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Conserved domains on  [gi|768035983|ref|XP_011542299|]
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peripheral plasma membrane protein CASK isoform X7 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Guanylate_kin pfam00625
Guanylate kinase;
547-720 4.32e-74

Guanylate kinase;


:

Pssm-ID: 395500  Cd Length: 182  Bit Score: 237.66  E-value: 4.32e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  547 KRKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYG 626
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  627 TKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTItPGLNE------DESLQRLQKESDILQRTYAHY-F 699
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSL-KVLQRrlkgrgKEQEEKINKRMAAAEQEFQHYeF 159

                         170       180
                  ....*....|....*....|.
gi 768035983  700 DLTIINNEIDETIRHLEEAVE 720
Cdd:pfam00625 160 DVIIVNDDLEEAYKKLKEALE 180
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 1-122 1.07e-73

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd14094:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 300  Bit Score: 240.91  E-value: 1.07e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14094  179 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 258

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 768035983  81 TVYEALNHPWLKERDRYAYKIHLPETVEQLRKFNARRKLKGA 122
Cdd:cd14094  259 TVYEALNHPWIKERDRYAYRIHLPETVEQLRKFNARRKLKGA 300
PDZ_CASK-like cd10831
PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related ...
 298-378 3.44e-56

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


:

Pssm-ID: 467267 [Multi-domain]  Cd Length: 81  Bit Score: 186.15  E-value: 3.44e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd10831    1 RLVQFQKNTDEPMGITLKMNEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKIV 80


                 .
gi 768035983 378 P 378
Cdd:cd10831   81 P 81
SH3_CASK cd12081
Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a ...
 425-486 2.83e-38

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 213014  Cd Length: 62  Bit Score: 136.18  E-value: 2.83e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPEL 486
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGTAGLIPSPEL 62
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 215-265 2.56e-14

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


:

Pssm-ID: 460717  Cd Length: 52  Bit Score: 67.45  E-value: 2.56e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 768035983  215 VQRAKEVLEEISCYPE-NNDAKELKRILTQPHFMALLQTHDVVAHEVYSDEA 265
Cdd:pfam02828   1 VELVLELLEDLQPLSEaSEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
157-210 1.54e-10

domain in receptor targeting proteins Lin-2 and Lin-7;


:

Pssm-ID: 197794  Cd Length: 53  Bit Score: 56.75  E-value: 1.54e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 768035983   157 SQVLDSLEEIHALTDCSEkDLDFLHSVFQDQHLHTLLDLYDKINTKSSPQIRNP 210
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53
 
Name Accession Description Interval E-value
Guanylate_kin pfam00625
Guanylate kinase;
547-720 4.32e-74

Guanylate kinase;


Pssm-ID: 395500  Cd Length: 182  Bit Score: 237.66  E-value: 4.32e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  547 KRKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYG 626
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  627 TKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTItPGLNE------DESLQRLQKESDILQRTYAHY-F 699
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSL-KVLQRrlkgrgKEQEEKINKRMAAAEQEFQHYeF 159

                         170       180
                  ....*....|....*....|.
gi 768035983  700 DLTIINNEIDETIRHLEEAVE 720
Cdd:pfam00625 160 DVIIVNDDLEEAYKKLKEALE 180
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
 1-122 1.07e-73

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: 240.91  E-value: 1.07e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14094  179 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 258

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 768035983  81 TVYEALNHPWLKERDRYAYKIHLPETVEQLRKFNARRKLKGA 122
Cdd:cd14094  259 TVYEALNHPWIKERDRYAYRIHLPETVEQLRKFNARRKLKGA 300
GuKc smart00072
Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to ...
 557-723 3.42e-59

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.


Pssm-ID: 214504 [Multi-domain]  Cd Length: 174  Bit Score: 197.52  E-value: 3.42e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   557 HGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLETIRKIH 636
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   637 EQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTITPGLNE-----DESLQRLQKESDILQRTYAHY--FDLTIINNEID 709
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRlrqrgTETSERIQKRLAAAQKEAQEYhlFDYVIVNDDLE 160

                          170
                   ....*....|....
gi 768035983   710 ETIRHLEEAVELVC 723
Cdd:smart00072 161 DAYEELKEILEAEQ 174
PDZ_CASK-like cd10831
PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related ...
 298-378 3.44e-56

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467267 [Multi-domain]  Cd Length: 81  Bit Score: 186.15  E-value: 3.44e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd10831    1 RLVQFQKNTDEPMGITLKMNEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKIV 80


                 .
gi 768035983 378 P 378
Cdd:cd10831   81 P 81
SH3_CASK cd12081
Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a ...
 425-486 2.83e-38

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213014  Cd Length: 62  Bit Score: 136.18  E-value: 2.83e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPEL 486
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGTAGLIPSPEL 62
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 1-91 5.28e-32

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 124.95  E-value: 5.28e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983     1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG--TKERLFEGIIKGKYKMNPRQWShISESAKDLVRRMLMLDPAE 78
Cdd:smart00220 163 MAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGddQLLELFKKIGKPKPPFPPPEWD-ISPEAKDLIRKLLVKDPEK 241

                           90
                   ....*....|...
gi 768035983    79 RITVYEALNHPWL 91
Cdd:smart00220 242 RLTAEEALQHPFF 254
guanyl_kin TIGR03263
guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP ...
 551-719 6.89e-31

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]


Pssm-ID: 213788  Cd Length: 179  Bit Score: 119.13  E-value: 6.89e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  551 LVLLGAHGVGRRHIKNTLITKHPDrFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:TIGR03263   3 IVISGPSGAGKSTLVKALLEEDPN-LKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  631 TIRKIHEQGLIAILDVEPQ-ALKVLRTAEFAPFvVFIAAPTItpglneDESLQRLQK-----ESDILQR--------TYA 696
Cdd:TIGR03263  82 PVEEALAAGKDVLLEIDVQgARQVKKKFPDAVS-IFILPPSL------EELERRLRKrgtdsEEVIERRlakakkeiAHA 154

                         170       180
                  ....*....|....*....|...
gi 768035983  697 HYFDLTIINNEIDETIRHLEEAV 719
Cdd:TIGR03263 155 DEFDYVIVNDDLEKAVEELKSII 177
Pkinase pfam00069
Protein kinase domain;
1-91 3.12e-30

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 118.89  E-value: 3.12e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983    1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYkMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:pfam00069 127 MAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNeIYELIIDQPY-AFPELPSNLSEEAKDLLKKLLKKDPSKR 205

                          90
                  ....*....|..
gi 768035983   80 ITVYEALNHPWL 91
Cdd:pfam00069 206 LTATQALQHPWF 217
GMPK cd00071
Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), ...
 551-716 3.16e-28

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.


Pssm-ID: 238026  Cd Length: 137  Bit Score: 110.31  E-value: 3.16e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:cd00071    2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 631 TIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPtitpglnedeslqrlqkesdilqrtyahyfDLTIINNEIDE 710
Cdd:cd00071   82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP------------------------------DYVIVNDDLEK 131


                 ....*.
gi 768035983 711 TIRHLE 716
Cdd:cd00071  132 AYEELK 137
Gmk COG0194
Guanylate kinase [Nucleotide transport and metabolism];
551-720 1.20e-27

Guanylate kinase [Nucleotide transport and metabolism];


Pssm-ID: 439964  Cd Length: 190  Bit Score: 110.16  E-value: 1.20e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGRRHIKNTLITKHPDrFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:COG0194    5 IVLSGPSGAGKTTLVKALLERDPD-LRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 631 TIRKIHEQGLIAILDVEPQ-ALKVLRTAEFAPFvVFIAAPTItpglneDESLQRLQK-----ESDILQR--------TYA 696
Cdd:COG0194   84 EVEEALAAGKDVLLEIDVQgARQVKKKFPDAVS-IFILPPSL------EELERRLRGrgtdsEEVIERRlakareelAHA 156

                        170       180
                 ....*....|....*....|....
gi 768035983 697 HYFDLTIINNEIDETIRHLEEAVE 720
Cdd:COG0194  157 DEFDYVVVNDDLDRAVEELKAIIR 180
gmk PRK00300
guanylate kinase; Provisional
 551-716 2.72e-24

guanylate kinase; Provisional


Pssm-ID: 234719  Cd Length: 205  Bit Score: 101.32  E-value: 2.72e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGrrhiKNTLIT---KHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGT 627
Cdd:PRK00300   8 IVLSGPSGAG----KSTLVKallERDPNLQLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 628 KLETIRKIHEQGLIAILDVEPQ-ALKVLRTAEFAPFvVFIAAPTItpglneDESLQRLQK---ESD--ILQR-------- 693
Cdd:PRK00300  84 PRSPVEEALAAGKDVLLEIDWQgARQVKKKMPDAVS-IFILPPSL------EELERRLRGrgtDSEevIARRlakareei 156

                        170       180
                 ....*....|....*....|...
gi 768035983 694 TYAHYFDLTIINNEIDETIRHLE 716
Cdd:PRK00300 157 AHASEYDYVIVNDDLDTALEELK 179
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 299-376 2.56e-17

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 76.94  E-value: 2.56e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  299 LVQFQKNTDEPMGITLKMNELNH---CIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFK 375
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGdpgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLT 79


                  .
gi 768035983  376 I 376
Cdd:pfam00595  80 I 80
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 215-265 2.56e-14

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


Pssm-ID: 460717  Cd Length: 52  Bit Score: 67.45  E-value: 2.56e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 768035983  215 VQRAKEVLEEISCYPE-NNDAKELKRILTQPHFMALLQTHDVVAHEVYSDEA 265
Cdd:pfam02828   1 VELVLELLEDLQPLSEaSEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 296-378 4.57e-14

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 68.17  E-value: 4.57e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   296 RVRLVQFQKNTdEPMGITLKMN--ELNHCIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSIT 373
Cdd:smart00228   1 EPRLVELEKGG-GGLGFSLVGGkdEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVT 78


                   ....*
gi 768035983   374 FKIVP 378
Cdd:smart00228  79 LTVLR 83
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
216-264 3.37e-12

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 61.76  E-value: 3.37e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 768035983   216 QRAKEVLEEISCYPE-NNDAKELKRILTQPHFMALLQTHDVVAHEVYSDE 264
Cdd:smart00569   1 QRLLELLEELQSLLSpSEDLQELRRLLQSPHLQALLKIHDKVAETELDPP 50
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 425-483 1.57e-11

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 59.86  E-value: 1.57e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983   425 YVRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLensKNGTAGLIPS 483
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRL---GRGKEGLFPS 52
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 1-109 7.00e-11

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 64.45  E-value: 7.00e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRqWshISESAKDLVRRMLMLDPAER 79
Cdd:PTZ00263 182 LAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDdTPFRIYEKILAGRLKF-PN-W--FDGRARDLVKGLLQTDHTKR 257

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 768035983  80 I-----TVYEALNHPWLKERD---RYAYKIHLPETVEQ 109
Cdd:PTZ00263 258 LgtlkgGVADVKNHPYFHGANwdkLYARYYPAPIPVRV 295
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
157-210 1.54e-10

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 56.75  E-value: 1.54e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 768035983   157 SQVLDSLEEIHALTDCSEkDLDFLHSVFQDQHLHTLLDLYDKINTKSSPQIRNP 210
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 156-203 3.08e-09

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


Pssm-ID: 460717  Cd Length: 52  Bit Score: 53.20  E-value: 3.08e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 768035983  156 VSQVLDSLEEIHALTDCSEkDLDFLHSVFQDQHLHTLLDLYDKINTKS 203
Cdd:pfam02828   1 VELVLELLEDLQPLSEASE-DLAELQKLLQSPHLQALLEAHDKVAQKV 47
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 427-483 1.87e-08

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 50.66  E-value: 1.87e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983  427 RAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLensKNGTAGLIPS 483
Cdd:pfam00018   1 VALYDYTAQEPDELS-------FKKGDIIIVLEKSEDGWWKGRN---KGGKEGLIPS 47
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
1-79 4.22e-08

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 56.17  E-value: 4.22e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:COG0515  175 MAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGdSPAELLRAHLREPPPPPSELRPDLPPALDAIVLRALAKDPEER 254
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
 311-378 2.72e-04

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440556 [Multi-domain]  Cd Length: 341  Bit Score: 43.71  E-value: 2.72e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 311 GITLKMNElNHCIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGS-ITFKIVP 378
Cdd:COG0793   63 GAELGEED-GKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAGTkVTLTIKR 129
 
Name Accession Description Interval E-value
Guanylate_kin pfam00625
Guanylate kinase;
547-720 4.32e-74

Guanylate kinase;


Pssm-ID: 395500  Cd Length: 182  Bit Score: 237.66  E-value: 4.32e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  547 KRKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYG 626
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  627 TKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTItPGLNE------DESLQRLQKESDILQRTYAHY-F 699
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSL-KVLQRrlkgrgKEQEEKINKRMAAAEQEFQHYeF 159

                         170       180
                  ....*....|....*....|.
gi 768035983  700 DLTIINNEIDETIRHLEEAVE 720
Cdd:pfam00625 160 DVIIVNDDLEEAYKKLKEALE 180
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
 1-122 1.07e-73

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: 240.91  E-value: 1.07e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14094  179 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 258

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 768035983  81 TVYEALNHPWLKERDRYAYKIHLPETVEQLRKFNARRKLKGA 122
Cdd:cd14094  259 TVYEALNHPWIKERDRYAYRIHLPETVEQLRKFNARRKLKGA 300
GuKc smart00072
Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to ...
 557-723 3.42e-59

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.


Pssm-ID: 214504 [Multi-domain]  Cd Length: 174  Bit Score: 197.52  E-value: 3.42e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   557 HGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLETIRKIH 636
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   637 EQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTITPGLNE-----DESLQRLQKESDILQRTYAHY--FDLTIINNEID 709
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRlrqrgTETSERIQKRLAAAQKEAQEYhlFDYVIVNDDLE 160

                          170
                   ....*....|....
gi 768035983   710 ETIRHLEEAVELVC 723
Cdd:smart00072 161 DAYEELKEILEAEQ 174
PDZ_CASK-like cd10831
PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related ...
 298-378 3.44e-56

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467267 [Multi-domain]  Cd Length: 81  Bit Score: 186.15  E-value: 3.44e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd10831    1 RLVQFQKNTDEPMGITLKMNEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKIV 80


                 .
gi 768035983 378 P 378
Cdd:cd10831   81 P 81
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 1-122 1.78e-47

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 169.91  E-value: 1.78e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT-KERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14086  170 LSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEdQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLINQMLTVNPAKR 249

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768035983  80 ITVYEALNHPWLKERDRYAYKIHLPETVEQLRKFNARRKLKGA 122
Cdd:cd14086  250 ITAAEALKHPWICQRDRVASMVHRQETVDCLKKFNARRKLKGA 292
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
 1-90 3.69e-44

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: 159.56  E-value: 3.69e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05117  168 VAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGeTEQELFEKILKGKYSFDSPEWKNVSEEAKDLIKRLLVVDPKKR 247

                         90
                 ....*....|.
gi 768035983  80 ITVYEALNHPW 90
Cdd:cd05117  248 LTAAEALNHPW 258
PDZ_MPP1-like cd10830
PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 ...
 298-378 8.47e-44

PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1, and related domains. MPP1 (also known as MAGUK p55 subfamily member 1, erythrocyte membrane protein p55, EMP55) is a membrane-associated guanylate kinase (MAGUK)-like protein which forms a complex with protein 4.1 and glycophorin C (GPC) at the cytoplasmic face of the plasma membrane; this complex is essential for cytoskeleton-membrane linkage in erythrocytes and many non-erythroid cells, and participates in the determination of membrane stability and cell shape. MPP1, by interacting with various scaffold proteins and cytoskeletal proteins in the postsynaptic density, also plays an important role in organizing synaptic and non-synaptic structures. MPP1 is also a component of the Crumbs protein complex in the mammalian retina and may link the Usher protein network and the Crumbs protein complex. The MPP1 PDZ domain binding partners include GPC, ABCC4, and CADM1/Necl-2/SynCAM1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467266 [Multi-domain]  Cd Length: 81  Bit Score: 152.33  E-value: 8.47e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd10830    1 RLVQFEKNTEEPMGITLKLNEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVI 80


                 .
gi 768035983 378 P 378
Cdd:cd10830   81 P 81
PDZ_MPP-like cd06726
PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 ...
 298-378 1.13e-41

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467208 [Multi-domain]  Cd Length: 80  Bit Score: 146.26  E-value: 1.13e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKMNElNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06726    1 RLVEFEKARDEPLGATIKMEE-DSVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKLI 79


                 .
gi 768035983 378 P 378
Cdd:cd06726   80 P 80
SH3_CASK cd12081
Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a ...
 425-486 2.83e-38

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213014  Cd Length: 62  Bit Score: 136.18  E-value: 2.83e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPEL 486
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGTAGLIPSPEL 62
SH3_MPP1-like cd12035
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1) ...
 425-486 2.99e-38

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212968  Cd Length: 62  Bit Score: 136.02  E-value: 2.99e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPEL 486
Cdd:cd12035    1 YVRAQFDYDPSKDDLIPCQQAGIAFKTGDILQIISKDDHNWWQARKPGASKEPAGLIPSPEL 62
SH3_MPP1 cd12080
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); ...
 425-486 6.29e-34

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213013  Cd Length: 62  Bit Score: 123.91  E-value: 6.29e-34
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPEL 486
Cdd:cd12080    1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEESAGLIPSPEL 62
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 1-91 5.28e-32

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 124.95  E-value: 5.28e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983     1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG--TKERLFEGIIKGKYKMNPRQWShISESAKDLVRRMLMLDPAE 78
Cdd:smart00220 163 MAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGddQLLELFKKIGKPKPPFPPPEWD-ISPEAKDLIRKLLVKDPEK 241

                           90
                   ....*....|...
gi 768035983    79 RITVYEALNHPWL 91
Cdd:smart00220 242 RLTAEEALQHPFF 254
PDZ_MPP6-MPP2-like cd10832
PDZ domain of membrane palmitoylated protein 6 (MPP6), MPP2, and related domains; PDZ (PSD-95 ...
 298-378 5.93e-32

PDZ domain of membrane palmitoylated protein 6 (MPP6), MPP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP6, MPP2, and related domains. MPP6 (also known as MAGUK p55 subfamily member, Protein associated with Lin-7, 2 (PALS2), Veli-associated MAGUK 1, and VAM-1) is a membrane-associated guanylate kinase (MAGUK)-like protein. MPP6 is a regulator of Lin-7 expression and localization. MPP6 is also known to bind cell-adhesion protein, nectin-like molecule-2 (Necl-2), and localize to the basolateral plasma membrane in mammalian epithelial cells. MPP2 (also known as MAGUK p55 subfamily member 2) is a postsynaptic protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Other members of this family include the Drosophila Vari protein, an essential basolateral septate junction protein which interacts with the cell-adhesion protein neurexin IV. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467268 [Multi-domain]  Cd Length: 78  Bit Score: 118.48  E-value: 5.93e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKMNElNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQtvEQLQKMLREMRGSITFKIV 377
Cdd:cd10832    1 RMVGIRKNPGEPLGVTVRLEE-GELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGSP--EQLQEMLKNASGSVTLKIL 77


                 .
gi 768035983 378 P 378
Cdd:cd10832   78 P 78
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
 1-90 3.44e-31

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: 122.63  E-value: 3.44e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMnprqWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd14003  165 AAPEVLLGRKYdGPKADVWSLGVILYAMLTGYLPFDDDNDSkLFRKILKGKYPI----PSHLSPDARDLIRRMLVVDPSK 240

                         90
                 ....*....|..
gi 768035983  79 RITVYEALNHPW 90
Cdd:cd14003  241 RITIEEILNHPW 252
guanyl_kin TIGR03263
guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP ...
 551-719 6.89e-31

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]


Pssm-ID: 213788  Cd Length: 179  Bit Score: 119.13  E-value: 6.89e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  551 LVLLGAHGVGRRHIKNTLITKHPDrFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:TIGR03263   3 IVISGPSGAGKSTLVKALLEEDPN-LKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  631 TIRKIHEQGLIAILDVEPQ-ALKVLRTAEFAPFvVFIAAPTItpglneDESLQRLQK-----ESDILQR--------TYA 696
Cdd:TIGR03263  82 PVEEALAAGKDVLLEIDVQgARQVKKKFPDAVS-IFILPPSL------EELERRLRKrgtdsEEVIERRlakakkeiAHA 154

                         170       180
                  ....*....|....*....|...
gi 768035983  697 HYFDLTIINNEIDETIRHLEEAV 719
Cdd:TIGR03263 155 DEFDYVIVNDDLEKAVEELKSII 177
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2-128 1.47e-30

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: 121.86  E-value: 1.47e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG--TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14085  168 APEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDerGDQYMFKRILNCDYDFVSPWWDDVSLNAKDLVKKLIVLDPKKR 247

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 768035983  80 ITVYEALNHPWLKERDryAYKIHLPETVEQLRKFNARRKLKGAVLAAVS 128
Cdd:cd14085  248 LTTQQALQHPWVTGKA--ANFAHMDTAQKKLQEFNARRKLKAAVKAVVA 294
Pkinase pfam00069
Protein kinase domain;
1-91 3.12e-30

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 118.89  E-value: 3.12e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983    1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYkMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:pfam00069 127 MAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNeIYELIIDQPY-AFPELPSNLSEEAKDLLKKLLKKDPSKR 205

                          90
                  ....*....|..
gi 768035983   80 ITVYEALNHPWL 91
Cdd:pfam00069 206 LTATQALQHPWF 217
SH3_MPP cd11862
Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) ...
 425-485 1.10e-29

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212796  Cd Length: 61  Bit Score: 111.52  E-value: 1.10e-29
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPE 485
Cdd:cd11862    1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGDPNGRAGLIPSQD 61
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
 1-125 1.13e-29

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


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 119.28  E-value: 1.13e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF-YG---TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd14091  165 VAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFaSGpndTPEVILARIGSGKIDLSGGNWDHVSDSAKDLVRKMLHVDP 244

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 768035983  77 AERITVYEALNHPWLKERDryaykiHLPETveQLRKFNARRKLKGAVLA 125
Cdd:cd14091  245 SQRPTAAQVLQHPWIRNRD------SLPQR--QLTDPQDAALVKGAVAA 285
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 2-90 2.43e-28

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


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 114.39  E-value: 2.43e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14083  170 APEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDsKLFAQILKAEYEFDSPYWDDISDSAKDFIRHLMEKDPNKRY 249

                         90
                 ....*....|
gi 768035983  81 TVYEALNHPW 90
Cdd:cd14083  250 TCEQALEHPW 259
GMPK cd00071
Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), ...
 551-716 3.16e-28

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.


