWEFVKTIGAGSMGKVKLAKhirtgekcAIKIIPRASnagLKKEREKRLEKEISRDIRT--IREAALSSLLNHPHICRLR 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 642 GVCAVGKPMCLLFEYMAYGDLNEFLrsmsphtvcsLSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFV 721
Cdd:cd14077    80 DFLRTPNHYYMLFEYVDGGQLLDYI----------ISHGKLKEKQARK--------------FARQIASALDYLHRNSIV 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSrNIYSAD----------YYKAdgndaipirwmpPESIFYNRYT-TESDVWAYGVV 790
Cdd:cd14077   136 HRDLKIENILISKSGNIKIIDFGLS-NLYDPRrllrtfcgslYFAA------------PELLQAQPYTgPEVDVWSFGVV 202

                  ..
gi 1937920432 791 LW 792
Cdd:cd14077   203 LY 204
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
580-847 4.05e-16

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: 78.99  E-value: 4.05e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPglLPYEPFTMVAVKMLKeeASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd08529     8 LGKGSFGVVYKVVRK--VDGRVYALKQIDISR--MSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYAEN 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMsphtvcslshsdlstRARvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVK 739
Cdd:cd08529    84 GDLHSLIKSQ---------------RGR-------PLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVK 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 740 IADFGLSRNIysadyyKADGNDAIPI----RWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGlQPYYGMAHEEVIYYVR 815
Cdd:cd08529   142 IGDLGVAKIL------SDTTNFAQTIvgtpYYLSPELCEDKPYNEKSDVWALGCVLYELCTGK-HPFEAQNQGALILKIV 214
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1937920432 816 DGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd08529   215 RGKYPPISASYSQDLSQLIDSCLTKDYRQRPD 246
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
574-847 4.16e-16

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 80.64  E-value: 4.16e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQAR-APGLLPYepftmvAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:PLN00034   76 LERVNRIGSGAGGTVYKVIhRPTGRLY------ALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQV 149
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGdlneflrsmsphtvcSLSHSDLSTRARVSSpgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:PLN00034  150 LLEFMDGG---------------SLEGTHIADEQFLAD-------------VARQILSGIAYLHRRHIVHRDIKPSNLLI 201
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRNIysADYYKADGNDAIPIRWMPPESI-------FYNRYTteSDVWAYGVVLWEiFSYGLQPyYGM 805
Cdd:PLN00034  202 NSAKNVKIADFGVSRIL--AQTMDPCNSSVGTIAYMSPERIntdlnhgAYDGYA--GDIWSLGVSILE-FYLGRFP-FGV 275
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 806 AHEEviyyvrDGNILAC----------PENCPLELYNLMRLCWSKLPADRPS 847
Cdd:PLN00034  276 GRQG------DWASLMCaicmsqppeaPATASREFRHFISCCLQREPAKRWS 321
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
578-857 4.90e-16

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: 78.85  E-value: 4.90e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLK--EEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd08224     6 KKIGKGQFSVVYRARclLDG-------RLVALKKVQifEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRsmsphtvcslshsdlsTRARVSSPGPPPLscaeqlcIAR---QVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd08224    79 LELADAGDLSRLIK----------------HFKKQKRLIPERT-------IWKyfvQLCSALEHMHSKRIMHRDIKPANV 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRnIYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSygLQ-PYYGmahEE 809
Cdd:cd08224   136 FITANGVVKLGDLGLGR-FFSSKTTAAHSLVGTPY-YMSPERIREQGYDFKSDIWSLGCLLYEMAA--LQsPFYG---EK 208
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 810 VIYYVRDGNILAC-----PENC-PLELYNLMRLCWSKLPADRPSFCSIHRILQR 857
Cdd:cd08224   209 MNLYSLCKKIEKCeypplPADLySQELRDLVAACIQPDPEKRPDISYVLDVAKR 262
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
580-847 5.14e-16

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: 79.06  E-value: 5.14e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEF---DNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd06917     9 VGRGSYGAVYRG-----YHVKTGRVVALKVLNLDTDDDDVSDIQKEVALLSQLklgQPKNIIKYYGSYLKGPSLWIIMDY 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRsmsphtvcslshsdlstrarvssPGPpplsCAEQLC--IARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd06917    84 CEGGSIRTLMR-----------------------AGP----IAERYIavIMREVLVALKFIHKDGIIHRDIKAANILVTN 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADyYKADGNDAIPIrWMPPESIFYNR-YTTESDVWAYGVVLWEIfSYGLQPYYGMAHEEVIYY 813
Cdd:cd06917   137 TGNVKLCDFGVAASLNQNS-SKRSTFVGTPY-WMAPEVITEGKyYDTKADIWSLGITTYEM-ATGNPPYSDVDALRAVML 213
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 814 VRDGNilacPENCPLELYN-LMR----LCWSKLPADRPS 847
Cdd:cd06917   214 IPKSK----PPRLEGNGYSpLLKefvaACLDEEPKDRLS 248
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
572-847 5.98e-16

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: 79.39  E-value: 5.98e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP-- 649
Cdd:cd06621     1 DKIVELSSLGEGAGGSVTKCRLR-----NTKTIFALKTITTDPNPDVQKQILRELEINKSCASPYIVKYYGAFLDEQDss 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstRARVSSPGPPPLscaeqLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06621    76 IGIAMEYCEGGSLDSIYKKV---------------KKKGGRIGEKVL-----GKIAESVLKGLSYLHSRKIIHRDIKPSN 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSA--------DYYkadgndaipirwMPPESIFYNRYTTESDVWAYGVVLWEI----FSY 797
Cdd:cd06621   136 ILLTRKGQVKLCDFGVSGELVNSlagtftgtSYY------------MAPERIQGGPYSITSDVWSLGLTLLEVaqnrFPF 203
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 798 ---GLQPYygMAHEEVIYYVRDGN--ILACPENC---PLELYNLMRLCWSKLPADRPS 847
Cdd:cd06621   204 ppeGEPPL--GPIELLSYIVNMPNpeLKDEPENGikwSESFKDFIEKCLEKDGTRRPG 259
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
580-796 6.20e-16

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: 79.65  E-value: 6.20e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAy 659
Cdd:cd07872    14 LGEGTYATVFKGRSK-----LTENLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLD- 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRS----MSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd07872    88 KDLKQYMDDcgniMSMHNVKIFLY---------------------------QILRGLAYCHRRKVLHRDLKPQNLLINER 140
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 736 MVVKIADFGLSRNiySADYYKADGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd07872   141 GELKLADFGLARA--KSVPTKTYSNEVVTLWYRPPDVLLgSSEYSTQIDMWGVGCIFFEMAS 200
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
572-818 6.53e-16

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: 79.40  E-value: 6.53e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapgllpYEPFT--MVAVKML-KEEASADMQADFQR-----EAALMAEFDNPNIVKLLGV 643
Cdd:cd14096     1 ENYRLINKIGEGAFSNVYKAV------PLRNTgkPVAIKVVrKADLSSDNLKGSSRanilkEVQIMKRLSHPNIVKLLDF 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 CAVGKPMCLLFEYMAYGDL-NEFLRsmspHTVCSlshSDLSTRarvsspgppplscaeqlcIARQVAAGMAYLSERKFVH 722
Cdd:cd14096    75 QESDEYYYIVLELADGGEIfHQIVR----LTYFS---EDLSRH------------------VITQVASAVKYLHEIGVVH 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 723 RDLATRNCLV---------------------------------GENMVVKIADFGLSRNIYSADYYKADGNdaipIRWMP 769
Cdd:cd14096   130 RDIKPENLLFepipfipsivklrkadddetkvdegefipgvggGGIGIVKLADFGLSKQVWDSNTKTPCGT----VGYTA 205
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 770 PESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRDGN 818
Cdd:cd14096   206 PEVVKDERYSKKVDMWALGCVLYTLLC-GFPPFYDESIETLTEKISRGD 253
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
573-847 7.35e-16

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: 79.02  E-value: 7.35e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARapgllpYEPF-TMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP-M 650
Cdd:cd06620     6 DLETLKDLGAGNGGSVSKVL------HIPTgTIMAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAFLNENNnI 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTVCSLSHsdlstrarvsspgppplscaeqlcIARQVAAGMAYL-SERKFVHRDLATRN 729
Cdd:cd06620    80 IICMEYMDCGSLDKILKKKGPFPEEVLGK------------------------IAVAVLEGLTYLyNVHRIIHRDIKPSN 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYS--ADYYKADGNdaipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLqPyYGMAH 807
Cdd:cd06620   136 ILVNSKGQIKLCDFGVSGELINsiADTFVGTST------YMSPERIQGGKYSVKSDVWSLGLSIIELALGEF-P-FAGSN 207
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 808 EEVIYYVRDGNIL------------ACPENC--PLELYNLMRLCWSKLPADRPS 847
Cdd:cd06620   208 DDDDGYNGPMGILdllqrivnepppRLPKDRifPKDLRDFVDRCLLKDPRERPS 261
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
580-796 7.74e-16

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 79.33  E-value: 7.74e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQarapGLLPYEPftmVAVKMLkeeaSADMQADFQREAALMAEF--DNPNIVKLLGVC----AVGKPMCLL 653
Cdd:cd14054     3 IGQGRYGTVWK----GSLDERP---VAVKVF----PARHRQNFQNEKDIYELPlmEHSNILRFIGADerptADGRMEYLL 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 -FEYMAYGDLNEFLR--SMSPHTVCSLSHSdlstrarvsspgppplscaeqlciarqVAAGMAYL-SERK--------FV 721
Cdd:cd14054    72 vLEYAPKGSLCSYLRenTLDWMSSCRMALS---------------------------LTRGLAYLhTDLRrgdqykpaIA 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNIYSADYYK----ADGNDAI----PIRWMPPESIF-------YNRYTTESDVWA 786
Cdd:cd14054   125 HRDLNSRNVLVKADGSCVICDFGLAMVLRGSSLVRgrpgAAENASIsevgTLRYMAPEVLEgavnlrdCESALKQVDVYA 204
                         250
                  ....*....|
gi 1937920432 787 YGVVLWEIFS 796
Cdd:cd14054   205 LGLVLWEIAM 214
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
28-103 9.30e-16

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 72.98  E-value: 9.30e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTRN-KILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANN 103
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNgEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
573-796 9.54e-16

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: 78.81  E-value: 9.54e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEEASADmqaDFQ----REAALMAEFDNPNIVKLLGVcAV 646
Cdd:cd07843     6 EYEKLNRIEEGTYGVVYRARdkKTG-------EIVALKKLKMEKEKE---GFPitslREINILLKLQHPNIVTVKEV-VV 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLF---EYMAYgDLNEFLRSMsphtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHR 723
Cdd:cd07843    75 GSNLDKIYmvmEYVEH-DLKSLMETM-----------------------KQPFLQSEVKCLMLQLLSGVAHLHDNWILHR 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSRNIYSadyykadgndaiPIRWM----------PPESIF-YNRYTTESDVWAYGVVLW 792
Cdd:cd07843   131 DLKTSNLLLNNRGILKICDFGLAREYGS------------PLKPYtqlvvtlwyrAPELLLgAKEYSTAIDMWSVGCIFA 198

                  ....
gi 1937920432 793 EIFS 796
Cdd:cd07843   199 ELLT 202
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
571-855 9.69e-16

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: 78.30  E-value: 9.69e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPglLPYEPFTMVAVKMLKEEAsadmqadfQREAALMAEFDNPNIVKLLGvCAVGkpm 650
Cdd:cd14047     5 RQDFKEIELIGSGGFGQVFKAKHR--IDGKTYAIKRVKLNNEKA--------EREVKALAKLDHPNIVRYNG-CWDG--- 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 cllFEYMAYgdlNEFLRSMSPHTVCSLSHSDLSTRARVSS----PGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd14047    71 ---FDYDPE---TSSSNSSRSKTKCLFIQMEFCEKGTLESwiekRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLK 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIysADYYKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQpyyGMA 806
Cdd:cd14047   145 PSNIFLVDTGKVKIGDFGLVTSL--KNDGKRTKSKGTL-SYMSPEQISSQDYGKEVDIYALGLILFELLHVCDS---AFE 218
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 807 HEEVIYYVRDGNI-LACPENCPLELYNLMRLCwSKLPADRPSFCSIHRIL 855
Cdd:cd14047   219 KSKFWTDLRNGILpDIFDKRYKIEKTIIKKML-SKKPEDRPNASEILRTL 267
I-set pfam07679
Immunoglobulin I-set domain;
28-117 1.02e-15

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 73.06  E-value: 1.02e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLfDTRYSIRENGQL--LTILSVEDSDDGIYCCTANNGV 105
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS-SDRFKVTYEGGTytLTISNVQPDDSGKYTCVATNSA 79
                          90
                  ....*....|...
gi 1937920432 106 GGAveSCGA-LQV 117
Cdd:pfam07679  80 GEA--EASAeLTV 90
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
605-855 1.45e-15

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; 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 domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 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: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 78.03  E-value: 1.45e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlsT 684
Cdd:cd05076    46 VVLKVL-DPSHHDIALAFFETASLMSQVSHTHLVFVHGVCVRGSENIMVEEFVEHGPLDVWLRK---------------E 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 685 RARVSSpgppplscAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV-------GENMVVKIADFGLSRNIYSadyyKA 757
Cdd:cd05076   110 KGHVPM--------AWKFVVARQLASALSYLENKNLVHGNVCAKNILLarlgleeGTSPFIKLSDPGVGLGVLS----RE 177
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 758 DGNDAIPirWMPPESI-FYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA-HEEVIYYVRDGNIlacPENCPLELYNLMR 835
Cdd:cd05076   178 ERVERIP--WIAPECVpGGNSLSTAADKWGFGATLLEICFNGEAPLQSRTpSEKERFYQRQHRL---PEPSCPELATLIS 252
                         250       260
                  ....*....|....*....|
gi 1937920432 836 LCWSKLPADRPSFCSIHRIL 855
Cdd:cd05076   253 QCLTYEPTQRPSFRTILRDL 272
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
580-860 1.70e-15

Catalytic domain of Transforming Growth Factor beta Receptor-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 receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-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: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 77.86  E-value: 1.70e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapglLPYEPftmVAVKM--LKEEASadmqadFQREAAL----MAEFDNpnIVKLLG----VCAVGKP 649
Cdd:cd13998     3 IGKGRFGEVWKAS----LKNEP---VAVKIfsSRDKQS------WFREKEIyrtpMLKHEN--ILQFIAaderDTALRTE 67
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSmspHTV-----CSLSHSdlstrarvsspgppplscaeqlciarqVAAGMAYLSERKF---- 720
Cdd:cd13998    68 LWLVTAFHPNGSL*DYLSL---HTIdwvslCRLALS---------------------------VARGLAHLHSEIPgctq 117
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 721 -----VHRDLATRNCLVGENMVVKIADFGLSRNIYSADyyKADGNDAIP----IRWMPPE----SIFYNRYTT--ESDVW 785
Cdd:cd13998   118 gkpaiAHRDLKSKNILVKNDGTCCIADFGLAVRLSPST--GEEDNANNGqvgtKRYMAPEvlegAINLRDFESfkRVDIY 195
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 786 AYGVVLWEIFS-----YGLQPYYGMAHEEVIyyvrdgnilacPENCPLElynLMR--LCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd13998   196 AMGLVLWEMASrctdlFGIVEEYKPPFYSEV-----------PNHPSFE---DMQevVVRDKQRPNIPNRWLSHPGLQSL 261

                  ..
gi 1937920432 859 CE 860
Cdd:cd13998   262 AE 263
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
568-848 1.72e-15

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: 77.74  E-value: 1.72e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIeyvrdIGEGAFGRVFQARAPGLLPYEpftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd14201     7 EYSRKDL-----VGHGAFAVVFKGRHRKKTDWE----VAIKSINKKNLSKSQILLGKEIKILKELQHENIVALYDVQEMP 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMSphtvcSLSHSDLstraRVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd14201    78 NSVFLVMEYCNGGDLADYLQAKG-----TLSEDTI----RV---------------FLQQIAAAMRILHSKGIIHRDLKP 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVG---------ENMVVKIADFGLSRNIYSAdyYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFsYG 798
Cdd:cd14201   134 QNILLSyasrkkssvSGIRIKIADFGFARYLQSN--MMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTVIYQCL-VG 209
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 799 LQPYYGMAHEEV-IYYVRDGNIL-ACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd14201   210 KPPFQANSPQDLrMFYEKNKNLQpSIPRETSPYLADLLLGLLQRNQKDRMDF 261
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
580-814 2.24e-15

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: 77.74  E-value: 2.24e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAy 659
Cdd:cd07873    10 LGEGTYATVYKGRSK-----LTDNLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLD- 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFL----RSMSPHTVcslshsdlstrarvsspgppplscaeQLCIArQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd07873    84 KDLKQYLddcgNSINMHNV--------------------------KLFLF-QLLRGLAYCHRRKVLHRDLKPQNLLINER 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSR--NIYSADYykadGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEIfSYGLQPYYGMAHEEVIY 812
Cdd:cd07873   137 GELKLADFGLARakSIPTKTY----SNEVVTLWYRPPDILLgSTDYSTQIDMWGVGCIFYEM-STGRPLFPGSTVEEQLH 211

                  ..
gi 1937920432 813 YV 814
Cdd:cd07873   212 FI 213
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
138-198 2.28e-15

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: 71.59  E-value: 2.28e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 138 AVLPCTTMGNPKPSVSWIKGDSALREN---SRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSsrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
580-846 2.46e-15

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: 2.46e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKM--LKEEASADMQADF----QREAALMAEFDNPNIVKLLGVCAVGK-PMCL 652
Cdd:cd13990     8 LGKGGFSEVYKA-----FDLVEQRYVACKIhqLNKDWSEEKKQNYikhaLREYEIHKSLDHPRIVKLYDVFEIDTdSFCT 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSmsphtvcslsHSDLSTRarvsspgppplscaEQLCIARQVAAGMAYLSERK--FVHRDLATRNC 730
Cdd:cd13990    83 VLEYCDGNDLDFYLKQ----------HKSIPER--------------EARSIIMQVVSALKYLNEIKppIIHYDLKPGNI 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMV---VKIADFGLSRnIYSADYYKADGND-----AIPIRWMPPESIFYN----RYTTESDVWAYGVVLWEIFsYG 798
Cdd:cd13990   139 LLHSGNVsgeIKITDFGLSK-IMDDESYNSDGMEltsqgAGTYWYLPPECFVVGktppKISSKVDVWSVGVIFYQML-YG 216
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 799 LQPY-YGM-----AHEEVIYYVRDGNILACPEnCPLELYNLMRLCWSKLPADRP 846
Cdd:cd13990   217 RKPFgHNQsqeaiLEENTILKATEVEFPSKPV-VSSEAKDFIRRCLTYRKEDRP 269
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
599-853 2.87e-15

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 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: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 76.90  E-value: 2.87e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 599 YEPFTMVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPhtvcsls 678
Cdd:cd05077    33 YEKEIKVILKVL-DPSHRDISLAFFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPLDLFMHRKSD------- 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 679 hsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV-------VKIADFGLSRNIYS 751
Cdd:cd05077   105 ----------------VLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdgecgpfIKLSDPGIPITVLS 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 752 adyyKADGNDAIPirWMPPESIFYNR-YTTESDVWAYGVVLWEIFSYGLQPYYG--MAHEEVIYyvrDGNILACPENCPl 828
Cdd:cd05077   169 ----RQECVERIP--WIAPECVEDSKnLSIAADKWSFGTTLWEICYNGEIPLKDktLAEKERFY---EGQCMLVTPSCK- 238
                         250       260
                  ....*....|....*....|....*
gi 1937920432 829 ELYNLMRLCWSKLPADRPSFCSIHR 853
Cdd:cd05077   239 ELADLMTHCMNYDPNQRPFFRAIMR 263
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
580-847 3.66e-15

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: 76.24  E-value: 3.66e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFqarapglLPYEPFT--MVAVKMLK-----EEASADMQAdFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd06625     8 LGQGAFGQVY-------LCYDADTgrELAVKQVEidpinTEASKEVKA-LECEIQLLKNLQHERIVQYYGCLQDEKSLSI 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSPhtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd06625    80 FMEYMPGGSVKDEIKAYGA------------------------LTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILR 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSR---NIYSADYYKA-DGNdaiPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFS-----YGLQPY- 802
Cdd:cd06625   136 DSNGNVKLGDFGASKrlqTICSSTGMKSvTGT---P-YWMSPEVINGEGYGRKADIWSVGCTVVEMLTtkppwAEFEPMa 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 803 --YGMAHEEVIYYVrdgnilacPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06625   212 aiFKIATQPTNPQL--------PPHVSEDARDFLSLIFVRNKKQRPS 250
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
570-801 3.97e-15

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: 76.61  E-value: 3.97e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEASADMQAdFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06646     7 PQHDYELIQRVGSGTYGDVYKARN-----LHTGELAAVKIIKLEPGDDFSL-IQQEIFMVKECKHCNIVAYFGSYLSREK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPHTVCSLSHsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06646    81 LWICMEYCGGGSLQDIYHVTGPLSELQIAY------------------------VCRETLQGLAYLHSKGKMHRDIKGAN 136
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 730 CLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNR---YTTESDVWAYGVVLWEIFSygLQP 801
Cdd:cd06646   137 ILLTDNGDVKLADFGVAAKI-TATIAKRKSFIGTPY-WMAPEVAAVEKnggYNQLCDIWAVGITAIELAE--LQP 207
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
580-792 4.44e-15

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: 76.15  E-value: 4.44e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVfqarapgLLPYEPFT--MVAVKML--KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14079    10 LGVGSFGKV-------KLAEHELTghKVAVKILnrQKIKSLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVME 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLrsmsphtvcslshsdlSTRARVSSPgppplscaEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14079    83 YVSGGELFDYI----------------VQKGRLSED--------EARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSN 138
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 736 MVVKIADFGLSRNIYSADYYK---ADGNDAipirwmPPESIFYNRYT-TESDVWAYGVVLW 792
Cdd:cd14079   139 MNVKIADFGLSNIMRDGEFLKtscGSPNYA------APEVISGKLYAgPEVDVWSCGVILY 193
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
573-809 5.27e-15

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: 75.76  E-value: 5.27e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKML--KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14116     6 DFEIGRPLGKGKFGNVYLAREK-----QSKFILALKVLfkAQLEKAGVEHQLRREVEIQSHLRHPNILRLYGYFHDATRV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSphtvcslSHSDLSTRARVSspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd14116    81 YLILEYAPLGTVYRELQKLS-------KFDEQRTATYIT-----------------ELANALSYCHSKRVIHRDIKPENL 136
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEiFSYGLQPYYGMAHEE 809
Cdd:cd14116   137 LLGSAGELKIADFGWSVHAPSSRRTTLCGT----LDYLPPEMIEGRMHDEKVDLWSLGVLCYE-FLVGKPPFEANTYQE 210
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
580-847 6.22e-15

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: 75.37  E-value: 6.22e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQArapglLPYEPFTMVAVKMLKEE---ASADMQADFQREAALMAEFDNPNIVKLLGVC---AVGKpMCLL 653
Cdd:cd14119     1 LGEGSYGKVKEV-----LDTETLCRRAVKILKKRklrRIPNGEANVKREIQILRRLNHRNVIKLVDVLyneEKQK-LYMV 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYmAYGDLNEFLrsmsphtvcslshsDLSTRARVsspgppPLSCAEqlCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd14119    75 MEY-CVGGLQEML--------------DSAPDKRL------PIWQAH--GYFVQLIDGLEYLHSQGIIHKDIKPGNLLLT 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSR--NIYSADY--YKADGNDAipirWMPPESIFYNRYTT--ESDVWAYGVVLWEIFSyGLQPYYGmah 807
Cdd:cd14119   132 TDGTLKISDFGVAEalDLFAEDDtcTTSQGSPA----FQPPEIANGQDSFSgfKVDIWSAGVTLYNMTT-GKYPFEG--- 203
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 808 eEVIYYVRDgNILAC----PENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14119   204 -DNIYKLFE-NIGKGeytiPDDVDPDLQDLLRGMLEKDPEKRFT 245
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
577-856 6.90e-15

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: 75.44  E-value: 6.90e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPgllpyEPFTMVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGvCAVGKPMCLLF- 654
Cdd:cd14069     6 VQTLGEGAFGEVFLAVNR-----NTEEAVAVKFVdMKRAPGDCPENIKKEVCIQKMLSHKNVVRFYG-HRREGEFQYLFl 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLN---EFLRSMSPHTVcslshsdlstrarvsspgppplscaeQLCIArQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd14069    80 EYASGGELFdkiEPDVGMPEDVA--------------------------QFYFQ-QLMAGLKYLHSCGITHRDIKPENLL 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGLsrniysADYYKADG-----NDAI-PIRWMPPESIFYNRYTTE-SDVWAYGVVL---------WEIF 795
Cdd:cd14069   133 LDENDNLKISDFGL------ATVFRYKGkerllNKMCgTLPYVAPELLAKKKYRAEpVDVWSCGIVLfamlagelpWDQP 206
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 796 SYGLQPYYGmaheeviyYVRDGNilacPENCPlelynlmrlcWSKLPAdrPSFCSIHRILQ 856
Cdd:cd14069   207 SDSCQEYSD--------WKENKK----TYLTP----------WKKIDT--AALSLLRKILT 243
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
580-804 7.13e-15

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: 75.34  E-value: 7.13e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF--QARAPGLLpyepftmVAVKMLKEEASADmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14103     1 LGRGKFGTVYrcVEKATGKE-------LAAKFIKCRKAKD-REDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYV 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLneFLRSMSphtvcslSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN--CLVGEN 735
Cdd:cd14103    73 AGGEL--FERVVD-------DDFELTERDCIL--------------FMRQICEGVQYMHKQGILHLDLKPENilCVSRTG 129
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 736 MVVKIADFGLSRniysadyyKADGNDAIPIRW-----MPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14103   130 NQIKIIDFGLAR--------KYDPDKKLKVLFgtpefVAPEVVNYEPISYATDMWSVGVICYVLLS-GLSPFMG 194
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
573-856 7.59e-15

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: 75.83  E-value: 7.59e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGLlpyePFTMVAVKMLKEEASADMQAdfQREAALMAEF-DNPNIVKLLGVCAVGKP-- 649
Cdd:cd13985     1 RYQVTKQLGEGGFSYVYLAHDVNT----GRRYALKRMYFNDEEQLRVA--IKEIEIMKRLcGHPNIVQYYDSAILSSEgr 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 --MCLLFEYMAyGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYL--SERKFVHRDL 725
Cdd:cd13985    75 keVLLLMEYCP-GSLVDILEKS----------------------PPSPLSEEEVLRIFYQICQAVGHLhsQSPPIIHRDI 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIP-IRWM------PPESI-FYNRY--TTESDVWAYGVVLWEI- 794
Cdd:cd13985   132 KIENILFSNTGRFKLCDFGSATTEHYPLERAEEVNIIEEeIQKNttpmyrAPEMIdLYSKKpiGEKADIWALGCLLYKLc 211
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 795 -FSYGLQPYYGMAheeviyyvrdgnILAC----PEN--CPLELYNLMRLCWSKLPADRPSFCSIHRILQ 856
Cdd:cd13985   212 fFKLPFDESSKLA------------IVAGkysiPEQprYSPELHDLIRHMLTPDPAERPDIFQVINIIT 268
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
570-801 7.66e-15

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: 75.85  E-value: 7.66e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEASADMqADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06645     9 PQEDFELIQRIGSGTYGDVYKARN-----VNTGELAAIKVIKLEPGEDF-AVVQQEIIMMKDCKHSNIVAYFGSYLRRDK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPhtvcsLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06645    83 LWICMEFCGGGSLQDIYHVTGP-----LSESQIAY-------------------VSRETLQGLYYLHSKGKMHRDIKGAN 138
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 730 CLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNR---YTTESDVWAYGVVLWEIFSygLQP 801
Cdd:cd06645   139 ILLTDNGHVKLADFGVSAQI-TATIAKRKSFIGTPY-WMAPEVAAVERkggYNQLCDIWAVGITAIELAE--LQP 209
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
580-858 9.95e-15

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 75.77  E-value: 9.95e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKML--KEEASadmqadFQREAALmaeFDN-----PNIVKLLGVCAVGKPMC- 651
Cdd:cd14056     3 IGKGRYGEVWLGKYRG-------EKVAVKIFssRDEDS------WFRETEI---YQTvmlrhENILGFIAADIKSTGSWt 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 ---LLFEYMAYGDLNEFLRSmspHTvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYL------SERK--F 720
Cdd:cd14056    67 qlwLITEYHEHGSLYDYLQR---NT----------------------LDTEEALRLAYSAASGLAHLhteivgTQGKpaI 121
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 721 VHRDLATRNCLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPI---RWMPPESIFYNRYTT------ESDVWAYGVVL 791
Cdd:cd14056   122 AHRDLKSKNILVKRDGTCCIADLGLAV-RYDSDTNTIDIPPNPRVgtkRYMAPEVLDDSINPKsfesfkMADIYSFGLVL 200
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 792 WEIF----------SYGLqPYYGMAH-----EEVIYYVRDGNILACPEN----CPL--ELYNLMRLCWSKLPADRPSFCS 850
Cdd:cd14056   201 WEIArrceiggiaeEYQL-PYFGMVPsdpsfEEMRKVVCVEKLRPPIPNrwksDPVlrSMVKLMQECWSENPHARLTALR 279

                  ....*...
gi 1937920432 851 IHRILQRM 858
Cdd:cd14056   280 VKKTLAKL 287
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
580-847 9.99e-15

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: 75.16  E-value: 9.99e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQAR--APGllpyepfTMVAVKMLKE-EASADMQAD----FQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd06630     8 LGTGAFSSCYQARdvKTG-------TLMAVKQVSFcRNSSSEQEEvveaIREEIRMMARLNHPNIVRMLGATQHKSHFNI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSPHTvcslshsdlstrarvsspgppplscaEQLCIA--RQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd06630    81 FVEWMAGGSVASLLSKYGAFS--------------------------ENVIINytLQILRGLAYLHDNQIIHRDLKGANL 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LV-GENMVVKIADFG----LSRNIYSADYYKadGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGM 805
Cdd:cd06630   135 LVdSTGQRLRIADFGaaarLASKGTGAGEFQ--GQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMAT-AKPPWNAE 211
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 806 A---HEEVIYYVrdgnilAC-------PENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06630   212 KisnHLALIFKI------ASattpppiPEHLSPGLRDVTLRCLELQPEDRPP 257
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
121-208 1.06e-14

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: 1.06e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALR-----ENSRIAVLESGSL----RIHNVQ-KEDAGQYRC 190
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRIVLPSGSLfflrVVHGRKgRSDEGVYVC 80
                          90
                  ....*....|....*...
gi 1937920432 191 VAKNSLGTAYSKLVKLEV 208
Cdd:cd07693    81 VAHNSLGEAVSRNASLEV 98
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
570-816 1.21e-14

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: 75.41  E-value: 1.21e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06659    19 PRQLLENYVKIGEGSTGVVCIAREK-----HSGRQVAVKMMDLRKQQRRELLFN-EVVIMRDYQHPNVVEMYKSYLVGEE 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRARVSSpgppplscaEQLC-IARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd06659    93 LWVLMEYLQGGAL-----------------TDIVSQTRLNE---------EQIAtVCEAVLQALAYLHSQGVIHRDIKSD 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHE 808
Cdd:cd06659   147 SILLTLDGRVKLSDFGFCAQI-SKDVPKRKSLVGTPY-WMAPEVISRCPYGTEVDIWSLGIMVIEMVD-GEPPYFSDSPV 223

                  ....*...
gi 1937920432 809 EVIYYVRD 816
Cdd:cd06659   224 QAMKRLRD 231
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
125-210 1.41e-14

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: 69.90  E-value: 1.41e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 125 RPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQK-EDAGQYRCVAKNSLGTAYSKl 203
Cdd:cd20958     5 RPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRsSDEGEYTCTARNQQGQSASR- 83

                  ....*..
gi 1937920432 204 vKLEVEV 210
Cdd:cd20958    84 -SVFVKV 89
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
573-858 2.08e-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: 74.68  E-value: 2.08e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFqaRAPGLLPYEPFTMVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd08229    25 NFRIEKKIGRGQFSEVY--RATCLLDGVPVALKKVQIF-DLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNI 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSphtvcslshsdlstRARVSSPGPPPLSCAEQLCIArqvaagMAYLSERKFVHRDLATRNCLV 732
Cdd:cd08229   102 VLELADAGDLSRMIKHFK--------------KQKRLIPEKTVWKYFVQLCSA------LEHMHSRRVMHRDIKPANVFI 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRnIYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSygLQ-PYYGmahEEVI 811
Cdd:cd08229   162 TATGVVKLGDLGLGR-FFSSKTTAAHSLVGTPY-YMSPERIHENGYNFKSDIWSLGCLLYEMAA--LQsPFYG---DKMN 234
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 812 YYVRDGNILACpENCPL-------ELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd08229   235 LYSLCKKIEQC-DYPPLpsdhyseELRQLVNMCINPDPEKRPDITYVYDVAKRM 287
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
580-848 2.20e-14

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: 73.94  E-value: 2.20e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLlPYEPftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14120     1 IGHGAFAVVFKGRHRKK-PDLP---VAIKCITKKNLSKSQNLLGKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNG 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSphtvcSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV------- 732
Cdd:cd14120    77 GDLADYLQAKG-----TLSEDTIRV-------------------FLQQIAAAMKALHSKGIVHRDLKPQNILLshnsgrk 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 --GENMVVKIADFGLSRniysadyYKADGNDAI-----PIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGM 805
Cdd:cd14120   133 psPNDIRLKIADFGFAR-------FLQDGMMAAtlcgsPM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFQAQ 203
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 806 AHEEV-IYYVRDGNIL-ACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd14120   204 TPQELkAFYEKNANLRpNIPSGTSPALKDLLLGLLKRNPKDRIDF 248
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
575-835 2.27e-14

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: 74.84  E-value: 2.27e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPglLPYEPFTMVAVKMLKEEASADMQAdfQREAALMAEFDNPNIVKLLGVCAVGKPMC--- 651
Cdd:cd07864    10 DIIGIIGEGTYGQVYKAKDK--DTGELVALKKVRLDNEKEGFPITA--IREIKILRQLNHRSVVNLKEIVTDKQDALdfk 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 -------LLFEYMAY---GDLNEFLRSMSPHTVCSLshsdlstrarvsspgppplscaeqlciARQVAAGMAYLSERKFV 721
Cdd:cd07864    86 kdkgafyLVFEYMDHdlmGLLESGLVHFSEDHIKSF---------------------------MKQLLEGLNYCHKKNFL 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEIFSYG-- 798
Cdd:cd07864   139 HRDIKCSNILLNNKGQIKLADFGLAR-LYNSEESRPYTNKVITLWYRPPELLLgEERYGPAIDVWSCGCILGELFTKKpi 217
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 799 LQPYYGMAHEEVIYYVRDGnilACPENCP----LELYNLMR 835
Cdd:cd07864   218 FQANQELAQLELISRLCGS---PCPAVWPdvikLPYFNTMK 255
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
577-857 2.69e-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: 74.67  E-value: 2.69e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARapgllPYEPFTMVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGvcavgkpmCLLF 654
Cdd:cd06634    20 LREIGHGSFGAVYFAR-----DVRNNEVVAIKKMSYSGkqSNEKWQDIIKEVKFLQKLRHPNTIEYRG--------CYLR 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNeflrsmsphtVCSLSHSDLSTRARvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd06634    87 EHTAWLVME----------YCLGSASDLLEVHK------KPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTE 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKadgndAIPIrWMPPESIFY---NRYTTESDVWAYGVVLWEIFSYGlQPYYGMAHEEVI 811
Cdd:cd06634   151 PGLVKLGDFGSASIMAPANSFV-----GTPY-WMAPEVILAmdeGQYDGKVDVWSLGITCIELAERK-PPLFNMNAMSAL 223
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 812 YYVRDGNILACPENCPLELY-NLMRLCWSKLPADRPSFCSI--HRILQR 857
Cdd:cd06634   224 YHIAQNESPALQSGHWSEYFrNFVDSCLQKIPQDRPTSDVLlkHRFLLR 272
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
580-847 2.70e-14

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: 73.88  E-value: 2.70e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--------RAPGLLPYEPFTMVAVKMLKEEASadmqadfqreaaLMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd06626     8 IGEGTFGKVYTAvnldtgelMAMKEIRFQDNDPKTIKEIADEMK------------VLEGLDHPNLVRYYGVEVHREEVY 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRsmspHTvcslshsdlstrarvsspgppplSCAEQLCI---ARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd06626    76 IFMEYCQEGTLEELLR----HG-----------------------RILDEAVIrvyTLQLLEGLAYLHENGIVHRDIKPA 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFG----LSRNIYSADYYKADGNDAIPIrWMPPESIFYNRYTTE---SDVWAYGVVLWEIFSyGLQP 801
Cdd:cd06626   129 NIFLDSNGLIKLGDFGsavkLKNNTTTMAPGEVNSLVGTPA-YMAPEVITGNKGEGHgraADIWSLGCVVLEMAT-GKRP 206
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 802 YYGMAHE-EVIYYVRDGNILACPENCPL--ELYNLMRLCWSKLPADRPS 847
Cdd:cd06626   207 WSELDNEwAIMYHVGMGHKPPIPDSLQLspEGKDFLSRCLESDPKKRPT 255
IgI_2_RPTP_IIa_LAR_like cd05738
Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; ...
123-208 2.94e-14

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.