Pssm-ID: 238026  Cd Length: 137  Bit Score: 110.31  E-value: 3.16e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:cd00071    2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 631 TIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPtitpglnedeslqrlqkesdilqrtyahyfDLTIINNEIDE 710
Cdd:cd00071   82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP------------------------------DYVIVNDDLEK 131


                 ....*.
gi 768035983 711 TIRHLE 716
Cdd:cd00071  132 AYEELK 137
Gmk COG0194
Guanylate kinase [Nucleotide transport and metabolism];
551-720 1.20e-27

Guanylate kinase [Nucleotide transport and metabolism];


Pssm-ID: 439964  Cd Length: 190  Bit Score: 110.16  E-value: 1.20e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGRRHIKNTLITKHPDrFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:COG0194    5 IVLSGPSGAGKTTLVKALLERDPD-LRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 631 TIRKIHEQGLIAILDVEPQ-ALKVLRTAEFAPFvVFIAAPTItpglneDESLQRLQK-----ESDILQR--------TYA 696
Cdd:COG0194   84 EVEEALAAGKDVLLEIDVQgARQVKKKFPDAVS-IFILPPSL------EELERRLRGrgtdsEEVIERRlakareelAHA 156

                        170       180
                 ....*....|....*....|....
gi 768035983 697 HYFDLTIINNEIDETIRHLEEAVE 720
Cdd:COG0194  157 DEFDYVVVNDDLDRAVEELKAIIR 180
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
 2-91 1.81e-27

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: 112.49  E-value: 1.81e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVK---REPYGKPVDVWGCGVILFILLSGCLPFYG--TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd14084  181 APEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEeyTQMSLKEQILSGKYTFIPKAWKNVSEEAKDLVKKMLVVDP 260

                         90
                 ....*....|....*
gi 768035983  77 AERITVYEALNHPWL 91
Cdd:cd14084  261 SRRPSIEEALEHPWL 275
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 1-118 4.89e-27

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: 111.62  E-value: 4.89e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14166  168 VAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEeTESRLFEKIKEGYYEFESPFWDDISESAKDFIRHLLEKNPSKR 247

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 768035983  80 ITVYEALNHPWLK-----ERDRYaykihlPETVEQLRKFNARRK 118
Cdd:cd14166  248 YTCEKALSHPWIIgntalHRDIY------PSVSEQIQKNFAKSK 285
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
 1-91 1.52e-26

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 109.75  E-value: 1.52e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKR------EPYGKPVDVWGCGVILFILLSGCLPFYGTKERL-FEGIIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14093  175 LAPEVLKCsmydnaPGYGKEVDMWACGVIMYTLLAGCPPFWHRKQMVmLRNIMEGKYEFGSPEWDDISDTAKDLISKLLV 254

                         90
                 ....*....|....*...
gi 768035983  74 LDPAERITVYEALNHPWL 91
Cdd:cd14093  255 VDPKKRLTAEEALEHPFF 272
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
 2-91 1.65e-26

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: 109.27  E-value: 1.65e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14081  168 CPEVIKGEKYdGRKADIWSCGVILYALLVGALPFDDDNLRqLLEKVKRGVFHI-P---HFISPDAQDLLRRMLEVNPEKR 243

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14081  244 ITIEEIKKHPWF 255
PDZ_MPP3-MPP4-MPP7-like cd06799
PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; ...
 297-378 6.39e-26

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467260 [Multi-domain]  Cd Length: 81  Bit Score: 101.55  E-value: 6.39e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 297 VRLVqfqKNtDEPMGITLKMNELNHCI-VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFK 375
Cdd:cd06799    3 VRLV---KN-NEPLGATIKRDEKTGAIvVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFK 78


                 ...
gi 768035983 376 IVP 378
Cdd:cd06799   79 LIP 81
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
 2-90 9.19e-26

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: 107.37  E-value: 9.19e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFY---------GTKERlfegIIKGKYKMNPRQWSHISESAKDLVRRML 72
Cdd:cd14089  170 APEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYsnhglaispGMKKR----IRNGQYEFPNPEWSNVSEEAKDLIRGLL 245

                         90
                 ....*....|....*...
gi 768035983  73 MLDPAERITVYEALNHPW 90
Cdd:cd14089  246 KTDPSERLTIEEVMNHPW 263
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
 2-90 2.69e-25

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: 105.87  E-value: 2.69e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFY---GTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd14095  167 APEILAETGYGLKVDIWAAGVITYILLCGFPPFRspdRDQEELFDLILAGEFEFLSPYWDNISDSAKDLISRMLVVDPEK 246

                         90
                 ....*....|..
gi 768035983  79 RITVYEALNHPW 90
Cdd:cd14095  247 RYSAGQVLDHPW 258
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
 1-91 8.98e-25

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: 104.34  E-value: 8.98e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE---------RLFEGIIKGKYKMNPRQWSHISESAKDLVRRM 71
Cdd:cd14088  166 LAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEAEeddyenhdkNLFRKILAGDYEFDSPYWDDISQAAKDLVTRL 245

                         90       100
                 ....*....|....*....|
gi 768035983  72 LMLDPAERITVYEALNHPWL 91
Cdd:cd14088  246 MEVEQDQRITAEEAISHEWI 265
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
 1-91 1.03e-24

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


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 104.15  E-value: 1.03e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14087  168 IAPEILLRKPYTQSVDMWAVGVIAYILLSGTMPFDDdNRTRLYRQILRAKYSYSGEPWPSVSNLAKDFIDRLLTVNPGER 247

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14087  248 LSATQALKHPWI 259
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
 1-90 1.63e-24

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270992 [Multi-domain]  Cd Length: 289  Bit Score: 104.42  E-value: 1.63e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV-----KREPYGKPVDVWGCGVILFILLSGCLPFYGT----------------KERLFEGIIKGKYKMNPRQWSH 59
Cdd:cd14090  178 MAPEVVdafvgEALSYDKRCDLWSLGVILYIMLCGYPPFYGRcgedcgwdrgeacqdcQELLFHSIQEGEYEFPEKEWSH 257

                         90       100       110
                 ....*....|....*....|....*....|.
gi 768035983  60 ISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd14090  258 ISAEAKDLISHLLVRDASQRYTAEQVLQHPW 288
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
 1-91 1.69e-24

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: 103.72  E-value: 1.69e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14105  178 VAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGdTKQETLANITAVNYDFDDEYFSNTSELAKDFIRQLLVKDPRKR 257

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14105  258 MTIQESLRHPWI 269
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
 1-129 1.77e-24

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 104.34  E-value: 1.77e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG----TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd14175  166 VAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFANgpsdTPEEILTRIGSGKFTLSGGNWNTVSDAAKDLVSKMLHVDP 245

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 768035983  77 AERITVYEALNHPWLKERDRyaykihLPETveQLRKFNARRkLKGAVLAAVSS 129
Cdd:cd14175  246 HQRLTAKQVLQHPWITQKDK------LPQS--QLNHQDVQL-VKGAMAATYSA 289
gmk PRK00300
guanylate kinase; Provisional
 551-716 2.72e-24

guanylate kinase; Provisional


Pssm-ID: 234719  Cd Length: 205  Bit Score: 101.32  E-value: 2.72e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGrrhiKNTLIT---KHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGT 627
Cdd:PRK00300   8 IVLSGPSGAG----KSTLVKallERDPNLQLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 628 KLETIRKIHEQGLIAILDVEPQ-ALKVLRTAEFAPFvVFIAAPTItpglneDESLQRLQK---ESD--ILQR-------- 693
Cdd:PRK00300  84 PRSPVEEALAAGKDVLLEIDWQgARQVKKKMPDAVS-IFILPPSL------EELERRLRGrgtDSEevIARRlakareei 156

                        170       180
                 ....*....|....*....|...
gi 768035983 694 TYAHYFDLTIINNEIDETIRHLE 716
Cdd:PRK00300 157 AHASEYDYVIVNDDLDTALEELK 179
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 1-91 4.13e-24

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


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 102.41  E-value: 4.13e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14167  170 VAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDaKLFEQILKAEYEFDSPYWDDISDSAKDFIQHLMEKDPEKR 249

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14167  250 FTCEQALQHPWI 261
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 1-91 4.97e-24

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: 102.66  E-value: 4.97e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14169  169 VAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDsELFNQILKAEYEFDSPYWDDISESAKDFIRHLLERDPEKR 248

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14169  249 FTCEQALQHPWI 260
SH3_MPP7 cd12033
Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); ...
 425-483 1.98e-23

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212966  Cd Length: 61  Bit Score: 93.93  E-value: 1.98e-23
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPS 483
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPS 59
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 2-91 2.83e-23

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: 100.59  E-value: 2.83e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14096  205 APEVVKDERYSKKVDMWALGCVLYTLLCGFPPFYDeSIETLTEKISRGDYTFLSPWWDEISKSAKDLISHLLTVDPAKRY 284

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14096  285 DIDEFLAHPWI 295
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
 1-92 5.58e-23

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: 98.70  E-value: 5.58e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnprqWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14007  165 LPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESkSHQETYKRIQNVDIKF----PSSVSPEAKDLISKLLQKDPSKR 240

                         90
                 ....*....|...
gi 768035983  80 ITVYEALNHPWLK 92
Cdd:cd14007  241 LSLEQVLNHPWIK 253
SH3_MPP2 cd12037
Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); ...
 425-483 2.31e-22

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212970  Cd Length: 59  Bit Score: 90.78  E-value: 2.31e-22
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenSKNGTAGLIPS 483
Cdd:cd12037    1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACH--VEGGSAGLIPS 57
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
 1-90 9.46e-22

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: 95.40  E-value: 9.46e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG---TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPA 77
Cdd:cd14185  166 VAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSperDQEELFQIIQLGHYEFLPPYWDNISEAAKDLISRLLVVDPE 245

                         90
                 ....*....|...
gi 768035983  78 ERITVYEALNHPW 90
Cdd:cd14185  246 KRYTAKQVLQHPW 258
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
 2-91 1.05e-21

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 95.03  E-value: 1.05e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP-VDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14079  169 APEVISGKLYAGPeVDVWSCGVILYALLCGSLPFDDEHiPNLFKKIKSGIYTI-P---SHLSPGARDLIKRMLVVDPLKR 244

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14079  245 ITIPEIRQHPWF 256
STKc_Mnk1 cd14174
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
 1-92 1.22e-21

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271076 [Multi-domain]  Cd Length: 289  Bit Score: 95.87  E-value: 1.22e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV-----KREPYGKPVDVWGCGVILFILLSGCLPFYGT----------------KERLFEGIIKGKYKMNPRQWSH 59
Cdd:cd14174  177 MAPEVVevftdEATFYDKRCDLWSLGVILYIMLSGYPPFVGHcgtdcgwdrgevcrvcQNKLFESIQEGKYEFPDKDWSH 256

                         90       100       110
                 ....*....|....*....|....*....|...
gi 768035983  60 ISESAKDLVRRMLMLDPAERITVYEALNHPWLK 92
Cdd:cd14174  257 ISSEAKDLISKLLVRDAKERLSAAQVLQHPWVQ 289
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 1-122 1.27e-21

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: 95.88  E-value: 1.27e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14168  177 VAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDsKLFEQILKADYEFDSPYWDDISDSAKDFIRNLMEKDPNKR 256

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 768035983  80 ITVYEALNHPWLKERDRYAYKIHlpETVE-QLRKFNARRKLKGA 122
Cdd:cd14168  257 YTCEQALRHPWIAGDTALCKNIH--ESVSaQIRKNFAKSKWRQA 298
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
 1-90 1.68e-21

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: 94.26  E-value: 1.68e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14006  157 VAPEIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGeDDQETLANISACRVDFSEEYFSSVSQEAKDFIRKLLVKEPRKR 236

                         90
                 ....*....|.
gi 768035983  80 ITVYEALNHPW 90
Cdd:cd14006  237 PTAQEALQHPW 247
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 1-90 2.54e-21

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: 93.74  E-value: 2.54e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05123  160 LAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAeNRKEIYEKILKSPLKF-P---EYVSPEAKSLISGLLQKDPTKR 235

                         90
                 ....*....|....
gi 768035983  80 IT---VYEALNHPW 90
Cdd:cd05123  236 LGsggAEEIKAHPF 249
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
 1-133 2.56e-21

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 95.86  E-value: 2.56e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG----TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd14176  184 VAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFANgpddTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLHVDP 263

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983  77 AERITVYEALNHPWLKERDRyaykihLPETveQLRKFNARRKLKGAVLAAVSSHKFN 133
Cdd:cd14176  264 HQRLTAALVLRHPWIVHWDQ------LPQY--QLNRQDAPHLVKGAMAATYSALNRN 312
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
 1-91 4.74e-21

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: 93.88  E-value: 4.74e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK------REPYGKPVDVWGCGVILFILLSGCLPFYGTKERL-FEGIIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14181  182 LAPEILKcsmdetHPGYGKEVDLWACGVILFTLLAGSPPFWHRRQMLmLRMIMEGRYQFSSPEWDDRSSTVKDLISRLLV 261

                         90
                 ....*....|....*...
gi 768035983  74 LDPAERITVYEALNHPWL 91
Cdd:cd14181  262 VDPEIRLTAEQALQHPFF 279
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
 1-95 1.18e-20

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 93.16  E-value: 1.18e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG----TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd14178  168 VAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFANgpddTPEEILARIGSGKYALSGGNWDSISDAAKDIVSKMLHVDP 247

                         90
                 ....*....|....*....
gi 768035983  77 AERITVYEALNHPWLKERD 95
Cdd:cd14178  248 HQRLTAPQVLRHPWIVNRE 266
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
 1-91 1.84e-20

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: 92.00  E-value: 1.84e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14194  178 VAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGdTKQETLANVSAVNYEFEDEYFSNTSALAKDFIRRLLVKDPKKR 257

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14194  258 MTIQDSLQHPWI 269
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
 1-91 2.16e-20

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: 91.56  E-value: 2.16e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14196  178 VAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGdTKQETLANITAVSYDFDEEFFSHTSELAKDFIRKLLVKETRKR 257

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14196  258 LTIQEALRHPWI 269
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
 1-91 5.54e-20

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: 90.26  E-value: 5.54e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14109  164 VSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDReTLTNVRSGKWSFDSSPLGNISDDARDFIKKLLVYIPESR 243

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14109  244 LTVDEALNHPWF 255
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 1-91 7.55e-20

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 90.05  E-value: 7.55e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFY---------GTKERlfegIIKGKYKMNPRQWSHISESAKDLVRRM 71
Cdd:cd14172  172 VAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYsntgqaispGMKRR----IRMGQYGFPNPEWAEVSEEAKQLIRHL 247

                         90       100
                 ....*....|....*....|
gi 768035983  72 LMLDPAERITVYEALNHPWL 91
Cdd:cd14172  248 LKTDPTERMTITQFMNHPWI 267
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
 1-91 9.38e-20

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: 89.21  E-value: 9.38e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14103  159 VAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGdNDAETLANVTRAKWDFDDEAFDDISDEAKDFISKLLVKDPRKR 238

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14103  239 MSAAQCLQHPWL 250
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 2-90 1.18e-19

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: 89.39  E-value: 1.18e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd14663  170 APEVLARRGYdGAKADIWSCGVILFVLLAGYLPFDDENlMALYRKIMKGEFEY-PR---WFSPGAKSLIKRILDPNPSTR 245

                         90
                 ....*....|.
gi 768035983  80 ITVYEALNHPW 90
Cdd:cd14663  246 ITVEQIMASPW 256
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
 1-91 1.22e-19

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: 89.53  E-value: 1.22e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEV--VKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRqwSHISESAKDLVRRMLMLDP 76
Cdd:cd14008  175 LAPELcdGDSKTYsGKAADIWALGVTLYCLVFGRLPFNGDNILeLYEAIQNQNDEFPIP--PELSPELKDLLRRMLEKDP 252

                         90
                 ....*....|....*
gi 768035983  77 AERITVYEALNHPWL 91
Cdd:cd14008  253 EKRITLKEIKEHPWV 267
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
 1-92 1.97e-19

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: 88.91  E-value: 1.97e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14195  178 VAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGeTKQETLTNISAVNYDFDEEYFSNTSELAKDFIRRLLVKDPKKR 257

                         90
                 ....*....|...
gi 768035983  80 ITVYEALNHPWLK 92
Cdd:cd14195  258 MTIAQSLEHSWIK 270
PLN02772 PLN02772
guanylate kinase
 549-726 3.79e-19

guanylate kinase


Pssm-ID: 215414 [Multi-domain]  Cd Length: 398  Bit Score: 90.28  E-value: 3.79e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 549 KTLVLLGAHGVGrrhiKNTLITK----HPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAM 624
Cdd:PLN02772 136 KPIVISGPSGVG----KGTLISMlmkeFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNL 211

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 625 YGTKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTITP--------GLNEDESLQ-RLQK-ESDILQRT 694
Cdd:PLN02772 212 YGTSIEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEElekrlrarGTETEEQIQkRLRNaEAELEQGK 291

                        170       180       190
                 ....*....|....*....|....*....|..
gi 768035983 695 YAHYFDLTIINNEIDETIRHLEEAVELVCTAP 726
Cdd:PLN02772 292 SSGIFDHILYNDNLEECYKNLKKLLGLDGLAA 323
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
 1-129 4.10e-19

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 88.53  E-value: 4.10e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG----TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd14177  169 VAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFANgpndTPEEILLRIGSGKFSLSGGNWDTVSDAAKDLLSHMLHVDP 248

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 768035983  77 AERITVYEALNHPWLKERDRyaykihLPEtvEQLRKFNARRKLKGAVLAAVSS 129
Cdd:cd14177  249 HQRYTAEQVLKHSWIACRDQ------LPH--YQLNRQDAPHLVKGAMAATYSA 293
STKc_Mnk2 cd14173
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
 1-91 4.41e-19

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271075 [Multi-domain]  Cd Length: 288  Bit Score: 88.16  E-value: 4.41e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKR-----EPYGKPVDVWGCGVILFILLSGCLPFYG----------------TKERLFEGIIKGKYKMNPRQWSH 59
Cdd:cd14173  177 MAPEVVEAfneeaSIYDKRCDLWSLGVILYIMLSGYPPFVGrcgsdcgwdrgeacpaCQNMLFESIQEGKYEFPEKDWAH 256

                         90       100       110
                 ....*....|....*....|....*....|..
gi 768035983  60 ISESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14173  257 ISCAAKDLISKLLVRDAKQRLSAAQVLQHPWV 288
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
 1-93 5.72e-19

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 87.66  E-value: 5.72e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK------REPYGKPVDVWGCGVILFILLSGCLPFYGTKERL-FEGIIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14182  176 LAPEIIEcsmddnHPGYGKEVDMWSTGVIMYTLLAGSPPFWHRKQMLmLRMIMSGNYQFGSPEWDDRSDTVKDLISRFLV 255

                         90       100
                 ....*....|....*....|
gi 768035983  74 LDPAERITVYEALNHPWLKE 93
Cdd:cd14182  256 VQPQKRYTAEEALAHPFFQQ 275
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 2-96 7.45e-19

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 88.13  E-value: 7.45e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP----YGKPVDVWGCGVILFILLSGCLPFYGTKER-----LFEGIIKGKYKMNPRQWSHISESAKDLVRRML 72
Cdd:cd14092  169 APEVLKQALstqgYDESCDLWSLGVILYTMLSGQVPFQSPSRNesaaeIMKRIKSGDFSFDGEEWKNVSSEAKSLIQGLL 248

                         90       100
                 ....*....|....*....|....
gi 768035983  73 MLDPAERITVYEALNHPWLKERDR 96
Cdd:cd14092  249 TVDPSKRLTMSELRNHPWLQGSSS 272
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
 1-91 7.76e-19

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: 87.22  E-value: 7.76e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14097  175 MAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAkSEEKLFEEIRKGDLTFTQSVWQSVSDAAKNVLQQLLKVDPAHR 254

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14097  255 MTASELLDNPWI 266
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 1-93 1.25e-18

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 87.40  E-value: 1.25e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFY---------GTKERlfegIIKGKYKMNPRQWSHISESAKDLVRRM 71
Cdd:cd14170  170 VAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYsnhglaispGMKTR----IRMGQYEFPNPEWSEVSEEVKMLIRNL 245

                         90       100
                 ....*....|....*....|..
gi 768035983  72 LMLDPAERITVYEALNHPWLKE 93
Cdd:cd14170  246 LKTEPTQRMTITEFMNHPWIMQ 267
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
 1-90 1.30e-18

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: 86.38  E-value: 1.30e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK----REP--YGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14098  169 LAPEILMskeqNLQggYSNLVDMWSVGCLVYVMLTGALPFDGsSQLPVEKRIRKGRYTQPPLVDFNISEEAIDFILRLLD 248

                         90
                 ....*....|....*..
gi 768035983  74 LDPAERITVYEALNHPW 90
Cdd:cd14098  249 VDPEKRMTAAQALDHPW 265
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 2-91 2.06e-18

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: 85.87  E-value: 2.06e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14106  178 APEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGdDKQETFLNISQCNLDFPEELFKDVSPLAIDFIKRLLVKDPEKRL 257

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14106  258 TAKECLEHPWL 268
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
 2-91 2.19e-18

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: 85.71  E-value: 2.19e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14114  169 APEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDdETLRNVKSCDWNFDDSAFSGISEEAKDFIRKLLLADPNKRM 248

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14114  249 TIHQALEHPWL 259
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
 1-95 2.44e-18

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: 85.73  E-value: 2.44e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYkmNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05579  175 LAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAeTPEEIFQNILNGKI--EWPEDPEVSDEAKDLISKLLTPDPEKR 252

                         90
                 ....*....|....*....
gi 768035983  80 I---TVYEALNHPWLKERD 95
Cdd:cd05579  253 LgakGIEEIKNHPFFKGID 271
SH3_MPP5 cd12036
Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); ...
 425-485 5.02e-18

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212969  Cd Length: 63  Bit Score: 78.61  E-value: 5.02e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQG--KLENSKNGTAGLIPSPE 485
Cdd:cd12036    1 HVRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQAyrEGEEDNQSLAGLIPSKS 63
STKc_MAPKAPK5 cd14171
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
 11-91 6.37e-18

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271073 [Multi-domain]  Cd Length: 289  Bit Score: 84.82  E-value: 6.37e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGT------KERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERITVYE 84
Cdd:cd14171  203 YDKSCDMWSLGVIIYIMLCGYPPFYSEhpsrtiTKDMKRKIMTGSYEFPEEEWSQISEMAKDIVRKLLCVDPEERMTIEE 282


                 ....*..
gi 768035983  85 ALNHPWL 91
Cdd:cd14171  283 VLHHPWL 289
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
 1-90 1.01e-17

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: 83.54  E-value: 1.01e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT---KERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPA 77
Cdd:cd14184  167 VAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSEnnlQEDLFDQILLGKLEFPSPYWDNITDSAKELISHMLQVNVE 246

                         90
                 ....*....|...
gi 768035983  78 ERITVYEALNHPW 90
Cdd:cd14184  247 ARYTAEQILSHPW 259
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
 2-91 1.21e-17

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: 83.20  E-value: 1.21e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKmNPRqWshISESAKDLVRRMLMLDPAER 79
Cdd:cd14078  170 APELIQGKPYiGSEADVWSMGVLLYALLCGFLPFDDDNvMALYRKIQSGKYE-EPE-W--LSPSSKLLLDQMLQVDPKKR 245

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14078  246 ITVKELLNHPWV 257
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
 2-91 1.29e-17

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 83.23  E-value: 1.29e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP-VDVWGCGVILFILLSGCLPFY--GTKERLFEgIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAE 78
Cdd:cd14074  171 APEILLGDEYDAPaVDIWSLGVILYMLVCGQPPFQeaNDSETLTM-IMDCKYTVPA----HVSPECKDLIRRMLIRDPKK 245

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd14074  246 RASLEEIENHPWL 258
PDZ_MPP5-like cd06798
PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related ...
 298-378 1.30e-17

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP5-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467259 [Multi-domain]  Cd Length: 79  Bit Score: 77.77  E-value: 1.30e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKnTDEPMGITLKmNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06798    1 KIVRIEK-TREPLGATVR-NEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHGTLTFLLI 78


                 .
gi 768035983 378 P 378
Cdd:cd06798   79 P 79
SH3_MPP3 cd12039
Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); ...
 425-483 1.69e-17

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212972  Cd Length: 62  Bit Score: 76.92  E-value: 1.69e-17
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPS 483
Cdd:cd12039    1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNLRAGLIPS 59
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
 2-91 1.81e-17

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: 82.88  E-value: 1.81e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14077  180 APELLQAQPYtGPEVDVWSFGVVLYVLVCGKVPFDDENmPALHAKIKKGKVEYP----SYLSSECKSLISRMLVVDPKKR 255

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14077  256 ATLEQVLNHPWM 267
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 299-376 2.56e-17

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 76.94  E-value: 2.56e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  299 LVQFQKNTDEPMGITLKMNELNH---CIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFK 375
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGdpgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLT 79


                  .
gi 768035983  376 I 376
Cdd:pfam00595  80 I 80
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
 1-91 2.75e-17

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: 82.38  E-value: 2.75e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKER--LFEGIIKGKyKMNPRQWSHISESAKDLVRRMLMLDPA 77
Cdd:cd14069  169 VAPELLAKKKYrAEPVDVWSCGIVLFAMLAGELPWDQPSDScqEYSDWKENK-KTYLTPWKKIDTAALSLLRKILTENPN 247

                         90
                 ....*....|....
gi 768035983  78 ERITVYEALNHPWL 91
Cdd:cd14069  248 KRITIEDIKKHPWY 261
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
 1-95 3.49e-17

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: 82.45  E-value: 3.49e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYkMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05609  182 IAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGdTPEELFGQVISDEI-EWPEGDDALPDDAQDLITRLLQQNPLER 260

                         90
                 ....*....|....*....
gi 768035983  80 I---TVYEALNHPWLKERD 95
Cdd:cd05609  261 LgtgGAEEVKQHPFFQDLD 279
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
 2-91 6.23e-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: 81.46  E-value: 6.23e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNPRQWsHISESAKDLVRRMLMLDPAER 79
Cdd:cd14080  172 APEILQGIPYdPKKYDIWSLGVILYIMLCGSMPFDDSNiKKMLKDQQNRKVRFPSSVK-KLSPECKDLIDQLLEPDPTKR 250

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14080  251 ATIEEILNHPWL 262
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
 1-93 6.63e-17

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: 81.58  E-value: 6.63e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT---KERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPA 77
Cdd:cd14183  172 VAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRGSgddQEVLFDQILMGQVDFPSPYWDNVSDSAKELITMMLQVDVD 251

                         90
                 ....*....|....*.
gi 768035983  78 ERITVYEALNHPWLKE 93
Cdd:cd14183  252 QRYSALQVLEHPWVND 267
gmk PRK14737
guanylate kinase; Provisional
 549-726 1.68e-16

guanylate kinase; Provisional


Pssm-ID: 173199  Cd Length: 186  Bit Score: 78.11  E-value: 1.68e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 549 KTLVLLGAHGVGRRHIKNTLITKHPDrFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTK 628
Cdd:PRK14737   5 KLFIISSVAGGGKSTIIQALLEEHPD-FLFSISCTTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGTP 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 629 LETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFV-VFIAAPT--------ITPGLNEDESLQRlQKESDILQRTYAHYF 699
Cdd:PRK14737  84 KAFIEDAFKEGRSAIMDIDVQGAKIIKEKFPERIVtIFIEPPSeeeweerlIHRGTDSEESIEK-RIENGIIELDEANEF 162

                        170       180
                 ....*....|....*....|....*..
gi 768035983 700 DLTIINNEIDETIRHLEeavELVCTAP 726
Cdd:PRK14737 163 DYKIINDDLEDAIADLE---AIICGKK 186
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 1-91 1.83e-16

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


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 79.87  E-value: 1.83e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEG-IIKGKY---KMNPRqwshISESAKDLVRRMLMLDP 76
Cdd:cd14111  167 MAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAkILVAKFdafKLYPN----VSQSASLFLKKVLSSYP 242

                         90
                 ....*....|....*
gi 768035983  77 AERITVYEALNHPWL 91
Cdd:cd14111  243 WSRPTTKDCFAHAWL 257
SH3_MPP6 cd12038
Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); ...
 425-483 2.53e-16

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212971  Cd Length: 61  Bit Score: 73.56  E-value: 2.53e-16
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKlENSKNGTAGLIPS 483
Cdd:cd12038    1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQAS-HVKEGGSAGLIPS 58
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
 1-93 1.19e-15

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


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 77.98  E-value: 1.19e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14104  165 YAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAeTNQQTIENIRNAEYAFDDEAFKNISIEALDFVDRLLVKERKSR 244

                         90
                 ....*....|....
gi 768035983  80 ITVYEALNHPWLKE 93
Cdd:cd14104  245 MTAQEALNHPWLKQ 258
SH3_MPP4 cd12034
Src Homology 3 domain of Membrane Protein, Palmitoylated 4 (or MAGUK p55 subfamily member 4); ...
 425-483 2.43e-15

Src Homology 3 domain of Membrane Protein, Palmitoylated 4 (or MAGUK p55 subfamily member 4); MPP4, also called Disks Large homolog 6 (DLG6) or Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 5 protein (ALS2CR5), is a retina-specific scaffolding protein that plays a role in organizing presynaptic protein complexes in the photoreceptor synapse, where it localizes to the plasma membrane. It is required in the proper localization of calcium ATPases and for maintenance of calcium homeostasis. MPP4 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212967  Cd Length: 61  Bit Score: 70.69  E-value: 2.43e-15
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPS 483
Cdd:cd12034    1 YVRAMVDYWPQQDPSIPCADAGLPFRKGDILQIVDQNDSLWWQARKLSDLAACAGLIPS 59
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
 2-91 3.12e-15

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: 76.22  E-value: 3.12e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14075  168 APELFKDEHYiGIYVDIWALGVLLYFMVTGVMPFRAeTVAKLKKCILEGTYTI-P---SYVSEPCQELIRGILQPVPSDR 243

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14075  244 YSIDEIKNSEWL 255
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
 1-91 4.42e-15

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: 75.63  E-value: 4.42e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVW--GCGVILfiLLSGCLPFYGTKER---LFEgIIKGKYKmnPRQWSHISESAKDLVRRMLMLD 75
Cdd:cd06606  168 MAPEVIRGEGYGRAADIWslGCTVIE--MATGKPPWSELGNPvaaLFK-IGSSGEP--PPIPEHLSEEAKDFLRKCLQRD 242

                         90
                 ....*....|....*.
gi 768035983  76 PAERITVYEALNHPWL 91
Cdd:cd06606  243 PKKRPTADELLQHPFL 258
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 2-92 5.78e-15

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 76.45  E-value: 5.78e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEG--------IIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14180  172 APELFSNQGYDESCDLWSLGVILYTMLSGQVPFQSKRGKMFHNhaadimhkIKEGDFSLEGEAWKGVSEEAKDLVRGLLT 251

                         90
                 ....*....|....*....
gi 768035983  74 LDPAERITVYEALNHPWLK 92
Cdd:cd14180  252 VDPAKRLKLSELRESDWLQ 270
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
 12-91 7.06e-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: 74.99  E-value: 7.06e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  12 GKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd14119  179 GFKVDIWSAGVTLYNMTTGKYPFEGDNIyKLFENIGKGEYTIPD----DVDPDLQDLLRGMLEKDPEKRFTIEQIRQHPW 254


                 .
gi 768035983  91 L 91
Cdd:cd14119  255 F 255
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
 2-91 7.65e-15

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: 75.12  E-value: 7.65e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYkmnpRQWSHISEsAKDLVRRMLMLDPAER 79
Cdd:cd14073  168 SPEIVNGTPYqGPEVDCWSLGVLLYTLVYGTMPFDGSDfKRLVKQISSGDY----REPTQPSD-ASGLIRWMLTVNPKRR 242

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14073  243 ATIEDIANHWWV 254
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 299-377 1.11e-14

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467153 [Multi-domain]  Cd Length: 81  Bit Score: 69.49  E-value: 1.11e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 299 LVQFQKNTDEPMGITLK--MNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd00136    1 TVTLEKDPGGGLGFSIRggKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80


                 .
gi 768035983 377 V 377
Cdd:cd00136   81 R 81
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
 1-90 1.25e-14

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 75.47  E-value: 1.25e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05571  162 LAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNRDhEVLFELILMEEVRF-PS---TLSPEAKSLLAGLLKKDPKKR 237

                         90
                 ....*....|....*.
gi 768035983  80 I-----TVYEALNHPW 90
Cdd:cd05571  238 LgggprDAKEIMEHPF 253
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
 1-90 1.70e-14

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: 73.80  E-value: 1.70e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14009  161 MAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVqLLRNIERSDAVIPFPIAAQLSPDCKDLLRRLLRRDPAER 240

                         90
                 ....*....|.
gi 768035983  80 ITVYEALNHPW 90
Cdd:cd14009  241 ISFEEFFAHPF 251
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
 1-91 2.13e-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: 73.74  E-value: 2.13e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV-KREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRqwSHISESAKDLVRRMLMLDPAE 78
Cdd:cd14099  168 IAPEVLeKKKGHSFEVDIWSLGVILYTLLVGKPPFETsDVKETYKRIKKNEYSFPSH--LSISDEAKDLIRSMLQPDPTK 245

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd14099  246 RPSLDEILSHPFF 258
STKc_SHIK cd13974
Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs ...
 1-88 2.46e-14

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270876 [Multi-domain]  Cd Length: 290  Bit Score: 74.36  E-value: 2.46e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFY-GTKERLFEGIIKGKYKMnPRQwSHISESAKDLVRRMLMLDPAE 78
Cdd:cd13974  200 ISPDVLSGKPYlGKPSDMWALGVVLFTMLYGQFPFYdSIPQELFRKIKAAEYTI-PED-GRVSENTVCLIRKLLVLNPQK 277

                         90
                 ....*....|
gi 768035983  79 RITVYEALNH 88
Cdd:cd13974  278 RLTASEVLDS 287
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 215-265 2.56e-14

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


Pssm-ID: 460717  Cd Length: 52  Bit Score: 67.45  E-value: 2.56e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 768035983  215 VQRAKEVLEEISCYPE-NNDAKELKRILTQPHFMALLQTHDVVAHEVYSDEA 265
Cdd:pfam02828   1 VELVLELLEDLQPLSEaSEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 1-90 2.76e-14

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 73.48  E-value: 2.76e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEGIIKGKYKMNprQWSHISESAKDLVRRMLML 74
Cdd:cd14665  164 IAPEVLLKKEYdGKIADVWSCGVTLYVMLVGAYPFEDPEEprnfrKTIQRILSVQYSIP--DYVHISPECRHLISRIFVA 241

                         90
                 ....*....|....*.
gi 768035983  75 DPAERITVYEALNHPW 90
Cdd:cd14665  242 DPATRITIPEIRNHEW 257
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
 1-89 3.55e-14

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: 73.27  E-value: 3.55e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRQWshiSESAKDLVRRMLMLDPAER 79
Cdd:cd08215  170 LSPELCENKPYNYKSDIWALGCVLYELCTLKHPFEANNLPaLVYKIVKGQYPPIPSQY---SSELRDLVNSMLQKDPEKR 246

                         90
                 ....*....|
gi 768035983  80 ITVYEALNHP 89
Cdd:cd08215  247 PSANEILSSP 256
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
 2-90 3.70e-14

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: 73.40  E-value: 3.70e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERL-FEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAERI 80
Cdd:cd05581  186 SPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLtFQKIVKLEYEFPE----NFPPDAKDLIQKLLVLDPSKRL 261

                         90
                 ....*....|....*.
gi 768035983  81 TV-----YEAL-NHPW 90
Cdd:cd05581  262 GVnenggYDELkAHPF 277
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 1-91 4.24e-14

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: 73.05  E-value: 4.24e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT-KERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14197  180 VAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGDdKQETFLNISQMNVSYSEEEFEHLSESAIDFIKTLLIKKPENR 259

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14197  260 ATAEDCLKHPWL 271
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
 1-90 4.28e-14

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: 72.88  E-value: 4.28e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEGIIKGKYKMNprQWSHISESAKDLVRRMLML 74
Cdd:cd14662  164 IAPEVLSRKEYdGKVADVWSCGVTLYVMLVGAYPFEDPDDpknfrKTIQRIMSVQYKIP--DYVRVSQDCRHLLSRIFVA 241

                         90
                 ....*....|....*.
gi 768035983  75 DPAERITVYEALNHPW 90
Cdd:cd14662  242 NPAKRITIPEIKNHPW 257
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
 1-91 4.36e-14

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: 73.02  E-value: 4.36e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14193  170 LAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDnETLNNILACQWDFEDEEFADISEEAKDFISKLLIKEKSWR 249

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14193  250 MSASEALKHPWL 261
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 296-378 4.57e-14

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 68.17  E-value: 4.57e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   296 RVRLVQFQKNTdEPMGITLKMN--ELNHCIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSIT 373
Cdd:smart00228   1 EPRLVELEKGG-GGLGFSLVGGkdEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVT 78


                   ....*
gi 768035983   374 FKIVP 378
Cdd:smart00228  79 LTVLR 83
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
 2-91 5.19e-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: 5.19e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP-VDVWGCGVILFILLSGCLPFYGT-----KERLFEGIIKGKYKMnprqwshiSESAKDLVRRMLMLD 75
Cdd:cd14071  166 APEVFEGKEYEGPqLDIWSLGVVLYVLVCGALPFDGStlqtlRDRVLSGRFRIPFFM--------STDCEHLIRRMLVLD 237

                         90
                 ....*....|....*.
gi 768035983  76 PAERITVYEALNHPWL 91
Cdd:cd14071  238 PSKRLTIEQIKKHKWM 253
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 1-91 6.49e-14

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: 72.27  E-value: 6.49e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKR-EPYGKPVDVWGCGVILFILLSGclpfygtkERLFEGiikgkyKMNPRQWSHI-----SESAKDLVRRMLML 74
Cdd:cd05118  167 RAPEVLLGaKPYGSSIDIWSLGCILAELLTG--------RPLFPG------DSEVDQLAKIvrllgTPEALDLLSKMLKY 232

                         90
                 ....*....|....*..
gi 768035983  75 DPAERITVYEALNHPWL 91
Cdd:cd05118  233 DPAKRITASQALAHPYF 249
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 11-91 6.61e-14

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: 72.27  E-value: 6.61e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKgkykmnprqWSHISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd14005  184 HGRPATVWSLGILLYDMLCGDIPFENDEQILRGNVLF---------RPRLSKECCDLISRCLQFDPSKRPSLEQILSHPW 254


                 .
gi 768035983  91 L 91
Cdd:cd14005  255 F 255
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
 1-90 8.84e-14

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 72.06  E-value: 8.84e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFyGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14082  172 LAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPF-NEDEDINDQIQNAAFMYPPNPWKEISPDAIDLINNLLQVKMRKRY 250

                         90
                 ....*....|
gi 768035983  81 TVYEALNHPW 90
Cdd:cd14082  251 SVDKSLSHPW 260
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
 1-95 1.07e-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: 72.23  E-value: 1.07e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05580  165 LAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDeNPMKIYEKILEGKIRF-PS---FFDPDAKDLIKRLLVVDLTKR 240

                         90       100
                 ....*....|....*....|.
gi 768035983  80 I-----TVYEALNHPWLKERD 95
Cdd:cd05580  241 LgnlknGVEDIKNHPWFAGID 261
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
 2-91 2.07e-13

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: 70.98  E-value: 2.07e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APE-VVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKE--------RLFegiikgKYKMN-PRQW-SHISESAKDLVR 69
Cdd:cd14076  175 APElVVSDSMYaGRKADIWSCGVILYAMLAGYLPFDDDPHnpngdnvpRLY------RYICNtPLIFpEYVTPKARDLLR 248

                         90       100
                 ....*....|....*....|..
gi 768035983  70 RMLMLDPAERITVYEALNHPWL 91
Cdd:cd14076  249 RILVPNPRKRIRLSAIMRHAWL 270
SH3_DLG-like cd11861
Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding ...
 425-483 2.34e-13

Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding proteins that cluster at synapses and are also called PSD (postsynaptic density)-95 proteins or SAPs (synapse-associated proteins). They play important roles in synaptic development and plasticity, cell polarity, migration and proliferation. They are members of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG-like proteins contain three PDZ domains and varying N-terminal regions. All DLG proteins exist as alternatively-spliced isoforms. Vertebrates contain four DLG proteins from different genes, called DLG1-4. DLG4 and DLG2 are found predominantly at postsynaptic sites and they mediate surface ion channel and receptor clustering. DLG3 is found axons and some presynaptic terminals. DLG1 interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212795 [Multi-domain]  Cd Length: 61  Bit Score: 65.04  E-value: 2.34e-13
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 425 YVRAQFEYDPAKDDLIPCKeaGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTA--GLIPS 483
Cdd:cd11861    1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARRVTPNGEEEevGVIPS 59
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
 1-91 3.77e-13

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: 70.03  E-value: 3.77e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14191  168 VAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDnETLANVTSATWDFDDEAFDEISDDAKDFISNLLKKDMKAR 247

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14191  248 LTCTQCLQHPWL 259
PK_TRB cd13976
Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to ...
 2-91 3.79e-13

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270878 [Multi-domain]  Cd Length: 242  Bit Score: 69.76  E-value: 3.79e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVK-REPY-GKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAE 78
Cdd:cd13976  154 SPEILNsGATYsGKAADVWSLGVILYTMLVGRYPFHDSEPaSLFAKIRRGQFAI-P---ETLSPRARCLIRSLLRREPSE 229

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd13976  230 RLTAEDILLHPWL 242
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 2-93 5.16e-13

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: 70.45  E-value: 5.16e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPF--------YGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14179  173 APELLNYNGYDESCDLWSLGVILYTMLSGQVPFqchdksltCTSAEEIMKKIKQGDFSFEGEAWKNVSQEAKDLIQGLLT 252

                         90       100
                 ....*....|....*....|
gi 768035983  74 LDPAERITVYEALNHPWLKE 93
Cdd:cd14179  253 VDPNKRIKMSGLRYNEWLQD 272
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
 2-91 6.06e-13

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: 69.47  E-value: 6.06e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP-VDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14072  166 APELFQGKKYDGPeVDVWSLGVILYTLVSGSLPFDGqNLKELRERVLRGKYRI-P---FYMSTDCENLLKKFLVLNPSKR 241

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14072  242 GTLEQIMKDRWM 253
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
 1-90 6.17e-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: 69.56  E-value: 6.17e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE---RLFEGIIKGKYKMN-PRqwsHISESAKDLVRRMLMLDP 76
Cdd:cd05572  159 VAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGDDEdpmKIYNIILKGIDKIEfPK---YIDKNAKNLIKQLLRRNP 235

                         90
                 ....*....|....*....
gi 768035983  77 AERITV----YEAL-NHPW 90
Cdd:cd05572  236 EERLGYlkggIRDIkKHKW 254
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
 1-91 7.33e-13

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: 69.22  E-value: 7.33e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14192  170 LAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGeTDAETMNNIVNCKWDFDAEAFENLSEEAKDFISRLLVKEKSCR 249

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14192  250 MSATQCLKHEWL 261
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 1-91 9.72e-13

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


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 68.76  E-value: 9.72e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14107  166 VAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRaTLLNVAEGVVSWDTPEITHLSEDAKDFIKRVLQPDPEKR 245

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14107  246 PSASECLSHEWF 257
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
 2-91 1.24e-12

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: 68.57  E-value: 1.24e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKErlfegIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14004  175 APEVLRGNPYgGKEQDIWALGVLLYTLVFKENPFYNIEE-----ILEADLRIP----YAVSEDLIDLISRMLNRDVGDRP 245

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14004  246 TIEELLTDPWL 256
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
 1-91 1.64e-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: 68.41  E-value: 1.64e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14190  170 LSPEVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDtETLNNVLMGNWYFDEETFEHVSDEAKDFVSNLIIKERSAR 249

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14190  250 MSATQCLKHPWL 261
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 1-92 1.74e-12

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 68.19  E-value: 1.74e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYG--KPVDVWGCGVILFILLSGCLPFYGTKERLFEG-IIKGKYKMNPRQWSHISESAKDLVRRMLMLDPA 77
Cdd:cd05583  167 MAPEVVRGGSDGhdKAVDWWSLGVLTYELLTGASPFTVDGERNSQSeISKRILKSHPPIPKTFSAEAKDFILKLLEKDPK 246

                         90       100
                 ....*....|....*....|
gi 768035983  78 ERI-----TVYEALNHPWLK 92
Cdd:cd05583  247 KRLgagprGAHEIKEHPFFK 266
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
 1-95 1.81e-12

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: 68.58  E-value: 1.81e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMnPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14209  165 LAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPiQIYEKIVSGKVRF-P---SHFSSDLKDLLRNLLQVDLTKR 240

                         90       100
                 ....*....|....*....|.
gi 768035983  80 I-----TVYEALNHPWLKERD 95
Cdd:cd14209  241 FgnlknGVNDIKNHKWFATTD 261
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
 1-92 1.84e-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: 69.24  E-value: 1.84e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMN-PRQwSHISESAKDLVRRmLMLDPAE 78
Cdd:cd05573  197 IAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSdSLVETYSKIMNWKESLVfPDD-PDVSPEAIDLIRR-LLCDPED 274

                         90
                 ....*....|....*
gi 768035983  79 RITVYEAL-NHPWLK 92
Cdd:cd05573  275 RLGSAEEIkAHPFFK 289
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
 1-90 2.34e-12

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: 68.16  E-value: 2.34e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK--REPY-GKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWShISESAKDLVRRMLMLDPA 77
Cdd:cd14118  182 MAPEALSesRKKFsGKALDIWAMGVTLYCFVFGRCPFEDDHILGLHEKIKTDPVVFPDDPV-VSEQLKDLILRMLDKNPS 260