Pssm-ID: 409400 [Multi-domain]  Cd Length: 91  Bit Score: 68.89  E-value: 2.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 123 ITRPPINVKIIEGLK-AVLPCTTMGNPKPSVSWIKG----DSAlRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd05738     1 IIDMGPQLKVVEKARtATMLCAASGNPDPEISWFKDflpvDTA-TSNGRIKQLRSGALQIENSEESDQGKYECVATNSAG 79
                          90
                  ....*....|.
gi 1937920432 198 TAYSKLVKLEV 208
Cdd:cd05738    80 TRYSAPANLYV 90
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
575-793 3.29e-14

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: 73.86  E-value: 3.29e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEEASAD-MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd07835     2 QKLEKIGEGTYGVVYKARdkLTG-------EIVALKKIRLETEDEgVPSTAIREISLLKELNHPNIVRLLDVVHSENKLY 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYgDLNEFLRSmSPHTvcslshsdlstrarvssPGPPPL--SCAEQLCiarqvaAGMAYLSERKFVHRDLATRN 729
Cdd:cd07835    75 LVFEFLDL-DLKKYMDS-SPLT-----------------GLDPPLikSYLYQLL------QGIAFCHSHRVLHRDLKPQN 129
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 730 CLVGENMVVKIADFGLSRniysadyykADGndaIPIR---------WM-PPESIFYNR-YTTESDVWAYGVVLWE 793
Cdd:cd07835   130 LLIDTEGALKLADFGLAR---------AFG---VPVRtythevvtlWYrAPEILLGSKhYSTPVDIWSVGCIFAE 192
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
701-847 3.31e-14

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: 73.73  E-value: 3.31e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 701 QLCIARQVAAGMAYLSErKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSAD----------YYkadgndaipirwMPP 770
Cdd:cd08217   113 QLLLALYECHNRSVGGG-KILHRDLKPANIFLDSDNNVKLGDFGLARVLSHDSsfaktyvgtpYY------------MSP 179
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 771 ESIFYNRYTTESDVWAYGVVLWEIFSygLQ-PYYGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd08217   180 ELLNEQSYDEKSDIWSLGCLIYELCA--LHpPFQAANQLELAKKIKEGKFPRIPSRYSSELNEVIKSMLNVDPDKRPS 255
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
578-847 4.18e-14

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: 73.46  E-value: 4.18e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRV-----FQARApgllpyepftmVAVK-MLKEEAS-ADmqadfqREAALMAEFDN-PNIVKLLGVCAVGKp 649
Cdd:cd13982     7 KVLGYGSEGTIvfrgtFDGRP-----------VAVKrLLPEFFDfAD------REVQLLRESDEhPNVIRYFCTEKDRQ- 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 mcllFEYMAYgdlnEFlrsmsphtvCSLSHSDLSTRARVS----SPGPPPLScaeqlcIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd13982    69 ----FLYIAL----EL---------CAASLQDLVESPRESklflRPGLEPVR------LLRQIASGLAHLHSLNIVHRDL 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLV-----GENMVVKIADFGLSRNIYSADY-YKADGNDAIPIRWMPPESI---FYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd13982   126 KPQNILIstpnaHGNVRAMISDFGLCKKLDVGRSsFSRRSGVAGTSGWIAPEMLsgsTKRRQTRAVDIFSLGCVFYYVLS 205
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 797 YGLQPYYGMaheeviyYVRDGNILA----CPE-----NCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd13982   206 GGSHPFGDK-------LEREANILKgkysLDKllslgEHGPEAQDLIERMIDFDPEKRPS 258
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
580-847 4.22e-14

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: 73.24  E-value: 4.22e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQarapGLLpyEPFTMVAVKMLKEEAS----ADMQAD-FQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd06631     9 LGKGAYGTVYC----GLT--STGQLIAVKQVELDTSdkekAEKEYEkLQEEVDLLKTLKHVNIVGYLGTCLEDNVVSIFM 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSMSPHtvcslshsdlstrarvsspgPPPLSCAeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd06631    83 EFVPGGSIASILARFGAL--------------------EEPVFCR----YTKQILEGVAYLHNNNVIHRDIKGNNIMLMP 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKADGNDAIPIR----WMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEV 810
Cdd:cd06631   139 NGVIKLIDFGCAKRLCINLSSGSQSQLLKSMRgtpyWMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMNPMAA 217
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1937920432 811 IYYV--RDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06631   218 IFAIgsGRKPVPRLPDKFSPEARDFVHACLTRDQDERPS 256
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
577-856 5.19e-14

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: 72.80  E-value: 5.19e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLLpYEpftmVAVKM-LKEEASADMQADFQR------EAALMA---EFDNPNIVKLLGVcav 646
Cdd:cd14004     5 LKEMGEGAYGQVNLAIYKSKG-KE----VVIKFiFKERILVDTWVRDRKlgtvplEIHILDtlnKRSHPNIVKLLDF--- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 gkpmcllFEymayGDLNEFLrSMSPHTVCSlshsDLSTRARVSspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd14004    77 -------FE----DDEFYYL-VMEKHGSGM----DLFDFIERK----PNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIK 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIYSADYYKADGNdaipIRWMPPESIFYNRYT-TESDVWAYGVVLWEIFsYGLQPYYGM 805
Cdd:cd14004   137 DENVILDGNGTIKLIDFGSAAYIKSGPFDTFVGT----IDYAAPEVLRGNPYGgKEQDIWALGVLLYTLV-FKENPFYNI 211
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 806 ahEEVIyyvrDGNILAcPENCPLELYNLMRLCWSKLPADRPsfcSIHRILQ 856
Cdd:cd14004   212 --EEIL----EADLRI-PYAVSEDLIDLISRMLNRDVGDRP---TIEELLT 252
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
580-847 5.67e-14

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: 72.59  E-value: 5.67e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpyEPFT--MVAVKMLKEE--ASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14099     9 LGKGGFAKCYEVT-------DMSTgkVYAGKVVPKSslTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLrsmsphtvcslshsdlstRARVsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14099    82 LCSNGSLMELL------------------KRRK------ALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDEN 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADY----------YKAdgndaipirwmpPESIFYNR-YTTESDVWAYGVVLWEIFsYGLQPYYG 804
Cdd:cd14099   138 MNVKIGDFGLAARLEYDGErkktlcgtpnYIA------------PEVLEKKKgHSFEVDIWSLGVILYTLL-VGKPPFET 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1937920432 805 MAHEEViyYVRdgnILAC----PENCPL--ELYNLMRLCWSKLPADRPS 847
Cdd:cd14099   205 SDVKET--YKR---IKKNeysfPSHLSIsdEAKDLIRSMLQPDPTKRPS 248
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
573-792 6.84e-14

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: 72.42  E-value: 6.84e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEyvRDIGEGAFGRVFQARApgllpYEPFTMVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd14071     3 DIE--RTIGKGNFAVVKLARH-----RITKTEVAIKIIdKSQLDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLY 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLrsmsphtvcslshsdlSTRARVSSPgppplscaeqlcIAR----QVAAGMAYLSERKFVHRDLAT 727
Cdd:cd14071    76 LVTEYASNGEIFDYL----------------AQHGRMSEK------------EARkkfwQILSAVEYCHKRHIVHRDLKA 127
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 728 RNCLVGENMVVKIADFGLSrNIYSADYYKADGNDAIPirWMPPESIFYNRYT-TESDVWAYGVVLW 792
Cdd:cd14071   128 ENLLLDANMNIKIADFGFS-NFFKPGELLKTWCGSPP--YAAPEVFEGKEYEgPQLDIWSLGVVLY 190
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
573-847 6.97e-14

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: 72.42  E-value: 6.97e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAP--GLLpyepftmVAVKMLKEEASADMQ-ADFQREA-ALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd13997     1 HFHELEQIGSGSFSEVFKVRSKvdGCL-------YAVKKSKKPFRGPKErARALREVeAHAALGQHPNIVRYYSSWEEGG 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd13997    74 HLYIQMELCENGSLQDALEELSPISK---------------------LSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPD 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGL-SRNIYSADYYKADGndaipiRWMPPESIFYN-RYTTESDVWAYGVVLWEIFSYGLQPYYGMA 806
Cdd:cd13997   133 NIFISNKGTCKIGDFGLaTRLETSGDVEEGDS------RYLAPELLNENyTHLPKADIFSLGVTVYEAATGEPLPRNGQQ 206
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1937920432 807 HEEviyyVRDGnILACPENCPL--ELYNLMRLCWSKLPADRPS 847
Cdd:cd13997   207 WQQ----LRQG-KLPLPPGLVLsqELTRLLKVMLDPDPTRRPT 244
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
575-795 7.31e-14

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: 73.71  E-value: 7.31e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEasadmqadFQ---------REAALMAEFDNPNIVKLLGVCA 645
Cdd:cd07834     3 ELLKPIGSGAYGVVCSAYDK-----RTGRKVAIKKISNV--------FDdlidakrilREIKILRHLKHENIIGLLDILR 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 VGKPMC-----LLFEYMAyGDLNEFLRSMSPhtvcsLSHSDLstrarvsspgppplscaeQLCIArQVAAGMAYLSERKF 720
Cdd:cd07834    70 PPSPEEfndvyIVTELME-TDLHKVIKSPQP-----LTDDHI------------------QYFLY-QILRGLKYLHSAGV 124
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 721 VHRDLATRNCLVGENMVVKIADFGLSRniySADYYKADGN--DAIPIRWM-PPESIF-YNRYTTESDVWAYGVVLWEIF 795
Cdd:cd07834   125 IHRDLKPSNILVNSNCDLKICDFGLAR---GVDPDEDKGFltEYVVTRWYrAPELLLsSKKYTKAIDIWSVGCIFAELL 200
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
317-440 1.08e-13

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.


Pssm-ID: 460190  Cd Length: 116  Bit Score: 68.36  E-value: 1.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 317 CAQYRGEVCDavlvkdSLVFFNTSYP------DPEEAQELLIHTAWNELKAVSPL-CRPAAEALLCNHLFQECS-SGVLP 388
Cdd:pfam01392   1 CEPITLPMCL------GLGYNATVFPnllghqTQEEAELSLAYLVLSEFEPLVDLsCSPSLRLFLCSLYFPPCTlGPSPK 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 389 TPMPICREYCLAVKElFCAKEWLAMEgkthrglyrSGMHFLPVPECSKLPSM 440
Cdd:pfam01392  75 PVCPPCRSLCEEVRY-GCEPLLEEAK---------FGFSWPEFLDCDSLPAD 116
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
623-802 1.14e-13

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: 72.39  E-value: 1.14e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 623 QREAALMAEFDNPNIVKLLGVcaVGKP----MCLLFEYMAYGDLneflrsmsphtvcslshsdlstrarVSSPGPPPLSC 698
Cdd:cd14118    62 YREIAILKKLDHPNVVKLVEV--LDDPnednLYMVFELVDKGAV-------------------------MEVPTDNPLSE 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 699 AEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYY--KADGNDAipirWMPPESIFYN 776
Cdd:cd14118   115 ETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLLLGDDGHVKIADFGVSNEFEGDDALlsSTAGTPA----FMAPEALSES 190
                         170       180
                  ....*....|....*....|....*....
gi 1937920432 777 R--YTTES-DVWAYGVVLWeIFSYGLQPY 802
Cdd:cd14118   191 RkkFSGKAlDIWAMGVTLY-CFVFGRCPF 218
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
577-795 1.48e-13

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: 71.92  E-value: 1.48e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQ--ARAPGLLpyepftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd07870     5 LEKLGEGSYATVYKgiSRINGQL-------VALKVISMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIHTKETLTFVF 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMaygdlneflrsmsphtvcslsHSDLstrARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd07870    78 EYM---------------------HTDL---AQYMIQHPGGLHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISY 133
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 735 NMVVKIADFGLSR--NIYSADYykadGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEIF 795
Cdd:cd07870   134 LGELKLADFGLARakSIPSQTY----SSEVVTLWYRPPDVLLgATDYSSALDIWGAGCIFIEML 193
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
572-803 1.62e-13

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: 71.84  E-value: 1.62e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapgLLPYEPFtmVAVKMLKEEASADM-QAD-FQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd05580     1 DDFEFLKTLGTGSFGRVRLVK---HKDSGKY--YALKILKKAKIIKLkQVEhVLNEKRILSEVRHPFIVNLLGSFQDDRN 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAeqLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05580    76 LYMVMEYVPGGELFSLLRRS----------------------GRFPNDVA--KFYAAEVVLALEYLHSLDIVYRDLKPEN 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNI----YS----ADYykadgndaipirwMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQP 801
Cdd:cd05580   132 LLLDSDGHIKITDFGFAKRVkdrtYTlcgtPEY-------------LAPEIILSKGHGKAVDWWALGILIYEMLA-GYPP 197

                  ..
gi 1937920432 802 YY 803
Cdd:cd05580   198 FF 199
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
580-851 1.64e-13

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: 71.43  E-value: 1.64e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARA--PGLlpyepftMVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14186     9 LGKGSFACVYRARSlhTGL-------EVAIKMIDKKAmqKAGMVQRVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSmsphtvcslshsdlstRARvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14186    82 MCHNGEMSRYLKN----------------RKK-------PFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRN 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSAD--YYKADGNDaipiRWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYYGMAHEEVIYY 813
Cdd:cd14186   139 MNIKIADFGLATQLKMPHekHFTMCGTP----NYISPEIATRSAHGLESDVWSLGCMFY-TLLVGRPPFDTDTVKNTLNK 213
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 814 VrdgnILA---CPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14186   214 V----VLAdyeMPAFLSREAQDLIHQLLRKNPADRLSLSSV 250
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
577-794 1.70e-13

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: 72.07  E-value: 1.70e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQAR--APGllpyepfTMVAVKMLKEEASAD-MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd07861     5 IEKIGEGTYGVVYKGRnkKTG-------QIVAMKKIRLESEEEgVPSTAIREISLLKELQHPNIVCLEDVLMQENRLYLV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYgDLNEFLRS------MSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd07861    78 FEFLSM-DLKKYLDSlpkgkyMDAELVKSYLY---------------------------QILQGILFCHSRRVLHRDLKP 129
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIysadyykadgndAIPIR----------WMPPESIF-YNRYTTESDVWAYGVVLWEI 794
Cdd:cd07861   130 QNLLIDNKGVIKLADFGLARAF------------GIPVRvythevvtlwYRAPEVLLgSPRYSTPVDIWSIGTIFAEM 195
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
580-802 1.71e-13

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: 71.56  E-value: 1.71e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpYEPFT-MVAVKML-KEEASADMQADF-QREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14162     8 LGHGSYAVVKKAY------STKHKcKVAIKIVsKKKAPEDYLQKFlPREIEVIKGLKHPNLICFYEAIETTSRVYIIMEL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSmspHTVCSlshsdlSTRARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd14162    82 AENGDLLDYIRK---NGALP------EPQARR---------------WFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNN 137
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 737 VVKIADFGLSRNIYSADYYKAD------GNDAipirWMPPE---SIFYNryTTESDVWAYGVVLWEIFsYGLQPY 802
Cdd:cd14162   138 NLKITDFGFARGVMKTKDGKPKlsetycGSYA----YASPEilrGIPYD--PFLSDIWSMGVVLYTMV-YGRLPF 205
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
580-744 1.76e-13

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 68.24  E-value: 1.76e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEASADMQaDFQREAALMAEFDNP--NIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd13968     1 MGEGASAKVFWAEG-----ECTTIGVAVKIGDDVNNEEGE-DLESEMDILRRLKGLelNIPKVLVTEDVDGPNILLMELV 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRsmsphTVCSlshSDLSTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd13968    75 KGGTLIAYTQ-----EEEL---DEKDVES-----------------IMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGN 129

                  ....*..
gi 1937920432 738 VKIADFG 744
Cdd:cd13968   130 VKLIDFG 136
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
580-796 1.84e-13

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: 71.64  E-value: 1.84e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPglLPYEpftMVAVKM--LKEEASADMQAdfQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd07844     8 LGEGSYATVYKGRSK--LTGQ---LVALKEirLEHEEGAPFTA--IREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 aYGDLNEFLRS----MSPHTVcslshsdlstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd07844    81 -DTDLKQYMDDcgggLSMHNV---------------------------RLFLFQLLRGLAYCHQRRVLHRDLKPQNLLIS 132
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 734 ENMVVKIADFGLSR--NIYSADYykadGNDAIPIRWMPPESIFYNR-YTTESDVWAYGVVLWEIFS 796
Cdd:cd07844   133 ERGELKLADFGLARakSVPSKTY----SNEVVTLWYRPPDVLLGSTeYSTSLDMWGVGCIFYEMAT 194
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
121-199 2.08e-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: 66.37  E-value: 2.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVL--ESG--SLRIHNVQKEDAGQYRCVAKNSL 196
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLvrENGrhSLIIEPVTKRDAGIYTCIARNRA 80

                  ...
gi 1937920432 197 GTA 199
Cdd:cd05744    81 GEN 83
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
580-803 2.25e-13

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: 71.20  E-value: 2.25e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyePFTMVAVKMLKEEASAdmQADFQREAALMAEF-DNPNIVKLLGVcAVGKPMCLLF--EY 656
Cdd:cd13987     1 LGEGTYGKVLLAVHKG-----SGTKMALKFVPKPSTK--LKDFLREYNISLELsVHPHIIKTYDV-AFETEDYYVFaqEY 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLneflRSMSPHTVcslshsdlstrarvsspGPPplSCAEQLCIArQVAAGMAYLSERKFVHRDLATRNCLV--GE 734
Cdd:cd13987    73 APYGDL----FSIIPPQV-----------------GLP--EERVKRCAA-QLASALDFMHSKNLVHRDIKPENVLLfdKD 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKadgNDAIPirWMPPE---SIFYNRYTTE--SDVWAYGVVL---------WEIFSYGLQ 800
Cdd:cd13987   129 CRRVKLCDFGLTRRVGSTVKRV---SGTIP--YTAPEvceAKKNEGFVVDpsIDVWAFGVLLfccltgnfpWEKADSDDQ 203

                  ...
gi 1937920432 801 PYY 803
Cdd:cd13987   204 FYE 206
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
580-848 2.36e-13

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: 70.78  E-value: 2.36e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyEPFTMVAVK-MLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd14121     3 LGSGTYATVYKAYRKS----GAREVVAVKcVSKSSLNKASTENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCS 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRS--MSPHTVCslshsdlstraRVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV--GE 734
Cdd:cd14121    79 GGDLSRFIRSrrTLPESTV-----------RR---------------FLQQLASALQFLREHNISHMDLKPQNLLLssRY 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRniysadyYKADGNDAIPIR----WMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHEEV 810
Cdd:cd14121   133 NPVLKLADFGFAQ-------HLKPNDEAHSLRgsplYMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRSFEEL 204
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1937920432 811 IYYVRDGNILACPENCPL-----ELynLMRLCwSKLPADRPSF 848
Cdd:cd14121   205 EEKIRSSKPIEIPTRPELsadcrDL--LLRLL-QRDPDRRISF 244
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
573-802 2.38e-13

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: 71.45  E-value: 2.38e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQArapgllpYEPFT--MVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd06619     2 DIQYQEILGHGNGGTVYKA-------YHLLTrrILAVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRI 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFlRSMSPHTVCSlshsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd06619    75 SICTEFMDGGSLDVY-RKIPEHVLGR---------------------------IAVAVVKGLTYLWSLKILHRDVKPSNM 126
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIfSYGLQPY 802
Cdd:cd06619   127 LVNTRGQVKLCDFGVSTQLVNSIAKTYVGTNA----YMAPERISGEQYGIHSDVWSLGISFMEL-ALGRFPY 193
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
578-819 2.52e-13

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: 71.04  E-value: 2.52e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARApgllpYEPFTMVAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14097     7 RKLGQGSFGVVIEATH-----KETQTKWAIKKInREKAGSSAVKLLEREVDILKHVNHAHIIHLEEVFETPKRMYLVMEL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRsmsphtvcslshsdlstRARVsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd14097    82 CEDGELKELLL-----------------RKGF-------FSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSSI 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 V-------VKIADFGLSRNIYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYYGMAHEE 809
Cdd:cd14097   138 IdnndklnIKVTDFGLSVQKYGLGEDMLQETCGTPI-YMAPEVISAHGYSQQCDIWSIGVIMY-MLLCGEPPFVAKSEEK 215
                         250
                  ....*....|
gi 1937920432 810 VIYYVRDGNI 819
Cdd:cd14097   216 LFEEIRKGDL 225
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
577-853 2.89e-13

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: 70.61  E-value: 2.89e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGllPYEPFTMVAVKMLKeeASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd08218     5 IKKIGEGSFGKALLVKSKE--DGKQYVIKEINISK--MSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLneflrsmsphtvcslsHSDLSTRARVSSPGPPPLSCAEQLCIArqvaagMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd08218    81 CDGGDL----------------YKRINAQRGVLFPEDQILDWFVQLCLA------LKHVHDRKILHRDIKSQNIFLTKDG 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNIYS----------ADYYkadgndaipirwMPPEsIFYNR-YTTESDVWAYGVVLWEIFSYGLQPYYGM 805
Cdd:cd08218   139 IIKLGDFGIARVLNStvelartcigTPYY------------LSPE-ICENKpYNNKSDIWALGCVLYEMCTLKHAFEAGN 205
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 806 AHEEVIYYVRdGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHR 853
Cdd:cd08218   206 MKNLVLKIIR-GSYPPVPSRYSYDLRSLVSQLFKRNPRDRPSINSILE 252
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
580-838 3.17e-13

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: 71.10  E-value: 3.17e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRV--FQARAPGLLpyepftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKllgVCAVGKPMCLL---- 653
Cdd:cd14039     1 LGTGGFGNVclYQNQETGEK-------IAIKSCRLELSVKNKDRWCHEIQIMKKLNHPNVVK---ACDVPEEMNFLvndv 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 ----FEYMAYGDLNEFLRsmSPHTVCSLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd14039    71 pllaMEYCSGGDLRKLLN--KPENCCGLKESQV-------------------LSLLSDIGSGIQYLHENKIIHRDLKPEN 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CL---VGENMVVKIADFGLSRNIysaDYYKADGNDAIPIRWMPPEsIFYNR-YTTESDVWAYGVVLWEI------FSYGL 799
Cdd:cd14039   130 IVlqeINGKIVHKIIDLGYAKDL---DQGSLCTSFVGTLQYLAPE-LFENKsYTVTVDYWSFGTMVFECiagfrpFLHNL 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 800 QPY------------YGMAHEEVIYYVRDGNILACPENC------PLELYNLMRLCW 838
Cdd:cd14039   206 QPFtwhekikkkdpkHIFAVEEMNGEVRFSTHLPQPNNLcslivePMEGWLQLMLNW 262
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
568-863 3.32e-13

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: 71.62  E-value: 3.32e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARapgllPYEPFTMVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGvca 645
Cdd:cd06635    21 EDPEKLFSDLREIGHGSFGAVYFAR-----DVRTSEVVAIKKMSYSGkqSNEKWQDIIKEVKFLQRIKHPNSIEYKG--- 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 vgkpmCLLFEYMAYGDLNeflrsmsphtVCSLSHSDLSTRARvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd06635    93 -----CYLREHTAWLVME----------YCLGSASDLLEVHK------KPLQEIEIAAITHGALQGLAYLHSHNMIHRDI 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGlSRNIYSAdyykADGNDAIPIrWMPPESIFY---NRYTTESDVWAYGVVLWEIFSYGlQPY 802
Cdd:cd06635   152 KAGNILLTEPGQVKLADFG-SASIASP----ANSFVGTPY-WMAPEVILAmdeGQYDGKVDVWSLGITCIELAERK-PPL 224
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 803 YGMAHEEVIYYVRDGNILACPENCPLELY-NLMRLCWSKLPADRPSFCSI--HRILQRmcERAE 863
Cdd:cd06635   225 FNMNAMSALYHIAQNESPTLQSNEWSDYFrNFVDSCLQKIPQDRPTSEELlkHMFVLR--ERPE 286
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
580-845 3.65e-13

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: 70.33  E-value: 3.65e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF--QARAPGllpyepfTMVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd05572     1 LGVGGFGRVElvQLKSKG-------RTFALKCVKKRHivQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLME 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSmsphtvcslshsdlstRARVSSPgppplscAEQLCIArQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd05572    74 YCLGGELWTILRD----------------RGLFDEY-------TARFYTA-CVVLAFEYLHSRGIIYRDLKPENLLLDSN 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSadyykadGNDAIPI----RWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG-----MA 806
Cdd:cd05572   130 GYVKLVDFGFAKKLGS-------GRKTWTFcgtpEYVAPEIILNKGYDFSVDYWSLGILLYELLT-GRPPFGGddedpMK 201
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1937920432 807 HEEVIyyVRDGNILACPENCPLELYNLM-RLCwSKLPADR 845
Cdd:cd05572   202 IYNII--LKGIDKIEFPKYIDKNAKNLIkQLL-RRNPEER 238
Ig5_Contactin-1 cd05852
Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth ...
121-201 3.75e-13

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409438  Cd Length: 89  Bit Score: 65.79  E-value: 3.75e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKII--EGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd05852     1 PTFEFNPMKKKILaaKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGK 80

                  ...
gi 1937920432 199 AYS 201
Cdd:cd05852    81 ANS 83
Ig3_Peroxidasin cd05745
Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
134-198 4.09e-13

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third 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: 143222 [Multi-domain]  Cd Length: 74  Bit Score: 65.34  E-value: 4.09e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 134 EGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGS 65
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
583-796 4.24e-13

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 70.82  E-value: 4.24e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 583 GAFGRVFQARAPGLLpyepftmVAVKM--LKEEASadmqadFQREAALmaeFDNP-----NIVKLLGVCAVGKPMC---- 651
Cdd:cd14053     6 GRFGAVWKAQYLNRL-------VAVKIfpLQEKQS------WLTEREI---YSLPgmkheNILQFIGAEKHGESLEaeyw 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSmspHTVcslshsdlstrarvsspgppplSCAEQLCIARQVAAGMAYLSE---RKF-------V 721
Cdd:cd14053    70 LITEFHERGSLCDYLKG---NVI----------------------SWNELCKIAESMARGLAYLHEdipATNgghkpsiA 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPI-RWMPPE----SIfynRYTTES----DVWAYGVVLW 792
Cdd:cd14053   125 HRDFKSKNVLLKSDLTACIADFGLAL-KFEPGKSCGDTHGQVGTrRYMAPEvlegAI---NFTRDAflriDMYAMGLVLW 200

                  ....
gi 1937920432 793 EIFS 796
Cdd:cd14053   201 ELLS 204
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
570-802 4.37e-13

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: 70.91  E-value: 4.37e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPGLlpyepFTMVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06655    17 PKKKYTRYEKIGQGASGTVFTAIDVAT-----GQEVAIKQINLQKQPKKELIIN-EILVMKELKNPNIVNFLDSFLVGDE 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRarvsspgppplSCAEQLCIA---RQVAAGMAYLSERKFVHRDLA 726
Cdd:cd06655    91 LFVVMEYLAGGSL-----------------TDVVTE-----------TCMDEAQIAavcRECLQALEFLHANQVIHRDIK 142
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd06655   143 SDNVLLGMDGSVKLTDFGFCAQI-TPEQSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 215
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
575-794 4.41e-13

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: 70.63  E-value: 4.41e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQAR--APGLLpyepftmVAVKMLKEEASAD-MQADFQREAALMAEF-DNPNIVKLLGVCAV---G 647
Cdd:cd07837     4 EKLEKIGEGTYGKVYKARdkNTGKL-------VALKKTRLEMEEEgVPSTALREVSLLQMLsQSIYIVRLLDVEHVeenG 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMC-LLFEYMAyGDLNEFLRsmsphtvcslshsdlSTRARVSSPGPPPL--SCAEQLCiarqvaAGMAYLSERKFVHRD 724
Cdd:cd07837    77 KPLLyLVFEYLD-TDLKKFID---------------SYGRGPHNPLPAKTiqSFMYQLC------KGVAHCHSHGVMHRD 134
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 725 LATRNCLVG-ENMVVKIADFGLSRNIYSAdyYKADGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEI 794
Cdd:cd07837   135 LKPQNLLVDkQKGLLKIADLGLGRAFTIP--IKSYTHEIVTLWYRAPEVLLgSTHYSTPVDMWSVGCIFAEM 204
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
580-847 4.90e-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: 70.13  E-value: 4.90e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpyEPFTMV--AVKMLKEEASADMQAdFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd06624    16 LGKGTFGVVYAAR-------DLSTQVriAIKEIPERDSREVQP-LHEEIALHSRLSHKNIVQYLGSVSEDGFFKIFMEQV 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPhtvcslshsdlstrarvsspgppPLSCAEQLCI--ARQVAAGMAYLSERKFVHRDLATRNCLVgeN 735
Cdd:cd06624    88 PGGSLSALLRSKWG-----------------------PLKDNENTIGyyTKQILEGLKYLHDNKIVHRDIKGDNVLV--N 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 M---VVKIADFGLSRNIysADYYKADGNDAIPIRWMPPESIFYNR--YTTESDVWAYGVVLWEIfSYGLQPYYGMAHEE- 809
Cdd:cd06624   143 TysgVVKISDFGTSKRL--AGINPCTETFTGTLQYMAPEVIDKGQrgYGPPADIWSLGCTIIEM-ATGKPPFIELGEPQa 219
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 810 ----VIYYVRDGNIlacPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd06624   220 amfkVGMFKIHPEI---PESLSEEAKSFILRCFEPDPDKRAT 258
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
605-747 5.10e-13

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 72.52  E-value: 5.10e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVkllGVCAVGK----P---McllfEYMAYGDLNEFLRSmsphtvc 675
Cdd:NF033483   35 VAVKVLRPDLARDpeFVARFRREAQSAASLSHPNIV---SVYDVGEdggiPyivM----EYVDGRTLKDYIRE------- 100
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 676 slsHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSR 747
Cdd:NF033483  101 ---HGPLSPEEAVE--------------IMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIAR 155
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
575-796 5.46e-13

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: 69.74  E-value: 5.46e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd14663     3 ELGRTLGEGTFAKVKFARN-----TKTGESVAIKIIDKEQVARegMVEQIKREIAIMKLLRHPNIVELHEVMATKTKIFF 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEflrsmsphtvcslshsdlstraRVSSPGPPPLSCAEQLciARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14663    78 VMELVTGGELFS----------------------KIAKNGRLKEDKARKY--FQQLIDAVDYCHSRGVFHRDLKPENLLL 133
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 733 GENMVVKIADFGLSrniYSADYYKADG----NDAIPiRWMPPESIFYNRYT-TESDVWAYGVVLWEIFS 796
Cdd:cd14663   134 DEDGNLKISDFGLS---ALSEQFRQDGllhtTCGTP-NYVAPEVLARRGYDgAKADIWSCGVILFVLLA 198
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
575-803 6.83e-13

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: 70.90  E-value: 6.83e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPGLLPYEPftmVAVKMLKEEASADMQADFQ-REAALMAEFDN-PNIVKLLGVcavgkpmcl 652
Cdd:cd07857     3 ELIKELGQGAYGIVCSARNAETSEEET---VAIKKITNVFSKKILAKRAlRELKLLRHFRGhKNITCLYDM--------- 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 lfEYMAYGDLNEFLRSMSphtvcsLSHSDLSTRARVSSPgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd07857    71 --DIVFPGNFNELYLYEE------LMEADLHQIIRSGQP----LTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLV 138
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 733 GENMVVKIADFGLSRNiYSADYYKADG--NDAIPIRWM-PPESIF-YNRYTTESDVWAYGVVLWEIfsYGLQPYY 803
Cdd:cd07857   139 NADCELKICDFGLARG-FSENPGENAGfmTEYVATRWYrAPEIMLsFQSYTKAIDVWSVGCILAEL--LGRKPVF 210
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
603-858 7.03e-13

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. 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 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-A/B 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: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 69.93  E-value: 7.03e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 603 TMVAVKMLkEEASADMQADFQREAALMAEFDNPNIVKLLGVCaVGKP-MCLLFEYMAYGDLNEFLRSMSPHT----VCSL 677
Cdd:cd14042    31 NLVAIKKV-NKKRIDLTREVLKELKHMRDLQHDNLTRFIGAC-VDPPnICILTEYCPKGSLQDILENEDIKLdwmfRYSL 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 678 SHsDLstrarvsspgppplscaeqlciarqvAAGMAYL--SERKFvHRDLATRNCLVGENMVVKIADFGLS--------R 747
Cdd:cd14042   109 IH-DI--------------------------VKGMHYLhdSEIKS-HGNLKSSNCVVDSRFVLKITDFGLHsfrsgqepP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 748 NIYSADYYKAdgndaipiRWMPPE----SIFYNRYTTESDVWAYGVVLWEIFS----YGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd14042   161 DDSHAYYAKL--------LWTAPEllrdPNPPPPGTQKGDVYSFGIILQEIATrqgpFYEEGPDLSPKEIIKKKVRNGEK 232
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 820 -----LACPENCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14042   233 ppfrpSLDELECPDEVLSLMQRCWAEDPEERPDFSTLRNKLKKL 276
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
578-804 7.30e-13

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: 69.50  E-value: 7.30e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARApgllpyEPFTM-VAVKML-KEEASADMQADF-QREAALMAEFDNPNIVKLLGVCAV-GKPMCLL 653
Cdd:cd14164     6 TTIGEGSFSKVKLATS------QKYCCkVAIKIVdRRRASPDFVQKFlPRELSILRRVNHPNIVQMFECIEVaNGRLYIV 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEyMAYGDLNEFLRSMspHTVCSLSHSDLSTrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLV- 732
Cdd:cd14164    80 ME-AAATDLLQKIQEV--HHIPKDLARDMFA----------------------QMVGAVNYLHDMNIVHRDLKCENILLs 134
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 733 GENMVVKIADFGLSRNI--YSADYYKADGNDAipirWMPPESIFYNRYTTES-DVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14164   135 ADDRKIKIADFGFARFVedYPELSTTFCGSRA----YTPPEVILGTPYDPKKyDVWSLGVVLYVMVT-GTMPFDE 204
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
615-847 7.49e-13

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 71.97  E-value: 7.49e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 615 SADMQADFQR-EAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRS-MSPHTvcslshsdlstrarvsspg 692
Cdd:PTZ00267  104 NDERQAAYARsELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSGGDLNKQIKQrLKEHL------------------- 164
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 693 ppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNiYSaDYYKADGNDAI---PIrWMP 769
Cdd:PTZ00267  165 --PFQEYEVGLLFYQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQ-YS-DSVSLDVASSFcgtPY-YLA 239
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 770 PESIFYNRYTTESDVWAYGVVLWEIFSYGlQPYYGMAHEEVIYYVRDGNILACPenCPLE--LYNLMRLCWSKLPADRPS 847
Cdd:PTZ00267  240 PELWERKRYSKKADMWSLGVILYELLTLH-RPFKGPSQREIMQQVLYGKYDPFP--CPVSsgMKALLDPLLSKNPALRPT 316
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
570-802 7.63e-13

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: 69.57  E-value: 7.63e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQArapglLPYEPFTMVAVKM--LKEEASADMQADfqrEAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd06647     5 PKKKYTRFEKIGQGASGTVYTA-----IDVATGQEVAIKQmnLQQQPKKELIIN---EILVMRENKNPNIVNYLDSYLVG 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRarvsspgppplSCAEQLCIA---RQVAAGMAYLSERKFVHRD 724
Cdd:cd06647    77 DELWVVMEYLAGGSL-----------------TDVVTE-----------TCMDEGQIAavcRECLQALEFLHSNQVIHRD 128
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd06647   129 IKSDNILLGMDGSVKLTDFGFCAQI-TPEQSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 203
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
708-858 1.02e-12

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. 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 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-C 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: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 69.14  E-value: 1.02e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 708 VAAGMAYLSERKF-VHRDLATRNCLVGENMVVKIADFGlsrniysadyykadGNDAIPIR---WMPPESIFYNRYTTESD 783
Cdd:cd14044   118 IAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFG--------------CNSILPPSkdlWTAPEHLRQAGTSQKGD 183
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 784 VWAYGVVLWEIFSYGlQPYYGMA---HEEVIYYVRDGN---------ILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14044   184 VYSYGIIAQEIILRK-ETFYTAAcsdRKEKIYRVQNPKgmkpfrpdlNLESAGEREREVYGLVKNCWEEDPEKRPDFKKI 262

                  ....*..
gi 1937920432 852 HRILQRM 858
Cdd:cd14044   263 ENTLAKI 269
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
573-845 1.03e-12

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: 69.30  E-value: 1.03e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARApgllPYEPfTMVAVKMLK-----EEASADMQADFQ-REAALMAEF-DNPNIVKLLGVCA 645
Cdd:cd13993     1 RYQLISPIGEGAYGVVYLAVD----LRTG-RKYAIKCLYksgpnSKDGNDFQKLPQlREIDLHRRVsRHPNIITLHDVFE 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 646 VGKPMCLLFEYMAYGDLNEflrsmsphtvcslshsdlSTRARVSSPGPPPLSCAeqlcIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd13993    76 TEVAIYIVLEYCPNGDLFE------------------AITENRIYVGKTELIKN----VFLQLIDAVKHCHSLGIYHRDI 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGEN-MVVKIADFGLS-RNIYSADYykADGNDaipiRWMPPESI--------FYnrYTTESDVWAYGVVLWEIF 795
Cdd:cd13993   134 KPENILLSQDeGTVKLCDFGLAtTEKISMDF--GVGSE----FYMAPECFdevgrslkGY--PCAAGDIWSLGIILLNLT 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 796 SyGLQPyYGMAHEEVI----YYVRDGNILACPENCPLELYNLMRLCWSKLPADR 845
Cdd:cd13993   206 F-GRNP-WKIASESDPifydYYLNSPNLFDVILPMSDDFYNLLRQIFTVNPNNR 257
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
572-856 1.10e-12

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: 70.39  E-value: 1.10e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADM--QADFQREAALMAEFDNPNIVKLlgVCAVGKP 649
Cdd:cd05573     1 DDFEVIKVIGRGAFGEVWLVRDK-----DTGQVYAMKILRKSDMLKReqIAHVRAERDILADADSPWIVRL--HYAFQDE 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 --MCLLFEYMAYGDLneflrsMSphtvcSLSHSDLSTRARVsspgppplscaeQLCIARQVAAgMAYLSERKFVHRDLAT 727
Cdd:cd05573    74 dhLYLVMEYMPGGDL------MN-----LLIKYDVFPEETA------------RFYIAELVLA-LDSLHKLGFIHRDIKP 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSAD---YYKADGNDA-------IPIRW-----------------MPPESIFYNRYTT 780
Cdd:cd05573   130 DNILLDADGHIKLADFGLCTKMNKSGdreSYLNDSVNTlfqdnvlARRRPhkqrrvraysavgtpdyIAPEVLRGTGYGP 209
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 781 ESDVWAYGVVLWEIFsYGLQPYYG----------MAHEEVIYYVRDGNIlacpencPLELYNLMR--LCWSKlpaDRpsF 848
Cdd:cd05573   210 ECDWWSLGVILYEML-YGFPPFYSdslvetyskiMNWKESLVFPDDPDV-------SPEAIDLIRrlLCDPE---DR--L 276

                  ....*...
gi 1937920432 849 CSIHRILQ 856
Cdd:cd05573   277 GSAEEIKA 284
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
575-795 1.16e-12

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: 69.89  E-value: 1.16e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQA--RAPGllpyepfTMVAVKMLKE--EASADMQADFqREAALMAEF-DNPNIVKLLGV--CAVG 647
Cdd:cd07852    10 EILKKLGKGAYGIVWKAidKKTG-------EVVALKKIFDafRNATDAQRTF-REIMFLQELnDHPNIIKLLNVirAEND 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMaygdlneflrsmsphtvcslsHSDLST--RARVsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd07852    82 KDIYLVFEYM---------------------ETDLHAviRANI-------LEDIHKQYIMYQLLKALKYLHSGGVIHRDL 133
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIYSADYYKADGN--DAIPIRWM-PPESIF-YNRYTTESDVWAYGVVLWEIF 795
Cdd:cd07852   134 KPSNILLNSDCRVKLADFGLARSLSQLEEDDENPVltDYVATRWYrAPEILLgSTRYTKGVDMWSVGCILGEML 207
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
125-202 1.22e-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: 63.95  E-value: 1.22e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 125 RPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALrENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSK 202
Cdd:cd05725     2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEAS 78
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
679-861 1.51e-12

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty 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: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 68.67  E-value: 1.51e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 679 HSDLSTRARVSspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNiysadyyKAD 758
Cdd:cd13975    88 HRDLYTGIKAG------LSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCKP-------EAM 154
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 759 GNDAI---PIRwMPPEsIFYNRYTTESDVWAYGVVLWEIFSYGL---QPYYGMAHEEVIY-YVRDGnilACPENCPL--- 828
Cdd:cd13975   155 MSGSIvgtPIH-MAPE-LFSGKYDNSVDVYAFGILFWYLCAGHVklpEAFEQCASKDHLWnNVRKG---VRPERLPVfde 229
                         170       180       190
                  ....*....|....*....|....*....|...
gi 1937920432 829 ELYNLMRLCWSKLPADRPSFCSIHRILQRMCER 861
Cdd:cd13975   230 ECWNLMEACWSGDPSQRPLLGIVQPKLQGIMDR 262
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
572-809 1.64e-12

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: 68.74  E-value: 1.64e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKML-KEEASAD-MQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd14117     6 DDFDIGRPLGKGKFGNVYLAREK-----QSKFIVALKVLfKSQIEKEgVEHQLRREIEIQSHLRHPNILRLYNYFHDRKR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMsphtvCSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd14117    81 IYLILEYAPRGELYKELQKH-----GRFDEQRTAT-------------------FMEELADALHYCHEKKVIHRDIKPEN 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHEE 809
Cdd:cd14117   137 LLMGYKGELKIADFGWSVHAPSLRRRTMCGT----LDYLPPEMIEGRTHDEKVDLWCIGVLCYELL-VGMPPFESASHTE 211
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
624-802 1.67e-12

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: 68.82  E-value: 1.67e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 624 REAALMAEFDNPNIVKLLGVcaVGKP----MCLLFEYMAYGDLNEFlrsmsphtvcslshsdlstrarvssPGPPPLSCA 699
Cdd:cd14200    72 QEIAILKKLDHVNIVKLIEV--LDDPaednLYMVFDLLRKGPVMEV-------------------------PSDKPFSED 124
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 700 EQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIysadyykaDGNDAI-------PIrWMPPES 772
Cdd:cd14200   125 QARLYFRDIVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQF--------EGNDALlsstagtPA-FMAPET 195
                         170       180       190
                  ....*....|....*....|....*....|...
gi 1937920432 773 IFYNRYTTES---DVWAYGVVLWeIFSYGLQPY 802
Cdd:cd14200   196 LSDSGQSFSGkalDVWAMGVTLY-CFVYGKCPF 227
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
572-805 1.85e-12

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: 68.95  E-value: 1.85e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd07869     5 DSYEKLEKLGEGSYATVYKGKSK-----VNGKLVALKVIRLQEEEGTPFTAIREASLLKGLKHANIVLLHDIIHTKETLT 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMaygdlneflrsmsphtvcslsHSDLSTRARVSSPGPPPLSCAEQLCiarQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd07869    80 LVFEYV---------------------HTDLCQYMDKHPGGLHPENVKLFLF---QLLRGLSYIHQRYILHRDLKPQNLL 135
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 732 VGENMVVKIADFGLSR--NIYSADYykadGNDAIPIRWMPPESIF-YNRYTTESDVWAYGVVLWEIFSyGLQPYYGM 805
Cdd:cd07869   136 ISDTGELKLADFGLARakSVPSHTY----SNEVVTLWYRPPDVLLgSTEYSTCLDMWGVGCIFVEMIQ-GVAAFPGM 207
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
578-857 1.87e-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: 68.25  E-value: 1.87e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARapgllpyEPFT--MVAVKMLK--EEASADMQADFQREAALMAEFDNPNIVKLLGvcavgkpmCLL 653
Cdd:cd06607     7 REIGHGSFGAVYYAR-------NKRTseVVAIKKMSysGKQSTEKWQDIIKEVKFLRQLRHPNTIEYKG--------CYL 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYgdlneflRSMSphtVCSLSHSDLSTRARvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd06607    72 REHTAW-------LVME---YCLGSASDIVEVHK------KPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLT 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGlSRNIYSAdyykADGNDAIPIrWMPPESIFY---NRYTTESDVWAYGVVLWEIfSYGLQPYYGMAHEEV 810
Cdd:cd06607   136 EPGTVKLADFG-SASLVCP----ANSFVGTPY-WMAPEVILAmdeGQYDGKVDVWSLGITCIEL-AERKPPLFNMNAMSA 208
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1937920432 811 IYYVRDGNILACPEN-CPLELYNLMRLCWSKLPADRPSF--CSIHRILQR 857
Cdd:cd06607   209 LYHIAQNDSPTLSSGeWSDDFRNFVDSCLQKIPQDRPSAedLLKHPFVTR 258
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
605-858 2.00e-12

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK 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: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 67.90  E-value: 2.00e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKMLK-EEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVcslSHSdls 683
Cdd:cd14057    21 IVAKILKvRDVTTRISRDFNEEYPRLRIFSHPNVLPVLGACNSPPNLVVISQYMPYGSLYNVLHEGTGVVV---DQS--- 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 684 trarvsspgppplscaEQLCIARQVAAGMAYLS--ERKFVHRDLATRNCLVGENMVVKI--ADFGLSRNIYSADYYKAdg 759
Cdd:cd14057    95 ----------------QAVKFALDIARGMAFLHtlEPLIPRHHLNSKHVMIDEDMTARInmADVKFSFQEPGKMYNPA-- 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 760 ndaipirWMPPESIFY---NRYTTESDVWAYGVVLWEIFSYGLqPYYGMAHEEV-IYYVRDGNILACPENCPLELYNLMR 835
Cdd:cd14057   157 -------WMAPEALQKkpeDINRRSADMWSFAILLWELVTREV-PFADLSNMEIgMKIALEGLRVTIPPGISPHMCKLMK 228
                         250       260
                  ....*....|....*....|...
gi 1937920432 836 LCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14057   229 ICMNEDPGKRPKFDMIVPILEKM 251
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
578-802 2.07e-12

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: 68.57  E-value: 2.07e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVfqarapgLLPYEP--FTMVAVKMLKEE-------ASADMQADFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd14084    12 RTLGSGACGEV-------KLAYDKstCKKVAIKIINKRkftigsrREINKPRNIETEIEILKKLSHPCIIKIEDFFDAED 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEflrsmsphtvcslshsdlstraRVSSPgpppLSCAEQLC--IARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd14084    85 DYYIVLELMEGGELFD----------------------RVVSN----KRLKEAICklYFYQMLLAVKYLHSNGIIHRDLK 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVG---ENMVVKIADFGLSRNIysadyykadGNDAI-------PIrWMPPE---SIFYNRYTTESDVWAYGVVLWE 793
Cdd:cd14084   139 PENVLLSsqeEECLIKITDFGLSKIL---------GETSLmktlcgtPT-YLAPEvlrSFGTEGYTRAVDCWSLGVILFI 208

                  ....*....
gi 1937920432 794 IFSyGLQPY 802
Cdd:cd14084   209 CLS-GYPPF 216
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
578-847 2.28e-12

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: 68.31  E-value: 2.28e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQArapglLPYEPFTMVAVKML-KEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd14070     8 RKLGEGSFAKVREG-----LHAVTGEKVAIKVIdKKKAKKDsyVTKNLRREGRIQQMIRHPNITQLLDILETENSYYLVM 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNeflrsmspHTVCSlshsdlstRARvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd14070    83 ELCPGGNLM--------HRIYD--------KKR--------LEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDE 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNI----YSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEIFS----YGLQPYYGMA 806
Cdd:cd14070   139 NDNIKLIDFGLSNCAgilgYSDPFSTQCGSPA----YAAPELLARKKYGPKVDVWSIGVNMYAMLTgtlpFTVEPFSLRA 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1937920432 807 -HEEVIyyvrDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14070   215 lHQKMV----DKEMNPLPTDLSPGAISFLRSLLEPDPLKRPN 252
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
45-111 2.35e-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.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 62.73  E-value: 2.35e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432  45 ATFMCAVESYPQPEISWTRN-KILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGAVES 111
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNgKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
572-847 2.50e-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: 68.36  E-value: 2.50e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAP-GLLPYepftmvAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP- 649
Cdd:cd14048     6 TDFEPIQCLGRGGFGVVFEAKNKvDDCNY------AVKRIRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPPe 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 ----------MCLLFEYMAYGDLNEFLRSMsphtvCSLSHSDLSTrarvsspgppplsCaeqLCIARQVAAGMAYLSERK 719
Cdd:cd14048    80 gwqekmdevyLYIQMQLCRKENLKDWMNRR-----CTMESRELFV-------------C---LNIFKQIASAVEYLHSKG 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 720 FVHRDLATRNCLVGENMVVKIADFGLSRNIYSAD-----------YYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYG 788
Cdd:cd14048   139 LIHRDLKPSNVFFSLDDVVKVGDFGLVTAMDQGEpeqtvltpmpaYAKHTGQVGTRL-YMSPEQIHGNQYSEKVDIFALG 217
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 789 VVLWE-IFSYGLQpyygMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14048   218 LILFElIYSFSTQ----MERIRTLTDVRKLKFPALFTNKYPEERDMVQQMLSPSPSERPE 273
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
580-822 2.50e-12

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: 67.68  E-value: 2.50e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQAR--APGLLpyepftmVAVKMLKEEAsaDMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14006     1 LGRGRFGVVKRCIekATGRE-------FAAKFIPKRD--KKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELC 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLrsMSPHTVCslshsdlstrarvsspgppplscaEQLCIA--RQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14006    72 SGGELLDRL--AERGSLS------------------------EEEVRTymRQLLEGLQYLHNHHILHLDLKPENILLADR 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MV--VKIADFGLSRNIysadyykadgNDAIPIR-------WMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMA 806
Cdd:cd14006   126 PSpqIKIIDFGLARKL----------NPGEELKeifgtpeFVAPEIVNGEPVSLATDMWSIGVLTYVLLS-GLSPFLGED 194
                         250
                  ....*....|....*.
gi 1937920432 807 HEEVIyyvrdGNILAC 822
Cdd:cd14006   195 DQETL-----ANISAC 205
PHA02988 PHA02988
hypothetical protein; Provisional
622-851 2.63e-12

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 68.23  E-value: 2.63e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 622 FQREAALMAEFDNPNIVKLLG-VCAVGKPMC---LLFEYMAYGDLNEFLRSmsphtvcslsHSDLSTRARVSspgpppls 697
Cdd:PHA02988   65 TENEIKNLRRIDSNNILKIYGfIIDIVDDLPrlsLILEYCTRGYLREVLDK----------EKDLSFKTKLD-------- 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 698 caeqlcIARQVAAGMAYLSER-KFVHRDLATRNCLVGENMVVKIADFGLsRNIYSADYYKaDGNDaipIRWMPPESI--F 774
Cdd:PHA02988  127 ------MAIDCCKGLYNLYKYtNKPYKNLTSVSFLVTENYKLKIICHGL-EKILSSPPFK-NVNF---MVYFSYKMLndI 195
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 775 YNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEvIY--YVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:PHA02988  196 FSEYTIKDDIYSLGVVLWEIFT-GKIPFENLTTKE-IYdlIINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEI 272
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
706-853 2.80e-12

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: 67.73  E-value: 2.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKAD--GNDaipiRWMPPESIFYNRYTTESD 783
Cdd:cd14188   108 RQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRRTicGTP----NYLSPEVLNKQGHGCESD 183
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 784 VWAYGVVLWEIFsYGLQPYYGMAHEEVIYYVRDGNiLACPENCPLELYNLMRLCWSKLPADRPSFCSIHR 853
Cdd:cd14188   184 IWALGCVMYTML-LGRPPFETTNLKETYRCIREAR-YSLPSSLLAPAKHLIASMLSKNPEDRPSLDEIIR 251
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
142-201 3.03e-12

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: 63.00  E-value: 3.03e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 142 CTTMGNPKPSVSWIKGDSALRENSRIAVlESGSLRIHNVQKEDAGQYRCVAKNSLGTAYS 201
Cdd:cd05728    21 CKASGNPRPAYRWLKNGQPLASENRIEV-EAGDLRITKLSLSDSGMYQCVAENKHGTIYA 79
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
580-808 3.13e-12

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: 68.07  E-value: 3.13e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF--QARAPGllpyepfTMVAVKMLKEEASADMQADFQREAALMAEF-DNPNIVKLLGVCAVGKPMC--LLF 654
Cdd:cd07831     7 IGEGTFSEVLkaQSRKTG-------KYYAIKCMKKHFKSLEQVNNLREIQALRRLsPHPNILRLIEVLFDRKTGRlaLVF 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMaygDLN--EFLRSmsphtvcslshsdlstRARvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd07831    80 ELM---DMNlyELIKG----------------RKR-------PLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILI 133
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 733 GENmVVKIADFGLSRNIYSADYYkadgNDAIPIRWM-PPESIFYN-RYTTESDVWAYGVVLWEIFSygLQPYYGMAHE 808
Cdd:cd07831   134 KDD-ILKLADFGSCRGIYSKPPY----TEYISTRWYrAPECLLTDgYYGPKMDIWAVGCVFFEILS--LFPLFPGTNE 204
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
575-845 3.99e-12

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: 67.82  E-value: 3.99e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPGLLpyEPFTMVAVK----MLKEEASadmQADFQREAALMAEfdNPNIVKLLGVCAVGKPM 650
Cdd:cd05609     3 ETIKLISNGAYGAVYLVRHRETR--QRFAMKKINkqnlILRNQIQ---QVFVERDILTFAE--NPFVVSMYCSFETKRHL 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAeQLCIARQVAAgMAYLSERKFVHRDLATRNC 730
Cdd:cd05609    76 CMVMEYVEGGDCATLLKNI----------------------GPLPVDMA-RMYFAETVLA-LEYLHSYGIVHRDLKPDNL 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSR--------NIYSaDYYKADGND-------AIPiRWMPPESIFYNRYTTESDVWAYGVVLWEiF 795
Cdd:cd05609   132 LITSMGHIKLTDFGLSKiglmslttNLYE-GHIEKDTREfldkqvcGTP-EYIAPEVILRQGYGKPVDWWAMGIILYE-F 208
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 796 SYGLQPYYGMAHEEVIYYVRDGNIL------ACPENCPLELYNLMRLCwsklPADR 845
Cdd:cd05609   209 LVGCVPFFGDTPEELFGQVISDEIEwpegddALPDDAQDLITRLLQQN----PLER 260
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
140-204 4.00e-12

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: 62.20  E-value: 4.00e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 140 LPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKLV 204
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMV 67
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
572-794 4.33e-12

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: 67.71  E-value: 4.33e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKE-EASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd07848     1 NKFEVLGVVGEGAYGVVLKCRHK-----ETKEIVAIKKFKDsEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKL 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLnEFLRSMsPHtvcslshsdlstrarvsspGPPPLSCAEQLciaRQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd07848    76 YLVFEYVEKNML-ELLEEM-PN-------------------GVPPEKVRSYI---YQLIKAIHWCHKNDIVHRDIKPENL 131
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIysadyykADGNDA-----IPIRWM-PPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd07848   132 LISHNDVLKLCDFGFARNL-------SEGSNAnyteyVATRWYrSPELLLGAPYGKAVDMWSVGCILGEL 194
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
579-811 4.80e-12

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: 67.35  E-value: 4.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 579 DIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd14194    12 ELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSSRRGVSREDIEREVSILKEIQHPNVITLHEVYENKTDVILILELVA 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRSMSphtvcSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV- 737
Cdd:cd14194    92 GGELFDFLAEKE-----SLTEEEATE-------------------FLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVp 147
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 738 ---VKIADFGLSRNIYSADYYKadgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd14194   148 kprIKIIDFGLAHKIDFGNEFK---NIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETL 220
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
575-853 4.90e-12

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: 67.08  E-value: 4.90e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPGLLPyepfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKpmCLLF 654
Cdd:cd08223     3 QFLRVIGKGSYGEVWLVRHKRDRK----QYVIKKLNLKNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGED--GFLY 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYgdlneflrsmsphtvCSlsHSDLSTRARVSSPGPPPLSCAEQLCIarQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd08223    77 IVMGF---------------CE--GGDLYTRLKEQKGVLLEERQVVEWFV--QIAMALQYMHERNILHRDLKTQNIFLTK 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSAdyykadgNDAIPIR-----WMPPEsIFYNR-YTTESDVWAYGVVLWEIFSYGlQPYYGMAHE 808
Cdd:cd08223   138 SNIIKVGDLGIARVLESS-------SDMATTLigtpyYMSPE-LFSNKpYNHKSDVWALGCCVYEMATLK-HAFNAKDMN 208
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1937920432 809 EVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIHR 853
Cdd:cd08223   209 SLVYKILEGKLPPMPKQYSPELGELIKAMLHQDPEKRPSVKRILR 253
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
573-818 4.93e-12

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: 67.13  E-value: 4.93e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGE----GAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd14105     2 NVEDFYDIGEelgsGQFAVVKKCREKSTGLEYAAKFIKKRRSKASRRGVSREDIEREVSILRQVLHPNIITLHDVFENKT 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLrsmsphtvcslshsdlstrARVSSpgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd14105    82 DVVLILELVAGGELFDFL-------------------AEKES-----LSEEEATEFLKQILDGVNYLHTKNIAHFDLKPE 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMV----VKIADFGLSRNIYSADYYKadgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14105   138 NIMLLDKNVpiprIKLIDFGLAHKIEDGNEFK---NIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLG 213
                         250
                  ....*....|....
gi 1937920432 805 MAHEEVIYYVRDGN 818
Cdd:cd14105   214 DTKQETLANITAVN 227
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
580-818 4.98e-12

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: 67.25  E-value: 4.98e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGLlpyepftMVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14190    12 LGGGKFGKVHTCteKRTGL-------KLAAKVINKQNSKDKEMVLL-EIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYV 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN--CLVGEN 735
Cdd:cd14190    84 EGGELFERIVDEDYH-----------------------LTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENilCVNRTG 140
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKAdgNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVR 815
Cdd:cd14190   141 HQVKIIDFGLARRYNPREKLKV--NFGTP-EFLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPFLGDDDTETLNNVL 216

                  ...
gi 1937920432 816 DGN 818
Cdd:cd14190   217 MGN 219
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
575-817 5.27e-12

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: 67.12  E-value: 5.27e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQArapglLPYEPFTMVAVKMLKEE----ASADMQAdFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14098     3 QIIDRLGSGTFAEVKKA-----VEVETGKMRAIKQIVKRkvagNDKNLQL-FQREINILKSLEHPGIVRLIDWYEDDQHI 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLrsmsphtvcslshsdlstrarVSSPGPPPLSCAEqlcIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd14098    77 YLVMEYVEGGDLMDFI---------------------MAWGAIPEQHARE---LTKQILEAMAYTHSMGITHRDLKPENI 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGEN--MVVKIADFGLSRNIYSADYYKA-DGNDAipirWMPPESIFY------NRYTTESDVWAYGVVLWEIFSYGLqP 801
Cdd:cd14098   133 LITQDdpVIVKISDFGLAKVIHTGTFLVTfCGTMA----YLAPEILMSkeqnlqGGYSNLVDMWSVGCLVYVMLTGAL-P 207
                         250
                  ....*....|....*.
gi 1937920432 802 YYGMAHEEVIYYVRDG 817
Cdd:cd14098   208 FDGSSQLPVEKRIRKG 223
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
577-853 5.50e-12

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: 67.75  E-value: 5.50e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGvcavgkpmCLLF 654
Cdd:cd06633    26 LHEIGHGSFGAVYFATNS-----HTNEVVAIKKMSYSGkqTNEKWQDIIKEVKFLQQLKHPNTIEYKG--------CYLK 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLnEFlrsmsphtvCSLSHSDLSTRARvsspgpPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd06633    93 DHTAWLVM-EY---------CLGSASDLLEVHK------KPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTE 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGlSRNIYSAdyykADGNDAIPIrWMPPESIFY---NRYTTESDVWAYGVVLWEIFSYGlQPYYGMAHEEVI 811
Cdd:cd06633   157 PGQVKLADFG-SASIASP----ANSFVGTPY-WMAPEVILAmdeGQYDGKVDIWSLGITCIELAERK-PPLFNMNAMSAL 229
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1937920432 812 YYVRDGNILACPENCPLELY-NLMRLCWSKLPADRPSFCSIHR 853
Cdd:cd06633   230 YHIAQNDSPTLQSNEWTDSFrGFVDYCLQKIPQERPSSAELLR 272
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
570-802 5.59e-12

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: 67.44  E-value: 5.59e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06656    17 PKKKYTRFEKIGQGASGTVYTA-----IDIATGQEVAIKQMNLQQQPKKELIIN-EILVMRENKNPNIVNYLDSYLVGDE 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRarvsspgppplSCAEQLCIA---RQVAAGMAYLSERKFVHRDLA 726
Cdd:cd06656    91 LWVVMEYLAGGSL-----------------TDVVTE-----------TCMDEGQIAavcRECLQALDFLHSNQVIHRDIK 142
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd06656   143 SDNILLGMDGSVKLTDFGFCAQI-TPEQSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 215
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
36-117 5.92e-12

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: 62.42  E-value: 5.92e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  36 TVDALVEEVATFMC-AVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLtILSVEDSDDGIYCCTANNGVGGAVESCGA 114
Cdd:cd05724     6 DTQVAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLL-IAEARKSDEGTYKCVATNMVGERESRAAR 84

                  ...
gi 1937920432 115 LQV 117
Cdd:cd05724    85 LSV 87
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
624-802 5.97e-12

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: 67.30  E-value: 5.97e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 624 REAALMAEFDNPNIVKLLGVcaVGKP----MCLLFEYMAYGDLNEFlrsmsphtvcslshsdlstrarvssPGPPPLSCA 699
Cdd:cd14199    74 QEIAILKKLDHPNVVKLVEV--LDDPsedhLYMVFELVKQGPVMEV-------------------------PTLKPLSED 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 700 EQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKAD--GNDAipirWMPPESIFYNR 777
Cdd:cd14199   127 QARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLVGEDGHIKIADFGVSNEFEGSDALLTNtvGTPA----FMAPETLSETR 202
                         170       180
                  ....*....|....*....|....*...
gi 1937920432 778 --YTTES-DVWAYGVVLWeIFSYGLQPY 802
Cdd:cd14199   203 kiFSGKAlDVWAMGVTLY-CFVFGQCPF 229
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
580-818 6.58e-12

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: 67.64  E-value: 6.58e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEA---SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05619    13 LGKGSFGKVFLAELKGTNQF-----FAIKALKKDVvlmDDDVECTMVEKRVLSLAWEHPFLTHLFCTFQTKENLFFVMEY 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSmsphtvcslSHS-DLStRARVSSpgppplscAEQLCiarqvaaGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd05619    88 LNGGDLMFHIQS---------CHKfDLP-RATFYA--------AEIIC-------GLQFLHSKGIVYRDLKLDNILLDKD 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 MVVKIADFGLSRNIYSADyYKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHEEVIYYVR 815
Cdd:cd05619   143 GHIKIADFGMCKENMLGD-AKTSTFCGTP-DYIAPEILLGQKYNTSVDWWSFGVLLYEML-IGQSPFHGQDEEELFQSIR 219

                  ...
gi 1937920432 816 DGN 818
Cdd:cd05619   220 MDN 222
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
572-810 6.83e-12

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: 67.80  E-value: 6.83e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd05593    15 NDFDYLKLLGKGTFGKVILVREKASGKY-----YAMKILKKEViiAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDR 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLrsmsphtvcslshsdlsTRARVSSPGPPPLSCAEqlciarqVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05593    90 LCFVMEYVNGGELFFHL-----------------SRERVFSEDRTRFYGAE-------IVSALDYLHSGKIVYRDLKLEN 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRN-IYSADYYKADGNDAipiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHE 808
Cdd:cd05593   146 LMLDKDGHIKITDFGLCKEgITDAATMKTFCGTP---EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHE 221

                  ..
gi 1937920432 809 EV 810
Cdd:cd05593   222 KL 223
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
35-106 7.93e-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: 61.75  E-value: 7.93e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432   35 ETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQL--LTILSVEDSDDGIYCCTANNGVG 106
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSG 75
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
570-802 8.11e-12

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: 67.06  E-value: 8.11e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06654    18 PKKKYTRFEKIGQGASGTVYTA-----MDVATGQEVAIRQMNLQQQPKKELIIN-EILVMRENKNPNIVNYLDSYLVGDE 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRarvsspgppplSCAEQLCIA---RQVAAGMAYLSERKFVHRDLA 726
Cdd:cd06654    92 LWVVMEYLAGGSL-----------------TDVVTE-----------TCMDEGQIAavcRECLQALEFLHSNQVIHRDIK 143
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd06654   144 SDNILLGMDGSVKLTDFGFCAQI-TPEQSKRSTMVGTPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPY 216
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
580-796 9.69e-12

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: 66.63  E-value: 9.69e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgllpYEPFTMVAVKMLKE-EASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd07847     9 IGEGSYGVVFKCRN-----RETGQIVAIKKFVEsEDDPVIKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEYCD 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRsmSPHTVcslshSDLSTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVV 738
Cdd:cd07847    84 HTVLNELEK--NPRGV-----PEHLIKK-----------------IIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQI 139
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 739 KIADFGLSR--NIYSADYykadgNDAIPIRWM-PPESIFYN-RYTTESDVWAYGVVLWEIFS 796
Cdd:cd07847   140 KLCDFGFARilTGPGDDY-----TDYVATRWYrAPELLVGDtQYGPPVDVWAIGCVFAELLT 196
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
580-855 1.04e-11

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: 66.13  E-value: 1.04e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASADMqadFQREAALMAEFDNPNIVKLLGvcAVGKPMCLLFEYMAY 659
Cdd:cd14068     2 LGDGGFGSVYRAVYRG-------EDVAVKIFNKHTSFRL---LRQELVVLSHLHHPSLVALLA--AGTAPRMLVMELAPK 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSPHTVCSLSHSdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV-----GE 734
Cdd:cd14068    70 GSLDALLQQDNASLTRTLQHR-----------------------IALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNC 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRyttESDVWAYGVVLWEIFSYGLQPYYGMA-------- 806
Cdd:cd14068   127 AIIAKIADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQ---QADVYSFGLLLYDILTCGERIVEGLKfpnefdel 203
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 807 --HEEVIYYVRDGNILACPencplELYNLMRLCWSKLPADRPSFCSIHRIL 855
Cdd:cd14068   204 aiQGKLPDPVKEYGCAPWP-----GVEALIKDCLKENPQCRPTSAQVFDIL 249
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
580-793 1.10e-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: 66.62  E-value: 1.10e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVKM-LKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC------- 651
Cdd:cd07865    20 IGQGTFGEVFKARHR-----KTGQIVALKKvLMENEKEGFPITALREIKILQLLKHENVVNLIEICRTKATPYnrykgsi 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 -LLFEYMAYgDLNEFLRSmsPHTVCSLShsdlstrarvsspgppplscaEQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd07865    95 yLVFEFCEH-DLAGLLSN--KNVKFTLS---------------------EIKKVMKMLLNGLYYIHRNKILHRDMKAANI 150
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKAD--GNDAIPIRWMPPESIFYNR-YTTESDVWAYGVVLWE 793
Cdd:cd07865   151 LITKDGVLKLADFGLARAFSLAKNSQPNryTNRVVTLWYRPPELLLGERdYGPPIDMWGAGCIMAE 216
IgI_SALM5_like cd05764
Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; ...
121-199 1.46e-11