                         90
                 ....*....|...
gi 768035983  78 ERITVYEALNHPW 90
Cdd:cd14118  261 ERITLPEIKEHPW 273
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
216-264 3.37e-12

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 61.76  E-value: 3.37e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 768035983   216 QRAKEVLEEISCYPE-NNDAKELKRILTQPHFMALLQTHDVVAHEVYSDE 264
Cdd:smart00569   1 QRLLELLEELQSLLSpSEDLQELRRLLQSPHLQALLKIHDKVAETELDPP 50
PK_TRB1 cd14023
Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein ...
 12-91 3.66e-12

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270925 [Multi-domain]  Cd Length: 242  Bit Score: 66.99  E-value: 3.66e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  12 GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd14023  166 GKSADVWSLGVMLYTLLVGRYPFHDSDpSALFSKIRRGQFCIP----DHVSPKARCLIRSLLRREPSERLTAPEILLHPW 241


                 .
gi 768035983  91 L 91
Cdd:cd14023  242 F 242
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
 2-93 3.77e-12

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: 67.94  E-value: 3.77e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV---KRepYGKPVDVWGCGVILFILLSGCLPFYGT----------------KERLFEGI--------IKGKYKMNP 54
Cdd:cd07834  173 APELLlssKK--YTKAIDIWSVGCIFAELLTRKPLFPGRdyidqlnlivevlgtpSEEDLKFIssekarnyLKSLPKKPK 250

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768035983  55 RQWSHI----SESAKDLVRRMLMLDPAERITVYEALNHPWLKE 93
Cdd:cd07834  251 KPLSEVfpgaSPEAIDLLEKMLVFNPKKRITADEALAHPYLAQ 293
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
 2-91 4.02e-12

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: 66.90  E-value: 4.02e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP-VDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYkmnpRQWSHISEsAKDLVRRMLMLDPAER 79
Cdd:cd14161  169 SPEIVNGRPYIGPeVDSWSLGVLLYILVHGTMPFDGHDYKiLVKQISSGAY----REPTKPSD-ACGLIRWLLMVNPERR 243

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14161  244 ATLEDVASHWWV 255
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
 1-91 4.53e-12

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: 67.25  E-value: 4.53e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT-KERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14198  179 LAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEdNQETFLNISQVNVDYSEETFSSVSQLATDFIQKLLVKNPEKR 258

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14198  259 PTAEICLSHSWL 270
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
 1-92 5.12e-12

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: 66.70  E-value: 5.12e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYgtKERLFEGiIKGKYKMNPRQWSH---ISESAKDLVRRMLMLDPA 77
Cdd:cd06648  170 MAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYF--NEPPLQA-MKRIRDNEPPKLKNlhkVSPRLRSFLDRMLVRDPA 246

                         90
                 ....*....|....*
gi 768035983  78 ERITVYEALNHPWLK 92
Cdd:cd06648  247 QRATAAELLNHPFLA 261
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
 1-90 5.42e-12

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: 66.54  E-value: 5.42e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14121  163 MAPEMILKKKYDARVDLWSVGVILYECLFGRAPFASrSFEELEEKIRSSKPIEIPTR-PELSADCRDLLLRLLQRDPDRR 241

                         90
                 ....*....|.
gi 768035983  80 ITVYEALNHPW 90
Cdd:cd14121  242 ISFEEFFAHPF 252
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
 1-92 7.26e-12

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: 66.08  E-value: 7.26e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK--ERLFEGIIKGKYKM-NPRQWSHiseSAKDLVRRMLMLDPA 77
Cdd:cd06614  164 MAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPplRALFLITTKGIPPLkNPEKWSP---EFKDFLNKCLVKDPE 240

                         90
                 ....*....|....*
gi 768035983  78 ERITVYEALNHPWLK 92
Cdd:cd06614  241 KRPSAEELLQHPFLK 255
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
 1-91 8.03e-12

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: 66.04  E-value: 8.03e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF-YGTKERLFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14186  169 ISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPFdTDTVKNTLNKVVLADYEMP----AFLSREAQDLIHQLLRKNPADR 244

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14186  245 LSLSSVLDHPFM 256
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
 2-91 9.16e-12

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: 66.53  E-value: 9.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEGIIKGKYKMNPRQ----WS-------------- 58
Cdd:cd07838  174 APEVLLQSSYATPVDMWSVGCIFAELFNRRPLFRGSSEadqlgKIFDVIGLPSEEEWPRNsalpRSsfpsytprpfksfv 253

                         90       100       110
                 ....*....|....*....|....*....|....
gi 768035983  59 -HISESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07838  254 pEIDEEGLDLLKKMLTFNPHKRISAFEALQHPYF 287
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
 1-91 9.64e-12

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: 65.74  E-value: 9.64e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd05578  166 MAPEVFMRAGYSFAVDWWSLGVTAYEMLRGKRPYEIHSRTSIEEIRAKFETASVLYPAGWSEEAIDLINKLLERDPQKRL 245

                         90
                 ....*....|..
gi 768035983  81 TVYEAL-NHPWL 91
Cdd:cd05578  246 GDLSDLkNHPYF 257
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
 1-91 1.03e-11

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: 65.74  E-value: 1.03e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKgkykmNPRQW-SHISESAKDLVRRMLMLDPAE 78
Cdd:cd14002  166 MAPELVQEQPYDHTADLWSLGCILYELFVGQPPFYTNSiYQLVQMIVK-----DPVKWpSNMSPEFKSFLQGLLNKDPSK 240

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd14002  241 RLSWPDLLEHPFV 253
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
 2-91 1.11e-11

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: 65.97  E-value: 1.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFE-----------GIIK-GKYKMNPRQWSH---- 59
Cdd:cd07829  166 APEILLGSKhYSTAVDIWSVGCIFAELITGKPLFPGDSEidqlfKIFQilgtpteeswpGVTKlPDYKPTFPKWPKndle 245

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 768035983  60 -----ISESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07829  246 kvlprLDPEGIDLLSKMLQYNPAKRISAKEALKHPYF 282
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 425-483 1.57e-11

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 59.86  E-value: 1.57e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983   425 YVRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLensKNGTAGLIPS 483
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRL---GRGKEGLFPS 52
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
 1-116 1.62e-11

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: 65.78  E-value: 1.62e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd06659  184 MAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRDSPPPKLKNSHKASPVLRDFLERMLVRDPQERA 263

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 768035983  81 TVYEALNHPWLkerdryaYKIHLPET----VEQLRKFNAR 116
Cdd:cd06659  264 TAQELLDHPFL-------LQTGLPEClvplIQQYRKRTST 296
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
 1-95 2.25e-11

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: 65.70  E-value: 2.25e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05570  163 IAPEILREQDYGFSVDWWALGVLLYEMLAGQSPFEGdDEDELFEAILNDEVLY-PR---WLSREAVSILKGLLTKDPARR 238

                         90       100
                 ....*....|....*....|.
gi 768035983  80 ITVY-----EALNHPWLKERD 95
Cdd:cd05570  239 LGCGpkgeaDIKAHPFFRNID 259
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
 2-91 2.29e-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: 64.80  E-value: 2.29e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPV-DVWGCGVILFILLSGCLPFYGTKERLFEGIIKgKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14165  174 APEVLQGIPYDPRIyDIWSLGVILYIMVCGSMPYDDSNVKKMLKIQK-EHRVRFPRSKNLTSECKDLIYRLLQPDVSQRL 252

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14165  253 CIDEVLSHPWL 263
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
 1-80 3.53e-11

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: 65.03  E-value: 3.53e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRQwshISESAKDLVRRMLMLDPAER 79
Cdd:cd05595  162 LAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDhERLFELILMEEIRF-PRT---LSPEAKSLLAGLLKKDPKQR 237


                 .
gi 768035983  80 I 80
Cdd:cd05595  238 L 238
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
 1-91 3.57e-11

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: 64.15  E-value: 3.57e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFY--GTKERLFEGIIKGKYKM-NPRQWshiSESAKDLVRRMLMLDPA 77
Cdd:cd05122  164 MAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSelPPMKALFLIATNGPPGLrNPKKW---SKEFKDFLKKCLQKDPE 240

                         90
                 ....*....|....
gi 768035983  78 ERITVYEALNHPWL 91
Cdd:cd05122  241 KRPTAEQLLKHPFI 254
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
 1-91 3.89e-11

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: 64.25  E-value: 3.89e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLML 74
Cdd:cd13994  169 MAPEVFTSGSYdGRAVDVWSCGIVLFALFTGRFPWRSAKKsdsayKAYEKSGDFTNGPYEPIENLLPSECRRLIYRMLHP 248

                         90
                 ....*....|....*..
gi 768035983  75 DPAERITVYEALNHPWL 91
Cdd:cd13994  249 DPEKRITIDEALNDPWV 265
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
 2-91 4.06e-11

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: 63.86  E-value: 4.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYgKPV--DVWGCGVILFILLSGCLPFYGTKER-LFEGIIKG-KYKMNPrqwsHISESAKDLVRRMLMLDPa 77
Cdd:cd14162  172 SPEILRGIPY-DPFlsDIWSMGVVLYTMVYGRLPFDDSNLKvLLKQVQRRvVFPKNP----TVSEECKDLILRMLSPVK- 245

                         90
                 ....*....|....
gi 768035983  78 ERITVYEALNHPWL 91
Cdd:cd14162  246 KRITIEEIKRDPWF 259
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
 1-92 5.45e-11

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: 63.65  E-value: 5.45e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFY-GTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05611  163 LAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHaETPDAVFDNILSRRINWPEEVKEFCSPEAVDLINRLLCMDPAKR 242

                         90
                 ....*....|....*.
gi 768035983  80 I---TVYEALNHPWLK 92
Cdd:cd05611  243 LganGYQEIKSHPFFK 258
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
 1-89 6.45e-11

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: 63.56  E-value: 6.45e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYkmnPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd08530  168 AAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEArTMQELRYKVCRGKF---PPIPPVYSQDLQQIIRSLLQVNPKKR 244

                         90
                 ....*....|
gi 768035983  80 ITVYEALNHP 89
Cdd:cd08530  245 PSCDKLLQSP 254
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
 1-109 7.00e-11

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 64.45  E-value: 7.00e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRqWshISESAKDLVRRMLMLDPAER 79
Cdd:PTZ00263 182 LAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDdTPFRIYEKILAGRLKF-PN-W--FDGRARDLVKGLLQTDHTKR 257

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 768035983  80 I-----TVYEALNHPWLKERD---RYAYKIHLPETVEQ 109
Cdd:PTZ00263 258 LgtlkgGVADVKNHPYFHGANwdkLYARYYPAPIPVRV 295
PK_TRB2 cd14022
Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein ...
 12-91 7.47e-11

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270924 [Multi-domain]  Cd Length: 242  Bit Score: 63.13  E-value: 7.47e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  12 GKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRQwshISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd14022  166 GKAADVWSLGVMLYTMLVGRYPFHDIEpSSLFSKIRRGQFNI-PET---LSPKAKCLIRSILRREPSERLTSQEILDHPW 241


                 .
gi 768035983  91 L 91
Cdd:cd14022  242 F 242
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 425-483 9.56e-11

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 57.47  E-value: 9.56e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLENSKngtAGLIPS 483
Cdd:cd00174    1 YARALYDYEAQDDDELS-------FKKGDIITVLEKDDDGWWEGELNGGR---EGLFPA 49
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 1-89 9.66e-11

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: 62.94  E-value: 9.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYkmnPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd08217  177 MSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAANqLELAKKIKEGKF---PRIPSRYSSELNEVIKSMLNVDPDKR 253

                         90
                 ....*....|
gi 768035983  80 ITVYEALNHP 89
Cdd:cd08217  254 PSVEELLQLP 263
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 2-90 1.15e-10

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


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 62.67  E-value: 1.15e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14115  159 APEVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDeSKEETCINVCRVDFSFPDEYFGDVSQAARDFINVILQEDPRRRP 238

                         90
                 ....*....|
gi 768035983  81 TVYEALNHPW 90
Cdd:cd14115  239 TAATCLQHPW 248
STKc_Cdc7 cd14019
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze ...
 2-91 1.20e-10

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270921 [Multi-domain]  Cd Length: 252  Bit Score: 62.62  E-value: 1.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKERlFEGIIkgkykmnprQWSHI--SESAKDLVRRMLMLDPAE 78
Cdd:cd14019  170 APEVLFKCPHqTTAIDIWSAGVILLSILSGRFPFFFSSDD-IDALA---------EIATIfgSDEAYDLLDKLLELDPSK 239

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd14019  240 RITAEEALKHPFF 252
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
157-210 1.54e-10

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 56.75  E-value: 1.54e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 768035983   157 SQVLDSLEEIHALTDCSEkDLDFLHSVFQDQHLHTLLDLYDKINTKSSPQIRNP 210
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
 2-91 1.63e-10

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: 62.29  E-value: 1.63e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEGIIKGKYKMnprqwshISESA------KDLVRR 70
Cdd:cd14133  169 APEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGASEvdqlaRIIGTIGIPPAHM-------LDQGKaddelfVDFLKK 241

                         90       100
                 ....*....|....*....|.
gi 768035983  71 MLMLDPAERITVYEALNHPWL 91
Cdd:cd14133  242 LLEIDPKERPTASQALSHPWL 262
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
 1-95 2.20e-10

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: 62.45  E-value: 2.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05612  165 LAPEVIQSKGHNKAVDWWALGILIYEMLVGYPPFFDdNPFGIYEKILAGKLEF-PR---HLDLYAKDLIKKLLVVDRTRR 240

                         90       100
                 ....*....|....*....|.
gi 768035983  80 I-----TVYEALNHPWLKERD 95
Cdd:cd05612  241 LgnmknGADDVKNHRWFKSVD 261
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 1-95 3.23e-10

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 62.24  E-value: 3.23e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK-REPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGK-YKMNPRQWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd05614  173 MAPEIIRgKSGHGKAVDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRiLKCDPPFPSFIGPVARDLLQKLLCKDPKK 252

                         90       100
                 ....*....|....*....|..
gi 768035983  79 RI-----TVYEALNHPWLKERD 95
Cdd:cd05614  253 RLgagpqGAQEIKEHPFFKGLD 274
PK_TRB3 cd14024
Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein ...
 1-91 3.25e-10

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270926 [Multi-domain]  Cd Length: 242  Bit Score: 61.05  E-value: 3.25e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV--KREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPA 77
Cdd:cd14024  153 VGPEILssRRSYSGKAADVWSLGVCLYTMLLGRYPFQDTEPAaLFAKIRRGAFSLP----AWLSPGARCLVSCMLRRSPA 228

                         90
                 ....*....|....
gi 768035983  78 ERITVYEALNHPWL 91
Cdd:cd14024  229 ERLKASEILLHPWL 242
PDZ3_DLG5-like cd06767
PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 298-376 3.88e-10

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467248 [Multi-domain]  Cd Length: 82  Bit Score: 56.57  E-value: 3.88e-10
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 298 RLVQFQKnTDEPMGITLKMNELNHCIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06767    4 RHVSIEK-GSEPLGISIVSGENGGIFVSSVTEGSLAHQAG-LEYGDQLLEVNGINLRNATEQQAALILRQCGDTITMLV 80
PDZ6_MUPP1-like cd06670
PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 ...
 304-366 4.23e-10

PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of multi-PDZ-domain protein 1 (MUPP1). MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ6 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467158 [Multi-domain]  Cd Length: 87  Bit Score: 56.88  E-value: 4.23e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983 304 KNTDEPMGITLKMN-ELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLR 366
Cdd:cd06670   10 VKGNSSLGITVSADkDGNGCIVKSIIHGGAVSRDGRISVGDFIVSINNESLRNVTNAQARAILR 73
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
 1-80 4.30e-10

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 61.65  E-value: 4.30e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05584  167 MAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAeNRKKTIDKILKGKLNLPP----YLTNEARDLLKKLLKRNVSSR 242


                 .
gi 768035983  80 I 80
Cdd:cd05584  243 L 243
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
 1-91 4.71e-10

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: 60.88  E-value: 4.71e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP--YGKPVDVW--GCGVILfiLLSGCLPFY--GTKErlfEGIIK-GKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd06624  176 MAPEVIDKGQrgYGPPADIWslGCTIIE--MATGKPPFIelGEPQ---AAMFKvGMFKIHPEIPESLSEEAKSFILRCFE 250

                         90
                 ....*....|....*...
gi 768035983  74 LDPAERITVYEALNHPWL 91
Cdd:cd06624  251 PDPDKRATASDLLQDPFL 268
SH3_DLG3 cd12029
Src Homology 3 domain of Disks Large homolog 3; DLG3, also called synapse-associated protein ...
 422-488 7.69e-10

Src Homology 3 domain of Disks Large homolog 3; DLG3, also called synapse-associated protein 102 (SAP102), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. Mutations in DLG3 cause midgestational embryonic lethality in mice and may be associated with nonsyndromic X-linked mental retardation in humans. It interacts with the NEDD4 (neural precursor cell-expressed developmentally downregulated 4) family of ubiquitin ligases and promotes apical tight junction formation. DLG3 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG3 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212962  Cd Length: 67  Bit Score: 55.48  E-value: 7.69e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 422 RQIYVRAQFEYDPAKDDLIPCKeaGIRFRVGDIIQIISKDDHNWWQGKL--ENSKNGTAGLIPSPELQE 488
Cdd:cd12029    1 RSLYVRALFDYDRTRDSCLPSQ--GLSFSYGDILHVINASDDEWWQARLvtPHGESEQIGVIPSKKRVE 67
SH3_DLG1 cd12031
Src Homology 3 domain of Disks Large homolog 1; DLG1, also called synapse-associated protein ...
 422-483 8.64e-10

Src Homology 3 domain of Disks Large homolog 1; DLG1, also called synapse-associated protein 97 (SAP97), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. DLG1 plays roles in regulating cell polarity, proliferation, migration, and cycle progression. It interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. It also interacts with PKCalpha and promotes wound healing. DLG1 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG1 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212964  Cd Length: 67  Bit Score: 55.47  E-value: 8.64e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983 422 RQIYVRAQFEYDPAKDDLIPCKeaGIRFRVGDIIQIISKDDHNWWQGK--LENSKNGTAGLIPS 483
Cdd:cd12031    1 RSLYVRALFDYDKTKDSGLPSQ--GLNFKFGDILHVVNASDDEWWQARqvTADGESEEIGVIPS 62
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
 1-91 1.17e-09

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: 60.04  E-value: 1.17e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd06657  183 MAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPKLKNLHKVSPSLKGFLDRLLVRDPAQRA 262

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd06657  263 TAAELLKHPFL 273
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 2-92 1.37e-09

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: 60.33  E-value: 1.37e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGK--YKMNPrqwsHISESAKDLVRRMLMLDPAE 78
Cdd:cd05574  200 APEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFKGsNRDETFSNILKKEltFPESP----PVSSEAKDLIRKLLVKDPSK 275

                         90
                 ....*....|....*...
gi 768035983  79 RI----TVYEALNHPWLK 92
Cdd:cd05574  276 RLgskrGASEIKRHPFFR 293
SH3_DLG2 cd12032
Src Homology 3 domain of Disks Large homolog 2; DLG2, also called postsynaptic density-93 ...
 422-483 1.37e-09

Src Homology 3 domain of Disks Large homolog 2; DLG2, also called postsynaptic density-93 (PSD93) or Channel-associated protein of synapse-110 (chapsyn 110), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. The DLG2 delta isoform binds inwardly rectifying potassium Kir2 channels, which determine resting membrane potential in neurons. It regulates the spatial and temporal distribution of Kir2 channels within neuronal membranes. DLG2 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG2 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212965  Cd Length: 74  Bit Score: 55.09  E-value: 1.37e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983 422 RQIYVRAQFEYDPAKDDLIPCKeaGIRFRVGDIIQIISKDDHNWWQGK--LENSKNGTAGLIPS 483
Cdd:cd12032    4 RSLYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQARrvTPDGDSEEMGVIPS 65
gmk PRK14738
guanylate kinase; Provisional
 551-713 1.45e-09

guanylate kinase; Provisional


Pssm-ID: 237809  Cd Length: 206  Bit Score: 58.59  E-value: 1.45e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 551 LVLLGAHGVGRRHIKNTLITKHPDrFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLE 630
Cdd:PRK14738  16 VVISGPSGVGKDAVLARMRERKLP-FHFVVTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNYYGVPKA 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 631 TIRKIHEQGLIAILDVEPQALKVLRtaEFAPFVVFI-AAPtitPGLNE------------DESL-QRLQKESDILQRTYA 696
Cdd:PRK14738  95 PVRQALASGRDVIVKVDVQGAASIK--RLVPEAVFIfLAP---PSMDEltrrlelrrtesPEELeRRLATAPLELEQLPE 169

                        170
                 ....*....|....*....
gi 768035983 697 hyFDLTIIN--NEIDETIR 713
Cdd:PRK14738 170 --FDYVVVNpeDRLDEAVA 186
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
 15-90 1.78e-09

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: 59.25  E-value: 1.78e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  15 VDVWGCGVILFILLSGCLPFyG---TKER-LFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd13990  201 VDVWSVGVIFYQMLYGRKPF-GhnqSQEAiLEENTILKATEVEFPSKPVVSSEAKDFIRRCLTYRKEDRPDVLQLANDPY 279
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
 1-95 1.86e-09

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: 59.14  E-value: 1.86e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER----LFEGIIKG-KYKMNPRQWShisESAKDLVRRMLMLD 75
Cdd:cd06623  167 MSPERIQGESYSYAADIWSLGLTLLECALGKFPFLPPGQPsffeLMQAICDGpPPSLPAEEFS---PEFRDFISACLQKD 243

                         90       100
                 ....*....|....*....|
gi 768035983  76 PAERITVYEALNHPWLKERD 95
Cdd:cd06623  244 PKKRPSAAELLQHPFIKKAD 263
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
 1-80 1.91e-09

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: 60.09  E-value: 1.91e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRQwshISESAKDLVRRMLMLDPAER 79
Cdd:cd05593  182 LAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDhEKLFELILMEDIKF-PRT---LSADAKSLLSGLLIKDPNKR 257


                 .
gi 768035983  80 I 80
Cdd:cd05593  258 L 258
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
 11-90 1.95e-09

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: 59.50  E-value: 1.95e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFE-----------GIIKGKYKMNPRQ-----------WSH-ISE 62
Cdd:cd07840  183 YGPEVDMWSVGCILAELFTGKPIFQGKTEleqleKIFElcgspteenwpGVSDLPWFENLKPkkpykrrlrevFKNvIDP 262

                         90       100
                 ....*....|....*....|....*...
gi 768035983  63 SAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07840  263 SALDLLDKLLTLDPKKRISADQALQHEY 290
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 1-92 1.96e-09