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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: 409421 [Multi-domain]  Cd Length: 88  Bit Score: 61.34  E-value: 1.46e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALREN-SRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNsSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEA 80
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
580-796 1.87e-11

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 65.86  E-value: 1.87e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApGLLPYEPFTMVAVKMLKEEASADmqadFQREAALMAEFD--NPNIVKLLGV----CAVGKPMCLL 653
Cdd:cd14055     3 VGKGRFAEVWKAKL-KQNASGQYETVAVKIFPYEEYAS----WKNEKDIFTDASlkHENILQFLTAeergVGLDRQYWLI 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspgppPLSCaEQLC-IARQVAAGMAYL-SERK--------FVHR 723
Cdd:cd14055    78 TAYHENGSLQDYLTRH-------------------------ILSW-EDLCkMAGSLARGLAHLhSDRTpcgrpkipIAHR 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSRNI---YSADYYKADGNDAIPiRWMPPESI--FYNRYTTES----DVWAYGVVLWEI 794
Cdd:cd14055   132 DLKSSNILVKNDGTCVLADFGLALRLdpsLSVDELANSGQVGTA-RYMAPEALesRVNLEDLESfkqiDVYSMALVLWEM 210

                  ..
gi 1937920432 795 FS 796
Cdd:cd14055   211 AS 212
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
30-117 1.99e-11

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: 60.49  E-value: 1.99e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  30 ITTPLETVdALVEEVATFMCAVESYPQPEISWTRNKIliKLFDTRYSIRENGQLLtILSVEDSDDGIYCCTANNGVGGAv 109
Cdd:cd05725     1 VKRPQNQV-VLVDDSAEFQCEVGGDPVPTVRWRKEDG--ELPKGRYEILDDHSLK-IRKVTAGDMGSYTCVAENMVGKI- 75

                  ....*...
gi 1937920432 110 ESCGALQV 117
Cdd:cd05725    76 EASATLTV 83
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
606-796 2.34e-11

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: 65.50  E-value: 2.34e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 606 AVKMLKEEASADMQADFQR----EAALMAEFDNPNIVkllGVCAVGK----PMCLLFEYmaygdlneflrsmsphtvCSL 677
Cdd:cd14001    32 AVKKINSKCDKGQRSLYQErlkeEAKILKSLNHPNIV---GFRAFTKsedgSLCLAMEY------------------GGK 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 678 SHSDLSTRARVSSPGPPPLSCAEQlcIARQVAAGMAYL-SERKFVHRDLATRNCLV-GENMVVKIADFGLSRNIYSADYY 755
Cdd:cd14001    91 SLNDLIEERYEAGLGPFPAATILK--VALSIARALEYLhNEKKILHGDIKSGNVLIkGDFESVKLCDFGVSLPLTENLEV 168
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 756 KADGNDAI----PirWMPPESIFYNR-YTTESDVWAYGVVLWEIFS 796
Cdd:cd14001   169 DSDPKAQYvgteP--WKAKEALEEGGvITDKADIFAYGLVLWEMMT 212
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
573-845 3.14e-11

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: 65.41  E-value: 3.14e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGllpyePFTMVAVKMLKEEA---SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd05616     1 DFNFLMVLGKGSFGKVMLAERKG-----TDELYAVKILKKDVviqDDDVECTMVEKRVLALSGKPPFLTQLHSCFQTMDR 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDL----NEFLRSMSPHTVCslshsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDL 725
Cdd:cd05616    76 LYFVMEYVNGGDLmyhiQQVGRFKEPHAVF----------------------------YAAEIAIGLFFLQSKGIIYRDL 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSR-NIYsadyykadgnDAIPIR-------WMPPESIFYNRYTTESDVWAYGVVLWEIFSy 797
Cdd:cd05616   128 KLDNVMLDSEGHIKIADFGMCKeNIW----------DGVTTKtfcgtpdYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA- 196
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1937920432 798 GLQPYYGMAHEEVIYYVRDGNIlACPENCPLELYNLMRLCWSKLPADR 845
Cdd:cd05616   197 GQAPFEGEDEDELFQSIMEHNV-AYPKSMSKEAVAICKGLMTKHPGKR 243
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
568-794 3.91e-11

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: 65.08  E-value: 3.91e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQarapglLPYEPFTMV-AVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAV 646
Cdd:cd06650     1 ELKDDDFEKISELGAGNGGVVFK------VSHKPSGLVmARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYS 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstrarvssPGPPPLSCAEQLCIArqVAAGMAYLSER-KFVHRDL 725
Cdd:cd06650    75 DGEISICMEHMDGGSLDQVLKK----------------------AGRIPEQILGKVSIA--VIKGLTYLREKhKIMHRDV 130
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIYSadyykADGNDAIPIR-WMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd06650   131 KPSNILVNSRGEIKLCDFGVSGQLID-----SMANSFVGTRsYMSPERLQGTHYSVQSDIWSMGLSLVEM 195
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
580-819 3.98e-11

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: 64.78  E-value: 3.98e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRV--FQARAPGLlpyepftMVAVKMLKEEASADMQaDFQR---EAALMAEFDNPNIVKL------LGVCAVGK 648
Cdd:cd13989     1 LGSGGFGYVtlWKHQDTGE-------YVAIKKCRQELSPSDK-NRERwclEVQIMKKLNHPNVVSArdvppeLEKLSPND 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLRSmsPHTVCSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd13989    73 LPLLAMEYCSGGDLRKVLNQ--PENCCGLKESEVRT-------------------LLSDISSAISYLHENRIIHRDLKPE 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCL---VGENMVVKIADFGlsrniYSADYYKADGNDAI--PIRWMPPESIFYNRYTTESDVWAYGVVLWEI------FSY 797
Cdd:cd13989   132 NIVlqqGGGRVIYKLIDLG-----YAKELDQGSLCTSFvgTLQYLAPELFESKKYTCTVDYWSFGTLAFECitgyrpFLP 206
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1937920432 798 GLQPYygMAHEEV---------IYYVRDGNI 819
Cdd:cd13989   207 NWQPV--QWHGKVkqkkpehicAYEDLTGEV 235
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
121-208 4.03e-11

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: 59.96  E-value: 4.03e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALR-ENSRIAV-LESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCeAGVGELHIQDVLPEDHGTYTCLAKNAAGQ 81
                          90
                  ....*....|
gi 1937920432 199 AYSKlVKLEV 208
Cdd:cd20976    82 VSCS-AWVTV 90
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
580-796 4.50e-11

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: 64.75  E-value: 4.50e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVK-MLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMA 658
Cdd:cd07846     9 VGEGSYGMVMKCRHK-----ETGQIVAIKkFLESEDDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVD 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 YGDLNEFLRSmsPHTVcslshsDLSTRARvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVV 738
Cdd:cd07846    84 HTVLDDLEKY--PNGL------DESRVRK----------------YLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVV 139
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 739 KIADFGLSRNIYS-ADYYkadgNDAIPIRWM-PPESIFYN-RYTTESDVWAYGVVLWEIFS 796
Cdd:cd07846   140 KLCDFGFARTLAApGEVY----TDYVATRWYrAPELLVGDtKYGKAVDVWAVGCLVTEMLT 196
IgI_M-protein_C cd05891
C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily ...
127-197 5.18e-11

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.


Pssm-ID: 143299  Cd Length: 92  Bit Score: 59.92  E-value: 5.18e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAV-LESG---SLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd05891     8 PDVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVkLEQGkyaSLTIKGVTSEDSGKYSINVKNKYG 82
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
578-802 5.46e-11

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: 64.03  E-value: 5.46e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGLLpyepfTMVAVKML-KEEASADMQADF-QREAALMAEFDNPNIVKLLGVCAV--GKpMCLL 653
Cdd:cd14165     7 INLGEGSYAKVKSAYSERLK-----CNVAIKIIdKKKAPDDFVEKFlPRELEILARLNHKSIIKTYEIFETsdGK-VYIV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEqlCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd14165    81 MELGVQGDLLEFIKLR----------------------GALPEDVAR--KMFHQLSSAIKYCHELDIVHRDLKCENLLLD 136
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 734 ENMVVKIADFGLSRNIYSadyykaDGNDAIPIR--------WMPPESIFYNRYTTE-SDVWAYGVVLWeIFSYGLQPY 802
Cdd:cd14165   137 KDFNIKLTDFGFSKRCLR------DENGRIVLSktfcgsaaYAAPEVLQGIPYDPRiYDIWSLGVILY-IMVCGSMPY 207
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
578-856 5.95e-11

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: 63.81  E-value: 5.95e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQA--RAPGLLpyepftmVAVKML-KEEASAD-MQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd14081     7 KTLGKGQTGLVKLAkhCVTGQK-------VAIKIVnKEKLSKEsVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLV 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMSphtvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd14081    80 LEYVSGGELFDYLVKKG------------------------RLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLD 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRniYSADYYKADGNDAIPiRWMPPESIFYNRYT-TESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIY 812
Cdd:cd14081   136 EKNNIKIADFGMAS--LQPEGSLLETSCGSP-HYACPEVIKGEKYDgRKADIWSCGVILYALLV-GALPFDDDNLRQLLE 211
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1937920432 813 YVRDGnILACPENCPLELYNLMRLCWSKLPADRpsfCSIHRILQ 856
Cdd:cd14081   212 KVKRG-VFHIPHFISPDAQDLLRRMLEVNPEKR---ITIEEIKK 251
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
575-796 6.65e-11

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 64.07  E-value: 6.65e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPgllpYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:PLN00009    5 EKVEKIGEGTYGVVYKARDR----VTNETIALKKIRLEQEDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYgDLNEFLRSmSPhtvcslshsDLSTRARVSSpgppplscaeqlCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:PLN00009   81 EYLDL-DLKKHMDS-SP---------DFAKNPRLIK------------TYLYQILRGIAYCHSHRVLHRDLKPQNLLIDR 137
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 735 -NMVVKIADFGLSRNIysadyykadgndAIPIR----------WMPPESIFYNR-YTTESDVWAYGVVLWEIFS 796
Cdd:PLN00009  138 rTNALKLADFGLARAF------------GIPVRtfthevvtlwYRAPEILLGSRhYSTPVDIWSVGCIFAEMVN 199
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
578-819 7.05e-11

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: 63.79  E-value: 7.05e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQ--ARAPGllpyepfTMVAVKMLKEEASA-DMQADFQRE-AALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd14198    14 KELGRGKFAVVRQciSKSTG-------QEYAAKFLKKRRRGqDCRAEILHEiAVLELAKSNPRVVNLHEVYETTSEIILI 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDlneflrsmsphtVCSLSHSDLSTRarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCL-- 731
Cdd:cd14198    87 LEYAAGGE------------IFNLCVPDLAEM----------VSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILls 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 ----VGEnmvVKIADFGLSRNIYSA-DYYKADGNDaipiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMA 806
Cdd:cd14198   145 siypLGD---IKIVDFGMSRKIGHAcELREIMGTP----EYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGED 216
                         250
                  ....*....|...
gi 1937920432 807 HEEVIYYVRDGNI 819
Cdd:cd14198   217 NQETFLNISQVNV 229
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
573-822 7.23e-11

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: 63.78  E-value: 7.23e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQA--RAPGLlpyepftMVAVKMLKEEASADmQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14193     5 NVNKEEILGGGRFGQVHKCeeKSSGL-------KLAAKIIKARSQKE-KEEVKNEIEVMNQLNHANLIQLYDAFESRNDI 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLneFLRSMSPHTvcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN- 729
Cdd:cd14193    77 VLVMEYVDGGEL--FDRIIDENY---------------------NLTELDTILFIKQICEGIQYMHQMYILHLDLKPENi 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 -CLVGENMVVKIADFGLSRNIYSADYYKAdgNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHE 808
Cdd:cd14193   134 lCVSREANQVKIIDFGLARRYKPREKLRV--NFGTP-EFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPFLGEDDN 209
                         250
                  ....*....|....
gi 1937920432 809 EVIyyvrdGNILAC 822
Cdd:cd14193   210 ETL-----NNILAC 218
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
707-847 7.39e-11

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: 63.60  E-value: 7.39e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWA 786
Cdd:cd08221   109 QIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISK-VLDSESSMAESIVGTPY-YMSPELVQGVKYNFKSDIWA 186
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 787 YGVVLWEIFSygLQPYYGMAHE-EVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd08221   187 VGCVLYELLT--LKRTFDATNPlRLAVKIVQGEYEDIDEQYSEEIIQLVHDCLHQDPEDRPT 246
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
121-201 7.46e-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: 59.36  E-value: 7.46e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVL----ESG--SLRIHNVQKEDAGQYRCVAKN 194
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYkiesEYGvhVLHIRRVTVEDSAVYSAVAKN 80

                  ....*..
gi 1937920432 195 SLGTAYS 201
Cdd:cd20951    81 IHGEASS 87
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
29-117 7.80e-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: 58.94  E-value: 7.80e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  29 VITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGqlLTILSVEDSDDGIYCCTANNgVGGA 108
Cdd:cd20978     3 FIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT--LTIINVQPEDTGYYGCVATN-EIGD 79

                  ....*....
gi 1937920432 109 VESCGALQV 117
Cdd:cd20978    80 IYTETLLHV 88
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
634-847 9.80e-11

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: 63.15  E-value: 9.80e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 634 NPNIVKLLGVCAVGKP------MCLLFEYMAYGDLNEFLrsmspHTVCSLshsdlstrarvsspgppplsCAEQLCI-AR 706
Cdd:cd14012    57 HPNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELL-----DSVGSV--------------------PLDTARRwTL 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENM---VVKIADFGLSRNIysADYYKADGNDAI-PIRWMPPESI-FYNRYTTE 781
Cdd:cd14012   112 QLLEALEYLHRNGVVHKSLHAGNVLLDRDAgtgIVKLTDYSLGKTL--LDMCSRGSLDEFkQTYWLPPELAqGSKSPTRK 189
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 782 SDVWAYGVVLWEIfSYGLqpyygmaheEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14012   190 TDVWDLGLLFLQM-LFGL---------DVLEKYTSPNPVLVSLDLSASLQDFLSKCLSLDPKKRPT 245
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
127-203 1.05e-10

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: 58.70  E-value: 1.05e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 127 PINVKIIE-------GLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKN----S 195
Cdd:cd20957     1 PLSATIDPpvqtvdfGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNdgdsA 80

                  ....*...
gi 1937920432 196 LGTAYSKL 203
Cdd:cd20957    81 QATAELKL 88
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
580-814 1.06e-10

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: 63.06  E-value: 1.06e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGLlpyepftMVAVKMLKEEASADmQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14192    12 LGGGRFGQVHKCteLSTGL-------TLAAKIIKVKGAKE-REEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYV 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHtvcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN--CLVGEN 735
Cdd:cd14192    84 DGGELFDRITDESYQ-----------------------LTELDAILFTRQICEGVHYLHQHYILHLDLKPENilCVNSTG 140
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKAdgNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYV 814
Cdd:cd14192   141 NQIKIIDFGLARRYKPREKLKV--NFGTP-EFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLGETDAETMNNI 215
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
570-837 1.25e-10

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: 63.47  E-value: 1.25e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQA--RAPGllpyepfTMVAVKMLkeEASADMQADFQREAALMAEFDN-PNIVKLLGVC-- 644
Cdd:cd06639    20 PSDTWDIIETIGKGTYGKVYKVtnKKDG-------SLAAVKIL--DPISDVDEEIEAEYNILRSLPNhPNVVKFYGMFyk 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 ---AVGKPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspgpppLSCAEQL------CIARQVAAGMAYL 715
Cdd:cd06639    91 adqYVGGQLWLVLELCNGGSVTELVKGL--------------------------LKCGQRLdeamisYILYGALLGLQHL 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 716 SERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADyYKADGNDAIPIrWMPPESI-----FYNRYTTESDVWAYGVV 790
Cdd:cd06639   145 HNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSAR-LRRNTSVGTPF-WMAPEVIaceqqYDYSYDARCDVWSLGIT 222
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 791 LWEIfSYGLQPYYGMAHEEVIYYVrdgnilacPENCPLELYNLMRLC 837
Cdd:cd06639   223 AIEL-ADGDPPLFDMHPVKALFKI--------PRNPPPTLLNPEKWC 260
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
580-803 1.35e-10

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: 62.77  E-value: 1.35e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGLLpyepftmVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14083    11 LGTGAFSEVVLAedKATGKL-------VAIKCIDKKALKGKEDSLENEIAVLRKIKHPNIVQLLDIYESKSHLYLVMELV 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLneFLRSMSPHtvcSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV---GE 734
Cdd:cd14083    84 TGGEL--FDRIVEKG---SYTEKDASH-------------------LIRQVLEAVDYLHSLGIVHRDLKPENLLYyspDE 139
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYY 803
Cdd:cd14083   140 DSKIMISDFGLSKMEDSGVMSTACGTPG----YVAPEVLAQKPYGKAVDCWSIGVISY-ILLCGYPPFY 203
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
578-858 1.40e-10

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 63.14  E-value: 1.40e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGllpyepfTMVAVKML--KEEASADMQADFQREAALMAEfdnpNIVKLLGVCAVGK----PMC 651
Cdd:cd14220     1 RQIGKGRYGEVWMGKWRG-------EKVAVKVFftTEEASWFRETEIYQTVLMRHE----NILGFIAADIKGTgswtQLY 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSMSphtvcslshsdLSTRArvsspgppplscaeQLCIARQVAAGMAYLSERKF--------VHR 723
Cdd:cd14220    70 LITDYHENGSLYDFLKCTT-----------LDTRA--------------LLKLAYSAACGLCHLHTEIYgtqgkpaiAHR 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSRNiYSADYYKADgndaIPI-------RWMPP----ESIFYNRYTT--ESDVWAYGVV 790
Cdd:cd14220   125 DLKSKNILIKKNGTCCIADLGLAVK-FNSDTNEVD----VPLntrvgtkRYMAPevldESLNKNHFQAyiMADIYSFGLI 199
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 791 LWE----------IFSYGLqPYYGMAHEEVIYyvRDGNILAC-------------PENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14220   200 IWEmarrcvtggiVEEYQL-PYYDMVPSDPSY--EDMREVVCvkrlrptvsnrwnSDECLRAVLKLMSECWAHNPASRLT 276
                         330
                  ....*....|.
gi 1937920432 848 FCSIHRILQRM 858
Cdd:cd14220   277 ALRIKKTLAKM 287
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
570-789 1.58e-10

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: 62.70  E-value: 1.58e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPGLlpyepFTMVAVKMLKEEAsaDMQADFQREAALMAEF-DNPNIVKLLGVCAVGK 648
Cdd:cd06608     4 PAGIFELVEVIGEGTYGKVYKARHKKT-----GQLAAIKIMDIIE--DEEEEIKLEINILRKFsNHPNIATFYGAFIKKD 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMC------LLFEYMAYGdlneflrsmsphtvcslSHSDLSTRARVSspgPPPLScAEQLC-IARQVAAGMAYLSERKFV 721
Cdd:cd06608    77 PPGgddqlwLVMEYCGGG-----------------SVTDLVKGLRKK---GKRLK-EEWIAyILRETLRGLAYLHENKVI 135
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 722 HRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKadgNDAI--PIrWMPPESIFYNR-----YTTESDVWAYGV 789
Cdd:cd06608   136 HRDIKGQNILLTEEAEVKLVDFGVSAQLDSTLGRR---NTFIgtPY-WMAPEVIACDQqpdasYDARCDVWSLGI 206
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
127-208 1.64e-10

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: 58.43  E-value: 1.64e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDS--------ALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd05726     6 PRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSqnllfpyqPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGS 85
                          90
                  ....*....|
gi 1937920432 199 AYSKlVKLEV 208
Cdd:cd05726    86 ILAK-AQLEV 94
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
575-802 1.70e-10

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: 62.66  E-value: 1.70e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgllPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd14185     3 EIGRTIGDGNFAVVKECR-----HWNENQEYAMKIIDKSKLKGKEDMIESEILIIKSLSHPNIVKLFEVYETEKEIYLIL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsphtvcslshsdlstraRVSSPGPPPLSCAEQLCIArqvaagMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd14185    78 EYVRGGDLFDAIIE------------------SVKFTEHDAALMIIDLCEA------LVYIHSKHIVHRDLKPENLLVQH 133
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 735 N----MVVKIADFGLSRNIySADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPY 802
Cdd:cd14185   134 NpdksTTLKLADFGLAKYV-TGPIFTVCGTPT----YVAPEILSEKGYGLEVDMWAAGVILY-ILLCGFPPF 199
I-set pfam07679
Immunoglobulin I-set domain;
213-296 1.84e-10

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 58.04  E-value: 1.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 213 RILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIqenVKDRVIDSRLQLFITK-----PGLYTCIATNK 287
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNvqpddSGKYTCVATNS 78

                  ....*....
gi 1937920432 288 HGEKFSTAK 296
Cdd:pfam07679  79 AGEAEASAE 87
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
706-851 1.94e-10

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: 62.25  E-value: 1.94e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKAD--GNDaipiRWMPPESIFYNRYTTESD 783
Cdd:cd14189   108 KQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTicGTP----NYLAPEVLLRQGHGPESD 183
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 784 VWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRDGNiLACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14189   184 VWSLGCVMYTLLC-GNPPFETLDLKETYRCIKQVK-YTLPASLSLPARHLLAGILKRNPGDRLTLDQI 249
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
39-106 1.98e-10

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: 58.40  E-value: 1.98e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432  39 ALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd05730    15 ANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAG 82
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
572-845 2.04e-10

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: 63.09  E-value: 2.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVR--------DIGEGAFGRVFQARAPGllpyePFTMVAVKMLKEEA---SADMQADFQrEAALMAEFDNPNIVKL 640
Cdd:cd05615     2 NNLDRVRltdfnflmVLGKGSFGKVMLAERKG-----SDELYAIKILKKDVviqDDDVECTMV-EKRVLALQDKPPFLTQ 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 641 LGVC-AVGKPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrARVSSPgppplscaEQLCIARQVAAGMAYLSERK 719
Cdd:cd05615    76 LHSCfQTVDRLYFVMEYVNGGDLMYHIQQV----------------GKFKEP--------QAVFYAAEISVGLFFLHKKG 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 720 FVHRDLATRNCLVGENMVVKIADFGLSrniysadyyKADGNDAIPIR-------WMPPESIFYNRYTTESDVWAYGVVLW 792
Cdd:cd05615   132 IIYRDLKLDNVMLDSEGHIKIADFGMC---------KEHMVEGVTTRtfcgtpdYIAPEIIAYQPYGRSVDWWAYGVLLY 202
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 793 EIFSyGLQPYYGMAHEEVIYYVRDGNIlACPENCPLELYNLMRLCWSKLPADR 845
Cdd:cd05615   203 EMLA-GQPPFDGEDEDELFQSIMEHNV-SYPKSLSKEAVSICKGLMTKHPAKR 253
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
580-861 2.06e-10

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function 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. The KSR2 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: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 62.33  E-value: 2.06e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepftMVAVKMLK-EEASADMQADFQREAALMAEFDNPNIVKLLGVCavgkpmcllfeyma 658
Cdd:cd14153     8 IGKGRFGQVYHGRWHG--------EVAIRLIDiERDNEEQLKAFKREVMAYRQTRHENVVLFMGAC-------------- 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 659 ygdlneflrsMSP-HTVCSLSHSDLSTRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd14153    66 ----------MSPpHLAIITSLCKGRTLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKV 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 738 VkIADFGLSRNIYSADYYKADGNDAIPIRW---MPPESIFYNRYTTE---------SDVWAYGVVLWEIFSYGLqPYYGM 805
Cdd:cd14153   136 V-ITDFGLFTISGVLQAGRREDKLRIQSGWlchLAPEIIRQLSPETEedklpfskhSDVFAFGTIWYELHAREW-PFKTQ 213
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 806 AHEEVIYYVRDGNILACPE-NCPLELYNLMRLCWSKLPADRPSFCSIHRILQRMCER 861
Cdd:cd14153   214 PAEAIIWQVGSGMKPNLSQiGMGKEISDILLFCWAYEQEERPTFSKLMEMLEKLPKR 270
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
580-845 2.10e-10

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: 62.80  E-value: 2.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApgLLPYEPFTMVAVKMLKEeASADMQaDFQR---EAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05582     3 LGQGSFGKVFLVRK--ITGPDAGTLYAMKVLKK-ATLKVR-DRVRtkmERDILADVNHPFIVKLHYAFQTEGKLYLILDF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLneFLRsmsphtvcsLSHSDLSTRARVsspgppplscaeQLCIArQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05582    79 LRGGDL--FTR---------LSKEVMFTEEDV------------KFYLA-ELALALDHLHSLGIIYRDLKPENILLDEDG 134
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSRNiySADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRD 816
Cdd:cd05582   135 HIKLTDFGLSKE--SIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQGKDRKETMTMILK 211
                         250       260
                  ....*....|....*....|....*....
gi 1937920432 817 GNiLACPENCPLELYNLMRLCWSKLPADR 845
Cdd:cd05582   212 AK-LGMPQFLSPEAQSLLRALFKRNPANR 239
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
580-802 2.18e-10

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: 62.77  E-value: 2.18e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApglLPYEPFTMVAVKMLKEEASADMQADFQ----REAALMAEFDNPNIVKLLGVCAVGK-PMCLLF 654
Cdd:cd14040    14 LGRGGFSEVYKAFD---LYEQRYAAVKIHQLNKSWRDEKKENYHkhacREYRIHKELDHPRIVKLYDYFSLDTdTFCTVL 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRsmsphtvcslSHSDLSTRarvsspgppplscaEQLCIARQVAAGMAYLSERK--FVHRDLATRNCLV 732
Cdd:cd14040    91 EYCEGNDLDFYLK----------QHKLMSEK--------------EARSIVMQIVNALRYLNEIKppIIHYDLKPGNILL 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMV---VKIADFGLSRnIYSADYYKADGND-----AIPIRWMPPESIFYN----RYTTESDVWAYGVVLWEIFsYGLQ 800
Cdd:cd14040   147 VDGTAcgeIKITDFGLSK-IMDDDSYGVDGMDltsqgAGTYWYLPPECFVVGkeppKISNKVDVWSVGVIFFQCL-YGRK 224

                  ..
gi 1937920432 801 PY 802
Cdd:cd14040   225 PF 226
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
126-208 2.19e-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: 57.90  E-value: 2.19e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 126 PPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRE-NSRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLGTAYSKL 203
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNGVPGSVEKR 87

                  ....*
gi 1937920432 204 VKLEV 208
Cdd:cd20970    88 ITLQV 92
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
578-802 2.38e-10

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: 62.12  E-value: 2.38e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRV----FQARAPGLLPYEpftmVAVKMLKEE--ASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd14076     7 RTLGEGEFGKVklgwPLPKANHRSGVQ----VAIKLIRRDtqQENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIG 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLrsmsphtvcsLSHSDLSTRArvsspgppplSCAeqlcIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd14076    83 IVLEFVSGGELFDYI----------LARRRLKDSV----------ACR----LFAQLISGVAYLHKKGVVHRDLKLENLL 138
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 732 VGENMVVKIADFGLsrniysADYYKADGNDAI------PIRWMPPESIFYNRYT-TESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd14076   139 LDKNRNLVITDFGF------ANTFDHFNGDLMstscgsPCYAAPELVVSDSMYAgRKADIWSCGVILYAMLA-GYLPF 209
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
218-296 2.47e-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: 57.79  E-value: 2.47e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTF--GSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKdrviDSRLQLFITKP---GLYTCIATNKHGEKF 292
Cdd:cd20978     6 KPEKNVVVkgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE----DGTLTIINVQPedtGYYGCVATNEIGDIY 81

                  ....
gi 1937920432 293 STAK 296
Cdd:cd20978    82 TETL 85
Ig3_L1-CAM cd05876
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here ...
133-199 2.47e-10

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. 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. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409460 [Multi-domain]  Cd Length: 83  Bit Score: 57.61  E-value: 2.47e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 133 IEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd05876     8 LRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSA 74
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
218-286 3.34e-10

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 57.19  E-value: 3.34e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQenvKDRVIDSRLQLFITKP-----GLYTCIATN 286
Cdd:pfam13927   8 PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTR---SRSLSGSNSTLTISNVtrsdaGTYTCVASN 78
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
570-794 4.68e-10

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: 61.57  E-value: 4.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQarapgLLPYEPFTMVAVKMLK--EEASADMQADFQreaALMAEFDNPNIVKLLGV---- 643
Cdd:cd06638    16 PSDTWEIIETIGKGTYGKVFK-----VLNKKNGSKAAVKILDpiHDIDEEIEAEYN---ILKALSDHPNVVKFYGMyykk 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 644 -CAVGKPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdLSTRARVSSPGPPplscaeqlCIARQVAAGMAYLSERKFVH 722
Cdd:cd06638    88 dVKNGDQLWLVLELCNGGSVTDLVKGF------------LKRGERMEEPIIA--------YILHEALMGLQHLHVNKTIH 147
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 723 RDLATRNCLVGENMVVKIADFGLSRNIYSADyYKADGNDAIPIrWMPPESI-----FYNRYTTESDVWAYGVVLWEI 794
Cdd:cd06638   148 RDVKGNNILLTTEGGVKLVDFGVSAQLTSTR-LRRNTSVGTPF-WMAPEVIaceqqLDSTYDARCDVWSLGITAIEL 222
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
606-803 4.83e-10

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: 61.22  E-value: 4.83e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 606 AVKM--LKEEASADMQADFQREAAlMAEFD-------NPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSmsphtVCS 676
Cdd:cd14093    32 AVKIidITGEKSSENEAEELREAT-RREIEilrqvsgHPNIIELHDVFESPTFIFLVFELCRKGELFDYLTE-----VVT 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 677 LSHSDlsTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYK 756
Cdd:cd14093   106 LSEKK--TRR-----------------IMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGEKLR 166
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 757 ----ADGndaipirWMPPE----SIFYNR--YTTESDVWAYGVVLWEIFSyGLQPYY 803
Cdd:cd14093   167 elcgTPG-------YLAPEvlkcSMYDNApgYGKEVDMWACGVIMYTLLA-GCPPFW 215
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
549-810 5.44e-10

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: 61.97  E-value: 5.44e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 549 PNPMYQRMPLLLNPKLLSLEYPRNNIEYVRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEA--SADMQADFQREA 626
Cdd:cd05594     2 PSDNSGAEEMEVSLTKPKHKVTMNDFEYLKLLGKGTFGKVILVKEKATGRY-----YAMKILKKEVivAKDEVAHTLTEN 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 627 ALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLrsmsphtvcslshsdlsTRARVSSPGPPPLSCAEqlciar 706
Cdd:cd05594    77 RVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHL-----------------SRERVFSEDRARFYGAE------ 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 qVAAGMAYL-SERKFVHRDLATRNCLVGENMVVKIADFGLSRN-IYSADYYKADGNDAipiRWMPPESIFYNRYTTESDV 784
Cdd:cd05594   134 -IVSALDYLhSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEgIKDGATMKTFCGTP---EYLAPEVLEDNDYGRAVDW 209
                         250       260
                  ....*....|....*....|....*.
gi 1937920432 785 WAYGVVLWEIFSyGLQPYYGMAHEEV 810
Cdd:cd05594   210 WGLGVVMYEMMC-GRLPFYNQDHEKL 234
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
570-857 5.67e-10

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: 61.18  E-value: 5.67e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLkeEASADMQADFQREAALMAEFDN-PNIVKLLGVCAVGK 648
Cdd:cd06636    14 PAGIFELVEVVGNGTYGQVYKGRH-----VKTGQLAAIKVM--DVTEDEEEEIKLEINMLKKYSHhRNIATYYGAFIKKS 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 P------MCLLFEYMAYGDLNEFLRSmsphtvcslshsdlsTRArvsspgppplSCAEQLCIA---RQVAAGMAYLSERK 719
Cdd:cd06636    87 PpghddqLWLVMEFCGAGSVTDLVKN---------------TKG----------NALKEDWIAyicREILRGLAHLHAHK 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 720 FVHRDLATRNCLVGENMVVKIADFGLS---------RNIYSADYYkadgndaipirWMPPESIFYNR-----YTTESDVW 785
Cdd:cd06636   142 VIHRDIKGQNVLLTENAEVKLVDFGVSaqldrtvgrRNTFIGTPY-----------WMAPEVIACDEnpdatYDYRSDIW 210
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 786 AYGVVLWEIfSYGLQPYYGMAHEEVIYYVrdgnilacPENCPLELYNLMrlcWSKLPADRPSFCSIHRILQR 857
Cdd:cd06636   211 SLGITAIEM-AEGAPPLCDMHPMRALFLI--------PRNPPPKLKSKK---WSKKFIDFIEGCLVKNYLSR 270
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
605-804 5.67e-10

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: 61.21  E-value: 5.67e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKML-KEEASADMQADFQREAA-LMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLneflrsmspHTVC----SLS 678
Cdd:cd14106    36 YAAKFLrKRRRGQDCRNEILHEIAvLELCKDCPRVVNLHEVYETRSELILILELAAGGEL---------QTLLdeeeCLT 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 679 HSDLstrarvsspgppplscaeQLCIaRQVAAGMAYLSERKFVHRDLATRNCLVGENMV---VKIADFGLSRNIysadyy 755
Cdd:cd14106   107 EADV------------------RRLM-RQILEGVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGISRVI------ 161
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 756 kadgNDAIPIR-------WMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14106   162 ----GEGEEIReilgtpdYVAPEILSYEPISLATDMWSIGVLTYVLLT-GHSPFGG 212
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
580-815 6.32e-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: 61.50  E-value: 6.32e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEA---SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05620     3 LGKGSFGKVLLAELKGKGEY-----FAVKALKKDVvliDDDVECTMVEKRVLALAWENPFLTHLYCTFQTKEHLFFVMEF 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSphtvcslsHSDLsTRARVSSpgppplscAEQLCiarqvaaGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05620    78 LNGGDLMFHIQDKG--------RFDL-YRATFYA--------AEIVC-------GLQFLHSKGIIYRDLKLDNVMLDRDG 133
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 VVKIADFGLSR-NIYSADyyKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHEEVIYYVR 815
Cdd:cd05620   134 HIKIADFGMCKeNVFGDN--RASTFCGTP-DYIAPEILQGLKYTFSVDWWSFGVLLYEML-IGQSPFHGDDEDELFESIR 209
IgI_3_Contactin cd04968
Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) ...
121-197 7.00e-10

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409357 [Multi-domain]  Cd Length: 88  Bit Score: 56.40  E-value: 7.00e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 121 PKI-TRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALrENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd04968     1 PSIkVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSP-SSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
573-821 7.06e-10

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: 60.74  E-value: 7.06e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGE----GAFGRVFQARapgllpyEPFTMV--AVKMLKEEASAD-----MQADFQREAALMAEFDNPNIVKLL 641
Cdd:cd14196     2 KVEDFYDIGEelgsGQFAIVKKCR-------EKSTGLeyAAKFIKKRQSRAsrrgvSREEIEREVSILRQVLHPNIITLH 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 642 GVCAVGKPMCLLFEYMAYGDLNEFLrsmsphtvcslshsdlstrARVSSpgpppLSCAEQLCIARQVAAGMAYLSERKFV 721
Cdd:cd14196    75 DVYENRTDVVLILELVSGGELFDFL-------------------AQKES-----LSEEEATSFIKQILDGVNYLHTKKIA 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 722 HRDLATRNCLVGENMV----VKIADFGLSRNIysadyykADGNDAIPIRWMP----PESIFYNRYTTESDVWAYGVVLWE 793
Cdd:cd14196   131 HFDLKPENIMLLDKNIpiphIKLIDFGLAHEI-------EDGVEFKNIFGTPefvaPEIVNYEPLGLEADMWSIGVITYI 203
                         250       260
                  ....*....|....*....|....*...
gi 1937920432 794 IFSyGLQPYYGMAHEEVIyyvrdGNILA 821
Cdd:cd14196   204 LLS-GASPFLGDTKQETL-----ANITA 225
PHA02785 PHA02785
IL-beta-binding protein; Provisional
79-304 7.22e-10

IL-beta-binding protein; Provisional


Pssm-ID: 165149 [Multi-domain]  Cd Length: 326  Bit Score: 61.57  E-value: 7.22e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  79 ENGQLLTILSVEDSDDGIYCCTANNGVggaveSCGALQVKMKpKITRPPINVKIIEGLKAV-------LPCTTMG----- 146
Cdd:PHA02785   79 DNGSNMLILNPTQSDSGIYICITKNET-----YCDMMSLNLT-IVSVSESNIDLISYPQIVnerstgeMVCPNINafias 152
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 147 NPKPSVSWiKGDSALReNSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGT-AY--SKLVKLEV--EVFARILRAPESH 221
Cdd:PHA02785  153 NVNADIIW-SGHRRLR-NKRLKQRTPGIITIEDVRKNDAGYYTCVLKYIYGDkTYnvTRIVKLEVrdRIIPPTMQLPEGV 230
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 222 NVTFGSFVTLRCTAIGMPvPTIS----WIEN------------GNAVSSGSIQENVKDRVIDSRLQLFITK---PGLYTC 282
Cdd:PHA02785  231 VTSIGSNLTIACRVSLRP-PTTDadvfWISNgmyyeeddedgdGRISVANKIYTTDKRRVITSRLNINPVKeedATTFTC 309
                         250       260
                  ....*....|....*....|..
gi 1937920432 283 IAtnkhgekFSTAKAAATVSIA 304
Cdd:PHA02785  310 MA-------FTIPSISKTVTIS 324
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
570-794 1.15e-09

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: 60.50  E-value: 1.15e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKMLkeEASADMQADFQREAALMAEFDN-PNIVKLLGVCAVGK 648
Cdd:cd06637     4 PAGIFELVELVGNGTYGQVYKGRH-----VKTGQLAAIKVM--DVTGDEEEEIKQEINMLKKYSHhRNIATYYGAFIKKN 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 P------MCLLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarvsspgppplscAEQLC--IARQVAAGMAYLSERKF 720
Cdd:cd06637    77 PpgmddqLWLVMEFCGAGSVTDLIKNTKGNTL------------------------KEEWIayICREILRGLSHLHQHKV 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 721 VHRDLATRNCLVGENMVVKIADFGLS---------RNIYSADYYkadgndaipirWMPPESIFYNR-----YTTESDVWA 786
Cdd:cd06637   133 IHRDIKGQNVLLTENAEVKLVDFGVSaqldrtvgrRNTFIGTPY-----------WMAPEVIACDEnpdatYDFKSDLWS 201

                  ....*...
gi 1937920432 787 YGVVLWEI 794
Cdd:cd06637   202 LGITAIEM 209
Ig3_L1-CAM_like cd05731
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar ...
129-199 1.19e-09

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.