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 60.42  E-value: 1.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:PTZ00267 238 LAPELWERKRYSKKADMWSLGVILYELLTLHRPFKGPSQReIMQQVLYGKYDPFP---CPVSSGMKALLDPLLSKNPALR 314

                         90
                 ....*....|...
gi 768035983  80 ITVYEALNHPWLK 92
Cdd:PTZ00267 315 PTTQQLLHTEFLK 327
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
 1-91 2.01e-09

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: 59.10  E-value: 2.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGkyKMNPRQWShISESAKDLVRRMLMLDPAER 79
Cdd:cd14164  168 TPPEVILGTPYdPKKYDVWSLGVVLYVMVTGTMPFDETNVRRLRLQQRG--VLYPSGVA-LEEPCRALIRTLLQFNPSTR 244

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14164  245 PSIQQVAGNSWL 256
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
 1-80 2.11e-09

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 59.64  E-value: 2.11e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG--TKErLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAE 78
Cdd:cd05575  163 LAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSrdTAE-MYDNILHKPLRLRT----NVSPSARDLLEGLLQKDRTK 237


                 ..
gi 768035983  79 RI 80
Cdd:cd05575  238 RL 239
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
 1-89 2.63e-09

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: 58.05  E-value: 2.63e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILlsgclpfygtkerlfegiikgkykmnprqwshisESAKDLVRRMLMLDPAERI 80
Cdd:cd00180  161 APPELLGGRYYGPKVDIWSLGVILYEL----------------------------------EELKDLIRRMLQYDPKKRP 206


                 ....*....
gi 768035983  81 TVYEALNHP 89
Cdd:cd00180  207 SAKELLEHL 215
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
 1-91 2.78e-09

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: 58.43  E-value: 2.78e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd14116  170 LPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEAnTYQETYKRISRVEFTFPD----FVTEGARDLISRLLKHNPSQR 245

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14116  246 PMLREVLEHPWI 257
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 156-203 3.08e-09

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


Pssm-ID: 460717  Cd Length: 52  Bit Score: 53.20  E-value: 3.08e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 768035983  156 VSQVLDSLEEIHALTDCSEkDLDFLHSVFQDQHLHTLLDLYDKINTKS 203
Cdd:pfam02828   1 VELVLELLEDLQPLSEASE-DLAELQKLLQSPHLQALLEAHDKVAQKV 47
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
 1-80 3.18e-09

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: 58.85  E-value: 3.18e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSH-ISESAKDLVRRMLMLDPAER 79
Cdd:cd05631  168 MAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERVKREEVDRRVKEDQEEYSEkFSEDAKSICRMLLTKNPKER 247


                 .
gi 768035983  80 I 80
Cdd:cd05631  248 L 248
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 1-91 5.46e-09

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: 57.44  E-value: 5.46e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWshiSESAKDLVRRMLMLDPAER 79
Cdd:cd08221  168 MSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTFDATNPlRLAVKIVQGEYEDIDEQY---SEEIIQLVHDCLHQDPEDR 244

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd08221  245 PTAEELLERPLL 256
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
 1-91 5.71e-09

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: 58.04  E-value: 5.71e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV--KREPY-GKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQwSHISESAKDLVRRMLMLDPA 77
Cdd:cd14200  191 MAPETLsdSGQSFsGKALDVWAMGVTLYCFVYGKCPFIDEFILALHNKIKNKPVEFPEE-PEISEELKDLILKMLDKNPE 269

                         90
                 ....*....|....
gi 768035983  78 ERITVYEALNHPWL 91
Cdd:cd14200  270 TRITVPEIKVHPWV 283
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
 1-91 8.38e-09

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: 57.03  E-value: 8.38e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKRE--PYGKPVDVW--GCGVILfiLLSGCLPFYGtkerlFEG---IIK-GKYKMNPRQWSHISESAKDLVRRML 72
Cdd:cd06632  168 MAPEVIMQKnsGYGLAVDIWslGCTVLE--MATGKPPWSQ-----YEGvaaIFKiGNSGELPPIPDHLSPDAKDFIRLCL 240

                         90
                 ....*....|....*....
gi 768035983  73 MLDPAERITVYEALNHPWL 91
Cdd:cd06632  241 QRDPEDRPTASQLLEHPFV 259
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
 1-90 9.88e-09

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: 56.95  E-value: 9.88e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEV---VKREPY--GKPVDVWGCGVILFILLSGCLP---------FYgtkeRLFEGIIKGKYKMNPRQWSHISESAKD 66
Cdd:cd13987  157 TAPEVceaKKNEGFvvDPSIDVWAFGVLLFCCLTGNFPwekadsddqFY----EEFVRWQKRKNTAVPSQWRRFTPKALR 232

                         90       100
                 ....*....|....*....|....*..
gi 768035983  67 LVRRMLMLDPAERIT---VYEALNHPW 90
Cdd:cd13987  233 MFKKLLAPEPERRCSikeVFKYLGDRW 259
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
 1-86 1.10e-08

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: 56.83  E-value: 1.10e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQW-SHISESAKDLVRRMLMLDPAER 79
Cdd:cd14014  168 MAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQEAPPPPSPLnPDVPPALDAIILRALAKDPEER 247


                 ....*..
gi 768035983  80 ITVYEAL 86
Cdd:cd14014  248 PQSAAEL 254
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
 1-91 1.13e-08

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: 56.77  E-value: 1.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKErlFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd06628  179 MAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPFPDCTQ--MQAIFKIGENASPTIPSNISSEARDFLEKTFEIDHNKRP 256

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd06628  257 TADELLKHPFL 267
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
 1-92 1.17e-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: 56.98  E-value: 1.17e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSH-ISESAKDLVRRMLMLDPAER 79
Cdd:cd05605  168 MAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAPFRARKEKVKREEVDRRVKEDQEEYSEkFSEEAKSICSQLLQKDPKTR 247

                         90
                 ....*....|....*...
gi 768035983  80 I-----TVYEALNHPWLK 92
Cdd:cd05605  248 LgcrgeGAEDVKSHPFFK 265
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
 1-80 1.19e-08

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: 57.73  E-value: 1.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRQwshISESAKDLVRRMLMLDPAER 79
Cdd:cd05594  193 LAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDhEKLFELILMEEIRF-PRT---LSPEAKSLLSGLLKKDPKQR 268


                 .
gi 768035983  80 I 80
Cdd:cd05594  269 L 269
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
 2-89 1.21e-08

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: 56.90  E-value: 1.21e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP---VDVWGCGVILFILLSGCL-PFYGTKERlfEG-IIKGKYKMNP--RQWSHISEsAKDLVRRMLML 74
Cdd:cd13982  175 APEMLSGSTKRRQtraVDIFSLGCVFYYVLSGGShPFGDKLER--EAnILKGKYSLDKllSLGEHGPE-AQDLIERMIDF 251

                         90
                 ....*....|....*
gi 768035983  75 DPAERITVYEALNHP 89
Cdd:cd13982  252 DPEKRPSAEEVLNHP 266
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
 425-483 1.30e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 51.38  E-value: 1.30e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDlipckEAGirFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11949    1 YVQALFDFDPQEDG-----ELG--FRRGDFIEVMDNSDPNWWKGAC----HGQTGMFPR 48
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
 1-87 1.62e-08

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: 56.48  E-value: 1.62e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT--KERLFEgIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAE 78
Cdd:cd14187  174 IAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSclKETYLR-IKKNEYSI-PK---HINPVAASLIQKMLQTDPTA 248


                 ....*....
gi 768035983  79 RITVYEALN 87
Cdd:cd14187  249 RPTINELLN 257
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
 1-92 1.77e-08

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: 56.59  E-value: 1.77e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYgtKERLFEGIIKGKYKMNPR-QWSH-ISESAKDLVRRMLMLDPAE 78
Cdd:cd06658  185 MAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYF--NEPPLQAMRRIRDNLPPRvKDSHkVSSVLRGFLDLMLVREPSQ 262

                         90
                 ....*....|....
gi 768035983  79 RITVYEALNHPWLK 92
Cdd:cd06658  263 RATAQELLQHPFLK 276
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 427-483 1.87e-08

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 50.66  E-value: 1.87e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983  427 RAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLensKNGTAGLIPS 483
Cdd:pfam00018   1 VALYDYTAQEPDELS-------FKKGDIIIVLEKSEDGWWKGRN---KGGKEGLIPS 47
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
 1-90 2.66e-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: 55.76  E-value: 2.66e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYK-MNPRQWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd14010  177 MAPELFQGGVHSFASDLWALGCVLYEMFTGKPPFVAESfTELVEKILNEDPPpPPPKVSSKPSPDFKSLLKGLLEKDPAK 256

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHP-W 90
Cdd:cd14010  257 RLSWDELVKHPfW 269
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
 2-90 2.67e-08

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: 56.08  E-value: 2.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLF-------EGI---------IKGKYKMNPRQW-- 57
Cdd:cd07843  174 APELLLGAKeYSTAIDMWSVGCIFAELLTKKPLFPGKSEidqlnKIFkllgtptEKIwpgfselpgAKKKTFTKYPYNql 253

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 768035983  58 ------SHISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07843  254 rkkfpaLSLSDNGFDLLNRLLTYDPAKRISAEDALKHPY 292
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
 1-91 2.92e-08

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: 55.74  E-value: 2.92e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK--REPY-GKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQwSHISESAKDLVRRMLMLDPA 77
Cdd:cd14199  193 MAPETLSetRKIFsGKALDVWAMGVTLYCFVFGQCPFMDERILSLHSKIKTQPLEFPDQ-PDISDDLKDLLFRMLDKNPE 271

                         90
                 ....*....|....
gi 768035983  78 ERITVYEALNHPWL 91
Cdd:cd14199  272 SRISVPEIKLHPWV 285
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 3-92 3.68e-08

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 55.24  E-value: 3.68e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPY-GKPVDVWGCGVILFILLSGCLPFygtkERlFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAERIT 81
Cdd:cd14101  176 PEWILYHQYhALPATVWSLGILLYDMVCGDIPF----ER-DTDILKAKPSFN----KRVSNDCRSLIRSCLAYNPSDRPS 246

                         90
                 ....*....|.
gi 768035983  82 VYEALNHPWLK 92
Cdd:cd14101  247 LEQILLHPWMM 257
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
 1-80 3.72e-08

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 55.39  E-value: 3.72e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYG--KPVDVWGCGVILFILLSGCLPFY--GTKERLFEgIIKGKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd05613  173 MAPEIVRGGDSGhdKAVDWWSLGVLMYELLTGASPFTvdGEKNSQAE-ISRRILKSEPPYPQEMSALAKDIIQRLLMKDP 251


                 ....
gi 768035983  77 AERI 80
Cdd:cd05613  252 KKRL 255
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
1-79 4.22e-08

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 56.17  E-value: 4.22e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:COG0515  175 MAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGdSPAELLRAHLREPPPPPSELRPDLPPALDAIVLRALAKDPEER 254
pk1 PHA03390
serine/threonine-protein kinase 1; Provisional
 3-92 4.23e-08

serine/threonine-protein kinase 1; Provisional


Pssm-ID: 223069 [Multi-domain]  Cd Length: 267  Bit Score: 55.25  E-value: 4.23e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEgiIKgkyKMNPRQW------SHISESAKDLVRRMLMLDP 76
Cdd:PHA03390 175 PEKIKGHNYDVSFDWWAVGVLTYELLTGKHPFKEDEDEELD--LE---SLLKRQQkklpfiKNVSKNANDFVQSMLKYNI 249

                         90
                 ....*....|....*..
gi 768035983  77 AERITVYEA-LNHPWLK 92
Cdd:PHA03390 250 NYRLTNYNEiIKHPFLK 266
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
 1-91 4.29e-08

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


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 54.92  E-value: 4.29e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFY--GTKERLfEGIIKGKYKMNpRQWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd14110  167 MAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSsdLNWERD-RNIRKGKVQLS-RCYAGLSGGAVNFLKSTLCAKPWG 244

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd14110  245 RPTASECLQNPWL 257
PDZ6_GRIP1-2-like cd06683
PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 300-376 4.91e-08

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467171 [Multi-domain]  Cd Length: 85  Bit Score: 50.77  E-value: 4.91e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 300 VQFQKNTDePMGITLKMNE--LNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06683    6 VELKRYGG-PLGITISGTEepFDPIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNAGDTVTLKI 83
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
 1-93 5.74e-08

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: 55.03  E-value: 5.74e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWS-HISESAKDLVRRMLMLDPAER 79
Cdd:cd05630  168 MAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPFQQRKKKIKREEVERLVKEVPEEYSeKFSPQARSLCSMLLCKDPAER 247

                         90
                 ....*....|....*....
gi 768035983  80 I-----TVYEALNHPWLKE 93
Cdd:cd05630  248 LgcrggGAREVKEHPLFKK 266
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
 2-93 6.76e-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: 6.76e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEV-VKREPYGKPVDVWGCGVILFILLSgCLPFYGTKERL-----------------FEGIIKGKYK-------MNPRQ 56
Cdd:cd07849  177 APEImLNSKGYTKAIDIWSVGCILAEMLS-NRPLFPGKDYLhqlnlilgilgtpsqedLNCIISLKARnyikslpFKPKV 255

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 768035983  57 -----WSHISESAKDLVRRMLMLDPAERITVYEALNHPWLKE 93
Cdd:cd07849  256 pwnklFPNADPKALDLLDKMLTFNPHKRITVEEALAHPYLEQ 297
PDZ1_APBA1_3-like cd06720
PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, ...
 300-377 7.46e-08

PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as (X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2), which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins such as APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This APBA1,2,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467203 [Multi-domain]  Cd Length: 86  Bit Score: 50.34  E-value: 7.46e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 300 VQFQKNTDEPMGITL------KMneLNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGS-- 371
Cdd:cd06720    3 VVVEKQKGEILGVVIvesgwgSL--LPTVVVANMMPGGPAARSGKLNIGDQIMSINGTSLVGLPLSTCQAIIKNLKNQtk 80


                 ....*.
gi 768035983 372 ITFKIV 377
Cdd:cd06720   81 VKLTVV 86
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 425-488 7.97e-08

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 49.13  E-value: 7.97e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983  425 YVRAQFEYdpakddlIPCKEAGIRFRVGDIIQIISKDDHNWWQGklenSKNGTAGLIPSPELQE 488
Cdd:pfam07653   1 YGRVIFDY-------VGTDKNGLTLKKGDVVKVLGKDNDGWWEG----ETGGRVGLVPSTAVEE 53
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
 2-91 8.18e-08

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 54.68  E-value: 8.18e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV-KREPYGKPVDVWGCGVILFILLSGCLPFYGT----KERLFEGIIKG---------------KYKMN----PRQ- 56
Cdd:cd07858  176 APELLlNCSEYTTAIDVWSVGCIFAELLGRKPLFPGKdyvhQLKLITELLGSpseedlgfirnekarRYIRSlpytPRQs 255

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 768035983  57 ----WSHISESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07858  256 farlFPHANPLAIDLLEKMLVFDPSKRITVEEALAHPYL 294
STKc_Sid2p_like cd05600
Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the ...
 1-95 8.30e-08

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270751 [Multi-domain]  Cd Length: 386  Bit Score: 55.04  E-value: 8.30e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKM------NPRQWSHISESAKDLVRRMLM 73
Cdd:cd05600  215 MAPEVLRGEGYDLTVDYWSLGCILFECLVGFPPFSGsTPNETWANLYHWKKTLqrpvytDPDLEFNLSDEAWDLITKLIT 294

                         90       100
                 ....*....|....*....|...
gi 768035983  74 lDPAERITVYEAL-NHPWLKERD 95
Cdd:cd05600  295 -DPQDRLQSPEQIkNHPFFKNID 316
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
 2-91 8.37e-08

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


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 54.21  E-value: 8.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14113  173 APEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDeSVEETCLNICRLDFSFPDDYFKGVSQKAKDFVCFLLQMDPAKRP 252

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14113  253 SAALCLQEQWL 263
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
 1-80 8.38e-08

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: 54.71  E-value: 8.38e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT-KERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05582  164 MAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKdRKETMTMILKAKLGM-PQ---FLSPEAQSLLRALFKRNPANR 239


                 .
gi 768035983  80 I 80
Cdd:cd05582  240 L 240
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
 2-91 8.44e-08

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: 54.05  E-value: 8.44e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFygTKE-----RLFEGIIKGkyKMNPRQwSHISESAKDLVRRMLMLDP 76
Cdd:cd14070  173 APELLARKKYGPKVDVWSIGVNMYAMLTGTLPF--TVEpfslrALHQKMVDK--EMNPLP-TDLSPGAISFLRSLLEPDP 247

                         90
                 ....*....|....*
gi 768035983  77 AERITVYEALNHPWL 91
Cdd:cd14070  248 LKRPNIKQALANRWL 262
STKc_LATS cd05598
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the ...
 1-105 9.51e-08

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: 54.63  E-value: 9.51e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-----TKERlfegIIKGKYKMNPRQWSHISESAKDLVRRmLMLD 75
Cdd:cd05598  172 IAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAqtpaeTQLK----VINWRTTLKIPHEANLSPEAKDLILR-LCCD 246

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 768035983  76 PAERI---TVYEALNHPWLK----ERDRYAYKIHLPE 105
Cdd:cd05598  247 AEDRLgrnGADEIKAHPFFAgidwEKLRKQKAPYIPT 283
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
 1-92 9.93e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 54.59  E-value: 9.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWS-HISESAKDLVRRMLMLDPAER 79
Cdd:cd05632  170 MAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSaKFSEEAKSICKMLLTKDPKQR 249

                         90
                 ....*....|....*...
gi 768035983  80 ITVY-----EALNHPWLK 92
Cdd:cd05632  250 LGCQeegagEVKRHPFFR 267
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
 1-87 1.03e-07

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: 53.81  E-value: 1.03e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE---RLFEGIIKGKYKmnPRQWSHISESAKDLVRRMLMLDPA 77
Cdd:cd08224  171 MSPERIREQGYDFKSDIWSLGCLLYEMAALQSPFYGEKMnlySLCKKIEKCEYP--PLPADLYSQELRDLVAACIQPDPE 248

                         90
                 ....*....|
gi 768035983  78 ERITVYEALN 87
Cdd:cd08224  249 KRPDISYVLD 258
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
 1-96 1.13e-07

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: 53.71  E-value: 1.13e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF-YGTKERLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd14117  171 LPPEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFeSASHTETYRRIVKVDLKFPP----FLSDGSRDLISKLLRYHPSER 246

                         90
                 ....*....|....*..
gi 768035983  80 ITVYEALNHPWLKERDR 96
Cdd:cd14117  247 LPLKGVMEHPWVKANSR 263
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
 1-92 1.23e-07

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 54.38  E-value: 1.23e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK---REP--------YGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEgiIKGK--------------- 49
Cdd:PTZ00024 190 MTSKVVTlwyRAPellmgaekYHFAVDMWSVGCIFAELLTGKPLFPGENEidqlgRIFE--LLGTpnednwpqakklply 267

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 768035983  50 ---YKMNPRQWS----HISESAKDLVRRMLMLDPAERITVYEALNHPWLK 92
Cdd:PTZ00024 268 tefTPRKPKDLKtifpNASDDAIDLLQSLLKLNPLERISAKEALKHEYFK 317
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
 425-482 1.23e-07

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 48.89  E-value: 1.23e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 425 YVRAQFEYDPAKDDLIpckeagiRFRVGDIIQIISKD--DHNWWQGKLenskNGTAGLIP 482
Cdd:cd11875    1 KARVLFDYEAENEDEL-------TLREGDIVTILSKDceDKGWWKGEL----NGKRGVFP 49
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
 424-488 1.41e-07

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 48.51  E-value: 1.41e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 768035983 424 IYVRAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKleNSKnGTAGLIPSPELQE 488
Cdd:cd11758    1 EYVRALFDFPGNDDEDLP-------FKKGEILTVIRKPEEQWWNAR--NSE-GKTGMIPVPYVEK 55
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
 1-80 1.41e-07

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: 53.94  E-value: 1.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIkgkyKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05587  164 IAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEdELFQSIM----EHNVSYPKSLSKEAVSICKGLLTKHPAKR 239


                 .
gi 768035983  80 I 80
Cdd:cd05587  240 L 240
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
 1-80 1.44e-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: 53.68  E-value: 1.44e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKRE-PYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSH-ISESAKDLVRRMLMLDPAE 78
Cdd:cd05577  161 MAPEVLQKEvAYDFSVDWFALGCMLYEMIAGRSPFRQRKEKVDKEELKRRTLEMAVEYPDsFSPEARSLCEGLLQKDPER 240


                 ..
gi 768035983  79 RI 80
Cdd:cd05577  241 RL 242
PKc_DYRK cd14210
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
 2-91 1.46e-07

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.