Pssm-ID: 409394 [Multi-domain]  Cd Length: 83  Bit Score: 55.49  E-value: 1.19e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 129 NVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALrENSRIAVLESG-SLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGEL-PKGRTKFENFNkTLKIENVSEADSGEYQCTASNTMGSA 74
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
575-804 1.29e-09

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: 59.96  E-value: 1.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVF--QARAPGL---LPYepftMVAVKMLKEEASADMQadfqREAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd05578     3 QILRVIGKGSFGKVCivQKKDTKKmfaMKY----MNKQKCIEKDSVRNVL----NELEILQELEHPFLVNLWYSFQDEED 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEflrsmspHtvcsLSHSDLSTRARVsspgppplscaeQLCIArQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd05578    75 MYMVVDLLLGGDLRY-------H----LQQKVKFSEETV------------KFYIC-EIVLALDYLHSKNIIHRDIKPDN 130
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 730 CLVGENMVVKIADFGLSRnIYSADYYKADGNDAIPirWMPPESIFYNRYTTESDVWAYGVVLWEiFSYGLQPYYG 804
Cdd:cd05578   131 ILLDEQGHVHITDFNIAT-KLTDGTLATSTSGTKP--YMAPEVFMRAGYSFAVDWWSLGVTAYE-MLRGKRPYEI 201
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
575-811 1.34e-09

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: 60.02  E-value: 1.34e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLF 654
Cdd:cd14195     8 EMGEELGSGQFAIVRKCREKGTGKEYAAKFIKKRRLSSSRRGVSREEIEREVNILREIQHPNIITLHDIFENKTDVVLIL 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLrsmsphtvcslshsdlstrARVSSpgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd14195    88 ELVSGGELFDFL-------------------AEKES-----LTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLD 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMV----VKIADFGLSRNIYSADYYKadgNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEV 810
Cdd:cd14195   144 KNVpnprIKLIDFGIAHKIEAGNEFK---NIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGETKQET 219

                  .
gi 1937920432 811 I 811
Cdd:cd14195   220 L 220
pknD PRK13184
serine/threonine-protein kinase PknD;
575-796 1.35e-09

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 62.10  E-value: 1.35e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFqarapglLPYEPFT--MVAVKMLKEEASAD--MQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:PRK13184    5 DIIRLIGKGGMGEVY-------LAYDPVCsrRVALKKIREDLSENplLKKRFLREAKIAADLIHPGIVPVYSICSDGDPV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTVCSlshSDLSTRARVSSpgppplscaeQLCIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:PRK13184   78 YYTMPYIEGYTLKSLLKSVWQKESLS---KELAEKTSVGA----------FLSIFHKICATIEYVHSKGVLHRDLKPDNI 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKAD----------GNDAIP------IRWMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:PRK13184  145 LLGLFGEVVILDWGAAIFKKLEEEDLLDidvdernicySSMTIPgkivgtPDYMAPERLLGVPASESTDIYALGVILYQM 224

                  ..
gi 1937920432 795 FS 796
Cdd:PRK13184  225 LT 226
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
146-208 1.48e-09

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: 55.29  E-value: 1.48e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 146 GNPKPSVSWIKGDSALRENSRIAVlESG----SLRIHNVQKEDAGQYRCVAKNSLGTAySKLVKLEV 208
Cdd:cd05748    18 GRPTPTVTWSKDGQPLKETGRVQI-ETTasstSLVIKNAKRSDSGKYTLTLKNSAGEK-SATINVKV 82
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
580-810 1.61e-09

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: 60.40  E-value: 1.61e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEA--SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd05595     3 LGKGTFGKVILVREKATGRY-----YAMKILRKEViiAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYA 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLrsmsphtvcslshsdlsTRARVSSPGPPPLSCAEqlciarqVAAGMAYLSERKFVHRDLATRNCLVGENMV 737
Cdd:cd05595    78 NGGELFFHL-----------------SRERVFTEDRARFYGAE-------IVSALEYLHSRDVVYRDIKLENLMLDKDGH 133
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 738 VKIADFGLSRNIYSaDYYKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEV 810
Cdd:cd05595   134 IKITDFGLCKEGIT-DGATMKTFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERL 203
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
580-803 1.70e-09

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 60.22  E-value: 1.70e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEASADM-QAD-FQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:PTZ00263   26 LGTGSFGRVRIAKHKGTGEY-----YAIKCLKKREILKMkQVQhVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFV 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMS--PHTVCSLSHSdlstrarvsspgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:PTZ00263  101 VGGELFTHLRKAGrfPNDVAKFYHA--------------------------ELVLAFEYLHSKDIIYRDLKPENLLLDNK 154
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 736 MVVKIADFGLSRNIYSADYYKAdgndAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEiFSYGLQPYY 803
Cdd:PTZ00263  155 GHVKVTDFGFAKKVPDRTFTLC----GTP-EYLAPEVIQSKGHGKAVDWWTMGVLLYE-FIAGYPPFF 216
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
570-816 1.84e-09

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: 59.67  E-value: 1.84e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVGKP 649
Cdd:cd06658    20 PREYLDSFIKIGEGSTGIVCIATEK-----HTGKQVAVKKMDLRKQQRRELLFN-EVVIMRDYHHENVVDMYNSYLVGDE 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRARVSSpgppplscaEQLC-IARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd06658    94 LWVVMEFLEGGAL-----------------TDIVTHTRMNE---------EQIAtVCLSVLRALSYLHNQGVIHRDIKSD 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHE 808
Cdd:cd06658   148 SILLTSDGRIKLSDFGFCAQV-SKEVPKRKSLVGTPY-WMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPYFNEPPL 224

                  ....*...
gi 1937920432 809 EVIYYVRD 816
Cdd:cd06658   225 QAMRRIRD 232
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
28-109 1.95e-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: 55.44  E-value: 1.95e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILI---KLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNG 104
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIstsTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                  ....*
gi 1937920432 105 VGGAV 109
Cdd:cd20974    81 SGQAT 85
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
606-802 2.13e-09

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: 59.67  E-value: 2.13e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 606 AVKMLkeeaSADMQADFQREAALMAEFD-NPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHsdlst 684
Cdd:cd14179    36 AVKIV----SKRMEANTQREIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKKKQHFSETEASH----- 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 685 rarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV---GENMVVKIADFGLSRniysadyYKADGND 761
Cdd:cd14179   107 -------------------IMRKLVSAVSHMHDVGVVHRDLKPENLLFtdeSDNSEIKIIDFGFAR-------LKPPDNQ 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 762 AIP-----IRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd14179   161 PLKtpcftLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPF 205
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
124-198 2.30e-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: 54.93  E-value: 2.30e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 124 TRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDS----ALRENsRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd05763     3 TKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGtdfpAARER-RMHVMpEDDVFFIVDVKIEDTGVYSCTAQNSAGS 81
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
574-858 2.37e-09

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 59.21  E-value: 2.37e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGllpyepftMVAVKMLKEEA-SADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd14152     2 IELGELIGQGRWGKVHRGRWHG--------EVAIRLLEIDGnNQDHLKLFKKEVMNYRQTRHENVVLFMGACMHPPHLAI 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSmsPHTVCSLShsdlSTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14152    74 ITSFCKGRTLYSFVRD--PKTSLDIN----KTRQ-----------------IAQEIIKGMGYLHAKGIVHKDLKSKNVFY 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVkIADFGLSRNIYSADYYKADGNDAIPIRW---MPPESIfynR------------YTTESDVWAYGVVLWEIFSY 797
Cdd:cd14152   131 DNGKVV-ITDFGLFGISGVVQEGRRENELKLPHDWlcyLAPEIV---RemtpgkdedclpFSKAADVYAFGTIWYELQAR 206
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 798 GLqPYYGMAHEEVIYYVRDG----NILACPeNCPLELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14152   207 DW-PLKNQPAEALIWQIGSGegmkQVLTTI-SLGKEVTEILSACWAFDLEERPSFTLLMDMLEKL 269
Ig_DSCAM cd05734
Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members ...
121-208 2.56e-09

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.


Pssm-ID: 409397 [Multi-domain]  Cd Length: 97  Bit Score: 55.19  E-value: 2.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSW--IKG------DSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVA 192
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkhSKGsgvpqfQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKV 81
                          90
                  ....*....|....*.
gi 1937920432 193 KNSLGTAYSKLVKLEV 208
Cdd:cd05734    82 SNDVGADISKSMYLTV 97
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
214-295 2.74e-09

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: 2.74e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 214 ILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSG----SIQENVKDRVIDSRLQlfitKPGLYTCIATNKHG 289
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKderiTTLENGSLQIKGAEKS----DTGEYTCVALNLSG 77

                  ....*.
gi 1937920432 290 EKFSTA 295
Cdd:cd20952    78 EATWSA 83
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
580-809 2.91e-09

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: 59.32  E-value: 2.91e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEA---SADMQADFQREAALMAEFDNPNIVKLLgvCAVGKPMCLLF-- 654
Cdd:cd05592     3 LGKGSFGKVMLAELKGTNQY-----FAIKALKKDVvleDDDVECTMIERRVLALASQHPFLTHLF--CTFQTESHLFFvm 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsphtvcslSHSDLSTRARVSSpgppplscAEQLCiarqvaaGMAYLSERKFVHRDLATRNCLVGE 734
Cdd:cd05592    76 EYLNGGDLMFHIQQ---------SGRFDEDRARFYG--------AEIIC-------GLQFLHSRGIIYRDLKLDNVLLDR 131
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 735 NMVVKIADFGLSR-NIYsaDYYKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAHEE 809
Cdd:cd05592   132 EGHIKIADFGMCKeNIY--GENKASTFCGTP-DYIAPEILKGQKYNQSVDWWSFGVLLYEML-IGQSPFHGEDEDE 203
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
578-817 2.95e-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: 59.27  E-value: 2.95e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVF--QARAPGllpyepfTMVAVKMLKEEASADMQADFQ--REAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd05630     6 RVLGKGGFGEVCacQVRATG-------KMYACKKLEKKRIKKRKGEAMalNEKQILEKVNSRFVVSLAYAYETKDALCLV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd05630    79 LTLMNGGDLKFHIYHM----------------------GQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLD 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 734 ENMVVKIADFGLSRNIYSADYYKADGNDaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY----GMAHEE 809
Cdd:cd05630   137 DHGHIRISDLGLAVHVPEGQTIKGRVGT---VGYMAPEVVKNERYTFSPDWWALGCLLYEMIA-GQSPFQqrkkKIKREE 212

                  ....*...
gi 1937920432 810 VIYYVRDG 817
Cdd:cd05630   213 VERLVKEV 220
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
580-814 3.48e-09

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: 58.48  E-value: 3.48e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQarapgLLPYEPFTMVAVKMLKEeASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14191    10 LGSGKFGQVFR-----LVEKKTKKVWAGKFFKA-YSAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSG 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEflrsmsphtvcSLSHSDLSTRARvsspgppplscaEQLCIARQVAAGMAYLSERKFVHRDLATRN--CLVGENMV 737
Cdd:cd14191    84 GELFE-----------RIIDEDFELTER------------ECIKYMRQISEGVEYIHKQGIVHLDLKPENimCVNKTGTK 140
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 738 VKIADFGLSRNIYSADYYKADGNDAipiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYV 814
Cdd:cd14191   141 IKLIDFGLARRLENAGSLKVLFGTP---EFVAPEVINYEPIGYATDMWSIGVICYILVS-GLSPFMGDNDNETLANV 213
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
571-804 3.49e-09

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: 59.21  E-value: 3.49e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVF--QARAPGllpyepfTMVAVKMLKEEASADMQADFQ--REAALMAEFDNPNIVKLLGVCAV 646
Cdd:cd05632     1 KNTFRQYRVLGKGGFGEVCacQVRATG-------KMYACKRLEKKRIKKRKGESMalNEKQILEKVNSQFVVNLAYAYET 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd05632    74 KDALCLVLTIMNGGDLKFHIYNM----------------------GNPGFEEERALFYAAEILCGLEDLHRENTVYRDLK 131
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd05632   132 PENILLDDYGHIRISDLGLAVKIPEGESIRGRVGT---VGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE-GQSPFRG 205
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
124-199 3.68e-09

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: 3.68e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 124 TRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESG----SLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSLGEA 80
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
575-794 3.72e-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: 59.30  E-value: 3.72e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARapgllpyEPFT--MVAVKMLKEeASADMQADFQ--REAALMAEFDNPNIVKLL------GVC 644
Cdd:cd07855     8 EPIETIGSGAYGVVCSAI-------DTKSgqKVAIKKIPN-AFDVVTTAKRtlRELKILRHFKHDNIIAIRdilrpkVPY 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 AVGKPMCLLFEYMAyGDLNEFLRSMSPHTVCSLSHsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRD 724
Cdd:cd07855    80 ADFKDVYVVLDLME-SDLHHIIHSDQPLTLEHIRY------------------------FLYQLLRGLKYIHSANVIHRD 134
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRNI-YSADYYKADGNDAIPIRWM-PPESIF-YNRYTTESDVWAYGVVLWEI 794
Cdd:cd07855   135 LKPSNLLVNENCELKIGDFGMARGLcTSPEEHKYFMTEYVATRWYrAPELMLsLPEYTQAIDMWSVGCIFAEM 207
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
229-294 3.72e-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: 53.87  E-value: 3.72e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 229 VTLRCTAIGMPVPTISWIENGNAVSSGSIQENvkdRVIDSRLQLFITKP-----GLYTCIATNKHGEKFST 294
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSR---RSELGNGTLTISNVtledsGTYTCVASNSAGGSASA 68
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
120-208 4.07e-09

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 53.94  E-value: 4.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 120 KPKITRPPINVKiiEGLKAVLPCTTMGNPKPSVSWIKGDSALRensriavlESGSLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:pfam13895   1 KPVLTPSPTVVT--EGEPVTLTCSAPGNPPPSYTWYKDGSAIS--------SSPNFFTLSVSAEDSGTYTCVARNGRGGK 70

                  ....*....
gi 1937920432 200 YSKLVKLEV 208
Cdd:pfam13895  71 VSNPVELTV 79
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
575-796 4.70e-09

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: 58.21  E-value: 4.70e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARApgllpYEPFTMVAVK------MLKEEASADMQadfqrEAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd08220     3 EKIRVVGRGAYGTVYLCRR-----KDDNKLVIIKqipveqMTKEERQAALN-----EVKVLSMLHHPNIIEYYESFLEDK 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLrsmsphtvcslshsdlstrarvSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd08220    73 ALMIVMEYAPGGTLFEYI----------------------QQRKGSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQ 130
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 729 NCLVGEN-MVVKIADFGLSRNIYSADyyKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd08220   131 NILLNKKrTVVKIGDFGISKILSSKS--KAYTVVGTPC-YISPELCEGKPYNQKSDIWALGCVLYELAS 196
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
573-804 5.06e-09

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: 58.60  E-value: 5.06e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVA----VKMLKEEasadmqaDFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd05612     2 DFERIKTIGTGTFGRVHLVRDRISEHYYALKVMAipevIRLKQEQ-------HVHNEKRVLKEVSHPFIIRLFWTEHDQR 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLRSMSPHTvcslshsdlSTRARVSSpgppplscAEQLCiarqvaaGMAYLSERKFVHRDLATR 728
Cdd:cd05612    75 FLYMLMEYVPGGELFSYLRNSGRFS---------NSTGLFYA--------SEIVC-------ALEYLHSKEIVYRDLKPE 130
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 729 NCLVGENMVVKIADFGLSRNIYSADYYKADGNDaipirWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd05612   131 NILLDKEGHIKLTDFGFAKKLRDRTWTLCGTPE-----YLAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPFFD 200
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
707-854 5.29e-09

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: 58.49  E-value: 5.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSER-KFVHRDLATRNCLVGENMVVKIADFGL----SRNIYSADYYKADGNDAIPI-----RWMPPESIFYN 776
Cdd:cd14011   122 QISEALSFLHNDvKLVHGNICPESVVINSNGEWKLAGFDFcissEQATDQFPYFREYDPNLPPLaqpnlNYLAPEYILSK 201
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 777 RYTTESDVWAYGVVLWEIFSYGLQPyYGMAHEEVIYYVR----DGNILACPENCPLELYNLMRLCWSKLPADRPSFCSIH 852
Cdd:cd14011   202 TCDPASDMFSLGVLIYAIYNKGKPL-FDCVNNLLSYKKNsnqlRQLSLSLLEKVPEELRDHVKTLLNVTPEVRPDAEQLS 280

                  ..
gi 1937920432 853 RI 854
Cdd:cd14011   281 KI 282
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
580-802 5.32e-09

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: 58.53  E-value: 5.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApglLPYEPFTMVAVKML----KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGK-PMCLLF 654
Cdd:cd14041    14 LGRGGFSEVYKAFD---LTEQRYVAVKIHQLnknwRDEKKENYHKHACREYRIHKELDHPRIVKLYDYFSLDTdSFCTVL 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsphtvcslsHSDLSTRarvsspgppplscaEQLCIARQVAAGMAYLSERK--FVHRDLATRNCLV 732
Cdd:cd14041    91 EYCEGNDLDFYLKQ----------HKLMSEK--------------EARSIIMQIVNALKYLNEIKppIIHYDLKPGNILL 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMV---VKIADFGLSRNIYSADYYKADGND-----AIPIRWMPPESIFYN----RYTTESDVWAYGVVLWEIFsYGLQ 800
Cdd:cd14041   147 VNGTAcgeIKITDFGLSKIMDDDSYNSVDGMEltsqgAGTYWYLPPECFVVGkeppKISNKVDVWSVGVIFYQCL-YGRK 225

                  ..
gi 1937920432 801 PY 802
Cdd:cd14041   226 PF 227
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
577-792 5.45e-09

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: 58.11  E-value: 5.45e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLlpYEPFTMVAVKMLKEEASADMqadFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14095     5 GRVIGDGNFAVVKECRDKAT--DKEYALKIIDKAKCKGKEHM---IENEVAILRRVKHPNIVQLIEEYDTDTELYLVMEL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSPHTvcslshsdlstrARVSSpgppplscaeqlCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN- 735
Cdd:cd14095    80 VKGGDLFDAITSSTKFT------------ERDAS------------RMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHe 135
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 736 ---MVVKIADFGLSRNIYSADY-------YKAdgndaipirwmpPESIFYNRYTTESDVWAYGVVLW 792
Cdd:cd14095   136 dgsKSLKLADFGLATEVKEPLFtvcgtptYVA------------PEILAETGYGLKVDIWAAGVITY 190
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
580-796 5.65e-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: 58.05  E-value: 5.65e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFqaRAPGLLPYEpftMVAVKMLKEEASADMQAdfQREAALMAEF------DNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd14133     7 LGKGTFGQVV--KCYDLLTGE---EVALKIIKNNKDYLDQS--LDEIRLLELLnkkdkaDKYHIVRLKDVFYFKNHLCIV 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYgDLNEFLRSMSPHtvcSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVG 733
Cdd:cd14133    80 FELLSQ-NLYEFLKQNKFQ---YLSLPRIRK-------------------IAQQILEALVFLHSLGLIHCDLKPENILLA 136
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 734 EN--MVVKIADFG----LSRNIYS---ADYYKAdgndaipirwmpPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd14133   137 SYsrCQIKIIDFGsscfLTQRLYSyiqSRYYRA------------PEVILGLPYDEKIDMWSLGCILAELYT 196
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
578-812 6.04e-09

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: 58.30  E-value: 6.04e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGllPYEPFtmvAVKMLKEeaSADMQAdFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14085     9 SELGRGATSVVYRCRQKG--TQKPY---AVKKLKK--TVDKKI-VRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLneFLRSMSPHTVCSLSHSDlstrarvsspgppplsCAEQLCIArqvaagMAYLSERKFVHRDLATRNCLV---GE 734
Cdd:cd14085    81 TGGEL--FDRIVEKGYYSERDAAD----------------AVKQILEA------VAYLHENGIVHRDLKPENLLYatpAP 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIysadyykadgNDAIPIR-------WMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYYGMAH 807
Cdd:cd14085   137 DAPLKIADFGLSKIV----------DQQVTMKtvcgtpgYCAPEILRGCAYGPEVDMWSVGVITY-ILLCGFEPFYDERG 205

                  ....*
gi 1937920432 808 EEVIY 812
Cdd:cd14085   206 DQYMF 210
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
580-803 6.23e-09

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: 57.98  E-value: 6.23e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyePFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14169    11 LGEGAFSEVVLAQERG-----SQRLVALKCIPKKALRGKEAMVENEIAVLRRINHENIVSLEDIYESPTHLYLAMELVTG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLRSMSPHTVCSLSHsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVG---ENM 736
Cdd:cd14169    86 GELFDRIIERGSYTEKDASQ------------------------LIGQVLQAVKYLHQLGIVHRDLKPENLLYAtpfEDS 141
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 737 VVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYY 803
Cdd:cd14169   142 KIMISDFGLSKIEAQGMLSTACGTPG----YVAPELLEQKPYGKAVDVWAIGVISY-ILLCGYPPFY 203
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
571-803 6.73e-09

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: 57.73  E-value: 6.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14167     2 RDIYDFREVLGTGAFSEVVLAEEK-----RTQKLVAIKCIAKKALEGKETSIENEIAVLHKIKHPNIVALDDIYESGGHL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEflrsmsphtvcslshsdlstraRVSSPGPPPLSCAEQLCiaRQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd14167    77 YLIMQLVSGGELFD----------------------RIVEKGFYTERDASKLI--FQILDAVKYLHDMGIVHRDLKPENL 132
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 731 L---VGENMVVKIADFGLSRNIYSADYYK-ADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYY 803
Cdd:cd14167   133 LyysLDEDSKIMISDFGLSKIEGSGSVMStACGTPG----YVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFY 204
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
580-856 7.73e-09

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: 57.25  E-value: 7.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA-RAPGLLPyepftmVAVK-MLKeeaSADMQ----ADFQR---EAALM---AEFDNPNIVKLLGVCAVG 647
Cdd:cd14005     8 LGKGGFGTVYSGvRIRDGLP------VAVKfVPK---SRVTEwamiNGPVPvplEIALLlkaSKPGVPGVIRLLDWYERP 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYmAYG--DLNEFLRSmsphtvcslsHSDLSTR-ARvsspgppplscaeqlCIARQVAAGMAYLSERKFVHRD 724
Cdd:cd14005    79 DGFLLIMER-PEPcqDLFDFITE----------RGALSENlAR---------------IIFRQVVEAVRHCHQRGVLHRD 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 725 LATRNCLVgeNMV---VKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRY-TTESDVWAYGVVLWEIFSyGLQ 800
Cdd:cd14005   133 IKDENLLI--NLRtgeVKLIDFGCGALLKDSVYTDFDGTRV----YSPPEWIRHGRYhGRPATVWSLGILLYDMLC-GDI 205
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 801 PYYgmaHEEVIYyvrDGNILACPENCPlELYNLMRLCWSKLPADRPSFcsiHRILQ 856
Cdd:cd14005   206 PFE---NDEQIL---RGNVLFRPRLSK-ECCDLISRCLQFDPSKRPSL---EQILS 251
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
577-808 7.99e-09

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: 58.25  E-value: 7.99e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFqREAALMAEFDNPNIVKLLGVCAVGKpmcllfey 656
Cdd:cd07854    10 LRPLGCGSNGLVFSA-----VDSDCDKRVAVKKIVLTDPQSVKHAL-REIKIIRRLDHDNIVKVYEVLGPSG-------- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 mayGDLNEFLRSM----SPHTVCSLSHSDLstrARVSSPGPppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd07854    76 ---SDLTEDVGSLtelnSVYIVQEYMETDL---ANVLEQGP--LSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFI 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 G-ENMVVKIADFGLSRnIYSADY-YKADGNDAIPIRWM-PPESIFY-NRYTTESDVWAYGVVLWEIFSYglQPYYGMAHE 808
Cdd:cd07854   148 NtEDLVLKIGDFGLAR-IVDPHYsHKGYLSEGLVTKWYrSPRLLLSpNNYTKAIDMWAAGCIFAEMLTG--KPLFAGAHE 224
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
578-858 8.19e-09

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 57.87  E-value: 8.19e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGllpyepfTMVAVKML--KEEASADMQADFQREAALMAEfdnpNIVKLLGVCAVGK----PMC 651
Cdd:cd14144     1 RSVGKGRYGEVWKGKWRG-------EKVAVKIFftTEEASWFRETEIYQTVLMRHE----NILGFIAADIKGTgswtQLY 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSmsphtvcslshSDLSTRArvsspgppplscaeQLCIARQVAAGMAYLSERKF--------VHR 723
Cdd:cd14144    70 LITDYHENGSLYDFLRG-----------NTLDTQS--------------MLKLAYSAACGLAHLHTEIFgtqgkpaiAHR 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLsrniysADYYKADGNDA-IPI-------RWMPPE----SIFYNRYTT--ESDVWAYGV 789
Cdd:cd14144   125 DIKSKNILVKKNGTCCIADLGL------AVKFISETNEVdLPPntrvgtkRYMAPEvldeSLNRNHFDAykMADMYSFGL 198
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 790 VLWEI----FSYGL-----QPYYGMAHEEVIYyvRDGNILACPE-------------NCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14144   199 VLWEIarrcISGGIveeyqLPYYDAVPSDPSY--EDMRRVVCVErrrpsipnrwssdEVLRTMSKLMSECWAHNPAARLT 276
                         330
                  ....*....|.
gi 1937920432 848 FCSIHRILQRM 858
Cdd:cd14144   277 ALRVKKTLGKL 287
PHA03211 PHA03211
serine/threonine kinase US3; Provisional
625-793 8.32e-09

serine/threonine kinase US3; Provisional


Pssm-ID: 223009 [Multi-domain]  Cd Length: 461  Bit Score: 58.75  E-value: 8.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 625 EAALMAEFDNPNIVKLLGVCAVGKPMCLLFeymaygdlneflrsmsPHTVCSLsHSDLSTRARvsspgppPLSCAEQLCI 704
Cdd:PHA03211  210 EARLLRRLSHPAVLALLDVRVVGGLTCLVL----------------PKYRSDL-YTYLGARLR-------PLGLAQVTAV 265
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 705 ARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFG---LSRNIYSAD-YYKADGNdaipIRWMPPESIFYNRYTT 780
Cdd:PHA03211  266 ARQLLSAIDYIHGEGIIHRDIKTENVLVNGPEDICLGDFGaacFARGSWSTPfHYGIAGT----VDTNAPEVLAGDPYTP 341
                         170
                  ....*....|...
gi 1937920432 781 ESDVWAYGVVLWE 793
Cdd:PHA03211  342 SVDIWSAGLVIFE 354
IgI_Myomesin_like_C cd05737
C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of ...
127-198 1.15e-08

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.