Pssm-ID: 271112 [Multi-domain]  Cd Length: 311  Bit Score: 53.70  E-value: 1.46e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIK---------------------GKYKMNPRQWSH 59
Cdd:cd14210  183 APEVILGLPYDTAIDMWSLGCILAELYTGYPLFPGENEEeQLACIMEvlgvppkslidkasrrkkffdSNGKPRPTTNSK 262

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 768035983  60 I-----------------SESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14210  263 GkkrrpgskslaqvlkcdDPSFLDFLKKCLRWDPSERMTPEEALQHPWI 311
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
 9-91 1.69e-07

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: 53.65  E-value: 1.69e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   9 EPYGKPVDVWGCGVILFILLSGCLPFYGTKERL-FEGIIKGKYKMNPRQW--------------------------SHIS 61
Cdd:cd07864  193 ERYGPAIDVWSCGCILGELFTKKPIFQANQELAqLELISRLCGSPCPAVWpdviklpyfntmkpkkqyrrrlreefSFIP 272

                         90       100       110
                 ....*....|....*....|....*....|
gi 768035983  62 ESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07864  273 TPALDLLDHMLTLDPSKRCTAEQALNSPWL 302
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
 1-91 1.74e-07

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: 53.15  E-value: 1.74e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV--KREPYGKPVDVWGCGVILFILLSGCLPFygTKERLFEGIIK-GKYKMNP--RQWSHISESAKDLVRRMLMLD 75
Cdd:cd06629  177 MAPEVIhsQGQGYSAKVDIWSLGCVVLEMLAGRRPW--SDDEAIAAMFKlGNKRSAPpvPEDVNLSPEALDFLNACFAID 254

                         90
                 ....*....|....*.
gi 768035983  76 PAERITVYEALNHPWL 91
Cdd:cd06629  255 PRDRPTAAELLSHPFL 270
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
 2-93 1.77e-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: 53.84  E-value: 1.77e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV-KREPYGKPVDVWGCGVILFILLSGCLPFYGT----------------KERLFEGI--------IKGKYKMNPRQ 56
Cdd:cd07851  183 APEIMlNWMHYNQTVDIWSVGCIMAELLTGKTLFPGSdhidqlkrimnlvgtpDEELLKKIssesarnyIQSLPQMPKKD 262

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768035983  57 WSHI----SESAKDLVRRMLMLDPAERITVYEALNHPWLKE 93
Cdd:cd07851  263 FKEVfsgaNPLAIDLLEKMLVLDPDKRITAAEALAHPYLAE 303
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
 1-91 1.78e-07

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: 53.00  E-value: 1.78e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVW--GCGVILfiLLSGCLPFYGTK--ERLFEgIIKGKYkmnPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd06627  166 MAPEVIEMSGVTTASDIWsvGCTVIE--LLTGNPPYYDLQpmAALFR-IVQDDH---PPLPENISPELRDFLLQCFQKDP 239

                         90
                 ....*....|....*
gi 768035983  77 AERITVYEALNHPWL 91
Cdd:cd06627  240 TLRPSAKELLKHPWL 254
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
 1-91 1.81e-07

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: 53.21  E-value: 1.81e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLP----------FYgtkerlfegiIKGKYKMNPRQWSHISESAKDLVRR 70
Cdd:cd06631  176 MAPEVINETGHGRKSDIWSIGCTVFEMATGKPPwadmnpmaaiFA----------IGSGRKPVPRLPDKFSPEARDFVHA 245

                         90       100
                 ....*....|....*....|.
gi 768035983  71 MLMLDPAERITVYEALNHPWL 91
Cdd:cd06631  246 CLTRDQDERPSAEQLLKHPFI 266
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
 2-91 1.93e-07

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: 53.31  E-value: 1.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTKErlfegiIKGKYKM-------NPRQWS--------------- 58
Cdd:cd07830  166 APEILLRSTsYSSPVDIWALGCIMAELYTLRPLFPGSSE------IDQLYKIcsvlgtpTKQDWPegyklasklgfrfpq 239

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 768035983  59 -----------HISESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07830  240 faptslhqlipNASPEAIDLIKDMLRWDPKKRPTASQALQHPYF 283
PDZ1_Par3-like cd06691
PDZ domain 1 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 296-381 2.10e-07

PDZ domain 1 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP) and related domains; Drosophila bazooka PDZ1 belongs to a different PDZ family. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include: Par-3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467178 [Multi-domain]  Cd Length: 98  Bit Score: 49.54  E-value: 2.10e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 296 RVRLVQFqKNTDEPMGI-------TLKMNELNHCIvARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLRE- 367
Cdd:cd06691    4 MTKTVEL-SNDGGPLGIhvvpfssSLSGRTLGLLI-RGIEEGSRAERDGRFQENDCIVEINGVDLIDKSFEQAQDIFRQa 81

                         90
                 ....*....|....*
gi 768035983 368 MRG-SITFKIVPSYR 381
Cdd:cd06691   82 MRSpEVKLHVVPAAN 96
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
 1-80 2.30e-07

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: 53.46  E-value: 2.30e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMnPRQwshISESAKDLVRRMLMLDPAER 79
Cdd:cd05616  168 IAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEdELFQSIMEHNVAY-PKS---MSKEAVAICKGLMTKHPGKR 243


                 .
gi 768035983  80 I 80
Cdd:cd05616  244 L 244
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
 1-95 2.63e-07

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: 53.16  E-value: 2.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIikgkykMNPRQW--SHISESAKDLVRRMLMLDPA 77
Cdd:cd05592  163 IAPEILKGQKYNQSVDWWSFGVLLYEMLIGQSPFHGEDEdELFWSI------CNDTPHypRWLTKEAASCLSLLLERNPE 236

                         90       100
                 ....*....|....*....|...
gi 768035983  78 ERITVYEAL-----NHPWLKERD 95
Cdd:cd05592  237 KRLGVPECPagdirDHPFFKTID 259
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
 2-93 2.72e-07

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: 53.33  E-value: 2.72e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEV-VKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-----ERLFEGI----------IKGKY------KMNPRQ--- 56
Cdd:cd07852  180 APEIlLGSTRYTKGVDMWSVGCILGEMLLGKPLFPGTStlnqlEKIIEVIgrpsaediesIQSPFaatmleSLPPSRpks 259

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768035983  57 ----WSHISESAKDLVRRMLMLDPAERITVYEALNHPWLKE 93
Cdd:cd07852  260 ldelFPKASPDALDLLKKLLVFNPNKRLTAEEALRHPYVAQ 300
PDZ3_harmonin cd06739
PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic ...
 297-367 2.85e-07

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467221 [Multi-domain]  Cd Length: 94  Bit Score: 48.84  E-value: 2.85e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 297 VRLVQFQKNTDEPMGITLKMNE--LNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLRE 367
Cdd:cd06739    3 VRLLRIKKNGPLDLALEGGIDSplGGKIVVSAVYEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEAEAALQR 75
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 1-89 3.13e-07

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: 52.43  E-value: 3.13e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIkgkYKMN-----PRQWSHISESAKDLVRRMLMLD 75
Cdd:cd06630  175 MAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKISNHLALI---FKIAsattpPPIPEHLSPGLRDVTLRCLELQ 251

                         90
                 ....*....|....
gi 768035983  76 PAERITVYEALNHP 89
Cdd:cd06630  252 PEDRPPARELLKHP 265
SH3_CACNB cd11863
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta; ...
 426-484 3.30e-07

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta; Voltage-dependent calcium channels (Ca(V)s) are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212797 [Multi-domain]  Cd Length: 62  Bit Score: 47.66  E-value: 3.30e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 426 VRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenSKNGTA-GLIPSP 484
Cdd:cd11863    3 VRTNVGYDGSLDDDSPVPGYAVSFEAKDFLHIKEKYNNDWWIGRL--VKEGCDiGFIPSP 60
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 1-87 3.58e-07

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: 52.29  E-value: 3.58e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSgclPFYGTKERL--FEGIIKGKYKMNPRQWsHISEsaKDLVRRMLMLDPAE 78
Cdd:cd13996  189 ASPEQLDGENYNEKADIYSLGIILFEMLH---PFKTAMERStiLTDLRNGILPESFKAK-HPKE--ADLIQSLLSKNPEE 262


                 ....*....
gi 768035983  79 RITVYEALN 87
Cdd:cd13996  263 RPSAEQLLR 271
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
 1-89 3.59e-07

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 52.60  E-value: 3.59e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSH--ISESAKDLVRRMLMLDPAE 78
Cdd:cd05607  170 MAPEILKEESYSYPVDWFAMGCSIYEMVAGRTPFRDHKEKVSKEELKRRTLEDEVKFEHqnFTEEAKDICRLFLAKKPEN 249

                         90
                 ....*....|.
gi 768035983  79 RITVYEALNHP 89
Cdd:cd05607  250 RLGSRTNDDDP 260
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
 1-95 3.59e-07

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 52.60  E-value: 3.59e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNprQWshISESAKDLVRRMLMLDPAER 79
Cdd:cd05590  163 IAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAeNEDDLFEAILNDEVVYP--TW--LSQDAVDILKAFMTKNPTMR 238

                         90       100
                 ....*....|....*....|..
gi 768035983  80 ITVYE------ALNHPWLKERD 95
Cdd:cd05590  239 LGSLTlggeeaILRHPFFKELD 260
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
 1-95 4.29e-07

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: 52.62  E-value: 4.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT-KERLFEGiIKGKYKMNPRqWshISESAKDLVRRMLMLDPAER 79
Cdd:cd05619  173 IAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQdEEELFQS-IRMDNPFYPR-W--LEKEAKDILVKLFVREPERR 248

                         90
                 ....*....|....*..
gi 768035983  80 ITVYEAL-NHPWLKERD 95
Cdd:cd05619  249 LGVRGDIrQHPFFREIN 265
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 3-91 4.39e-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: 51.89  E-value: 4.39e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKErlfegIIKGKYKMNPRqwshISESAKDLVRRMLMLDPAERIT 81
Cdd:cd14100  174 PEWIRFHRYhGRSAAVWSLGILLYDMVCGDIPFEHDEE-----IIRGQVFFRQR----VSSECQHLIKWCLALRPSDRPS 244

                         90
                 ....*....|
gi 768035983  82 VYEALNHPWL 91
Cdd:cd14100  245 FEDIQNHPWM 254
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
 426-483 4.52e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 47.03  E-value: 4.52e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11840    2 VIALFPYTAQNED-------ELSFQKGDIINVLSKDDPDWWRGEL----NGQTGLFPS 48
PDZ2_DLG5-like cd06765
PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 310-377 4.93e-07

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PSZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467246 [Multi-domain]  Cd Length: 77  Bit Score: 47.73  E-value: 4.93e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 310 MGITLKmnelNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06765   10 SGISLE----NGVFISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKSLSECEALLRSCRDSLSLSLM 73
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
 1-92 5.23e-07

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: 52.25  E-value: 5.23e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGiIKGKYKMNPRqWshISESAKDLVRRMLMLDPAER 79
Cdd:cd05620  163 IAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEdELFES-IRVDTPHYPR-W--ITKESKDILEKLFERDPTRR 238

                         90
                 ....*....|....
gi 768035983  80 ITVYEALN-HPWLK 92
Cdd:cd05620  239 LGVVGNIRgHPFFK 252
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
 2-95 5.24e-07

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 52.23  E-value: 5.24e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGtkerlfEGIIKGKYK-MNPRQW------SHISESAKDLVRRmLML 74
Cdd:cd05599  168 APEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCS------DDPQETCRKiMNWRETlvfppeVPISPEAKDLIER-LLC 240

                         90       100
                 ....*....|....*....|....
gi 768035983  75 DPAERI---TVYEALNHPWLKERD 95
Cdd:cd05599  241 DAEHRLganGVEEIKSHPFFKGVD 264
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
 1-80 5.84e-07

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: 52.33  E-value: 5.84e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05602  175 LAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSrNTAEMYDNILNKPLQLKP----NITNSARHLLEGLLQKDRTKR 250


                 .
gi 768035983  80 I 80
Cdd:cd05602  251 L 251
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
 1-94 7.19e-07

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: 51.42  E-value: 7.19e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKR-----------EPYGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFE-----------GIIKGKY--- 50
Cdd:cd07841  159 MTHQVVTRwyrapellfgaRHYGVGVDMWSVGCIFAELLLRVPFLPGDSDidqlgKIFEalgtpteenwpGVTSLPDyve 238

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 768035983  51 --KMNPRQWSHI----SESAKDLVRRMLMLDPAERITVYEALNHPWLKER 94
Cdd:cd07841  239 fkPFPPTPLKQIfpaaSDDALDLLQRLLTLNPNKRITARQALEHPYFSND 288
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
 1-92 7.24e-07

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: 51.47  E-value: 7.24e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd06647  170 MAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLNRCLEMDVEKRG 249

                         90
                 ....*....|..
gi 768035983  81 TVYEALNHPWLK 92
Cdd:cd06647  250 SAKELLQHPFLK 261
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
 1-91 8.16e-07

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: 50.87  E-value: 8.16e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKMNPRQWshiSESAKDLVRRMLMLDPAER 79
Cdd:cd08529  168 LSPELCEDKPYNEKSDVWALGCVLYELCTGKHPFEAQNQgALILKIVRGKYPPISASY---SQDLSQLIDSCLTKDYRQR 244

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd08529  245 PDTTELLRNPSL 256
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
 1-113 9.31e-07

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: 51.09  E-value: 9.31e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGcLPFYGTKER---LFEgIIKGKYKMNPRqwSHISESAKDLVRRMLMLDPA 77
Cdd:cd06609  165 MAPEVIKQSGYDEKADIWSLGITAIELAKG-EPPLSDLHPmrvLFL-IPKNNPPSLEG--NKFSKPFKDFVELCLNKDPK 240

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768035983  78 ERITVYEALNHPWLKERDRYAYkihLPETVEQLRKF 113
Cdd:cd06609  241 ERPSAKELLKHKFIKKAKKTSY---LTLLIERIKKW 273
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
 1-92 9.42e-07

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: 51.26  E-value: 9.42e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK--ERLFEGIIKGKYKM-NPRQWSHIsesAKDLVRRMLMLDPA 77
Cdd:cd06655  182 MAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENplRALYLIATNGTPELqNPEKLSPI---FRDFLNRCLEMDVE 258

                         90
                 ....*....|....*
gi 768035983  78 ERITVYEALNHPWLK 92
Cdd:cd06655  259 KRGSAKELLQHPFLK 273
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
 1-80 1.00e-06

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 51.51  E-value: 1.00e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNPRQwshiSESAKDLVRRMLMLDPAER 79
Cdd:cd05603  163 LAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDvSQMYDNILHKPLHLPGGK----TVAACDLLQGLLHKDQRRR 238


                 .
gi 768035983  80 I 80
Cdd:cd05603  239 L 239
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
 1-90 1.01e-06

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: 50.82  E-value: 1.01e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGtkerlFE---GIIK-GKYKMNPRQWSHISESAKDLVRRMLMLDP 76
Cdd:cd06625  171 MSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPWAE-----FEpmaAIFKiATQPTNPQLPPHVSEDARDFLSLIFVRNK 245

                         90
                 ....*....|....
gi 768035983  77 AERITVYEALNHPW 90
Cdd:cd06625  246 KQRPSAEELLSHSF 259
SH3_DLG4 cd12030
Src Homology 3 domain of Disks Large homolog 4; DLG4, also called postsynaptic density-95 ...
 425-483 1.11e-06

Src Homology 3 domain of Disks Large homolog 4; DLG4, also called postsynaptic density-95 (PSD95) or synapse-associated protein 90 (SAP90), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. It is responsible for the membrane clustering and retention of many transporters and receptors such as potassium channels and PMCA4b, a P-type ion transport ATPase, among others. DLG4 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG4 contains three PDZ domains. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212963  Cd Length: 66  Bit Score: 46.46  E-value: 1.11e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 425 YVRAQFEYDPAKDdlipCK--EAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGT--AGLIPS 483
Cdd:cd12030    3 YIRALFDYDKTKD----CGflSQALSFRFGDVLHVIDAGDEEWWQARRVHSDSETeeIGFIPS 61
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
 1-91 1.36e-06

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 50.68  E-value: 1.36e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK--------REPY--GKPVDVWGCGVILFILLSGCLPFYgtkeRLFEGIIKGKYKMNPR---QWSHISE-SAKD 66
Cdd:cd14131  171 MSPEAIKdtsasgegKPKSkiGRPSDVWSLGCILYQMVYGKTPFQ----HITNPIAKLQAIIDPNheiEFPDIPNpDLID 246

                         90       100
                 ....*....|....*....|....*
gi 768035983  67 LVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14131  247 VMKRCLQRDPKKRPSIPELLNHPFL 271
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
 1-79 1.41e-06

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: 50.23  E-value: 1.41e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF--YGTKERLFEGIIKGKYKMNPrqwSHISESAKDLVRRMLMLDPAE 78
Cdd:cd13999  158 MAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFkeLSPIQIAAAVVQKGLRPPIP---PDCPPELSKLIKRCWNEDPEK 234


                 .
gi 768035983  79 R 79
Cdd:cd13999  235 R 235
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
 425-482 1.45e-06

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 45.56  E-value: 1.45e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 425 YVRAQFEYDPAKddlipckEAGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11951    1 FVQAQYDFSAED-------PSQLSFRRGDIIEVLDCPDPNWWRGRI----SGRVGFFP 47
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
 2-91 1.48e-06

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 50.22  E-value: 1.48e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKP-VDVWGCGVILFILLSGCLPF---YGTKERLFEGIIKGKYKMN--PRQwshISESAKDLVRRMLMLD 75
Cdd:cd14112  167 SPEFHNPETPITVqSDIWGLGVLTFCLLSGFHPFtseYDDEEETKENVIFVKCRPNliFVE---ATQEALRFATWALKKS 243

                         90
                 ....*....|....*.
gi 768035983  76 PAERITVYEALNHPWL 91
Cdd:cd14112  244 PTRRMRTDEALEHRWL 259
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
 3-91 1.49e-06

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: 50.34  E-value: 1.49e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTKErlfegIIKGKYKMNPRqwshISESAKDLVRRMLMLDPAERIT 81
Cdd:cd14102  173 PEWIRYHRYhGRSATVWSLGVLLYDMVCGDIPFEQDEE-----ILRGRLYFRRR----VSPECQQLIKWCLSLRPSDRPT 243

                         90
                 ....*....|
gi 768035983  82 VYEALNHPWL 91
Cdd:cd14102  244 LEQIFDHPWM 253
PDZ_GOPC-like cd06800
PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and ...
 298-377 1.50e-06

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GOPC-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467261 [Multi-domain]  Cd Length: 83  Bit Score: 46.60  E-value: 1.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 298 RLVQFQKNTDEPMGITLKM-NELNHCIVARIMHGGMI-HRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFK 375
Cdd:cd06800    1 RKVLLSKEPHEGLGISITGgKEHGVPILISEIHEGQPaDRCGGLYVGDAILSVNGIDLRDAKHKEAVTILSQQRGEITLE 80


                 ..
gi 768035983 376 IV 377
Cdd:cd06800   81 VV 82
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
 2-93 1.54e-06

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: 50.87  E-value: 1.54e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEV-VKREPYGKPVDVWGCGVILFILLSGcLPFYGTK---ERLFEgIIK-------------------------GKYKM 52
Cdd:cd07857  177 APEImLSFQSYTKAIDVWSVGCILAELLGR-KPVFKGKdyvDQLNQ-ILQvlgtpdeetlsrigspkaqnyirslPNIPK 254

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768035983  53 NPRQWSHISES--AKDLVRRMLMLDPAERITVYEALNHPWLKE 93
Cdd:cd07857  255 KPFESIFPNANplALDLLEKLLAFDPTKRISVEEALEHPYLAI 297
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
 2-91 1.55e-06

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 50.37  E-value: 1.55e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPY-GKPVDVWGCGVILFILLSGCLPFYGTK--ERLFEgiiKGKYKMNPRQWShISESAKDLVRRMLMLDPAE 78
Cdd:cd14163  169 APEVLQGVPHdSRKGDIWSMGVVLYVMLCAQLPFDDTDipKMLCQ---QQKGVSLPGHLG-VSRTCQDLLKRLLEPDMVL 244

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd14163  245 RPSIEEVSWHPWL 257
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
 1-91 1.56e-06

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 50.73  E-value: 1.56e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNPrqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05604  164 LAPEVIRKQPYDNTVDWWCLGSVLYEMLYGLPPFYCRDtAEMYENILHKPLVLRP----GISLTAWSILEELLEKDRQLR 239

                         90
                 ....*....|....*.
gi 768035983  80 ITVYEAL----NHPWL 91
Cdd:cd05604  240 LGAKEDFleikNHPFF 255
PDZ_Par6-like cd06718
PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F ...
 324-367 1.90e-06

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par6-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467202 [Multi-domain]  Cd Length: 84  Bit Score: 46.41  E-value: 1.90e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 768035983 324 VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLRE 367
Cdd:cd06718   31 ISRLVLGSLADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMMVA 74
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
 1-91 1.98e-06

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


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 49.90  E-value: 1.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER-LFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAeR 79
Cdd:cd14108  165 VAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRtTLMNIRNYNVAFEESMFKDLCREAKGFIIKVLVSDRL-R 243

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd14108  244 PDAEETLEHPWF 255
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
 2-97 2.00e-06

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: 50.51  E-value: 2.00e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP-YGKPVDVWGCGVILFILLSGCLPF---------------YGTK--ERLF---EG----IIKGKYKMNPRQ 56
Cdd:cd07853  172 APEILMGSRhYTSAVDIWSVGCIFAELLGRRILFqaqspiqqldlitdlLGTPslEAMRsacEGarahILRGPHKPPSLP 251

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 768035983  57 W-----SHISESAKDLVRRMLMLDPAERITVYEALNHPWLKE-RDRY 97
Cdd:cd07853  252 VlytlsSQATHEAVHLLCRMLVFDPDKRISAADALAHPYLDEgRLRY 298
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
 1-80 2.07e-06

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: 50.38  E-value: 2.07e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIkgkyKMNPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05615  178 IAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEdELFQSIM----EHNVSYPKSLSKEAVSICKGLMTKHPAKR 253


                 .
gi 768035983  80 I 80
Cdd:cd05615  254 L 254
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
 425-482 2.22e-06

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 45.00  E-value: 2.22e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 425 YVRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11826    1 KVVALYDYTADKDD-------ELSFQEGDIIYVTKKNDDGWYEGVL----NGVTGLFP 47
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
 1-89 2.22e-06

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270761 [Multi-domain]  Cd Length: 349  Bit Score: 50.26  E-value: 2.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRQWSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05610  224 LAPELLLGKPHGPAVDWWALGVCLFEFLTGIPPFNDeTPQQVFQNILNRDIPW-PEGEEELSVNAQNAIEILLTMDPTKR 302

                         90
                 ....*....|
gi 768035983  80 ITVYEALNHP 89
Cdd:cd05610  303 AGLKELKQHP 312
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
 425-483 2.34e-06

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 44.97  E-value: 2.34e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 425 YVRAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKL-ENSKNGTAGLIPS 483
Cdd:cd11883    1 VVVALYDFTPKSKNQLS-------FKAGDIIYVLNKDPSGWWDGVIiSSSGKVKRGWFPS 53
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
 427-483 2.39e-06

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 45.02  E-value: 2.39e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 427 RAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11874    3 KVLFSYTPQNED-------ELELKVGDTIEVLGEVEEGWWEGKL----NGKVGVFPS 48
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
 1-92 2.41e-06

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: 50.11  E-value: 2.41e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK--ERLFEGIIKGKYKM-NPRQWSHIsesAKDLVRRMLMLDPA 77
Cdd:cd06656  182 MAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENplRALYLIATNGTPELqNPERLSAV---FRDFLNRCLEMDVD 258

                         90
                 ....*....|....*
gi 768035983  78 ERITVYEALNHPWLK 92
Cdd:cd06656  259 RRGSAKELLQHPFLK 273
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
 2-91 2.67e-06

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 50.41  E-value: 2.67e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE--------------------RLFEGIikGKYKMNPRQ----- 56
Cdd:cd07876  190 APEVILGMGYKENVDIWSVGCIMGELVKGSVIFQGTDHidqwnkvieqlgtpsaefmnRLQPTV--RNYVENRPQypgis 267

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768035983  57 -------WSHISES---------AKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07876  268 feelfpdWIFPSESerdklktsqARDLLSKMLVIDPDKRISVDEALRHPYI 318
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
 425-482 2.68e-06

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 45.15  E-value: 2.68e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 425 YVRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISK--DDHNWWQGKLenskNGTAGLIP 482
Cdd:cd12142    1 YCRVLFDYNPVAPD-------ELALKKGDVIEVISKetEDEGWWEGEL----NGRRGFFP 49
PKc_CLK3 cd14214
Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity ...
 3-91 2.70e-06

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 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: 271116 [Multi-domain]  Cd Length: 331  Bit Score: 50.01  E-value: 2.70e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER----LFEGII------------KGKY--------KMNPRQWS 58
Cdd:cd14214  202 PEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHENRehlvMMEKILgpipshmihrtrKQKYfykgslvwDENSSDGR 281

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 768035983  59 HISESAK-----------------DLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14214  282 YVSENCKplmsymlgdslehtqlfDLLRRMLEFDPALRITLKEALLHPFF 331
PKc_CLK cd14134
Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity ...
 2-91 3.23e-06

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271036 [Multi-domain]  Cd Length: 332  Bit Score: 49.87  E-value: 3.23e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPF----------------------------YGTKERLF--------EGI 45
Cdd:cd14134  199 APEVILGLGWSYPCDVWSIGCILVELYTGELLFqthdnlehlammerilgplpkrmirrakKGAKYFYFyhgrldwpEGS 278

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983  46 IKGKY-KMNPRQWSHISESAK-------DLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14134  279 SSGRSiKRVCKPLKRLMLLVDpehrllfDLIRKMLEYDPSKRITAKEALKHPFF 332
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
 2-91 3.34e-06

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 49.53  E-value: 3.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGT--------------------------KERLFE------------ 43
Cdd:cd14135  172 APEIILGLPYDYPIDMWSVGCTLYELYTGKILFPGKtnnhmlklmmdlkgkfpkkmlrkgqfKDQHFDenlnfiyrevdk 251

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983  44 --------------------GIIKGKYKMN---PRQWSHIsesaKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14135  252 vtkkevrrvmsdikptkdlkTLLIGKQRLPdedRKKLLQL----KDLLDKCLMLDPEKRITPNEALQHPFI 318
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
 425-483 3.53e-06

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 44.70  E-value: 3.53e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 425 YVRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHN----WWQGKLenskNGTAGLIPS 483
Cdd:cd11762    1 LVRALYDYEAQSDE-------ELSFPEGAIIRILRKDDNGvddgWWEGEF----NGRVGVFPS 52
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
 426-483 3.73e-06

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 44.55  E-value: 3.73e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKlenSKNGTaGLIPS 483
Cdd:cd11964    3 VRAIYDFEAAEDN-------ELTFKAGDIITILDDSDPNWWKGE---TPQGT-GLFPS 49
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
 1-88 4.02e-06

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: 48.77  E-value: 4.02e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14189  168 LAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDlKETYRCIKQVKYTLP----ASLSLPARHLLAGILKRNPGDR 243


                 ....*....
gi 768035983  80 ITVYEALNH 88
Cdd:cd14189  244 LTLDQILEH 252
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
 1-89 4.78e-06

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: 48.52  E-value: 4.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLfegiiKGKYKMN----PRQWSHISESAKDLVRRMLMLD 75
Cdd:cd14120  167 MAPEVIMSLQYDAKADLWSIGTIVYQCLTGKAPFQAqTPQEL-----KAFYEKNanlrPNIPSGTSPALKDLLLGLLKRN 241

                         90
                 ....*....|....
gi 768035983  76 PAERITVYEALNHP 89
Cdd:cd14120  242 PKDRIDFEDFFSHP 255
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
 427-483 4.84e-06

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 44.23  E-value: 4.84e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 427 RAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLEnskNGTAGLIPS 483
Cdd:cd11819    3 KALYDYQAAEDNEIS-------FVEGDIITQIEQIDEGWWLGVNA---KGQKGLFPA 49
PDZ3_GRIP1-2-like cd06684
PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 299-378 4.85e-06

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467172 [Multi-domain]  Cd Length: 87  Bit Score: 45.32  E-value: 4.85e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 299 LVQFQKNTDEPMGITLkmNELNHC-----IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLRE-MRGSI 372
Cdd:cd06684    4 LVEIEKTPGSSLGITL--STSTHRnkqviVIDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLLASnSGDQV 81


                 ....*.
gi 768035983 373 TFKIVP 378
Cdd:cd06684   82 KLEILP 87
PDZ_Lin-7-like cd06796
PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), ...
 298-373 4.86e-06

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Lin-7-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467258 [Multi-domain]  Cd Length: 86  Bit Score: 45.12  E-value: 4.86e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 298 RLVQFQKnTDEPMGITLkM--NELNHCI-VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSIT 373
Cdd:cd06796    3 RVVELPK-TEEGLGFNV-MggKEQNSPIyISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVK 79
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 1-92 5.11e-06

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: 49.08  E-value: 5.11e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKRE-PYGKPV-----DVWGCGVILFILLSGCLPF----YGTKERLFEGIIKGKykmNPRQWSHISESAKDLVRR 70
Cdd:cd06622  168 MAPERIKSGgPNQNPTytvqsDVWSLGLSILEMALGRYPYppetYANIFAQLSAIVDGD---PPTLPSGYSDDAQDFVAK 244

                         90       100
                 ....*....|....*....|..
gi 768035983  71 MLMLDPAERITVYEALNHPWLK 92
Cdd:cd06622  245 CLNKIPNRRPTYAQLLEHPWLV 266
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
 2-93 5.74e-06

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: 48.90  E-value: 5.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV-KREPYGKPVDVWGCGVILFILLSGCLPFYGTKE----------------RLFEGIIK----GKYKMnPRQ---- 56
Cdd:cd07845  176 APELLlGCTTYTTAIDMWAVGCILAELLAHKPLLPGKSEieqldliiqllgtpneSIWPGFSDlplvGKFTL-PKQpynn 254

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768035983  57 ----WSHISESAKDLVRRMLMLDPAERITVYEALNHPWLKE 93
Cdd:cd07845  255 lkhkFPWLSEAGLRLLNFLLMYDPKKRATAEEALESSYFKE 295
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 1-92 5.78e-06

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: 48.57  E-value: 5.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKER------LFEGIIKGK-YKM-----NPRQWshiSESAKDLV 68
Cdd:cd06621  170 MAPERIQGGPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPplgpieLLSYIVNMPnPELkdepeNGIKW---SESFKDFI 246

                         90       100
                 ....*....|....*....|....
gi 768035983  69 RRMLMLDPAERITVYEALNHPWLK 92
Cdd:cd06621  247 EKCLEKDGTRRPGPWQMLAHPWIK 270
cpPDZ_CPP-like cd06782
circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, ...
 311-366 6.85e-06

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467623 [Multi-domain]  Cd Length: 88  Bit Score: 44.78  E-value: 6.85e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 311 GITLKMNELNHCIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLR 366
Cdd:cd06782    5 GIEIGKDDDGYLVVVSPIPGGPAEKAG-IKPGDVIVAVDGESVRGMSLDEVVKLLR 59
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
 426-483 6.99e-06

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 43.83  E-value: 6.99e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDLIPCKEagirfrvGDIIQIISKDDHNWWQGKLENSKngtaGLIPS 483
Cdd:cd11772    2 FRALYDYEAQHPDELSFEE-------GDLLYISDKSDPNWWKATCGGKT----GLIPS 48
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
 2-98 7.20e-06

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 48.56  E-value: 7.20e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK--------------------ERLfeGIIKGKYKMN-PRQWSH- 59
Cdd:cd07850  169 APEVILGMGYKENVDIWSVGCIMGEMIRGTVLFPGTDhidqwnkiieqlgtpsdefmSRL--QPTVRNYVENrPKYAGYs 246

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983  60 --------------------ISESAKDLVRRMLMLDPAERITVYEALNHP----WLKERDRYA 98
Cdd:cd07850  247 feelfpdvlfppdseehnklKASQARDLLSKMLVIDPEKRISVDDALQHPyinvWYDPSEVEA 309
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
 2-90 7.27e-06

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: 48.25  E-value: 7.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV-KREPYGKPVDVWGCGVILFILLSGCLPFYGTK----------------ERLFEGI-----IKGKYKMNPRQ--- 56
Cdd:cd07836  168 APDVLlGSRTYSTSIDIWSVGCIMAEMITGRPLFPGTNnedqllkifrimgtptESTWPGIsqlpeYKPTFPRYPPQdlq 247

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768035983  57 --WSHISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07836  248 qlFPHADPLGIDLLHRLLQLNPELRISAHDALQHPW 283
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
 2-87 7.34e-06

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: 48.10  E-value: 7.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV---KREPYGKPVDVWGCGVILFILLSGCLPFygtKERLFEGIIKGKYKM--NPRQwshiSESAKDLVRRMLMLDP 76
Cdd:cd13985  182 APEMIdlySKKPIGEKADIWALGCLLYKLCFFKLPF---DESSKLAIVAGKYSIpeQPRY----SPELHDLIRHMLTPDP 254

                         90
                 ....*....|.
gi 768035983  77 AERITVYEALN 87
Cdd:cd13985  255 AERPDIFQVIN 265
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
 426-483 7.48e-06

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 43.56  E-value: 7.48e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLEnsknGTAGLIPS 483
Cdd:cd11827    2 CKALYAYDAQDTD-------ELSFNEGDIIEILKEDPSGWWTGRLR----GKEGLFPG 48
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
 2-88 7.85e-06

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: 48.05  E-value: 7.85e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVkrEPY-GKPV----DVWGCGVILFILLSGCLPFygtKERLFEGIIKGKYKM--NPRQwshiSESAKDLVRRMLML 74
Cdd:cd14037  187 APEMI--DLYrGKPIteksDIWALGCLLYKLCFYTTPF---EESGQLAILNGNFTFpdNSRY----SKRLHKLIRYMLEE 257

                         90
                 ....*....|....
gi 768035983  75 DPAERITVYEALNH 88
Cdd:cd14037  258 DPEKRPNIYQVSYE 271
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 3-85 8.07e-06

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: 48.27  E-value: 8.07e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYKmnPRQWSHISESAKDLVRRMLMLDPAERIT 81
Cdd:cd08528  183 PEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMlTLATKIVEAEYE--PLPEGMYSDDITFVIRSCLTPDPEARPD 260


                 ....
gi 768035983  82 VYEA 85
Cdd:cd08528  261 IVEV 264
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
 1-90 8.50e-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: 48.15  E-value: 8.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFygTKERLFEGIIK-GKYKMNPRQWSHISESAKDLVRRmLMLDPAER 79
Cdd:cd06651  181 MSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPW--AEYEAMAAIFKiATQPTNPQLPSHISEHARDFLGC-IFVEARHR 257

                         90
                 ....*....|.
gi 768035983  80 ITVYEALNHPW 90
Cdd:cd06651  258 PSAEELLRHPF 268
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
 438-483 8.61e-06

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 43.43  E-value: 8.61e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 768035983 438 DLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11996    8 DYTANNEDELSFSKGQLINVLNKDDPDWWQGEI----NGVTGLFPS 49
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
 427-488 8.76e-06

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 43.49  E-value: 8.76e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 427 RAQFEYDPAKDDLIPCKEagirfrvGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd11823    3 KALYSYTANREDELSLQP-------GDIIEVHEKQDDGWWLGEL----NGKKGIFPATYVEE 53
PDZ4_MAGI-1_3-like cd06734
PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 300-378 9.33e-06

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467216 [Multi-domain]  Cd Length: 84  Bit Score: 44.53  E-value: 9.33e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 300 VQFQKNTDEPMGITL--KMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06734    4 VTLTRRENEGFGFVIisSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTIV 83


                 .
gi 768035983 378 P 378
Cdd:cd06734   84 P 84
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
 1-92 1.13e-05

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: 47.80  E-value: 1.13e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK--ERLFEGIIKGKYKM-NPRQWSHIsesAKDLVRRMLMLDPA 77
Cdd:cd06654  183 MAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENplRALYLIATNGTPELqNPEKLSAI---FRDFLNRCLEMDVE 259

                         90
                 ....*....|....*
gi 768035983  78 ERITVYEALNHPWLK 92
Cdd:cd06654  260 KRGSAKELLQHQFLK 274
PDZ2_Scribble-like cd06703
PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 324-373 1.16e-05

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467187 [Multi-domain]  Cd Length: 92  Bit Score: 44.17  E-value: 1.16e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 768035983 324 VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSIT 373
Cdd:cd06703   36 ISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSSSPTIT 85
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 427-488 1.17e-05

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 43.06  E-value: 1.17e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 427 RAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd12055    3 QVAFSYLPQNED-------ELELKVGDIIEVVGEVEEGWWEGVL----NGKTGMFPSNFIKE 53
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
 1-105 1.20e-05

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: 47.82  E-value: 1.20e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVV-----KREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGKYK--MNPRQWshiSESAKDLVRRML 72
Cdd:cd06611  170 MAPEVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPmRVLLKILKSEPPtlDQPSKW---SSSFNDFLKSCL 246

                         90       100       110
                 ....*....|....*....|....*....|....
gi 768035983  73 MLDPAERITVYEALNHPWLKER-DRYAYKIHLPE 105
Cdd:cd06611  247 VKDPDDRPTAAELLKHPFVSDQsDNKAIKDLLAE 280
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
 2-91 1.22e-05

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: 47.80  E-value: 1.22e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLF-------EGIIKG-----KYKMNPRQWS----- 58
Cdd:cd07861  169 APEVLLGSPrYSTPVDIWSIGTIFAEMATKKPLFHGDSEidqlfRIFrilgtptEDIWPGvtslpDYKNTFPKWKkgslr 248

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 768035983  59 ----HISESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07861  249 tavkNLDEDGLDLLEKMLIYDPAKRISAKKALVHPYF 285
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
 1-92 1.33e-05

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 48.33  E-value: 1.33e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:PTZ00283 212 VAPEIWRRKPYSKKADMFSLGVLLYELLTLKRPFDGENmEEVMHKTLAGRYDPLP---PSISPEMQEIVTALLSSDPKRR 288

                         90
                 ....*....|...
gi 768035983  80 ITVYEALNHPWLK 92
Cdd:PTZ00283 289 PSSSKLLNMPICK 301
PKc_DYRK1 cd14226
Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and ...
 3-92 1.36e-05

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271128 [Multi-domain]  Cd Length: 339  Bit Score: 47.70  E-value: 1.36e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   3 PEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE--------------------------RLFEGIIKGKY------ 50
Cdd:cd14226  186 PEVLLGLPYDLAIDMWSLGCILVEMHTGEPLFSGANEvdqmnkivevlgmppvhmldqapkarKFFEKLPDGTYylkktk 265

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  51 -KMNPRQWSHISESA---------------------------KDLVRRMLMLDPAERITVYEALNHPWLK 92
Cdd:cd14226  266 dGKKYKPPGSRKLHEilgvetggpggrragepghtvedylkfKDLILRMLDYDPKTRITPAEALQHSFFK 335
SH3_CACNB1 cd12041
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta-1; The beta1 ...
 426-484 1.36e-05

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta-1; The beta1 subunit of voltage-dependent calcium channels (Ca(V)s) is one of four beta subunits present in vertebrates. It is the only beta subunit, as the beta1a variant, expressed in skeletal muscle; the beta1b variant is also widely expressed in other tissues including the heart and brain. Knockout of the beta1 gene in mice results in embryonic lethality, demonstrating its importance in development. Ca(V)s are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212974  Cd Length: 68  Bit Score: 43.42  E-value: 1.36e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 426 VRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenSKNG-TAGLIPSP 484
Cdd:cd12041    7 VRTNVGYNPSPGDDVPVQGMAISFEPKDFLHIKEKYNNDWWIGRL--VKEGcEVGFIPSP 64
PDZ4_LNX1_2-like cd06680
PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ ...
 317-378 1.37e-05

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467168 [Multi-domain]  Cd Length: 89  Bit Score: 43.88  E-value: 1.37e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 317 NELNHC----IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIVP 378
Cdd:cd06680   21 YEESHGnqpfFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQRGRVTLTVVS 86
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
 1-80 1.37e-05

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: 47.68  E-value: 1.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMnPRqwsHISESAKDLVRRMLMLDPAER 79
Cdd:cd05589  168 LAPEVLTDTSYTRAVDWWGLGVLIYEMLVGESPFPGdDEEEVFDSIVNDEVRY-PR---FLSTEAISIMRRLLRKNPERR 243


                 .
gi 768035983  80 I 80
Cdd:cd05589  244 L 244
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
 425-484 1.49e-05

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 42.62  E-value: 1.49e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 425 YVRAQFEYDPakddlipcKEAG-IRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSP 484
Cdd:cd11805    1 RVQALYDFNP--------QEPGeLEFRRGDIITVLDSSDPDWWKGEL----RGRVGIFPAN 49
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 1-91 1.50e-05

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: 47.42  E-value: 1.50e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLsgCLpfygtkERLFEG---------IIKGKykmNPRQWSHISESAKDLVRRM 71
Cdd:cd08222  172 MSPEVLKHEGYNSKSDIWSLGCILYEMC--CL------KHAFDGqnllsvmykIVEGE---TPSLPDKYSKELNAIYSRM 240

                         90       100
                 ....*....|....*....|
gi 768035983  72 LMLDPAERITVYEALNHPWL 91
Cdd:cd08222  241 LNKDPALRPSAAEILKIPFI 260
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
 11-90 1.53e-05

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: 47.27  E-value: 1.53e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGTKE-------------------RLFEGIIKGKYKMNPRQWS-------HISESA 64
Cdd:cd07831  176 YGPKMDIWAVGCVFFEILSLFPLFPGTNEldqiakihdvlgtpdaevlKKFRKSRHMNYNFPSKKGTglrkllpNASAEG 255

                         90       100
                 ....*....|....*....|....*.
gi 768035983  65 KDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07831  256 LDLLKKLLAYDPDERITAKQALRHPY 281
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
 1-34 1.59e-05

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: 47.10  E-value: 1.59e-05
                         10        20        30
                 ....*....|....*....|....*....|....
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF 34
Cdd:cd14059  147 MAPEVIRNEPCSEKVDIWSFGVVLWELLTGEIPY 180
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
 2-90 1.72e-05

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: 47.36  E-value: 1.72e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKRE-PYGKPVDVWGCGVI---------------------LFILLSGC-----------LPFYgTKERLFEGiikG 48
Cdd:cd07865  191 PPELLLGErDYGPPIDMWGAGCImaemwtrspimqgnteqhqltLISQLCGSitpevwpgvdkLELF-KKMELPQG---Q 266

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768035983  49 KYKMNPRQWSHISE-SAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07865  267 KRKVKERLKPYVKDpYALDLIDKLLVLDPAKRIDADTALNHDF 309
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
 427-483 1.77e-05

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 42.48  E-value: 1.77e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 427 RAQFEYDPAKDDlipckEAGIRFRVGDIIQIISKDDHNWWQGklENSKnGTAGLIPS 483
Cdd:cd11962    1 RAVVLYDYEKDE-----DNEIELVEGEIVTNIEMVDEDWWMG--TNSK-GESGLFPS 49
STKc_DMPK_like cd05597
Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; ...
 11-95 2.00e-05

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270748 [Multi-domain]  Cd Length: 331  Bit Score: 47.34  E-value: 2.00e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGtkERLFE--GII---KGKYKMnPRQWSHISESAKDLVRRmLMLDPAERI---TV 82
Cdd:cd05597  185 YGPECDWWSLGVCMYEMLYGETPFYA--ESLVEtyGKImnhKEHFSF-PDDEDDVSEEAKDLIRR-LICSRERRLgqnGI 260

                         90
                 ....*....|...
gi 768035983  83 YEALNHPWLKERD 95
Cdd:cd05597  261 DDFKKHPFFEGID 273
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 425-482 2.12e-05

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 42.50  E-value: 2.12e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEagirfrvGDIIQIISKD--DHNWWQGKLenskNGTAGLIP 482
Cdd:cd12056    3 YCKALFHYEGTNEDELDFKE-------GEIILIISKDtgEPGWWKGEL----NGKEGVFP 51
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 430-488 2.27e-05

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 42.26  E-value: 2.27e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 430 FEYdpakddlIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd12054    7 FEY-------VPQNEDELELKVGDIIDINEEVEEGWWSGTL----NGKSGLFPSNFVKE 54
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
 2-91 2.51e-05

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: 46.90  E-value: 2.51e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLF-------EGIIKG-----KYKMN-----PRQWS 58
Cdd:cd07835  167 APEILLGSKhYSTPVDIWSVGCIFAEMVTRRPLFPGDSEidqlfRIFrtlgtpdEDVWPGvtslpDYKPTfpkwaRQDLS 246

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 768035983  59 HI----SESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07835  247 KVvpslDEDGLDLLSQMLVYDPAKRISAKAALQHPYF 283
PDZ5_INAD-like cd23066
PDZ domain 5 of inactivation no after potential D (INAD), and related domains; PDZ (PSD-95 ...
 300-377 2.89e-05

PDZ domain 5 of inactivation no after potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ45 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467279 [Multi-domain]  Cd Length: 80  Bit Score: 42.88  E-value: 2.89e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 300 VQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd23066    2 VELMKKAGKELGLSLSPNEGIGCTIADLLPGGYAEIDGKLQKGDIITKFNGDALSGLPFQVCYALFKGANGKISLEVT 79
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 429-488 3.49e-05

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 41.80  E-value: 3.49e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 429 QFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd12052    5 EFDYKAQHED-------ELTITVGDIITKIKKDDGGWWEGEI----KGRRGLFPDNFVRE 53
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
 426-487 3.74e-05

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 41.64  E-value: 3.74e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 426 VRAQFEYDPAKDDLipcKEagIRFRVGDIIQIisKDDH-NWWQGKlenSKNGTAGLIPSPELQ 487
Cdd:cd11855    2 ARALYPYDASPDDP---NE--LSFEKGEILEV--SDTSgKWWQAR---KSNGETGICPSNYLQ 54
PDZ1_GgSTXBP4-like cd06692
PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, ...
 305-366 4.40e-05

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467179 [Multi-domain]  Cd Length: 88  Bit Score: 42.59  E-value: 4.40e-05
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gi 768035983 305 NTDEPMGITLKmnelnhcivaRIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLR 366
Cdd:cd06692   21 NTGEEFGIFIK----------RILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILR 72
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
 426-482 4.49e-05

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 41.48  E-value: 4.49e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 426 VRAQFEYDPAKDDlipckEAGIRfrVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11873    2 VIVEFDYDAEEPD-----ELTLK--VGDIITNVKKMEEGWWEGTL----NGKRGMFP 47
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
 426-483 4.62e-05

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 41.48  E-value: 4.62e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11995    3 VIGMYDYTAQNDDELA-------FSKGQIINVLNKEDPDWWKGEL----NGQVGLFPS 49
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
 426-483 4.79e-05

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 41.30  E-value: 4.79e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGklenSKNGTAGLIPS 483
Cdd:cd11820    3 VRALYDFEAAEDN-------ELTFKAGEIITVLDDSDPNWWKG----SNHRGEGLFPA 49
PDZ_GIPC cd06707
PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and ...
 307-374 4.95e-05

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467191 [Multi-domain]  Cd Length: 89  Bit Score: 42.60  E-value: 4.95e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 307 DEP-MGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITF 374
Cdd:cd06707   12 SEDaLGLTITDNGAGYAFIKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEIPIGETF 80
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
 1-95 5.09e-05