Pssm-ID: 319300  Cd Length: 92  Bit Score: 52.98  E-value: 1.15e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAV-LESG---SLRIHNVQKEDAGQYRCVAKNSLGT 198
Cdd:cd05737     8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLkVEAGrtvYFTINGVSSEDSGKYGLVVKNKYGS 83
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
701-846 1.18e-08

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: 57.13  E-value: 1.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 701 QLCIArqvaagMAYL-SERKFVHRDLATRNCLVGENMVVKIADFGLSRNiYSADYYKADGNDAIPIRWMpPESIFYNRYT 779
Cdd:cd08528   121 QMVLA------LRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQ-KGPESSKMTSVVGTILYSC-PEIVQNEPYG 192
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 780 TESDVWAYGVVLWEIFSygLQPYYgmaHEEVIYYVRDGNILACPENCPLELY-----NLMRLCWSKLPADRP 846
Cdd:cd08528   193 EKADIWALGCILYQMCT--LQPPF---YSTNMLTLATKIVEAEYEPLPEGMYsdditFVIRSCLTPDPEARP 259
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
580-796 1.18e-08

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. 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 (a pseudokinase in the case of IRAK3), 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. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 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: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 57.20  E-value: 1.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApGLLPYepftmvAVKMLKEEASADMQADFQR---EAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14160     1 IGEGEIFEVYRVRI-GNRSY------AVKLFKQEKKMQWKKHWKRflsELEVLLLFQHPNILELAAYFTETEKFCLVYPY 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERK---FVHRDLATRNCLVG 733
Cdd:cd14160    74 MQNGTLFDRLQCHG---------------------VTKPLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLD 132
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 734 ENMVVKIADFGLSR----NIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd14160   133 DQMQPKLTDFALAHfrphLEDQSCTINMTTALHKHLWYMPEEYIRQGKLSVKTDVYSFGIVIMEVLT 199
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
579-803 1.31e-08

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: 57.05  E-value: 1.31e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 579 DIGEGAFGRVfqARAPGLLPYEPFtmvAVKML--KEEASADMQaDFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14086     8 ELGKGAFSVV--RRCVQKSTGQEF---AAKIIntKKLSARDHQ-KLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEFLRSMSPHTVCSLSHsdlstrarvsspgppplscaeqlCIaRQVAAGMAYLSERKFVHRDLATRNCLVG--- 733
Cdd:cd14086    82 VTGGELFEDIVAREFYSEADASH-----------------------CI-QQILESVNHCHQNGIVHRDLKPENLLLAsks 137
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 734 ENMVVKIADFGLSRNIYSAD--YYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYY 803
Cdd:cd14086   138 KGAAVKLADFGLAIEVQGDQqaWFGFAGTPG----YLSPEVLRKDPYGKPVDIWACGVILY-ILLVGYPPFW 204
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
570-836 1.33e-08

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: 57.34  E-value: 1.33e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 570 PRNNIEYVRDIGEGAFGRVFQA--RAPGLLpyepftmVAVKMLKEEASADMQADFQrEAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd06657    18 PRTYLDNFIKIGEGSTGIVCIAtvKSSGKL-------VAVKKMDLRKQQRRELLFN-EVVIMRDYQHENVVEMYNSYLVG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLneflrsmsphtvcslshSDLSTRARVSSpgppplscaEQLC-IARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd06657    90 DELWVVMEFLEGGAL-----------------TDIVTHTRMNE---------EQIAaVCLAVLKALSVLHAQGVIHRDIK 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENMVVKIADFGLSRNIySADYYKADGNDAIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMA 806
Cdd:cd06657   144 SDSILLTHDGRVKLSDFGFCAQV-SKEVPRRKSLVGTPY-WMAPELISRLPYGPEVDIWSLGIMVIEMVD-GEPPYFNEP 220
                         250       260       270
                  ....*....|....*....|....*....|
gi 1937920432 807 HEEVIYYVRDgnilacpeNCPLELYNLMRL 836
Cdd:cd06657   221 PLKAMKMIRD--------NLPPKLKNLHKV 242
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
572-803 1.38e-08

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 58.60  E-value: 1.38e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  572 NNIEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQAdfqrEAALMAEFDNPNIVKLLG--VCAVGKP 649
Cdd:PTZ00266    13 NEYEVIKKIGNGRFGEVFLVKHKRTQEFFCWKAISYRGLKEREKSQLVI----EVNVMRELKHKNIVRYIDrfLNKANQK 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  650 MCLLFEYMAYGDLNEFLRSmsphtvCSLSHSDLSTRARVSspgppplscaeqlcIARQVAAGMAYLSERK-------FVH 722
Cdd:PTZ00266    89 LYILMEFCDAGDLSRNIQK------CYKMFGKIEEHAIVD--------------ITRQLLHALAYCHNLKdgpngerVLH 148
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  723 RDLATRNCLVGENM-----------------VVKIADFGLSRNIYSADYykADGNDAIPIRWmPPESIFY--NRYTTESD 783
Cdd:PTZ00266   149 RDLKPQNIFLSTGIrhigkitaqannlngrpIAKIGDFGLSKNIGIESM--AHSCVGTPYYW-SPELLLHetKSYDDKSD 225
                          250       260
                   ....*....|....*....|
gi 1937920432  784 VWAYGVVLWEIFSyGLQPYY 803
Cdd:PTZ00266   226 MWALGCIIYELCS-GKTPFH 244
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
580-796 1.44e-08

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; 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. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 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: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 57.15  E-value: 1.44e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGLlPYepftmvAVKMLKE---EASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14157     1 ISEGTFADIYKGYRHGK-QY------VIKRLKEtecESPKSTERFFQTEVQICFRCCHPNILPLLGFCVESDCHCLIYPY 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLNEflrsmsphtvcSLSHSDlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd14157    74 MPNGSLQD-----------RLQQQG----------GSHPLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNL 132
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 737 VVKIADFGLsrNIYSAD----YYKADGND-AIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd14157   133 LPKLGHSGL--RLCPVDkksvYTMMKTKVlQISLAYLPEDFVRHGQLTEKVDIFSCGVVLAEILT 195
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
127-201 1.64e-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: 52.58  E-value: 1.64e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYS 201
Cdd:cd05723     4 PSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQA 78
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
605-746 1.71e-08

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: 56.19  E-value: 1.71e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKML-KEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLneflrsmsphtvcslsHSDLS 683
Cdd:cd14075    30 VAIKILdKTKLDQKTQRLLSREISSMEKLHHPNIIRLYEVVETLSKLHLVMEYASGGEL----------------YTKIS 93
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 684 TRARVSSPGPPPLscaeqlciARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLS 746
Cdd:cd14075    94 TEGKLSESEAKPL--------FAQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFS 148
IgI_3_Contactin-1 cd05851
Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) ...
126-197 1.77e-08

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 143259  Cd Length: 88  Bit Score: 52.33  E-value: 1.77e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 126 PPINVKI-----IEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVleSGS-LRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd05851     2 ADINVKFkdtyaLKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISM--SGAvLKIFNIQPEDEGTYECEAENIKG 77
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
568-794 1.80e-08

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: 56.98  E-value: 1.80e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARapgllpYEPFTMV-AVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAV 646
Cdd:cd06649     1 ELKDDDFERISELGAGNGGVVTKVQ------HKPSGLImARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYS 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 647 GKPMCLLFEYMAYGDLNEFLRSMSphtvcslshsdlstraRVsspgppPLSCAEQLCIArqVAAGMAYLSER-KFVHRDL 725
Cdd:cd06649    75 DGEISICMEHMDGGSLDQVLKEAK----------------RI------PEEILGKVSIA--VLRGLAYLREKhQIMHRDV 130
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNIYSADyykadGNDAIPIR-WMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd06649   131 KPSNILVNSRGEIKLCDFGVSGQLIDSM-----ANSFVGTRsYMSPERLQGTHYSVQSDIWSMGLSLVEL 195
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
580-796 1.96e-08

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: 56.21  E-value: 1.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFqarapglLPYEPFT--MVAVKMLK-----EEASADMQAdFQREAALMAEFDNPNIVKLLGVC--AVGKPM 650
Cdd:cd06652    10 LGQGAFGRVY-------LCYDADTgrELAVKQVQfdpesPETSKEVNA-LECEIQLLKNLLHERIVQYYGCLrdPQERTL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTvcslshsDLSTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd06652    82 SIFMEYMPGGSIKDQLKSYGALT-------ENVTRK-----------------YTRQILEGVHYLHSNMIVHRDIKGANI 137
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSAdYYKADGNDAI---PIrWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd06652   138 LRDSVGNVKLGDFGASKRLQTI-CLSGTGMKSVtgtPY-WMSPEVISGEGYGRKADIWSVGCTVVEMLT 204
IgI_1_Neogenin_like cd05722
First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of ...
127-208 1.97e-08

First 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 first 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: 409387  Cd Length: 97  Bit Score: 52.48  E-value: 1.97e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 127 PINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENS--RIAVLESGSLRIHNVQ-----KEDAGQYRCVAKN-SLGT 198
Cdd:cd05722     8 PSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSdeRRQQLPNGSLLITSVVhskhnKPDEGFYQCVAQNeSLGS 87
                          90
                  ....*....|
gi 1937920432 199 AYSKLVKLEV 208
Cdd:cd05722    88 IVSRTARVTV 97
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
711-847 2.06e-08

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: 56.16  E-value: 2.06e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 711 GMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAipiRWMPPEsIFYNRYTTESDVWAYGVV 790
Cdd:cd14050   112 GLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLVVELDKEDIHDAQEGDP---RYMAPE-LLQGSFTKAADIFSLGIT 187
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 791 LWEIFSYGLQPYYGMAHEEviyyVRDGNIlacPENC----PLELYNLMRLCWSKLPADRPS 847
Cdd:cd14050   188 ILELACNLELPSGGDGWHQ----LRQGYL---PEEFtaglSPELRSIIKLMMDPDPERRPT 241
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
580-792 2.21e-08

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: 56.24  E-value: 2.21e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVfqARAPGLLPYEpftMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAY 659
Cdd:cd14078    11 IGSGGFAKV--KLATHILTGE---KVAIKIMDKKALGDDLPRVKTEIEALKNLSHQHICRLYHVIETDNKIFMVLEYCPG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 660 GDLNEFLrsmsphtvcsLSHSDLS-TRARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVV 738
Cdd:cd14078    86 GELFDYI----------VAKDRLSeDEARV---------------FFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNL 140
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 739 KIADFGL---SRNIYSADYYKADGNDAipirWMPPESIFYNRYT-TESDVWAYGVVLW 792
Cdd:cd14078   141 KLIDFGLcakPKGGMDHHLETCCGSPA----YAAPELIQGKPYIgSEADVWSMGVLLY 194
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
574-860 2.30e-08

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 56.60  E-value: 2.30e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPGllpyepfTMVAVKML--KEEASADMQADFQREAALMAEfdnpNIVKLLGVCAVGK--- 648
Cdd:cd14219     7 IQMVKQIGKGRYGEVWMGKWRG-------EKVAVKVFftTEEASWFRETEIYQTVLMRHE----NILGFIAADIKGTgsw 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 -PMCLLFEYMAYGDLNEFLRS--MSPHTVCSLSHSDLSTRARV-----SSPGPPPLScaeqlciarqvaagmaylserkf 720
Cdd:cd14219    76 tQLYLITDYHENGSLYDYLKSttLDTKAMLKLAYSSVSGLCHLhteifSTQGKPAIA----------------------- 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 721 vHRDLATRNCLVGENMVVKIADFGLSRNIYSadyykaDGNDA-IPI-------RWMPP----ESIFYNRYTT--ESDVWA 786
Cdd:cd14219   133 -HRDLKSKNILVKKNGTCCIADLGLAVKFIS------DTNEVdIPPntrvgtkRYMPPevldESLNRNHFQSyiMADMYS 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 787 YGVVLWEIF----------SYGLqPYYGMAHEEVIYyvRDGNILAC-------------PENCPLELYNLMRLCWSKLPA 843
Cdd:cd14219   206 FGLILWEVArrcvsggiveEYQL-PYHDLVPSDPSY--EDMREIVCikrlrpsfpnrwsSDECLRQMGKLMTECWAHNPA 282
                         330
                  ....*....|....*..
gi 1937920432 844 DRPSFCSIHRILQRMCE 860
Cdd:cd14219   283 SRLTALRVKKTLAKMSE 299
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
578-794 2.49e-08

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: 56.21  E-value: 2.49e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVF--QARAPGllpyepfTMVAVKML--------KEEASADMqadfqrEAALMAEFDNPNIVKLLGVCAVG 647
Cdd:cd05605     6 RVLGKGGFGEVCacQVRATG-------KMYACKKLekkrikkrKGEAMALN------EKQILEKVNSRFVVSLAYAYETK 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05605    73 DALCLVLTIMNGGDLKFHIYNM----------------------GNPGFEEERAVFYAAEITCGLEHLHSERIVYRDLKP 130
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 728 RNCLVGENMVVKIADFGLSRNIYSADYYKAD-GNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd05605   131 ENILLDDHGHVRISDLGLAVEIPEGETIRGRvGT----VGYMAPEVVKNERYTFSPDWWGLGCLIYEM 194
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
121-201 2.50e-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: 52.20  E-value: 2.50e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVG 81

                  ....
gi 1937920432 198 TAYS 201
Cdd:cd20972    82 SDTT 85
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
580-859 2.54e-08

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 56.30  E-value: 2.54e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyepfTMVAVKML--KEEASADMQADFQREAALMAEfdnpNIvklLGVCAVGKP-------M 650
Cdd:cd14143     3 IGKGRFGEVWRGRWRG-------EDVAVKIFssREERSWFREAEIYQTVMLRHE----NI---LGFIAADNKdngtwtqL 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLR--SMSPHTVCSLSHSDLSTRAR-----VSSPGPPPLScaeqlciarqvaagmaylserkfvHR 723
Cdd:cd14143    69 WLVSDYHEHGSLFDYLNryTVTVEGMIKLALSIASGLAHlhmeiVGTQGKPAIA------------------------HR 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 724 DLATRNCLVGENMVVKIADFGLSRNIYSAdyykadgNDAIPI---------RWMPPE----SIFYNRYTT--ESDVWAYG 788
Cdd:cd14143   125 DLKSKNILVKKNGTCCIADLGLAVRHDSA-------TDTIDIapnhrvgtkRYMAPEvlddTINMKHFESfkRADIYALG 197
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 789 VVLWEIfsyGLQPYYGMAHEE--VIYY--------VRDGNILACPENCPLELYN-------------LMRLCWSKLPADR 845
Cdd:cd14143   198 LVFWEI---ARRCSIGGIHEDyqLPYYdlvpsdpsIEEMRKVVCEQKLRPNIPNrwqscealrvmakIMRECWYANGAAR 274
                         330
                  ....*....|....
gi 1937920432 846 PSFCSIHRILQRMC 859
Cdd:cd14143   275 LTALRIKKTLSQLS 288
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
705-819 2.96e-08

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: 56.25  E-value: 2.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 705 ARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSR-NIYSADYYKA-----DgndaipirWMPPESIFYNRY 778
Cdd:cd05587   103 AAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKeGIFGGKTTRTfcgtpD--------YIAPEIIAYQPY 174
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 779 TTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd05587   175 GKSVDWWAYGVLLYEMLA-GQPPFDGEDEDELFQSIMEHNV 214
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
606-794 3.57e-08

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: 55.90  E-value: 3.57e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 606 AVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdlstr 685
Cdd:cd06615    30 ARKLIHLEIKPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKA---------------- 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 686 arvsspGPPPLSCAEQLCIArqVAAGMAYLSE-RKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADyykadGNDAIP 764
Cdd:cd06615    94 ------GRIPENILGKISIA--VLRGLTYLREkHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSM-----ANSFVG 160
                         170       180       190
                  ....*....|....*....|....*....|.
gi 1937920432 765 IR-WMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd06615   161 TRsYMSPERLQGTHYTVQSDIWSLGLSLVEM 191
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
580-810 3.77e-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: 56.15  E-value: 3.77e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFqarapgLLPYEPF-TMVAVKMLKEeasADMQADFQREAaLMAE---FD------NPNIVKLLGVCAVGKP 649
Cdd:cd05589     7 LGRGHFGKVL------LAEYKPTgELFAIKALKK---GDIIARDEVES-LMCEkriFEtvnsarHPFLVNLFACFQTPEH 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLneflrsMSpHTvcslsHSDL--STRARVSSpgppplSCaeqlciarqVAAGMAYLSERKFVHRDLAT 727
Cdd:cd05589    77 VCFVMEYAAGGDL------MM-HI-----HEDVfsEPRAVFYA------AC---------VVLGLQFLHEHKIVYRDLKL 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENMVVKIADFGLSR-NIYSADyyKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMA 806
Cdd:cd05589   130 DNLLLDTEGYVKIADFGLCKeGMGFGD--RTSTFCGTP-EFLAPEVLTDTSYTRAVDWWGLGVLIYEML-VGESPFPGDD 205

                  ....
gi 1937920432 807 HEEV 810
Cdd:cd05589   206 EEEV 209
IgI_NCAM-1_like cd05732
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar ...
120-208 3.78e-08

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 409395 [Multi-domain]  Cd Length: 96  Bit Score: 51.76  E-value: 3.78e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 120 KPKITRPPiNVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENS-----RIAVLE---SGSLRIHNVQKEDAGQYRCV 191
Cdd:cd05732     2 QPKITYLE-NQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEgdldgRIVVRGharVSSLTLKDVQLTDAGRYDCE 80
                          90
                  ....*....|....*..
gi 1937920432 192 AKNSLGtAYSKLVKLEV 208
Cdd:cd05732    81 ASNRIG-GDQQSMYLEV 96
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
579-815 3.80e-08

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: 55.28  E-value: 3.80e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 579 DIGEGAFGRVFQA--RAPGLLPYEPFTMVAVKMLKEEAsadmqadfQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd14114     9 ELGTGAFGVVHRCteRATGNNFAAKFIMTPHESDKETV--------RKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLneFLRSMSPHTVcslshsdlstrarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN--CLVGE 734
Cdd:cd14114    81 LSGGEL--FERIAAEHYK---------------------MSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENimCTTKR 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 735 NMVVKIADFGLSRNIYSADYYKADGNDAipiRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYV 814
Cdd:cd14114   138 SNEVKLIDFGLATHLDPKESVKVTTGTA---EFAAPEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPFAGENDDETLRNV 213

                  .
gi 1937920432 815 R 815
Cdd:cd14114   214 K 214
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
126-197 3.81e-08

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: 51.43  E-value: 3.81e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 126 PPINVKIIEGLKAVLPCT-TMGNPKPSVSWIKGDSALRENSRIAVLE----SGSLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSaSTGSPGPDVTWSKEGGTLIESLKVKHDNgrttQSSLLISNVTKEDAGTYTCVVNNPGG 78
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
574-796 3.82e-08

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: 56.29  E-value: 3.82e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARAPgllpyepftmvavKMLKEEASADMQADFQ---------REAALMAEFDNPNIVKLLGVC 644
Cdd:cd07853     2 VEPDRPIGYGAFGVVWSVTDP-------------RDGKRVALKKMPNVFQnlvsckrvfRELKMLCFFKHDNVLSALDIL 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 645 AVGKPMCllFEYMaygdlneflrsmspHTVCSLSHSDLStRARVSspgPPPLSCAEQLCIARQVAAGMAYLSERKFVHRD 724
Cdd:cd07853    69 QPPHIDP--FEEI--------------YVVTELMQSDLH-KIIVS---PQPLSSDHVKVFLYQILRGLKYLHSAGILHRD 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 725 LATRNCLVGENMVVKIADFGLSRnIYSAD------------YYKAdgndaipirwmpPESIFYNR-YTTESDVWAYGVVL 791
Cdd:cd07853   129 IKPGNLLVNSNCVLKICDFGLAR-VEEPDeskhmtqevvtqYYRA------------PEILMGSRhYTSAVDIWSVGCIF 195

                  ....*
gi 1937920432 792 WEIFS 796
Cdd:cd07853   196 AELLG 200
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
705-811 3.89e-08

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: 55.38  E-value: 3.89e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 705 ARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNI----------YSADYYKADGNDAIPIR----WMPP 770
Cdd:cd14010   100 GRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREgeilkelfgqFSDEGNVNKVSKKQAKRgtpyYMAP 179
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1937920432 771 ESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd14010   180 ELFQGGVHSFASDLWALGCVLYEMFT-GKPPFVAESFTELV 219
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
580-796 3.99e-08

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: 55.42  E-value: 3.99e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF--------QARAPGLLPYEPFTmvavkmlkEEASADMQAdFQREAALMAEFDNPNIVKLLGVC--AVGKP 649
Cdd:cd06653    10 LGRGAFGEVYlcydadtgRELAVKQVPFDPDS--------QETSKEVNA-LECEIQLLKNLRHDRIVQYYGCLrdPEEKK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSMSPHTvcslshsDLSTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd06653    81 LSIFVEYMPGGSVKDQLKAYGALT-------ENVTRR-----------------YTRQILQGVSYLHSNMIVHRDIKGAN 136
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIYSAdYYKADGNDAI---PIrWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd06653   137 ILRDSAGNVKLGDFGASKRIQTI-CMSGTGIKSVtgtPY-WMSPEVISGEGYGRKADVWSVACTVVEMLT 204
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
706-847 4.12e-08

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: 55.45  E-value: 4.12e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSA-DYYKADGNDAIPIR---------------WMP 769
Cdd:cd14046   111 RQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLATSNKLNvELATQDINKSTSAAlgssgdltgnvgtalYVA 190
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 770 PE--SIFYNRYTTESDVWAYGVVLWEIFSYglqPYYGMAHEEVIYYVRDGNIL----ACPENCPLElYNLMRLCWSKLPA 843
Cdd:cd14046   191 PEvqSGTKSTYNEKVDMYSLGIIFFEMCYP---FSTGMERVQILTALRSVSIEfppdFDDNKHSKQ-AKLIRWLLNHDPA 266

                  ....
gi 1937920432 844 DRPS 847
Cdd:cd14046   267 KRPS 270
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
578-813 4.15e-08

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: 55.39  E-value: 4.15e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQArapglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14183    12 RTIGDGNFAVVKEC-----VERSTGREYALKIINKSKCRGKEHMIQNEVSILRRVKHPNIVLLIEEMDMPTELYLVMELV 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHTvcslsHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENM- 736
Cdd:cd14183    87 KGGDLFDAITSTNKYT-----ERDASG-------------------MLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQd 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 737 ---VVKIADFGLSrNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYYGMAHEEVIYY 813
Cdd:cd14183   143 gskSLKLGDFGLA-TVVDGPLYTVCGTPT----YVAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPFRGSGDDQEVLF 216
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
578-863 4.19e-08

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: 55.59  E-value: 4.19e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVFQARAPGllpyePFTMVAVKMLkeeASADMQADFQ--REAALMAEFD-NPNIVKLLGVCAVGKP----M 650
Cdd:cd14036     6 RVIAEGGFAFVYEAQDVG-----TGKEYALKRL---LSNEEEKNKAiiQEINFMKKLSgHPNIVQFCSAASIGKEesdqG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 C---LLFEYMAYGDLNEFLRSMSPhtvcslshsdlstrarvsspgPPPLSCAEQLCIARQVAAGMAYLSERK--FVHRDL 725
Cdd:cd14036    78 QaeyLLLTELCKGQLVDFVKKVEA---------------------PGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDL 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 726 ATRNCLVGENMVVKIADFGLSRNI-YSADYYKADGN-----DAIPIRWMP----PESI-FYNRY--TTESDVWAYGVVLW 792
Cdd:cd14036   137 KIENLLIGNQGQIKLCDFGSATTEaHYPDYSWSAQKrslveDEITRNTTPmyrtPEMIdLYSNYpiGEKQDIWALGCILY 216
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 793 eIFSYGLQPYYGMAHEEVIyyvrDGNILACPENCPLELY-NLMRLCWSKLPADRPsfcSIHRILQRMCERAE 863
Cdd:cd14036   217 -LLCFRKHPFEDGAKLRII----NAKYTIPPNDTQYTVFhDLIRSTLKVNPEERL---SITEIVEQLQELAA 280
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
579-817 4.25e-08

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: 55.21  E-value: 4.25e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 579 DIGEGAFGRVFQA--RAPG------LLPYEPFTMvavkmlkeeasadmqadfqREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14109    11 DEKRAAQGAPFHVteRSTGrnflaqLRYGDPFLM-------------------REVDIHNSLDHPNIVQMHDAYDDEKLA 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAygdlneflrsmsphtvcslshsdlSTRARVSSPGPPPLSCAEQLCIA---RQVAAGMAYLSERKFVHRDLAT 727
Cdd:cd14109    72 VTVIDNLA------------------------STIELVRDNLLPGKDYYTERQVAvfvRQLLLALKHMHDLGIAHLDLRP 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 728 RNCLVGENmVVKIADFGLSRNIysadyykADGNDAIPIRWMP----PESIfyNRY--TTESDVWAYGVVLWEIFSyGLQP 801
Cdd:cd14109   128 EDILLQDD-KLKLADFGQSRRL-------LRGKLTTLIYGSPefvsPEIV--NSYpvTLATDMWSVGVLTYVLLG-GISP 196
                         250
                  ....*....|....*.
gi 1937920432 802 YYGMAHEEVIYYVRDG 817
Cdd:cd14109   197 FLGDNDRETLTNVRSG 212
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
620-804 4.62e-08

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: 55.63  E-value: 4.62e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 620 ADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLN-EFLRSMSPHTVCS---LSHsdlstrarvsspgppp 695
Cdd:cd14094    50 EDLKREASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGADLCfEIVKRADAGFVYSeavASH---------------- 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 696 lscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVG--ENMV-VKIADFGLSRNIySADYYKADGNDAIPiRWMPPES 772
Cdd:cd14094   114 --------YMRQILEALRYCHDNNIIHRDVKPHCVLLAskENSApVKLGGFGVAIQL-GESGLVAGGRVGTP-HFMAPEV 183
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1937920432 773 IFYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd14094   184 VKREPYGKPVDVWGCGVILFILLS-GCLPFYG 214
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
577-794 4.80e-08

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: 55.51  E-value: 4.80e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPgllpYEPFTMVAVKMLKEEAS-ADMQADFQREAALMAEFDN---PNIVKLLGVCAVGKPMCL 652
Cdd:cd14052     5 VELIGSGEFSQVYKVSER----VPTGKVYAVKKLKPNYAgAKDRLRRLEEVSILRELTLdghDNIVQLIDSWEYHGHLYI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSPHTVCSlshsdlstRARVSSpgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14052    81 QTELCENGSLDVFLSELGLLGRLD--------EFRVWK-------------ILVELSLGLRFIHDHHFVHLDLKPANVLI 139
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 733 GENMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:cd14052   140 TFEGTLKIGDFGMATVWPLIRGIEREGDRE----YIAPEILSEHMYDKPADIFSLGLILLEA 197
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
135-197 5.04e-08

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 51.49  E-value: 5.04e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 135 GLKAVLPCTTMGNPKPSVSWIKGDSAL--RENSRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKNGMDInpKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGG 80
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
121-199 5.12e-08

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: 51.31  E-value: 5.12e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALREN-SRIAVLESGS----LRIHNVQKEDAGQYRCVAKNS 195
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNE 80

                  ....
gi 1937920432 196 LGTA 199
Cdd:cd05892    81 AGVV 84
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
706-851 5.12e-08

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: 54.96  E-value: 5.12e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLV----GEnmvVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTE 781
Cdd:cd14102   112 RQVLEAVRHCYSCGVVHRDIKDENLLVdlrtGE---LKLIDFGSGALLKDTVYTDFDGTRV----YSPPEWIRYHRYHGR 184
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 782 S-DVWAYGVVLWEIFsYGLQPYygmAHEEVIYYVRdgniLACPENCPLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd14102   185 SaTVWSLGVLLYDMV-CGDIPF---EQDEEILRGR----LYFRRRVSPECQQLIKWCLSLRPSDRPTLEQI 247
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
572-830 5.69e-08

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: 55.79  E-value: 5.69e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARAPGllpYEPFtmVAVKMLKEEASADMQAD---FQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd05602     7 SDFHFLKVIGKGSFGKVLLARHKS---DEKF--YAVKVLQKKAILKKKEEkhiMSERNVLLKNVKHPFLVGLHFSFQTTD 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLRSmsphtvcslSHSDLSTRARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd05602    82 KLYFVLDYINGGELFYHLQR---------ERCFLEPRARF---------------YAAEIASALGYLHSLNIVYRDLKPE 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLSR-NIysadyyKADGNDAI---PIRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYG 804
Cdd:cd05602   138 NILLDSQGHIVLTDFGLCKeNI------EPNGTTSTfcgTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEML-YGLPPFYS 210
                         250       260
                  ....*....|....*....|....*.
gi 1937920432 805 MAHEEVIyyvrdGNILacpeNCPLEL 830
Cdd:cd05602   211 RNTAEMY-----DNIL----NKPLQL 227
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
140-199 5.86e-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: 51.02  E-value: 5.86e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 140 LPCTTMGNPKPSVSWIKGDSALRENSRIA----VLESG----SLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd20956    21 LKCVASGNPLPQITWTLDGFPIPESPRFRvgdyVTSDGdvvsYVNISSVRVEDGGEYTCTATNDVGSV 88
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
580-849 6.01e-08

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: 55.35  E-value: 6.01e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGV------CAVGKPMCLL 653
Cdd:cd14038     2 LGTGGFGNVLRWINQ-----ETGEQVAIKQCRQELSPKNRERWCLEIQIMKRLNHPNVVAARDVpeglqkLAPNDLPLLA 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLNEFLRSMspHTVCSLSHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV- 732
Cdd:cd14038    77 MEYCQGGDLRKYLNQF--ENCCGLREGAILT-------------------LLSDISSALRYLHENRIIHRDLKPENIVLq 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 -GENMVV-KIADFGLSRNIysaDYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYY------- 803
Cdd:cd14038   136 qGEQRLIhKIIDLGYAKEL---DQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECIT-GFRPFLpnwqpvq 211
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 804 ------GMAHEEVIYY------VRDGNILACPENC------PLELYNLMRLCWS-----KLPADRPSFC 849
Cdd:cd14038   212 whgkvrQKSNEDIVVYedltgaVKFSSVLPTPNNLngilagKLERWLQCMLMWHprqrgTDPPQNPNGC 280
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
704-848 6.16e-08

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: 55.12  E-value: 6.16e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 704 IARQVAAGMAYLSER-KFVHRDLATRNCLVGENMVVKIADFGLSRNIYSAdyyKADGNDAIPIRWMPPESIFYNR----Y 778
Cdd:cd06617   108 IAVSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGISGYLVDS---VAKTIDAGCKPYMAPERINPELnqkgY 184
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 779 TTESDVWAYGVVLWEIfSYGLQPY--YGMAHEEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd06617   185 DVKSDVWSLGITMIEL-ATGRFPYdsWKTPFQQLKQVVEEPSPQLPAEKFSPEFQDFVNKCLKKNYKERPNY 255
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
218-296 6.43e-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: 50.58  E-value: 6.43e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSiqENVKDRVIDSRLQLFITKP-----GLYTCIATNKHGEKF 292
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAES--GRFSVSRSGSTSTLTISNVtpedsGTYTCAATNSSGSAS 78

                   ....
gi 1937920432  293 STAK 296
Cdd:smart00410  79 SGTT 82
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
571-817 6.49e-08

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: 55.00  E-value: 6.49e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVF--QARAPGLLpyepFTMVAVKmlKEEASADmqADFQREAALMAEFDNPNIVKLLGVCAVGK 648
Cdd:cd14166     2 RETFIFMEVLGSGAFSEVYlvKQRSTGKL----YALKCIK--KSPLSRD--SSLENEIAVLKRIKHENIVTLEDIYESTT 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLFEYMAYGDLNEFLRSMSPHTvcslsHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATR 728
Cdd:cd14166    74 HYYLVMQLVSGGELFDRILERGVYT-----EKDASR-------------------VINQVLSAVKYLHENGIVHRDLKPE 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLV---GENMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYYGM 805
Cdd:cd14166   130 NLLYltpDENSKIMITDFGLSKMEQNGIMSTACGTPG----YVAPEVLAQKPYSKAVDCWSIGVITY-ILLCGYPPFYEE 204
                         250
                  ....*....|..
gi 1937920432 806 AHEEVIYYVRDG 817
Cdd:cd14166   205 TESRLFEKIKEG 216
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
574-848 6.66e-08

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: 54.85  E-value: 6.66e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 574 IEYVRDIGEGAFGRVFQARapgllpYEPFTMV-AVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd06622     3 IEVLDELGKGNYGSVYKVL------HRPTGVTmAMKEIRLELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYM 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFlrsmsphtvcslshsdlsTRARVSSPGPPPLSCAEqlcIARQVAAGMAYLSER-KFVHRDLATRNCL 731
Cdd:cd06622    77 CMEYMDAGSLDKL------------------YAGGVATEGIPEDVLRR---ITYAVVKGLKFLKEEhNIIHRDVKPTNVL 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 VGENMVVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYN------RYTTESDVWAYGVVLWEIfSYGLQPYYGM 805
Cdd:cd06622   136 VNGNGQVKLCDFGVSGNLVASLAKTNIGCQS----YMAPERIKSGgpnqnpTYTVQSDVWSLGLSILEM-ALGRYPYPPE 210
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 806 AHEEV---IYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd06622   211 TYANIfaqLSAIVDGDPPTLPSGYSDDAQDFVAKCLNKIPNRRPTY 256
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
33-108 7.08e-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: 50.57  E-value: 7.08e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432  33 PLETVDAlVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQlLTILSVEDSDDGIYCCTANNGVGGA 108
Cdd:cd20952     6 PQNQTVA-VGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGS-LQIKGAEKSDTGEYTCVALNLSGEA 79
IgI_2_FGFRL1-like cd05856
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1 ...
226-296 7.10e-08

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); 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 like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. 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: 409442  Cd Length: 92  Bit Score: 51.01  E-value: 7.10e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1937920432 226 GSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRVIdsrLQLFITKP---GLYTCIATNKHGEKFSTAK 296
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWT---LSLKNLKPedsGKYTCHVSNRAGEINATYK 89
IgI_L1-CAM_like cd05733
Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; ...
139-206 7.50e-08

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. 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. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.


Pssm-ID: 409396 [Multi-domain]  Cd Length: 94  Bit Score: 50.87  E-value: 7.50e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 139 VLPCTTMGNPKPSVSWIKG----------DSALRENSRIAVLESGSLRIHNVQkedaGQYRCVAKNSLGTAYSKLVKL 206
Cdd:cd05733    20 TIKCEAKGNPQPTFRWTKDgkffdpakdpRVSMRRRSGTLVIDNHNGGPEDYQ----GEYQCYASNELGTAISNEIRL 93
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
226-290 7.55e-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: 51.02  E-value: 7.55e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 226 GSFVTLRCTAIGMPVPTISWIENGNAVSSgSIQENVKDRV-IDSRL--QLFITK-----PGLYTCIATNKHGE 290
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDGFPIPE-SPRFRVGDYVtSDGDVvsYVNISSvrvedGGEYTCTATNDVGS 87
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
213-304 7.70e-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: 51.01  E-value: 7.70e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 213 RILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRVIDSRLQLFI---------TKPGLYTCI 283
Cdd:cd07693     2 RIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLrvvhgrkgrSDEGVYVCV 81
                          90       100
                  ....*....|....*....|.
gi 1937920432 284 ATNKHGEKFStakAAATVSIA 304
Cdd:cd07693    82 AHNSLGEAVS---RNASLEVA 99
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
707-796 7.82e-08

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: 55.00  E-value: 7.82e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYN--RYTTESDV 784
Cdd:cd07849   114 QILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNskGYTKAIDI 193
                          90
                  ....*....|..
gi 1937920432 785 WAYGVVLWEIFS 796
Cdd:cd07849   194 WSVGCILAEMLS 205
IgI_1_NCAM-1_like cd04977
First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar ...
115-208 7.97e-08

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 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-nonNCAM) 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 the Ig1, Ig2, and Ig3 domains. 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). 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: 409366  Cd Length: 95  Bit Score: 50.71  E-value: 7.97e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 115 LQVKMKPKitrppiNVKIIEGLKAVLPCTTMGNPKpSVSWI--KGDSALRENSRIAVLESG----SLRIHNVQKEDAGQY 188
Cdd:cd04977     1 LQVKIIPS------YAEISVGESKFFLCKVSGDAK-NINWVspNGEKVLTKHGNLKVVNHGsvlsSLTIYNANINDAGIY 73
                          90       100
                  ....*....|....*....|
gi 1937920432 189 RCVAKNSLGTAYSKLVKLEV 208
Cdd:cd04977    74 KCVATNGKGTESEATVKLDI 93
STKc_KIS cd14020
Catalytic domain of the Serine/Threonine Kinase, Kinase Interacting with Stathmin (also called ...
580-796 1.05e-07

Catalytic domain of the Serine/Threonine Kinase, Kinase Interacting with Stathmin (also called U2AF homology motif (UHM) kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KIS (or UHMK1) contains an N-terminal kinase domain and a C-terminal domain with a UHM motif, a protein interaction motif initially found in the pre-mRNA splicing factor U2AF. It phosphorylates the splicing factor SF1, which enhances binding to the splice site to promote spliceosome assembly. KIS was first identified as a kinase that interacts with stathmin, a phosphoprotein that plays a role in axon development and microtubule dynamics. It localizes in RNA granules in neurons and is important in neurite outgrowth. The KIS/UHMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270922 [Multi-domain]  Cd Length: 285  Bit Score: 54.56  E-value: 1.05e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARApGLLPYEPFTMVAVKMLKEEASADMQA-DFQREAALMAEFD-NPNIVKLLGV-----CAVGKPMCL 652
Cdd:cd14020     8 LGQGSSASVYRVSS-GRGADQPTSALKEFQLDHQGSQESGDyGFAKERAALEQLQgHRNIVTLYGVftnhySANVPSRCL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYgDLNEFLRSMSP--HTVCSLSHsdlstrarvsspgppplscaeqlCiARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd14020    87 LLELLDV-SVSELLLRSSNqgCSMWMIQH-----------------------C-ARDVLEALAFLHHEGYVHADLKPRNI 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 L-VGENMVVKIADFGLSRNIYSAD--YYKADGNDAipirwmpPESIFYNRY-----------TTESDVWAYGVVLWEIFS 796
Cdd:cd14020   142 LwSAEDECFKLIDFGLSFKEGNQDvkYIQTDGYRA-------PEAELQNCLaqaglqsetecTSAVDLWSLGIVLLEMFS 214
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
605-803 1.06e-07

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: 54.21  E-value: 1.06e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 605 VAVKMLKEEASADMQADFQREAALMAEFDN-PNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdls 683
Cdd:cd14181    45 VTAERLSPEQLEEVRSSTLKEIHILRQVSGhPSIITLIDSYESSTFIFLVFDLMRRGELFDYLTE--------------- 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 684 traRVSspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADyyKADGNDAI 763
Cdd:cd14181   110 ---KVT------LSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPGE--KLRELCGT 178
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1937920432 764 PiRWMPPESI------FYNRYTTESDVWAYGVVLWEIFSyGLQPYY 803
Cdd:cd14181   179 P-GYLAPEILkcsmdeTHPGYGKEVDLWACGVILFTLLA-GSPPFW 222
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
572-848 1.23e-07

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: 54.30  E-value: 1.23e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 572 NNIEYVRDIGEGAFGRVFQARapgllpYEPF-TMVAVK-MLKEEASADMQADFQREAALMAEFDNPNIVKLLGvcavgkp 649
Cdd:cd06618    15 NDLENLGEIGSGTCGQVYKMR------HKKTgHVMAVKqMRRSGNKEENKRILMDLDVVLKSHDCPYIVKCYG------- 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 mCLLFEYmaygdlnEFLRSMSPHTVCSlshSDLSTRARvsspGPPPLSCAEQLCIArqVAAGMAYLSERKFV-HRDLATR 728
Cdd:cd06618    82 -YFITDS-------DVFICMELMSTCL---DKLLKRIQ----GPIPEDILGKMTVS--IVKALHYLKEKHGViHRDVKPS 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFGLS-RNIYSADYYKADGNDAipirWMPPESI---FYNRYTTESDVWAYGVVLWEIFSyGLQPYYG 804
Cdd:cd06618   145 NILLDESGNVKLCDFGISgRLVDSKAKTRSAGCAA----YMAPERIdppDNPKYDIRADVWSLGISLVELAT-GQFPYRN 219
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1937920432 805 MAHE-EVIYYVRDGNILACP--ENCPLELYNLMRLCWSKLPADRPSF 848
Cdd:cd06618   220 CKTEfEVLTKILNEEPPSLPpnEGFSPDFCSFVDLCLTKDHRYRPKY 266
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
609-819 1.34e-07

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: 53.79  E-value: 1.34e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 609 MLKEEASADMQADFQRE-AALMAEFDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLneflrsmspHTVCSLSHSDLSTRAR 687
Cdd:cd14197    42 MRKRRKGQDCRMEIIHEiAVLELAQANPWVINLHEVYETASEMILVLEYAAGGEI---------FNQCVADREEAFKEKD 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 688 VSSpgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGENMV---VKIADFGLSRNIYSADYYKADGNDAip 764
Cdd:cd14197   113 VKR-------------LMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPlgdIKIVDFGLSRILKNSEELREIMGTP-- 177
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 765 iRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVIYYVRDGNI 819
Cdd:cd14197   178 -EYVAPEILSYEPISTATDMWSIGVLAYVMLT-GISPFLGDDKQETFLNISQMNV 230
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
580-796 1.41e-07

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: 54.28  E-value: 1.41e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRV---FQARApGLlpyepftMVAVKMLKEEASADMQADFQ-REAALMAEFDNPNIVKLLGVCAVGKpmcllfe 655
Cdd:cd07877    25 VGSGAYGSVcaaFDTKT-GL-------RVAVKKLSRPFQSIIHAKRTyRELRLLKHMKHENVIGLLDVFTPAR------- 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 ymaygDLNEFlrsMSPHTVCSLSHSDLSTRARVSSpgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd07877    90 -----SLEEF---NDVYLVTHLMGADLNNIVKCQK-----LTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNED 156
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 736 MVVKIADFGLSRniYSADyykaDGNDAIPIRWMPPESIFYN--RYTTESDVWAYGVVLWEIFS 796
Cdd:cd07877   157 CELKILDFGLAR--HTDD----EMTGYVATRWYRAPEIMLNwmHYNQTVDIWSVGCIMAELLT 213
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
122-208 1.41e-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: 50.02  E-value: 1.41e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 122 KITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALREN----SRIAVLESGsLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG-LLINKVTQDDTGEYTCRAYQVNS 79
                          90
                  ....*....|.
gi 1937920432 198 TAySKLVKLEV 208
Cdd:cd20949    80 IA-SDMQERTV 89
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
135-213 1.50e-07

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: 49.93  E-value: 1.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 135 GLKAVLPCTTMGNPKPSVSWIKGDSALR-ENSRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLGTAYSklvKLEVEVFA 212
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIEsGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEA---EIHLKVFA 94

                  .
gi 1937920432 213 R 213
Cdd:cd05730    95 K 95
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
706-847 1.51e-07

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: 53.78  E-value: 1.51e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIysadyyKADGNDAIPI----RWMPPESIFYNRYTTE 781
Cdd:cd14187   114 RQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKV------EYDGERKKTLcgtpNYIAPEVLSKKGHSFE 187
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 782 SDVWAYGVVLWEIFsYGLQPYYGMAHEEViyYVR-DGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:cd14187   188 VDIWSIGCIMYTLL-VGKPPFETSCLKET--YLRiKKNEYSIPKHINPVAASLIQKMLQTDPTARPT 251
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
42-106 1.67e-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: 49.75  E-value: 1.67e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432  42 EEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd04978    14 GETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
49-117 1.72e-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: 49.77  E-value: 1.72e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432  49 CAVESYPQPEISWTRNKILIKLfDTRYSIRENGQLLtILSVEDSDDGIYCCTANNGVGGAvESCGALQV 117
Cdd:cd04969    24 CKPKASPKPTISWSKGTELLTN-SSRICILPDGSLK-IKNVTKSDEGKYTCFAVNFFGKA-NSTGSLSV 89
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
575-819 1.80e-07

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: 54.24  E-value: 1.80e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARAPGLLPYEPFTMVA-VKMLKEEASADmqadFQREAALMAEFDNPNIVKLLGVCAVGKPMCLL 653
Cdd:cd05622    76 EVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSkFEMIKRSDSAF----FWEERDIMAFANSPWVVQLFYAFQDDRYLYMV 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYGDLneflrsmsphtVCSLSHSDLSTR-ARVSSPgppplscaeqlciarQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd05622   152 MEYMPGGDL-----------VNLMSNYDVPEKwARFYTA---------------EVVLALDAIHSMGFIHRDVKPDNMLL 205
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRNIYSADYYKADGNDAIPiRWMPPESI-------FYNRyttESDVWAYGVVLWEIFsYGLQPYYG- 804
Cdd:cd05622   206 DKSGHLKLADFGTCMKMNKEGMVRCDTAVGTP-DYISPEVLksqggdgYYGR---ECDWWSVGVFLYEML-VGDTPFYAd 280
                         250       260
                  ....*....|....*....|....
gi 1937920432 805 ---------MAHEEVIYYVRDGNI 819
Cdd:cd05622   281 slvgtyskiMNHKNSLTFPDDNDI 304
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
575-792 1.89e-07

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: 53.23  E-value: 1.89e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFG--RVFQARAPGLLpyepftmVAVKMLkeEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd14662     3 ELVKDIGSGNFGvaRLMRNKETKEL-------VAVKYI--ERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAI 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEflrsmsphtvcslshsdlstraRVSSPGppPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14662    74 VMEYAAGGELFE----------------------RICNAG--RFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLL 129
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 733 GENMV--VKIADFGLSRNiySADYYKADGNDAIPIrWMPPESIFYNRYTTE-SDVWAYGVVLW 792
Cdd:cd14662   130 DGSPAprLKICDFGYSKS--SVLHSQPKSTVGTPA-YIAPEVLSRKEYDGKvADVWSCGVTLY 189
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
706-848 1.93e-07

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: 53.05  E-value: 1.93e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLVGENM-VVKIADFGLSRNIYSADYYKADGNDAipirWMPPESIFYNRYTTES-D 783
Cdd:cd14100   113 RQVLEAVRHCHNCGVLHRDIKDENILIDLNTgELKLIDFGSGALLKDTVYTDFDGTRV----YSPPEWIRFHRYHGRSaA 188
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 784 VWAYGVVLWEIFSyGLQPYygmAHEEVIyyVRdGNILACPENCPlELYNLMRLCWSKLPADRPSF 848
Cdd:cd14100   189 VWSLGILLYDMVC-GDIPF---EHDEEI--IR-GQVFFRQRVSS-ECQHLIKWCLALRPSDRPSF 245
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
707-794 2.39e-07

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: 53.73  E-value: 2.39e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSR-------NIYSADYYKAdgndaipirwmPPESIFYNRYT 779
Cdd:cd07856   116 QILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARiqdpqmtGYVSTRYYRA-----------PEIMLTWQKYD 184
                          90
                  ....*....|....*
gi 1937920432 780 TESDVWAYGVVLWEI 794
Cdd:cd07856   185 VEVDIWSAGCIFAEM 199
pk1 PHA03390
serine/threonine-protein kinase 1; Provisional
628-802 2.43e-07

serine/threonine-protein kinase 1; Provisional


Pssm-ID: 223069 [Multi-domain]  Cd Length: 267  Bit Score: 52.94  E-value: 2.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 628 LMAefDNPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstrarvsspgPPPLScaEQLC--IA 705
Cdd:PHA03390   64 LMK--DNPNFIKLYYSVTTLKGHVLIMDYIKDGDLFDLLKK------------------------EGKLS--EAEVkkII 115
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 706 RQVAAGMAYLSERKFVHRDLATRNCLVGENMV-VKIADFGLSRNIYSADYYkaDGNdaipIRWMPPESIFYNRYTTESDV 784
Cdd:PHA03390  116 RQLVEALNDLHKHNIIHNDIKLENVLYDRAKDrIYLCDYGLCKIIGTPSCY--DGT----LDYFSPEKIKGHNYDVSFDW 189
                         170
                  ....*....|....*...
gi 1937920432 785 WAYGVVLWEIFSYGlQPY 802
Cdd:PHA03390  190 WAVGVLTYELLTGK-HPF 206
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
580-794 2.50e-07

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: 53.30  E-value: 2.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVF--QARAPG-LLPYEPFTMVAVKMLKEEASAdmqadfQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEY 656
Cdd:cd05577     1 LGRGGFGEVCacQVKATGkMYACKKLDKKRIKKKKGETMA------LNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTL 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 657 MAYGDLneflrsmsphtvcslshsdlstRARVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENM 736
Cdd:cd05577    75 MNGGDL----------------------KYHIYNVGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHG 132
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 737 VVKIADFGLSRNIYSADYYKAdgnDAIPIRWMPPESIFYNR-YTTESDVWAYGVVLWEI 794
Cdd:cd05577   133 HVRISDLGLAVEFKGGKKIKG---RVGTHGYMAPEVLQKEVaYDFSVDWFALGCMLYEM 188
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
649-792 2.72e-07

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: 53.33  E-value: 2.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 649 PMCLLF--EYMAYGDLNEFLRSMSPHTVCSLShsdlstrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLA 726
Cdd:cd13977   107 ACYLWFvmEFCDGGDMNEYLLSRRPDRQTNTS-------------------------FMLQLSSALAFLHRNQIVHRDLK 161
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 727 TRNCLVGENM---VVKIADFGLSR-------------NIYSADYYKADGNDAipirWMPPEsIFYNRYTTESDVWAYGVV 790
Cdd:cd13977   162 PDNILISHKRgepILKVADFGLSKvcsgsglnpeepaNVNKHFLSSACGSDF----YMAPE-VWEGHYTAKADIFALGII 236

                  ..
gi 1937920432 791 LW 792
Cdd:cd13977   237 IW 238
IgI_1_Contactin-5 cd05848
First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; ...
137-202 2.96e-07

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409435  Cd Length: 96  Bit Score: 49.17  E-value: 2.96e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 137 KAVLPCTTMGNPKPSVSWIKGDSALRENS--RIAVLEsGSLRIHNVQK-EDAGQYRCVAKNSLGTAYSK 202
Cdd:cd05848    21 KVILNCEARGNPVPTYRWLRNGTEIDTESdyRYSLID-GNLIISNPSEvKDSGRYQCLATNSIGSILSR 88
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
218-287 2.98e-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: 49.04  E-value: 2.98e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNavssgSIQENVKDRVIDSRLQ-LFITK-----PGLYTCIATNK 287
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGN-----LIIEFNTRYIVRENGTtLTIRNirrsdMGIYLCIASNG 79
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
568-793 3.19e-07

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: 53.45  E-value: 3.19e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPrNNIEYVRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEasadmqadFQ---------REAALMAEFDNPNIV 638
Cdd:cd07851    12 EVP-DRYQNLSPVGSGAYGQVCSAFDTKTGRK-----VAIKKLSRP--------FQsaihakrtyRELRLLKHMKHENVI 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 639 KLLGVCAVGKP------MCLLFEYMAyGDLNEFLRS--MSPHTVCSLSHsdlstrarvsspgppplscaeqlciarQVAA 710
Cdd:cd07851    78 GLLDVFTPASSledfqdVYLVTHLMG-ADLNNIVKCqkLSDDHIQFLVY---------------------------QILR 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 711 GMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRniySADyykADGNDAIPIRW-MPPESIF-YNRYTTESDVWAYG 788
Cdd:cd07851   130 GLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLAR---HTD---DEMTGYVATRWyRAPEIMLnWMHYNQTVDIWSVG 203

                  ....*
gi 1937920432 789 VVLWE 793
Cdd:cd07851   204 CIMAE 208
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
576-802 3.54e-07

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: 52.69  E-value: 3.54e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 576 YVRDIGEGAFGRVF--QARAPGllpyepfTMVAVKMLKEEASADMQADFQ--REAALMAEFDNPNIVKLLGVCAVGKPMC 651
Cdd:cd05631     4 HYRVLGKGGFGEVCacQVRATG-------KMYACKKLEKKRIKKRKGEAMalNEKRILEKVNSRFVVSLAYAYETKDALC 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSMsphtvcslshsdlstrarvsspGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd05631    77 LVLTIMNGGDLKFHIYNM----------------------GNPGFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENIL 134
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 732 VGENMVVKIADFGLSRNIYSADYYKADGNDaipIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGLQPY 802
Cdd:cd05631   135 LDDRGHIRISDLGLAVQIPEGETVRGRVGT---VGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQ-GQSPF 201
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
215-290 3.97e-07

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: 48.65  E-value: 3.97e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 215 LRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVssgsiQENVKDRVI---DSRLQLFITK-----PGLYTCIATN 286
Cdd:cd05744     4 LQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPV-----RPDSAHKMLvreNGRHSLIIEPvtkrdAGIYTCIARN 78

                  ....
gi 1937920432 287 KHGE 290
Cdd:cd05744    79 RAGE 82
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
214-293 4.36e-07

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 48.16  E-value: 4.36e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 214 ILRAPESHnVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQenvkdrvidSRLQLFITKPGLYTCIATNKHGEKFS 293
Cdd:pfam13895   3 VLTPSPTV-VTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNF---------FTLSVSAEDSGTYTCVARNGRGGKVS 72
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
573-813 4.38e-07

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 53.06  E-value: 4.38e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGllpyEPFTMVAVKML-KEEASADMQADFQ-REAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:PTZ00426   31 DFNFIRTLGTGSFGRVILATYKN----EDFPPVAIKRFeKSKIIKQKQVDHVfSERKILNYINHPFCVNLYGSFKDESYL 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSmsphtvcslshsdlstrarvSSPGPPPLSCAeqlcIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:PTZ00426  107 YLVLEFVIGGEFFTFLRR--------------------NKRFPNDVGCF----YAAQIVLIFEYLQSLNIVYRDLKPENL 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSADYYKADGNDaipirWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYgmAHEEV 810
Cdd:PTZ00426  163 LLDKDGFIKMTDFGFAKVVDTRTYTLCGTPE-----YIAPEILLNVGHGKAADWWTLGIFIYEIL-VGCPPFY--ANEPL 234

                  ...
gi 1937920432 811 IYY 813
Cdd:PTZ00426  235 LIY 237
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
650-847 4.79e-07

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 53.33  E-value: 4.79e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 650 MCLLFEYMAYGDLNEFLRSmsphtvcslshsdlstRARVSSPgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:PTZ00283  114 IALVLDYANAGDLRQEIKS----------------RAKTNRT----FREHEAGLLFIQVLLAVHHVHSKHMIHRDIKSAN 173
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRnIYSADYYKADGND--AIPIrWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGlQPYYGMAH 807
Cdd:PTZ00283  174 ILLCSNGLVKLGDFGFSK-MYAATVSDDVGRTfcGTPY-YVAPEIWRRKPYSKKADMFSLGVLLYELLTLK-RPFDGENM 250
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1937920432 808 EEVIYYVRDGNILACPENCPLELYNLMRLCWSKLPADRPS 847
Cdd:PTZ00283  251 EEVMHKTLAGRYDPLPPSISPEMQEIVTALLSSDPKRRPS 290
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
577-845 4.82e-07

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: 52.62  E-value: 4.82e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARAPGLLPYepftmVAVK-MLKEEASAD---MQADFQREaaLMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd05574     6 IKLLGKGDVGRVYLVRLKGTGKL-----FAMKvLDKEEMIKRnkvKRVLTERE--ILATLDHPFLPTLYASFQTSTHLCF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRsMSPHTVCSLSHsdlstrARVsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd05574    79 VMDYCPGGELFRLLQ-KQPGKRLPEEV------ARF---------------YAAEVLLALEYLHLLGFVYRDLKPENILL 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GENMVVKIADFGLSRN--------IYSADYYKADGNDAIPIR-------------------WMPPESIFYNRYTTESDVW 785
Cdd:cd05574   137 HESGHIMLTDFDLSKQssvtpppvRKSLRKGSRRSSVKSIEKetfvaepsarsnsfvgteeYIAPEVIKGDGHGSAVDWW 216
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 786 AYGVVLWEIFsYGLQPYYGMAHEEVIYyvrdgNILA----CPENCPL--ELYNLMRLCWSKLPADR 845
Cdd:cd05574   217 TLGILLYEML-YGTTPFKGSNRDETFS-----NILKkeltFPESPPVssEAKDLIRKLLVKDPSKR 276
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
121-202 4.95e-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: 48.28  E-value: 4.95e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKItRPPINVKIIEGLKAVLPC-TTMGNPKPSVSWIKGDSALR----ENSRIAVLESGS-LRIHNVQKEDAGQYRCVAKN 194
Cdd:cd05750     1 PKL-KEMKSQTVQEGSKLVLKCeATSENPSPRYRWFKDGKELNrkrpKNIKIRNKKKNSeLQINKAKLEDSGEYTCVVEN 79

                  ....*...
gi 1937920432 195 SLGTAYSK 202
Cdd:cd05750    80 ILGKDTVT 87
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
571-858 5.06e-07

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: 52.29  E-value: 5.06e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 571 RNNIEYVRDIGEGAFGRVFQARAPgllpyePFTMVAVkmLKEEASADMQA--DFQREAALMAEF-DNPNIVKLLGVCAVG 647
Cdd:cd14037     2 SHHVTIEKYLAEGGFAHVYLVKTS------NGGNRAA--LKRVYVNDEHDlnVCKREIEIMKRLsGHKNIVGYIDSSANR 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 648 KP-----MCLLFEYMAYGDLNEFlrsMSPHtvcslshsdLSTRarvsspgpppLSCAEQLCIARQVAAGMAYLSERK--F 720
Cdd:cd14037    74 SGngvyeVLLLMEYCKGGGVIDL---MNQR---------LQTG----------LTESEILKIFCDVCEAVAAMHYLKppL 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 721 VHRDLATRNCLVGENMVVKIADFG-------LSRNIYSADYYKADGNDAIPIRWMPPESI-FYNR--YTTESDVWAYGVV 790
Cdd:cd14037   132 IHRDLKVENVLISDSGNYKLCDFGsattkilPPQTKQGVTYVEEDIKKYTTLQYRAPEMIdLYRGkpITEKSDIWALGCL 211
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 791 LWEIFsyglqpYYGMAHEEV-IYYVRDGNiLACPENCPL--ELYNLMRLCWSKLPADRPSFCSIHRILQRM 858
Cdd:cd14037   212 LYKLC------FYTTPFEESgQLAILNGN-FTFPDNSRYskRLHKLIRYMLEEDPEKRPNIYQVSYEAFEL 275
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
568-802 5.23e-07

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: 52.37  E-value: 5.23e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 568 EYPRNNIEYVRDIGEGAFGRVFQARAPgllpyEPFTMVAVKMLKEEASADMQADFQREA-ALMAEFDNPNIVKLLG---- 642
Cdd:cd06616     2 EFTAEDLKDLGEIGRGAFGTVNKMLHK-----PSGTIMAVKRIRSTVDEKEQKRLLMDLdVVMRSSDCPYIVKFYGalfr 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 643 --VCAvgkpMCLlfEYMA------YGDLNEFLRSMSPHTVcsLSHSDLSTrarvsspgppplscaeqlciarqVAAgMAY 714
Cdd:cd06616    77 egDCW----ICM--ELMDisldkfYKYVYEVLDSVIPEEI--LGKIAVAT-----------------------VKA-LNY 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 715 LSER-KFVHRDLATRNCLVGENMVVKIADFGLSRNIYSAdyyKADGNDAIPIRWMPPESIFYNR----YTTESDVWAYGV 789
Cdd:cd06616   125 LKEElKIIHRDVKPSNILLDRNGNIKLCDFGISGQLVDS---IAKTRDAGCRPYMAPERIDPSAsrdgYDVRSDVWSLGI 201
                         250
                  ....*....|...
gi 1937920432 790 VLWEIfSYGLQPY 802
Cdd:cd06616   202 TLYEV-ATGKFPY 213
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
580-802 5.34e-07

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: 51.96  E-value: 5.34e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQA--RAPGllpyepfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCLLFEYM 657
Cdd:cd14184     9 IGDGNFAVVKECveRSTG-------KEFALKIIDKAKCCGKEHLIENEVSILRRVKHPNIIMLIEEMDTPAELYLVMELV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 658 AYGDLNEFLRSMSPHTvcslsHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLVGE--- 734
Cdd:cd14184    82 KGGDLFDAITSSTKYT-----ERDASA-------------------MVYNLASALKYLHGLCIVHRDIKPENLLVCEypd 137
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 735 -NMVVKIADFGLSrNIYSADYYKADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPY 802
Cdd:cd14184   138 gTKSLKLGDFGLA-TVVEGPLYTVCGTPT----YVAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPF 200
STKc_LATS cd05598
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the ...
575-837 5.93e-07

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: 52.32  E-value: 5.93e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQARApgllpYEPFTMVAVKML-KEEASADMQ-ADFQREAALMAEFDNPNIVKLLgvCAVGKPMCL 652
Cdd:cd05598     4 EKIKTIGVGAFGEVSLVRK-----KDTNALYAMKTLrKKDVLKRNQvAHVKAERDILAEADNEWVVKLY--YSFQDKENL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LF--EYMAYGDLneflrsMSphtvcslshsdLSTRARVSspgPPPLScaeQLCIARQVAAgMAYLSERKFVHRDLATRNC 730
Cdd:cd05598    77 YFvmDYIPGGDL------MS-----------LLIKKGIF---EEDLA---RFYIAELVCA-IESVHKMGFIHRDIKPDNI 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 731 LVGENMVVKIADFGLS---RNIYSADYYKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPYYGMAH 807
Cdd:cd05598   133 LIDRDGHIKLTDFGLCtgfRWTHDSKYYLAHSLVGTP-NYIAPEVLLRTGYTQLCDWWSVGVILYEML-VGQPPFLAQTP 210
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1937920432 808 EE----VIYYVRDGNILACPENCPLELYNLMRLC 837
Cdd:cd05598   211 AEtqlkVINWRTTLKIPHEANLSPEAKDLILRLC 244
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
705-811 6.07e-07

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: 52.22  E-value: 6.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 705 ARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSR-NIYSA----------DYykadgndaipirwMPPESI 773
Cdd:cd05570   102 AAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKeGIWGGnttstfcgtpDY-------------IAPEIL 168
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1937920432 774 FYNRYTTESDVWAYGVVLWEIFSyGLQPYYGMAHEEVI 811
Cdd:cd05570   169 REQDYGFSVDWWALGVLLYEMLA-GQSPFEGDDEDELF 205
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
701-796 6.32e-07

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 51.96  E-value: 6.32e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 701 QLC-IARQVAAGMAYLSER----------KFVHRDLATRNCLVGENMVVKIADFGLSRNiYSADYYKADGNDAIPI-RWM 768
Cdd:cd14141    93 ELChIAQTMARGLAYLHEDipglkdghkpAIAHRDIKSKNVLLKNNLTACIADFGLALK-FEAGKSAGDTHGQVGTrRYM 171
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1937920432 769 PPESI-----FYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd14141   172 APEVLegainFQRDAFLRIDMYAMGLVLWELAS 204
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
124-199 6.48e-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: 48.21  E-value: 6.48e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 124 TRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENS--RIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTA 199
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPedMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
28-106 6.76e-07

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 48.03  E-value: 6.76e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILI--KLFDtRYSIRENGQLLTILSVEDSDDGIYCCTANNGV 105
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDInpKLSK-QLTLIANGSELHISNVRYEDTGAYTCIAKNEG 79

                  .
gi 1937920432 106 G 106
Cdd:cd05736    80 G 80
IgI_Lingo-1 cd20969
Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing ...
134-208 6.84e-07

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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: 409561  Cd Length: 92  Bit Score: 48.15  E-value: 6.84e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 134 EGLKAVLPCTTMGNPKPSVSWI---KGDSALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAySKLVKLEV 208
Cdd:cd20969    16 EGHTVQFVCRADGDPPPAILWLsprKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGND-SMPAHLHV 92
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
577-851 7.40e-07

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: 51.53  E-value: 7.40e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQARapGLLPYEPFTMVAVKMlkeeASADMQADFQREAALMAEFDNPNIVKLLGVCAV-----GKPMC 651
Cdd:cd13986     5 QRLLGEGGFSFVYLVE--DLSTGRLYALKKILC----HSKEDVKEAMREIENYRLFNHPNILRLLDSQIVkeaggKKEVY 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 652 LLFEYMAYGDLNEFLRSMSPHTVcslshsdlstrarvsspgppPLSCAEQLCIARQVAAGMAYLSE---RKFVHRDLATR 728
Cdd:cd13986    79 LLLPYYKRGSLQDEIERRLVKGT--------------------FFPEDRILHIFLGICRGLKAMHEpelVPYAHRDIKPG 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 729 NCLVGENMVVKIADFG-------LSRNIYSADYYKADGNDAIPIRWMPPE--SIFYNRYTTE-SDVWAYGVVLWEIFsYG 798
Cdd:cd13986   139 NVLLSEDDEPILMDLGsmnpariEIEGRREALALQDWAAEHCTMPYRAPElfDVKSHCTIDEkTDIWSLGCTLYALM-YG 217
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 799 LQPyYGMAHEE---VIYYVRDGNIlACPENC--PLELYNLMRLCWSKLPADRPSFCSI 851
Cdd:cd13986   218 ESP-FERIFQKgdsLALAVLSGNY-SFPDNSrySEELHQLVKSMLVVNPAERPSIDDL 273
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
578-796 8.48e-07

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: 51.42  E-value: 8.48e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 578 RDIGEGAFGRVF--QARAPGllpyepfTMVAVKMLKEEASADMQAdFQR---EAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd05608     7 RVLGKGGFGEVSacQMRATG-------KLYACKKLNKKRLKKRKG-YEGamvEKRILAKVHSRFIVSLAYAFQTKTDLCL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSPhtvcslshsdlstrarvSSPG-PPPLSCAeqlcIARQVAAGMAYLSERKFVHRDLATRNCL 731
Cdd:cd05608    79 VMTIMNGGDLRYHIYNVDE-----------------ENPGfQEPRACF----YTAQIISGLEHLHQRRIIYRDLKPENVL 137
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 732 VGENMVVKIADFGLSRNIySADYYKADGNDAIPiRWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd05608   138 LDDDGNVRISDLGLAVEL-KDGQTKTKGYAGTP-GFMAPELLLGEEYDYSVDYFTLGVTLYEMIA 200
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
214-301 8.76e-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: 47.80  E-value: 8.76e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 214 ILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSI--------QENVKDRVIDsrlQLFITKPGLYTCIAT 285
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkykiesEYGVHVLHIR---RVTVEDSAVYSAVAK 79
                          90
                  ....*....|....*.
gi 1937920432 286 NKHGEkfstAKAAATV 301
Cdd:cd20951    80 NIHGE----ASSSASV 91
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
606-807 9.91e-07

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: 51.13  E-value: 9.91e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 606 AVKMLKEEASADMQADFQREAAlmaefDNPNIVKLLGVCA--VGKPMCLL--FEYMAYGDLNEflrsmsphtvcslshsd 681
Cdd:cd14089    30 ALKVLRDNPKARREVELHWRAS-----GCPHIVRIIDVYEntYQGRKCLLvvMECMEGGELFS----------------- 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 682 lstraRVSSPGPPPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV---GENMVVKIADFGLSRNIYSAD----- 753
Cdd:cd14089    88 -----RIQERADSAFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYsskGPNAILKLTDFGFAKETTTKKslqtp 162
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 754 ----YYkadgndaipirwMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYYGMAH 807
Cdd:cd14089   163 cytpYY------------VAPEVLGPEKYDKSCDMWSLGVIMY-ILLCGYPPFYSNHG 207
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
580-792 1.01e-06

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: 50.87  E-value: 1.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARapgllpyEPFT--MVAVKMLKEEASADMQAD--FQrEAALMAEFDNPNIVKLLGVCAVGKPMCLLFE 655
Cdd:cd14074    11 LGRGHFAVVKLAR-------HVFTgeKVAVKVIDKTKLDDVSKAhlFQ-EVRCMKLVQHPNVVRLYEVIDTQTKLYLILE 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 656 YMAYGDLNEFLRSmspHTvCSLSHSdlstRARvsspgppplscaeqlCIARQVAAGMAYLSERKFVHRDLATRNCLVGEN 735
Cdd:cd14074    83 LGDGGDMYDYIMK---HE-NGLNED----LAR---------------KYFRQIVSAISYCHKLHVVHRDLKPENVVFFEK 139
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 736 M-VVKIADFGLSRNIYSADYYK-ADGNDAipirWMPPESIFYNRYTTES-DVWAYGVVLW 792
Cdd:cd14074   140 QgLVKLTDFGFSNKFQPGEKLEtSCGSLA----YSAPEILLGDEYDAPAvDIWSLGVILY 195
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
119-198 1.06e-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: 47.60  E-value: 1.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 119 MKPKITRPpinvkiiEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESG----SLRIHNVQKEDAGQYRCVAKN 194
Cdd:cd05729    10 EEREHALP-------AANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEekgwSLIIERAIPRDKGKYTCIVEN 82

                  ....
gi 1937920432 195 SLGT 198
Cdd:cd05729    83 EYGS 86
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
695-794 1.11e-06

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 51.29  E-value: 1.11e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 695 PLSCAEQLCIARQVAAGMAYLSERKF--------VHRDLATRNCLVGENMVVKIADFGLS-RNIYSADYYKADGNDAIPI 765
Cdd:cd14142    98 TLDHQEMLRLALSAASGLVHLHTEIFgtqgkpaiAHRDLKSKNILVKSNGQCCIADLGLAvTHSQETNQLDVGNNPRVGT 177
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1937920432 766 -RWMPP----ESIFYNRYTT--ESDVWAYGVVLWEI 794
Cdd:cd14142   178 kRYMAPevldETINTDCFESykRVDIYAFGLVLWEV 213
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
707-796 1.22e-06

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: 51.49  E-value: 1.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSadyykaDGNDAIPIRWM-PPESIF-YNRYTTESDV 784
Cdd:cd07880   126 QMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQTDS------EMTGYVVTRWYrAPEVILnWMHYTQTVDI 199
                          90
                  ....*....|..
gi 1937920432 785 WAYGVVLWEIFS 796
Cdd:cd07880   200 WSVGCIMAEMLT 211
IgI_NCAM-1 cd05869
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members ...
120-197 1.28e-06

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(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. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 143277 [Multi-domain]  Cd Length: 97  Bit Score: 47.28  E-value: 1.28e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 120 KPKITrppinvkIIEGLKAV-------LPCTTMGNPKPSVSW-------------IKGDSALRENSRIAvlesgSLRIHN 179
Cdd:cd05869     2 KPKIT-------YVENQTAMeleeqitLTCEASGDPIPSITWrtstrnisseektLDGHIVVRSHARVS-----SLTLKY 69
                          90
                  ....*....|....*...
gi 1937920432 180 VQKEDAGQYRCVAKNSLG 197
Cdd:cd05869    70 IQYTDAGEYLCTASNTIG 87
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
575-803 1.30e-06

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: 51.20  E-value: 1.30e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 575 EYVRDIGEGAFGRVFQA--RAPGllpyepfTMVAVKMLKEEASADMQADFQREAALMAEFDNPNIVKLLGVCAVGKPMCL 652
Cdd:cd14168    13 EFKEVLGTGAFSEVVLAeeRATG-------KLFAVKCIPKKALKGKESSIENEIAVLRKIKHENIVALEDIYESPNHLYL 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 653 LFEYMAYGDLNEFLRSMSPHTvcslsHSDLSTrarvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd14168    86 VMQLVSGGELFDRIVEKGFYT-----EKDAST-------------------LIRQVLDAVYYLHRMGIVHRDLKPENLLY 141
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 733 ---GENMVVKIADFGLSRNIYSADYYK-ADGNDAipirWMPPESIFYNRYTTESDVWAYGVVLWeIFSYGLQPYY 803
Cdd:cd14168   142 fsqDEESKIMISDFGLSKMEGKGDVMStACGTPG----YVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFY 211
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
573-813 1.45e-06

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: 50.87  E-value: 1.45e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 573 NIEYVRDIGEGAFGRVFQARAPGLLPYepftmVAVKMLKEEASADMQ--ADFQREAALMAEFDNPNIVKLLGVCAVGKPM 650
Cdd:cd14209     2 DFDRIKTLGTGSFGRVMLVRHKETGNY-----YAMKILDKQKVVKLKqvEHTLNEKRILQAINFPFLVKLEYSFKDNSNL 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMsphtvcslshsdlstrARVSSPgppplscaeQLCI-ARQVAAGMAYLSERKFVHRDLATRN 729
Cdd:cd14209    77 YMVMEYVPGGEMFSHLRRI----------------GRFSEP---------HARFyAAQIVLAFEYLHSLDLIYRDLKPEN 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 730 CLVGENMVVKIADFGLSRNIysadyykaDGND----AIPiRWMPPESIFYNRYTTESDVWAYGVVLWEiFSYGLQPYYgm 805
Cdd:cd14209   132 LLIDQQGYIKVTDFGFAKRV--------KGRTwtlcGTP-EYLAPEIILSKGYNKAVDWWALGVLIYE-MAAGYPPFF-- 199

                  ....*...
gi 1937920432 806 AHEEVIYY 813
Cdd:cd14209   200 ADQPIQIY 207
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
27-106 1.69e-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: 46.86  E-value: 1.69e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  27 APVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
707-794 1.88e-06

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: 50.94  E-value: 1.88e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKADGNDAIPIRWM-PPE--SIFYNRYTTESD 783
Cdd:cd07859   111 QLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVAFNDTPTAIFWTDYVATRWYrAPElcGSFFSKYTPAID 190
                          90
                  ....*....|.
gi 1937920432 784 VWAYGVVLWEI 794
Cdd:cd07859   191 IWSIGCIFAEV 201
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
577-795 1.88e-06

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: 50.82  E-value: 1.88e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 577 VRDIGEGAFGRVFQArapgllpYEPFTM--VAVKMLKEEASADMQADFQ-REAALMAEFDNPNIVKLLGVcavgkpmcll 653
Cdd:cd07878    20 LTPVGSGAYGSVCSA-------YDTRLRqkVAVKKLSRPFQSLIHARRTyRELRLLKHMKHENVIGLLDV---------- 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 654 FEYMAYG-DLNEFlrsmspHTVCSLSHSDLSTRARVSSpgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLV 732
Cdd:cd07878    83 FTPATSIeNFNEV------YLVTNLMGADLNNIVKCQK-----LSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAV 151
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 733 GENMVVKIADFGLSRNiysADyykADGNDAIPIRWMPPESIFYN--RYTTESDVWAYGVVLWEIF 795
Cdd:cd07878   152 NEDCELRILDFGLARQ---AD---DEMTGYVATRWYRAPEIMLNwmHYNQTVDIWSVGCIMAELL 210
STKc_PINK1 cd14018
Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze ...
707-847 1.95e-06

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: 50.57  E-value: 1.95e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLV----GENMVVKIADFGLS--------RNIYSADYYKADGNDAIpirwMPPE--- 771
Cdd:cd14018   146 QLLEGVDHLVRHGIAHRDLKSDNILLeldfDGCPWLVIADFGCCladdsiglQLPFSSWYVDRGGNACL----MAPEvst 221
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 772 -------SIFYNRytteSDVWAYGVVLWEIFSYGlQPYYGM--AHEEVIYYvRDGNILACPENCPLELYNLMRLCWSKLP 842
Cdd:cd14018   222 avpgpgvVINYSK----ADAWAVGAIAYEIFGLS-NPFYGLgdTMLESRSY-QESQLPALPSAVPPDVRQVVKDLLQRDP 295

                  ....*
gi 1937920432 843 ADRPS 847
Cdd:cd14018   296 NKRVS 300
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
45-112 1.96e-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: 46.80  E-value: 1.96e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432  45 ATFMCAVESYPQPEISWTRNKILIKLfDTRYSIRENGQLLTILSVED---SDDGIYCCTANNGVGGAVESC 112
Cdd:cd20973    15 ARFDCKVEGYPDPEVKWMKDDNPIVE-SRRFQIDQDEDGLCSLIISDvcgDDSGKYTCKAVNSLGEATCSA 84
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
707-796 2.06e-06

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: 50.67  E-value: 2.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 707 QVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRniySADyykADGNDAIPIRWM-PPESIF-YNRYTTESDV 784
Cdd:cd07879   125 QMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGLAR---HAD---AEMTGYVVTRWYrAPEVILnWMHYNQTVDI 198
                          90
                  ....*....|..
gi 1937920432 785 WAYGVVLWEIFS 796
Cdd:cd07879   199 WSVGCIMAEMLT 210
Ig3_L1-CAM_like cd05731
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar ...
36-108 2.18e-06

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.


Pssm-ID: 409394 [Multi-domain]  Cd Length: 83  Bit Score: 46.25  E-value: 2.18e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432  36 TVDALVEEVATFMCAVESYPQPEISWtrNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGA 108
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRW--IKLGGELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSA 74
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
215-296 2.31e-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: 46.44  E-value: 2.31e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 215 LRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRVIDSRLQLfiTKPGLYTCIATNKHGEKFST 294
Cdd:cd05728     3 LKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSL--SDSGMYQCVAENKHGTIYAS 80

                  ..
gi 1937920432 295 AK 296
Cdd:cd05728    81 AE 82
Ig3_L1-CAM cd05876
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here ...
39-108 2.32e-06

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. 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. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409460 [Multi-domain]  Cd Length: 83  Bit Score: 46.44  E-value: 2.32e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  39 ALVEEVATFMCAVESYPQPEISWTRnkILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVGGA 108
Cdd:cd05876     7 ALRGQSLVLECIAEGLPTPTVKWLR--PSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSA 74
IgI_NCAM-1_like cd05732
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar ...
28-111 2.48e-06

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 409395 [Multi-domain]  Cd Length: 96  Bit Score: 46.75  E-value: 2.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTpLETVDALVEEVATFMCAVESYPQPEISWTRNKILI----KLFDTRYSIRENGQL--LTILSVEDSDDGIYCCTA 101
Cdd:cd05732     3 PKITY-LENQTAVELEQITLTCEAEGDPIPEITWRRATRGIsfeeGDLDGRIVVRGHARVssLTLKDVQLTDAGRYDCEA 81
                          90
                  ....*....|
gi 1937920432 102 NNGVGGAVES 111
Cdd:cd05732    82 SNRIGGDQQS 91
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
580-796 2.51e-06

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: 50.08  E-value: 2.51e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFqarapglLPYEPFT--MVAVKMLK-----EEASADMQAdFQREAALMAEFDNPNIVKLLGVCA--VGKPM 650
Cdd:cd06651    15 LGQGAFGRVY-------LCYDVDTgrELAAKQVQfdpesPETSKEVSA-LECEIQLLKNLQHERIVQYYGCLRdrAEKTL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 651 CLLFEYMAYGDLNEFLRSMSPHTvcslshsDLSTRArvsspgppplscaeqlcIARQVAAGMAYLSERKFVHRDLATRNC 730
Cdd:cd06651    87 TIFMEYMPGGSVKDQLKAYGALT-------ESVTRK-----------------YTRQILEGMSYLHSNMIVHRDIKGANI 142
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 731 LVGENMVVKIADFGLSRNIYSAdYYKADGNDAI--PIRWMPPESIFYNRYTTESDVWAYGVVLWEIFS 796
Cdd:cd06651   143 LRDSAGNVKLGDFGASKRLQTI-CMSGTGIRSVtgTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLT 209
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
625-794 2.75e-06

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 50.76  E-value: 2.75e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 625 EAALMAEFDNPNIVKLLGVCAVGKPMCLLFeymaygdlneflrsmsPHTVCSLsHSDLSTRARvsspgpppLSCAEQLCI 704
Cdd:PHA03212  133 EAHILRAINHPSIIQLKGTFTYNKFTCLIL----------------PRYKTDL-YCYLAAKRN--------IAICDILAI 187
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 705 ARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLS---RNIYSADYYKADGNdaipIRWMPPESIFYNRYTTE 781
Cdd:PHA03212  188 ERSVLRAIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGAAcfpVDINANKYYGWAGT----IATNAPELLARDPYGPA 263
                         170
                  ....*....|...
gi 1937920432 782 SDVWAYGVVLWEI 794
Cdd:PHA03212  264 VDIWSAGIVLFEM 276
IgI_3_RPTP_IIa_LAR_like cd05739
Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F ...
124-198 3.14e-06

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).


Pssm-ID: 409401  Cd Length: 82  Bit Score: 46.05  E-value: 3.14e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 124 TRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLESGsLRIHNVQkeDAGQYRCVAKNSLGT 198
Cdd:cd05739     1 SIPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRNV-LELTNIY--ESANYTCVAISSLGM 72
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
580-814 3.21e-06

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: 50.18  E-value: 3.21e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPgllpyEPFTMVAVKM---LKEEASADMQadfQREAALMAEFDNPNIVKLLGV--CAVGKPMCLLF 654
Cdd:cd13988     1 LGQGATANVFRGRHK-----KTGDLYAVKVfnnLSFMRPLDVQ---MREFEVLKKLNHKNIVKLFAIeeELTTRHKVLVM 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EYMAYGDLNEFLRSmsPHTVCSLSHSDLstrarvsspgppplscaeqLCIARQVAAGMAYLSERKFVHRDLATRNCL--V 732
Cdd:cd13988    73 ELCPCGSLYTVLEE--PSNAYGLPESEF-------------------LIVLRDVVAGMNHLRENGIVHRDIKPGNIMrvI 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 733 GEN--MVVKIADFGLSRNIYSADYYKA-DGNDaipiRWMPPEsiFYNR----------YTTESDVWAYGVVLWEIFSYGL 799
Cdd:cd13988   132 GEDgqSVYKLTDFGAARELEDDEQFVSlYGTE----EYLHPD--MYERavlrkdhqkkYGATVDLWSIGVTFYHAATGSL 205
                         250
                  ....*....|....*...
gi 1937920432 800 --QPY-YGMAHEEVIYYV 814
Cdd:cd13988   206 pfRPFeGPRRNKEVMYKI 223
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
36-110 3.41e-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: 46.17  E-value: 3.41e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  36 TVDALVEEV-----ATFMCAVESYPQPEISWTRNKILIKL---FDTRYSIRENGqlLTILSVEDSDDGIYCCTANNGVGG 107
Cdd:cd20949     3 TENAYVTTVkegqsATILCEVKGEPQPNVTWHFNGQPISAsvaDMSKYRILADG--LLINKVTQDDTGEYTCRAYQVNSI 80

                  ...
gi 1937920432 108 AVE 110
Cdd:cd20949    81 ASD 83
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
122-197 3.91e-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: 45.81  E-value: 3.91e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 122 KITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDSALRENSRIAVLES---GSLRIHNVQKEDAGQYRCVAKNSLG 197
Cdd:cd05747     5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTeykSTFEISKVQMSDEGNYTVVVENSEG 83
IgI_1_Contactin cd04967
First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; ...
121-202 4.27e-06

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409356 [Multi-domain]  Cd Length: 96  Bit Score: 46.08  E-value: 4.27e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGL---KAVLPCTTMGNPKPSVSWIK--GDSALRENSRIAVLeSGSLRIHN-VQKEDAGQYRCVAKN 194
Cdd:cd04967     2 PVFEEQPDDTIFPEDSdekKVALNCRARANPVPSYRWLMngTEIDLESDYRYSLV-DGTLVISNpSKAKDAGHYQCLATN 80

                  ....*...
gi 1937920432 195 SLGTAYSK 202
Cdd:cd04967    81 TVGSVLSR 88
STKc_HIPK3 cd14229
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; ...
580-814 4.34e-06

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: 49.64  E-value: 4.34e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 580 IGEGAFGRVFQARAPGllpyePFTMVAVKMLKEEASADMQAdfQREAALMAEFDNPN-----IVKLLGVCAVGKPMCLLF 654
Cdd:cd14229     8 LGRGTFGQVVKCWKRG-----TNEIVAVKILKNHPSYARQG--QIEVGILARLSNENadefnFVRAYECFQHRNHTCLVF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 655 EyMAYGDLNEFLRSmsphtvcslshsdlstrarvSSPGPPPLSCAEQlcIARQVAAGMAYLSERKFVHRDLATRNCL--- 731
Cdd:cd14229    81 E-MLEQNLYDFLKQ--------------------NKFSPLPLKVIRP--ILQQVATALKKLKSLGLIHADLKPENIMlvd 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 732 -VGENMVVKIADFG----LSRNIYS----ADYYKAdgndaipirwmpPESIFYNRYTTESDVWAYGVVLWEIFsYGLQPY 802
Cdd:cd14229   138 pVRQPYRVKVIDFGsashVSKTVCStylqSRYYRA------------PEIILGLPFCEAIDMWSLGCVIAELF-LGWPLY 204
                         250
                  ....*....|..
gi 1937920432 803 YGMAHEEVIYYV 814
Cdd:cd14229   205 PGALEYDQIRYI 216
IgI_1_Neogenin_like cd05722
First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of ...
34-111 5.05e-06

First 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 first 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: 409387  Cd Length: 97  Bit Score: 45.93  E-value: 5.05e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  34 LETVDALVEEVATFM--CAVESYPQPEISWTRNKILIKL-FDTRYSIRENGQLLtILSVEDS-----DDGIYCCTANNGV 105
Cdd:cd05722     6 SEPSDIVAMRGGPVVlnCSAESDPPPKIEWKKDGVLLNLvSDERRQQLPNGSLL-ITSVVHSkhnkpDEGFYQCVAQNES 84

                  ....*.
gi 1937920432 106 GGAVES 111
Cdd:cd05722    85 LGSIVS 90
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
121-197 5.24e-06

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 45.62  E-value: 5.24e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 121 PKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKgDSALREN---------SRIAVLESGSLRIHNVQKEDAGQYRCV 191
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEK-QVPGKENlimrpnhvrGNVVVTNIGQLVIYNAQPQDAGLYTCT 79

                  ....*.
gi 1937920432 192 AKNSLG 197
Cdd:cd05765    80 ARNSGG 85
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
704-809 5.48e-06

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: 48.87  E-value: 5.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 704 IARQVAAGMAYLSERKFVHRDLATRNCLVG---ENMVVKIADFGLSRnIYSADYYKADGNDaipiRWMPPESIFYNRYTT 780
Cdd:cd14088   104 VIRQVLEAVAYLHSLKIVHRNLKLENLVYYnrlKNSKIVISDFHLAK-LENGLIKEPCGTP----EYLAPEVVGRQRYGR 178
                          90       100
                  ....*....|....*....|....*....
gi 1937920432 781 ESDVWAYGVVLWEIFSyGLQPYYGMAHEE 809
Cdd:cd14088   179 PVDCWAIGVIMYILLS-GNPPFYDEAEED 206
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
30-118 6.21e-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: 45.72  E-value: 6.21e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  30 ITTPLETVDALVEEVaTFMCAVESYPQPEISWTRNKILIKLF-------DTRYSIRENGQlLTILSVEDSDDGIYCCTAN 102
Cdd:cd05726     3 VVKPRDQVVALGRTV-TFQCETKGNPQPAIFWQKEGSQNLLFpyqppqpSSRFSVSPTGD-LTITNVQRSDVGYYICQAL 80
                          90
                  ....*....|....*.
gi 1937920432 103 NgVGGAVESCGALQVK 118
Cdd:cd05726    81 N-VAGSILAKAQLEVT 95
PHA03207 PHA03207
serine/threonine kinase US3; Provisional
664-794 6.37e-06

serine/threonine kinase US3; Provisional


Pssm-ID: 165473 [Multi-domain]  Cd Length: 392  Bit Score: 49.46  E-value: 6.37e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 664 EFLRSMSPHTVCSLSHS----------------DLSTRARVSSPgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLAT 727
Cdd:PHA03207  138 DILKTISHRAIINLIHAyrwkstvcmvmpkykcDLFTYVDRSGP----LPLEQAITIQRRLLEALAYLHGRGIIHRDVKT 213
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 728 RNCLVGENMVVKIADFG----LSRNIYSADYYKADGNdaipIRWMPPESIFYNRYTTESDVWAYGVVLWEI 794
Cdd:PHA03207  214 ENIFLDEPENAVLGDFGaackLDAHPDTPQCYGWSGT----LETNSPELLALDPYCAKTDIWSAGLVLFEM 280
IgI_SALM5_like cd05764
Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; ...
226-295 7.42e-06

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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: 409421 [Multi-domain]  Cd Length: 88  Bit Score: 45.16  E-value: 7.42e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432 226 GSFVTLRCTAIGMPVPTISWIE-NGNAVSSGSiqenvKDRVIDS-RLQLFIT---KPGLYTCIATNKHGEkfSTA 295
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWISpEGKLISNSS-----RTLVYDNgTLDILITtvkDTGAFTCIASNPAGE--ATA 82
IgI_2_FGFRL1-like cd05856
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1 ...
118-197 7.47e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); 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 like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. 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: 409442  Cd Length: 92  Bit Score: 45.24  E-value: 7.47e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 118 KMKPKITRPPINVKIieglkaVLPCTTMGNPKPSVSWIKGDSAL-----RENSRiavlESGSLRIHNVQKEDAGQYRCVA 192
Cdd:cd05856     8 KMRRRVIARPVGSSV------RLKCVASGNPRPDITWLKDNKPLtppeiGENKK----KKWTLSLKNLKPEDSGKYTCHV 77

                  ....*
gi 1937920432 193 KNSLG 197
Cdd:cd05856    78 SNRAG 82
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
213-295 9.70e-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: 44.75  E-value: 9.70e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 213 RILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSiqENVKDRVIDSRLQLFITKP---GLYTCIATNKHG 289
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAP--EDMRRTVDGRTLIFSNLQPndtAVYQCNASNVHG 78

                  ....*.
gi 1937920432 290 EKFSTA 295
Cdd:cd04978    79 YLLANA 84
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
226-290 1.01e-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: 44.92  E-value: 1.01e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 226 GSFVTLRCTAIGMPVPTISWIENGNAVSSG----SIQENVKDRVIdsrlqLFITK--PGLYTCIATNKHGE 290
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIESGeekySFNEDGSEMTI-----LDVDKldEAEYTCIAENKAGE 83
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
215-301 1.17e-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: 44.31  E-value: 1.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 215 LRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQenVKDrviDSRLQLFITKP---GLYTCIATNKHGEk 291
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYE--ILD---DHSLKIRKVTAgdmGSYTCVAENMVGK- 74
                          90
                  ....*....|
gi 1937920432 292 fSTAKAAATV 301
Cdd:cd05725    75 -IEASATLTV 83
Ig3_Peroxidasin cd05745
Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
35-106 1.64e-05

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third 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: 143222 [Multi-domain]  Cd Length: 74  Bit Score: 43.77  E-value: 1.64e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432  35 ETVDalveevatFMCAVESYPQPEISWTRNKILIKLfDTRYSIRENGQlLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd05745     3 QTVD--------FLCEAQGYPQPVIAWTKGGSQLSV-DRRHLVLSSGT-LRISRVALHDQGQYECQAVNIVG 64
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
215-296 1.67e-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: 43.72  E-value: 1.67e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 215 LRAPESHNVTFgsfvtlRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRVIDSrLQLFITKPGLYTCIATNKHGEKFST 294
Cdd:cd05723     7 IYAHESMDIVF------ECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQV-LGLVKSDEGFYQCIAENDVGNAQAS 79

                  ..
gi 1937920432 295 AK 296
Cdd:cd05723    80 AQ 81
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
221-290 1.67e-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: 44.13  E-value: 1.67e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432 221 HNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRVIDSRLQLFITKP---GLYTCIATNKHGE 290
Cdd:cd05729    14 HALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPrdkGKYTCIVENEYGS 86
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
43-117 2.07e-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: 44.08  E-value: 2.07e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  43 EVATFMCAVESYPQPEISWTRN----KILIKLFDTRYSIRENGQLLtILSV-----EDSDDGIYCCTANNGVGGAVESCG 113
Cdd:cd07693    16 DPATLNCKAEGRPTPTIQWLKNgqplETDKDDPRSHRIVLPSGSLF-FLRVvhgrkGRSDEGVYVCVAHNSLGEAVSRNA 94

                  ....
gi 1937920432 114 ALQV 117
Cdd:cd07693    95 SLEV 98
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
45-106 2.20e-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: 43.64  E-value: 2.20e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432  45 ATFMCAVESYPQPEISWTRNKILIKlFDTRYSI--RENGQL-LTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd05744    18 CRFDCKVSGLPTPDLFWQLNGKPVR-PDSAHKMlvRENGRHsLIIEPVTKRDAGIYTCIARNRAG 81
IgI_2_RPTP_IIa_LAR_like cd05738
Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; ...
45-106 3.19e-05

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.


Pssm-ID: 409400 [Multi-domain]  Cd Length: 91  Bit Score: 43.46  E-value: 3.19e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432  45 ATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRE-NGQLLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd05738    17 ATMLCAASGNPDPEISWFKDFLPVDTATSNGRIKQlRSGALQIENSEESDQGKYECVATNSAG 79
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
218-303 3.79e-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: 42.77  E-value: 3.79e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTFGSFVTLRCTA-IGMPVPTISWIENGNAVSSGSIQenvkdRVIDSRLQLFITKP-----GLYTCIATNKHGEK 291
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNER-----VRIVDDGNLLIAEArksdeGTYKCVATNMVGER 78
                          90
                  ....*....|..
gi 1937920432 292 FStakAAATVSI 303
Cdd:cd05724    79 ES---RAARLSV 87
Ig_DSCAM cd05734
Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members ...
49-109 4.44e-05

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.


Pssm-ID: 409397 [Multi-domain]  Cd Length: 97  Bit Score: 43.25  E-value: 4.44e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432  49 CAVESYPQPEISWTRNK-------ILIKLFDTRYSIRENGQLLtILSVEDSDDGIYCCTANNGVGGAV 109
Cdd:cd05734    23 CSADGYPPPTIVWKHSKgsgvpqfQHIVPLNGRIQLLSNGSLL-IKHVLEEDSGYYLCKVSNDVGADI 89
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
218-286 4.71e-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: 42.90  E-value: 4.71e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNA-VSSGSIQENVKDRVIDSRLQLfiTKPGLYTCIATN 286
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPlGHSSRVQILSEDVLVIPSVKR--EDKGMYQCFVRN 75
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
217-301 5.76e-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: 42.62  E-value: 5.76e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 217 APESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRVIDSRLQLFITKP-GLYTCIATNKHGEkfSTA 295
Cdd:cd20976     7 VPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDhGTYTCLAKNAAGQ--VSC 84

                  ....*.
gi 1937920432 296 KAAATV 301
Cdd:cd20976    85 SAWVTV 90
IgI_7_Dscam cd20954
Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar ...
34-106 5.97e-05

Seventh 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 seventh 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: 409546 [Multi-domain]  Cd Length: 96  Bit Score: 42.68  E-value: 5.97e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  34 LETVDALVEEVATFM--CAVESYPQPEISWTRN--------KILikLFDTRYSIRENGQLLtILSVEDSDDGIYCCTANN 103
Cdd:cd20954     6 VEPVDANVAAGQDVMlhCQADGFPTPTVTWKKAtgstpgeyKDL--LYDPNVRILPNGTLV-FGHVQKENEGHYLCEAKN 82

                  ...
gi 1937920432 104 GVG 106
Cdd:cd20954    83 GIG 85
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
218-289 6.84e-05

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 42.25  E-value: 6.84e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSG-----SIQENVKDRVIDSrlqLFITKPGLYTCIATNKHG 289
Cdd:cd05736     7 PEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKlskqlTLIANGSELHISN---VRYEDTGAYTCIAKNEGG 80
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
212-291 7.53e-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: 42.34  E-value: 7.53e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 212 ARILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSgSIQENVKDRVIDSRLQLF---ITKPGLYTCIATNKH 288
Cdd:cd05747     4 ATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVS-SQRHQITSTEYKSTFEISkvqMSDEGNYTVVVENSE 82

                  ...
gi 1937920432 289 GEK 291
Cdd:cd05747    83 GKQ 85
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
217-289 1.01e-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: 41.80  E-value: 1.01e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1937920432 217 APESHNVTFGSFVTLRCTAI-GMPVPTISWIENGNAVSSGSIQENVKDRVIDSRLQLFITKP---GLYTCIATNKHG 289
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKedaGTYTCVVNNPGG 78
IgI_1_Contactin cd04967
First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; ...
42-116 1.58e-04

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409356 [Multi-domain]  Cd Length: 96  Bit Score: 41.46  E-value: 1.58e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432  42 EEVATFMCAVESYPQPEISWTRNKILIKL-FDTRYSIReNGQLLTILSVEDSDDGIYCCTANNGVGGAVESCGALQ 116
Cdd:cd04967    19 EKKVALNCRARANPVPSYRWLMNGTEIDLeSDYRYSLV-DGTLVISNPSKAKDAGHYQCLATNTVGSVLSREATLQ 93
Ig5_Contactin-1 cd05852
Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth ...
49-117 1.65e-04

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409438  Cd Length: 89  Bit Score: 41.14  E-value: 1.65e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432  49 CAVESYPQPEISWTRNKILIkLFDTRYSIRENGQLlTILSVEDSDDGIYCCTANNGVGGAvESCGALQV 117
Cdd:cd05852    24 CKPKAAPKPKFSWSKGTELL-VNNSRISIWDDGSL-EILNITKLDEGSYTCFAENNRGKA-NSTGVLSV 89
IgI_3_RPTP_IIa_LAR_like cd05739
Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F ...
216-296 1.79e-04

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).


Pssm-ID: 409401  Cd Length: 82  Bit Score: 41.04  E-value: 1.79e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 216 RAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGS---IQENVkdrvidsrLQLF-ITKPGLYTCIATNKHGEK 291
Cdd:cd05739     2 IPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDempVGRNV--------LELTnIYESANYTCVAISSLGMI 73

                  ....*
gi 1937920432 292 FSTAK 296
Cdd:cd05739    74 EATAQ 78
IgI_4_Neogenin_like cd05723
Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set ...
47-108 1.88e-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: 41.03  E-value: 1.88e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432  47 FMCAVESYPQPEISWTRNKILIKLFDTRYSIREngQLLTILSVEDSDDGIYCCTANNGVGGA 108
Cdd:cd05723    17 FECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKE--HNLQVLGLVKSDEGFYQCIAENDVGNA 76
IgI_3_Contactin-1 cd05851
Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) ...
28-103 1.89e-04

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 143259  Cd Length: 88  Bit Score: 41.16  E-value: 1.89e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTrnKILIKLFDTRySIRENGQLLTILSVEDSDDGIYCCTANN 103
Cdd:cd05851     2 ADINVKFKDTYALKGQNVTLECFALGNPVPVIRWR--KILEPMPATA-EISMSGAVLKIFNIQPEDEGTYECEAEN 74
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
33-108 2.20e-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: 40.64  E-value: 2.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  33 PLETVDALVEEVATFMC-AVESYPQPEISW----TRNKILIKLFDTRYSIRENGqlLTILSVEDSDDGIYCCTANNGVGG 107
Cdd:pfam00047   2 APPTVTVLEGDSATLTCsASTGSPGPDVTWskegGTLIESLKVKHDNGRTTQSS--LLISNVTKEDAGTYTCVVNNPGGS 79

                  .
gi 1937920432 108 A 108
Cdd:pfam00047  80 A 80
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
41-106 2.57e-04

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 41.00  E-value: 2.57e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1937920432  41 VEEVATFMCAVESYPQPEISWT-----RNKILIKLFDTRYSI--RENGQLLtILSVEDSDDGIYCCTANNGVG 106
Cdd:cd05765    14 VGETASFHCDVTGRPQPEITWEkqvpgKENLIMRPNHVRGNVvvTNIGQLV-IYNAQPQDAGLYTCTARNSGG 85
IgI_1_Contactin-5 cd05848
First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; ...
229-293 3.29e-04

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409435  Cd Length: 96  Bit Score: 40.70  E-value: 3.29e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1937920432 229 VTLRCTAIGMPVPTISWIENGNAVssgSIQENVKDRVIDSrlQLFITKP------GLYTCIATNKHGEKFS 293
Cdd:cd05848    22 VILNCEARGNPVPTYRWLRNGTEI---DTESDYRYSLIDG--NLIISNPsevkdsGRYQCLATNSIGSILS 87
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
222-293 3.33e-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: 40.24  E-value: 3.33e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 222 NVTF--GSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQ----------ENVkDRVIDSrlqlfitkpGLYTCIATNKHG 289
Cdd:cd20958     9 NLTAvaGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQrvfpngtlviENV-QRSSDE---------GEYTCTARNQQG 78

                  ....
gi 1937920432 290 EKFS 293
Cdd:cd20958    79 QSAS 82
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
223-295 3.37e-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: 40.41  E-value: 3.37e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432 223 VTFGSFVTLRCTAIGMPVPTISWIENGNAVSSgSIQENVKDRVIDSRLQLFITK-----PGLYTCIATNKHGEKFSTA 295
Cdd:cd20974    12 VLEGSTATFEAHVSGKPVPEVSWFRDGQVIST-STLPGVQISFSDGRAKLSIPAvtkanSGRYSLTATNGSGQATSTA 88
IgI_1_Contactin cd04967
First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; ...
229-294 4.79e-04

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409356 [Multi-domain]  Cd Length: 96  Bit Score: 40.30  E-value: 4.79e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432 229 VTLRCTAIGMPVPTISWIENGNAVSSGSiqeNVKDRVIDSrlQLFITKP------GLYTCIATNKHGEKFST 294
Cdd:cd04967    22 VALNCRARANPVPSYRWLMNGTEIDLES---DYRYSLVDG--TLVISNPskakdaGHYQCLATNTVGSVLSR 88
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
49-108 5.80e-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: 39.09  E-value: 5.80e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  49 CAVESYPQPEISWTRNKILIKLfDTRYSIRENGQLlTILSVEDSDDGIYCCTANNGVGGA 108
Cdd:cd05746     5 CSAQGDPEPTITWNKDGVQVTE-SGKFHISPEGYL-AIRDVGVADQGRYECVARNTIGYA 62
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
213-296 5.96e-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: 39.87  E-value: 5.96e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 213 RILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVssgsiqENVKDRVIDSRLQL--------FITKPGLYTCIA 284
Cdd:cd20972     3 QFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL------QNSPDIQIHQEGDLhsliiaeaFEEDTGRYSCLA 76
                          90
                  ....*....|..
gi 1937920432 285 TNKHGEKFSTAK 296
Cdd:cd20972    77 TNSVGSDTTSAE 88
IgI_NCAM-1 cd05869
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members ...
28-111 6.00e-04

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(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. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 143277 [Multi-domain]  Cd Length: 97  Bit Score: 39.96  E-value: 6.00e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTpLETVDAL-VEEVATFMCAVESYPQPEISWTRNKILI----KLFDTRYSIRENGQL--LTILSVEDSDDGIYCCT 100
Cdd:cd05869     3 PKITY-VENQTAMeLEEQITLTCEASGDPIPSITWRTSTRNIsseeKTLDGHIVVRSHARVssLTLKYIQYTDAGEYLCT 81
                          90
                  ....*....|.
gi 1937920432 101 ANNGVGGAVES 111
Cdd:cd05869    82 ASNTIGQDSQS 92
IgI_3_Contactin cd04968
Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) ...
214-289 6.09e-04

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409357 [Multi-domain]  Cd Length: 88  Bit Score: 39.45  E-value: 6.09e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432 214 ILRAPESHNVTFGSFVTLRCTAIGMPVPTISWIEngnavSSGSIQENVKDRVIDSRLQLF---ITKPGLYTCIATNKHG 289
Cdd:cd04968     4 KVRFPADTYALKGQTVTLECFALGNPVPQIKWRK-----VDGSPSSQWEITTSEPVLEIPnvqFEDEGTYECEAENSRG 77
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
218-303 9.01e-04

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: 39.14  E-value: 9.01e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTFGSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKdrVIDSRLQLFIT--KP---GLYTCIATNKHGekf 292
Cdd:cd05763     6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMH--VMPEDDVFFIVdvKIedtGVYSCTAQNSAG--- 80
                          90
                  ....*....|.
gi 1937920432 293 sTAKAAATVSI 303
Cdd:cd05763    81 -SISANATLTV 90
Ig3_L1-CAM cd05876
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here ...
218-303 9.63e-04

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. 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. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409460 [Multi-domain]  Cd Length: 83  Bit Score: 38.74  E-value: 9.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTF-GSFVTLRCTAIGMPVPTISWIENGNAVSS--GSIQENVKDRVIDSRLQlfiTKPGLYTCIATNKHGekfsT 294
Cdd:cd05876     1 SSSSLVALrGQSLVLECIAEGLPTPTVKWLRPSGPLPPdrVKYQNHNKTLQLLNVGE---SDDGEYVCLAENSLG----S 73

                  ....*....
gi 1937920432 295 AKAAATVSI 303
Cdd:cd05876    74 ARHAYYVTV 82
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
45-118 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: 38.94  E-value: 1.07e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1937920432  45 ATFMCAVESYPQPEISWTRNKILIK--LFDTRYSIRENG--QLLTILSVEDSDDGIYCCTANNgVGGAVESCGALQVK 118
Cdd:cd20951    18 AKLRVEVQGKPDPEVKWYKNGVPIDpsSIPGKYKIESEYgvHVLHIRRVTVEDSAVYSAVAKN-IHGEASSSASVVVE 94
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
44-106 1.37e-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: 38.75  E-value: 1.37e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432  44 VATFMCAVESYPQPEISWTRN--KILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd05763    16 TARLECAATGHPTPQIAWQKDggTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
30-117 1.37e-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: 38.67  E-value: 1.37e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  30 ITTPLETVDalVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENgqLLTILSVEDSDDGIYCCTANNGVGGAv 109
Cdd:cd20957     6 IDPPVQTVD--FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED--VLVIPSVKREDKGMYQCFVRNDGDSA- 80

                  ....*...
gi 1937920432 110 ESCGALQV 117
Cdd:cd20957    81 QATAELKL 88
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
226-296 1.57e-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: 38.32  E-value: 1.57e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1937920432 226 GSFVTLRCTAIGMPVPTISWIENGNAVSSGSIQENVKDRviDSRLQLFITKP-----GLYTCIATNKHGEKFSTAK 296
Cdd:cd20973    12 GSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDE--DGLCSLIISDVcgddsGKYTCKAVNSLGEATCSAE 85
IgI_3_Contactin cd04968
Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) ...
35-106 2.17e-03

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409357 [Multi-domain]  Cd Length: 88  Bit Score: 37.91  E-value: 2.17e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432  35 ETVDALVEEVATFMCAVESYPQPEISWtrNKILIKLFdTRYSIRENGQLLTILSVEDSDDGIYCCTANNGVG 106
Cdd:cd04968     9 ADTYALKGQTVTLECFALGNPVPQIKW--RKVDGSPS-SQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77
IgI_M-protein_C cd05891
C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily ...
49-107 3.32e-03

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.


Pssm-ID: 143299  Cd Length: 92  Bit Score: 37.58  E-value: 3.32e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1937920432  49 CAVESYPQPEISWTRNKILIKLFDtRYSIR-ENGQL--LTILSVEDSDDGIYCCTANNGVGG 107
Cdd:cd05891    23 CTVFGNPDPEVIWFKNDQDIELSE-HYSVKlEQGKYasLTIKGVTSEDSGKYSINVKNKYGG 83
IgI_7_Dscam cd20954
Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar ...
218-286 3.62e-03

Seventh 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 seventh 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: 409546 [Multi-domain]  Cd Length: 96  Bit Score: 37.68  E-value: 3.62e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432 218 PESHNVTFGSFVTLRCTAIGMPVPTISWIEngnavSSGSIQENVKDRVIDSRLQ------LFITK-----PGLYTCIATN 286
Cdd:cd20954     8 PVDANVAAGQDVMLHCQADGFPTPTVTWKK-----ATGSTPGEYKDLLYDPNVRilpngtLVFGHvqkenEGHYLCEAKN 82
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
33-106 4.24e-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: 37.16  E-value: 4.24e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1937920432  33 PLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLfDTRYSIRENGQLlTILSVE-DSDDGIYCCTANNGVG 106
Cdd:cd20958     6 PMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPL-NHRQRVFPNGTL-VIENVQrSSDEGEYTCTARNQQG 78
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
49-111 7.08e-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: 36.77  E-value: 7.08e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  49 CAVESYPQPEISWTRNKILIKlFDTRYSI----RENGQL---LTILSVEDSDDGIYCCTANNGVGGAVES 111
Cdd:cd20956    23 CVASGNPLPQITWTLDGFPIP-ESPRFRVgdyvTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGSVSHS 91
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
49-114 8.49e-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: 36.29  E-value: 8.49e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1937920432  49 CAVESYPQPEISWTRNKILIKLFDTRYSIRENGQ---LLTILSVEDSDDGIYCCTANNGVGgaVESCGA 114
Cdd:cd05892    22 CQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNCgriCLLIQNANKKDAGWYTVSAVNEAG--VVSCNA 88
IgI_SALM5_like cd05764
Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; ...
28-119 9.25e-03

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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: 409421 [Multi-domain]  Cd Length: 88  Bit Score: 36.30  E-value: 9.25e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1937920432  28 PVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLlTILSVEDSDDGIYCCTANNGVGg 107
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTL-DILITTVKDTGAFTCIASNPAG- 78
                          90
                  ....*....|..
gi 1937920432 108 avESCGALQVKM 119
Cdd:cd05764    79 --EATARVELHI 88
 
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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