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 46.02  E-value: 5.09e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP-YGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMnPRqwSHISESAKDLVRRMLMLDPAE 78
Cdd:cd05586  163 LAPEVLLDEKgYTKMVDFWSLGVLVFEMCCGWSPFYAEDtQQMYRNIAFGKVRF-PK--DVLSDEGRSFVKGLLNRNPKH 239

                         90       100
                 ....*....|....*....|.
gi 768035983  79 RITVY----EALNHPWLKERD 95
Cdd:cd05586  240 RLGAHddavELKEHPFFADID 260
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
 1-88 5.15e-05

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: 45.39  E-value: 5.15e-05
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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd14188  168 LSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNlKETYRCIREARYSLP----SSLLAPAKHLIASMLSKNPEDR 243


                 ....*....
gi 768035983  80 ITVYEALNH 88
Cdd:cd14188  244 PSLDEIIRH 252
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
 1-80 5.60e-05

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 46.17  E-value: 5.60e-05
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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF--------YGTKERLFEGIIKGKYKMnPRqwsHISESAKDLVRRML 72
Cdd:cd05617  183 IAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFdiitdnpdMNTEDYLFQVILEKPIRI-PR---FLSVKASHVLKGFL 258


                 ....*...
gi 768035983  73 MLDPAERI 80
Cdd:cd05617  259 NKDPKERL 266
PDZ_GIPC3 cd23079
PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 ...
 306-376 6.13e-05

PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC3, and related domains. GIPC3 (also known as C19orf64) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467292 [Multi-domain]  Cd Length: 89  Bit Score: 42.21  E-value: 6.13e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 306 TDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd23079   12 TEDALGLTITDNGAGYAFIKRIKEGSIIDRIKAVCVGDHIEAINDQSIVGCRHYEVAKMLRELPKSQPFTL 82
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
 1-95 6.13e-05

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 45.64  E-value: 6.13e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNprqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd05585  161 LAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENtNEMYRKILQEPLRFP----DGFDRDAKDLLIGLLNRDPTKR 236

                         90
                 ....*....|....*....
gi 768035983  80 ITV---YEALNHPWLKERD 95
Cdd:cd05585  237 LGYngaQEIKNHPFFDQID 255
PDZ7_PDZD2-PDZ4_hPro-IL-16-like cd06763
PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 ...
 323-357 6.29e-05

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467244 [Multi-domain]  Cd Length: 86  Bit Score: 42.22  E-value: 6.29e-05
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQT 357
Cdd:cd06763   31 TIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLT 65
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
 54-94 6.31e-05

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: 45.82  E-value: 6.31e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 768035983  54 PRQWSHI----SESAKDLVRRMLMLDPAERITVYEALNHPWLKER 94
Cdd:cd07855  258 PVPWETLypkaDQQALDLLSQMLRFDPSERITVAEALQHPFLAKY 302
STKc_MRCK_alpha cd05623
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ...
 1-72 6.63e-05

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270773 [Multi-domain]  Cd Length: 409  Bit Score: 45.78  E-value: 6.63e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVK-----REPYGKPVDVWGCGVILFILLSGCLPFYGtkERLFE---GIIKGKYKMN-PRQWSHISESAKDLVRRM 71
Cdd:cd05623  241 ISPEILQamedgKGKYGPECDWWSLGVCMYEMLYGETPFYA--ESLVEtygKIMNHKERFQfPTQVTDVSENAKDLIRRL 318


                 .
gi 768035983  72 L 72
Cdd:cd05623  319 I 319
PDZ5_MAGI-1_3-like cd06735
PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 323-357 7.25e-05

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467217 [Multi-domain]  Cd Length: 84  Bit Score: 41.80  E-value: 7.25e-05
                         10        20        30
                 ....*....|....*....|....*....|....*
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQT 357
Cdd:cd06735   29 YVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMT 63
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
 428-483 7.51e-05

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T 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. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. 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. MLK2, also called MAP3K10, 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. MLK3, also called MAP3K11, 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. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 40.91  E-value: 7.51e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 428 AQFEYDPAKDDlipckeaGIRFRVGDIIQIISKD-----DHNWWQGKLenskNGTAGLIPS 483
Cdd:cd12059    4 AVFDYEASAED-------ELTLRRGDRVEVLSKDsavsgDEGWWTGKI----NDRVGIFPS 53
PKc_CLK1_4 cd14213
Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; ...
 2-91 7.78e-05

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK1/4 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: 271115 [Multi-domain]  Cd Length: 330  Bit Score: 45.61  E-value: 7.78e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVW--GCGVILFILLSGCLPFYGTKERL--FEGII------------KGKYKMNPR-QWSHISESA 64
Cdd:cd14213  200 APEVILALGWSQPCDVWsiGCILIEYYLGFTVFQTHDSKEHLamMERILgplpkhmiqktrKRKYFHHDQlDWDEHSSAG 279

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768035983  65 K------------------------DLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14213  280 RyvrrrckplkefmlsqdvdheqlfDLIQKMLEYDPAKRITLDEALKHPFF 330
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
 425-483 7.92e-05

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212712 [Multi-domain]  Cd Length: 51  Bit Score: 40.56  E-value: 7.92e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDlipckEAGIRfrVGDIIQIISKDDHNWWQgklENSKNGTAGLIPS 483
Cdd:cd11778    1 YVEALYDYEAQGDD-----EISIR--VGDRIAVIRGDDGSGWT---YGEINGVKGLFPT 49
PDZ1_harmonin cd06737
PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic ...
 296-376 8.39e-05

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467219 [Multi-domain]  Cd Length: 85  Bit Score: 41.86  E-value: 8.39e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 296 RVRLVQFQKNTDEPMGITLKMNELNHC--IVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREmRGSIT 373
Cdd:cd06737    1 KLRLVRLDRRGPESLGFSVRGGLEHGCglFVSHVSPGSQADNKG-LRVGDEIVRINGYSISQCTHEEVINLIKT-KKTVS 78


                 ...
gi 768035983 374 FKI 376
Cdd:cd06737   79 LKV 81
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
 2-90 8.48e-05

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: 45.21  E-value: 8.48e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV-KREPYGKPVDVWGCGVI---------LFI------LLSGCLPFYGT-KERLFEGIIKGKYKMNPRQWS------ 58
Cdd:cd07837  178 APEVLlGSTHYSTPVDMWSVGCIfaemsrkqpLFPgdselqQLLHIFRLLGTpNEEVWPGVSKLRDWHEYPQWKpqdlsr 257

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 768035983  59 ---HISESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07837  258 avpDLEPEGVDLLTKMLAYDPAKRISAKAALQHPY 292
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
 1-91 9.87e-05

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: 44.62  E-value: 9.87e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14202  176 MAPEVIMSQHYDAKADLWSIGTIIYQCLTGKAPFQASSPQDLRLFYEKNKSLSPNIPRETSSHLRQLLLGLLQRNQKDRM 255

                         90
                 ....*....|.
gi 768035983  81 TVYEALNHPWL 91
Cdd:cd14202  256 DFDEFFHHPFL 266
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
 428-483 1.14e-04

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T 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. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 40.57  E-value: 1.14e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 428 AQFEYDPAKDDlipckeaGIRFRVGDIIQIISKD-----DHNWWQGKLENSkngtAGLIPS 483
Cdd:cd11876    4 ALFDYDARGED-------ELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDK----VGIFPS 53
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
 425-487 1.27e-04

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 40.04  E-value: 1.27e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983 425 YVRAQFEYDPakddlipcKEAG-IRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQ 487
Cdd:cd11786    1 CAKALYNYEG--------KEPGdLSFKKGDIILLRKRIDENWYHGEC----NGKQGFFPASYVQ 52
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
 449-482 1.27e-04

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 40.11  E-value: 1.27e-04
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 768035983 449 FRVGDIIQIISK--DDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11866   18 FKRGDLIYIISKeyDSFGWWVGEL----NGKVGLVP 49
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
 1-96 1.48e-04

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: 44.26  E-value: 1.48e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF-------YGTKERLFEGIIKGKykmNPRQWSHI-SESAKDLVRRML 72
Cdd:cd06605  165 MAPERISGGKYTVKSDIWSLGLSLVELATGRFPYpppnakpSMMIFELLSYIVDEP---PPLLPSGKfSPDFQDFVSQCL 241

                         90       100
                 ....*....|....*....|....
gi 768035983  73 MLDPAERITVYEALNHPWLKERDR 96
Cdd:cd06605  242 QKDPTERPSYKELMEHPFIKRYEY 265
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
 425-488 1.60e-04

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212827  Cd Length: 56  Bit Score: 39.92  E-value: 1.60e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 425 YVRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKD---DHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd11894    1 FVKALYDYEGQTDD-------ELSFPEGAIIRILNKEnqdDDGFWEGEF----NGRIGVFPSVLVEE 56
SH3_CACNB2 cd12040
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta2; The beta2 ...
 426-484 1.61e-04

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta2; The beta2 subunit of voltage-dependent calcium channels (Ca(V)s) is one of four beta subunits present in vertebrates. It is expressed in the heart and is present in specific neuronal cells including cerebellar Purkinje cells, hippocampal pyramidal neurons, and photoreceptors. Knockout of the beta2 gene in mice results in embryonic lethality, demonstrating its importance in development. Ca(V)s are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212973  Cd Length: 69  Bit Score: 40.40  E-value: 1.61e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 426 VRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenSKNGTA-GLIPSP 484
Cdd:cd12040    8 VRTNVGYSAAHEDDVPVPGMAISFEAKDFLHVKEKFNNDWWIGRL--VKEGCEiGFIPSP 65
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 425-482 1.61e-04

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 39.88  E-value: 1.61e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 425 YVRAQFEYDPAKDDLIPCKEagirfrvGDIIQIISKD--DHNWWQGKLenskNGTAGLIP 482
Cdd:cd12057    1 YCKVLFPYEAQNEDELTIKE-------GDIVTLISKDciDAGWWEGEL----NGRRGVFP 49
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
 423-490 1.62e-04

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 39.99  E-value: 1.62e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 423 QIYVRAQFEYDPA-KDDLIPCKeagirfrvGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQEWR 490
Cdd:cd12060    1 QLVVKARFNFKQTnEDELSVCK--------GDIIYVTRVEEGGWWEGTL----NGKTGWFPSNYVREIK 57
SH3_CACNB3 cd12042
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta3; The beta3 ...
 426-488 1.62e-04

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta3; The beta3 subunit of voltage-dependent calcium channels (Ca(V)s) is one of four beta subunits present in vertebrates. It is the main beta subunit present in smooth muscles and is strongly expressed in the brain; it is predominant in the olfactory bulb, cortex, and hippocampus. It may play a role in regulating the NMDAR (N-methyl-d-aspartate receptor) activity in the hippocampus and thus, activity-dependent synaptic plasticity and cognitive behaviors. Ca(V)s are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212975  Cd Length: 68  Bit Score: 40.39  E-value: 1.62e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 426 VRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENsKNGTAGLIPSPELQE 488
Cdd:cd12042    7 VRTNVSYCGALDEECPVQGAAINFEAKDFLHIKEKYSNDWWIGRLVK-EGGDIAFIPSPQRLE 68
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
 1-80 1.82e-04

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 44.25  E-value: 1.82e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF----------YGTKERLFEGIIKGKYKMnPRQwshISESAKDLVRR 70
Cdd:cd05618  188 IAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFdivgssdnpdQNTEDYLFQVILEKQIRI-PRS---LSVKAASVLKS 263

                         90
                 ....*....|
gi 768035983  71 MLMLDPAERI 80
Cdd:cd05618  264 FLNKDPKERL 273
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
 1-36 2.08e-04

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: 43.88  E-value: 2.08e-04
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG 36
Cdd:cd14145  180 MAPEVIRSSMFSKGSDVWSYGVLLWELLTGEVPFRG 215
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
 426-483 2.15e-04

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 39.69  E-value: 2.15e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKlenSKNGTAGLIPS 483
Cdd:cd11960    2 ARALYDYQAADDT-------EISFDPGDIITDIEQIDEGWWRGT---GPDGTYGLFPA 49
PDZ_GIPC2 cd23078
PDZ domain of PDZ domain-containing protein GIPC2, and related domains; PDZ (PSD-95 ...
 306-376 2.16e-04

PDZ domain of PDZ domain-containing protein GIPC2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC2, and related domains. GIPC2 belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc2 gene have been linked to cancer. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467291  Cd Length: 93  Bit Score: 40.67  E-value: 2.16e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 306 TDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd23078   14 SEDSLGLTITDNGVGYAFIKRIKDGSVIDSVKTICVGDHIECINGENIVGWRHYEVAKKLKELKKEELFTL 84
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
 11-90 2.24e-04

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: 43.81  E-value: 2.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGTK--------------ERLFE-----------GIIK-------------GKY-K 51
Cdd:cd07842  193 YTKAIDIWAIGCIFAELLTLEPIFKGREakikksnpfqrdqlERIFEvlgtptekdwpDIKKmpeydtlksdtkaSTYpN 272

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768035983  52 MNPRQWSHI----SESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07842  273 SLLAKWMHKhkkpDSQGFDLLRKLLEYDPTKRITAEEALEHPY 315
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
 426-488 2.29e-04

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 39.67  E-value: 2.29e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd12061    2 VRAKFNFQQTNED-------ELSFSKGDVIHVTRVEEGGWWEGTH----NGRTGWFPSNYVRE 53
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
 1-36 2.36e-04

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: 43.54  E-value: 2.36e-04
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG 36
Cdd:cd14061  168 MAPEVIKSSTFSKASDVWSYGVLLWELLTGEVPYKG 203
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
 1-36 2.50e-04

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: 43.49  E-value: 2.50e-04
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG 36
Cdd:cd14146  178 MAPEVIKSSLFSKGSDIWSYGVLLWELLTGEVPYRG 213
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
 426-483 2.58e-04

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 39.22  E-value: 2.58e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11877    2 VRAKFNFEGTNED-------ELSFDKGDIITVTQVVEGGWWEGTL----NGKTGWFPS 48
SH3_SH3RF_2 cd11787
Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
 427-482 2.59e-04

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212721 [Multi-domain]  Cd Length: 53  Bit Score: 39.24  E-value: 2.59e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 427 RAQFEYDPAKDDLIPCkeagIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11787    3 KALYDFEMKDEDEKDC----LTFKKGDVITVIRRVDENWAEGRL----GDKIGIFP 50
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 1-89 2.63e-04

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: 43.18  E-value: 2.63e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSgclpfygtKERLFEG---------IIKGKYKMNPRQWshiSESAKDLVRRM 71
Cdd:cd08220  168 ISPELCEGKPYNQKSDIWALGCVLYELAS--------LKRAFEAanlpalvlkIMRGTFAPISDRY---SEELRHLILSM 236

                         90
                 ....*....|....*...
gi 768035983  72 LMLDPAERITVYEALNHP 89
Cdd:cd08220  237 LHLDPNKRPTLSEIMAQP 254
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
 311-378 2.72e-04

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440556 [Multi-domain]  Cd Length: 341  Bit Score: 43.71  E-value: 2.72e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 311 GITLKMNElNHCIVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGS-ITFKIVP 378
Cdd:COG0793   63 GAELGEED-GKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAGTkVTLTIKR 129
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
 426-483 2.99e-04

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 39.23  E-value: 2.99e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGklENSKNgtAGLIPS 483
Cdd:cd11963    4 VRALYDFEAVEDN-------ELTFKHGEIIIVLDDSDANWWKG--ENHRG--VGLFPS 50
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
 1-95 3.06e-04

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 43.63  E-value: 3.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-RLFEGIIKGK--YKMnprqWshISESAKDLVRRMLMLDPA 77
Cdd:cd05591  163 IAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEdDLFESILHDDvlYPV----W--LSKEAVSILKAFMTKNPA 236

                         90       100
                 ....*....|....*....|....*
gi 768035983  78 ERITVYEA-------LNHPWLKERD 95
Cdd:cd05591  237 KRLGCVASqggedaiRQHPFFREID 261
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
 2-90 3.76e-04

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: 43.07  E-value: 3.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV---KRepYGKPVDVWGCGVILFILLSG-------------------C-------------LPfyGTKERLFEGII 46
Cdd:cd07866  194 PPELLlgeRR--YTTAVDIWGIGCVFAEMFTRrpilqgksdidqlhlifklCgtpteetwpgwrsLP--GCEGVHSFTNY 269

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 768035983  47 KGKYKMnpRQWSHISESAkDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07866  270 PRTLEE--RFGKLGPEGL-DLLSKLLSLDPYKRLTASDALEHPY 310
STKc_CK2_alpha cd14132
Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the ...
 15-89 3.77e-04

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271034 [Multi-domain]  Cd Length: 306  Bit Score: 43.30  E-value: 3.77e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  15 VDVWGCGVILFILLSGCLPFY----------------GTKErLFE-----GI--------IKGKYKMNPrqWSH------ 59
Cdd:cd14132  194 LDMWSLGCMLASMIFRKEPFFhghdnydqlvkiakvlGTDD-LYAyldkyGIelpprlndILGRHSKKP--WERfvnsen 270

                         90       100       110
                 ....*....|....*....|....*....|...
gi 768035983  60 ---ISESAKDLVRRMLMLDPAERITVYEALNHP 89
Cdd:cd14132  271 qhlVTPEALDLLDKLLRYDHQERITAKEAMQHP 303
PDZ3_PDZD2-PDZ1_hPro-IL-16-like cd06759
PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 ...
 309-376 3.93e-04

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467240 [Multi-domain]  Cd Length: 87  Bit Score: 39.95  E-value: 3.93e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 309 PMGITLKmnelnhcivaRIMHGGMIHRQGTLHVGDEIREINGISVANQT-VEQLQKMLREMRGSITFKI 376
Cdd:cd06759   28 PMGIYVK----------TIFPGGAAAEDGRLKEGDEILEVNGESLQGLThQEAIQKFKQIKKGLVVLTV 86
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
 2-87 4.03e-04

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: 42.88  E-value: 4.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV---KREPYGKPVDVWGCGVILFILLSGCLPFY-GTKERlfegIIKGKYKM--NPRQWSHISesakDLVRRMLMLD 75
Cdd:cd14036  190 TPEMIdlySNYPIGEKQDIWALGCILYLLCFRKHPFEdGAKLR----IINAKYTIppNDTQYTVFH----DLIRSTLKVN 261

                         90
                 ....*....|..
gi 768035983  76 PAERITVYEALN 87
Cdd:cd14036  262 PEERLSITEIVE 273
SH3_CACNB4 cd12043
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4; The beta4 ...
 426-484 4.18e-04

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4; The beta4 subunit of voltage-dependent calcium channels (Ca(V)s) is one of four beta subunits present in vertebrates. It is the only beta subunit expressed in the cochlea and is highly expressed in the brain, predominantly in the cerebellum. Ca(V)s are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212976  Cd Length: 68  Bit Score: 39.19  E-value: 4.18e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 426 VRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLenSKNGTA-GLIPSP 484
Cdd:cd12043    7 VRTNVSYCGALDEDVPVPGTAISFDAKDFLHIKEKYNNDWWIGRL--VKEGCEiGFIPSP 64
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
 11-91 4.24e-04

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: 43.03  E-value: 4.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGTK-----------------ERLFEGIIK-GKYK------MNPRQ----WSHISE 62
Cdd:cd07870  176 YSSALDIWGAGCIFIEMLQGQPAFPGVSdvfeqlekiwtvlgvptEDTWPGVSKlPNYKpewflpCKPQQlrvvWKRLSR 255

                         90       100       110
                 ....*....|....*....|....*....|.
gi 768035983  63 --SAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07870  256 ppKAEDLASQMLMMFPKDRISAQDALLHPYF 286
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 1-79 4.38e-04

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: 42.71  E-value: 4.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLF---EGIIKGKYKMNPRQwsHISESAKDLVRRMLMLDPA 77
Cdd:cd08228  173 MSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDKMNLFslcQKIEQCDYPPLPTE--HYSEKLRELVSMCIYPDPD 250


                 ..
gi 768035983  78 ER 79
Cdd:cd08228  251 QR 252
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 1-88 4.41e-04

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: 42.94  E-value: 4.41e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLsgcLPFYGTKERL--FEGIIKGKYkmnPRQWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd14048  197 MSPEQIHGNQYSEKVDIFALGLILFELI---YSFSTQMERIrtLTDVRKLKF---PALFTNKYPEERDMVQQMLSPSPSE 270

                         90
                 ....*....|
gi 768035983  79 RITVYEALNH 88
Cdd:cd14048  271 RPEAHEVIEH 280
PDZ_shroom2_3_4-like cd06750
PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic ...
 309-362 4.47e-04

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467232 [Multi-domain]  Cd Length: 82  Bit Score: 39.63  E-value: 4.47e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 309 PMGITLKmNELNHC---IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQ 362
Cdd:cd06750   12 PWGFTLK-GGLEHGeplVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQ 67
PDZ1_PTPN13_FRMPD2-like cd06694
PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ ...
 296-376 4.75e-04

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467180 [Multi-domain]  Cd Length: 92  Bit Score: 39.69  E-value: 4.75e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 296 RVRLVQFQKNTDEPMGITL----KMNELNHCI-VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRG 370
Cdd:cd06694    1 EIVIVTLKKDPQKGLGFTIvggeNSGSLDLGIfVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAPD 80


                 ....*.
gi 768035983 371 SITFKI 376
Cdd:cd06694   81 KVELII 86
PDZ4_PDZD2-PDZ2_hPro-IL-16-like cd06760
PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 of human pro-interleukin-16 ...
 300-376 4.75e-04

PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the second PDZ domain (PDZ2) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467241 [Multi-domain]  Cd Length: 90  Bit Score: 39.56  E-value: 4.75e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 300 VQFQKNTDEPMGITLKMNELNHCIVARIMH----GGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMR-GSITF 374
Cdd:cd06760    7 VTLNKEPGVGLGIGLCCLPLENDIPGIFIHhlspGSVAHMDGRLRRGDQILEINGTSLRNVTLNEAYAILSQCKpGPVTL 86


                 ..
gi 768035983 375 KI 376
Cdd:cd06760   87 II 88
PDZ_Dishevelled-like cd06717
PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related ...
 320-376 5.04e-04

PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DVL1-3, and related domains. The dishevelleds (DVL1, 2 and 3 in humans) act downstream of Frizzled (FZD) receptors in both the canonical and non-canonical WNT signaling pathway; they bind the cytoplasmic C-terminus of frizzled family members and transduce the Wnt signal to down-stream effectors. They bind to several proteins known to modulate Wnt signaling. Binding partners of the DVL1 PDZ domain include nucleoredoxin (NXN), Van Gogh-like (VANGL1), Wnt receptor RYK, Dapper 1 (DACT1), Frizzled7 (FZD7), transmembrane protein 88 (TMEM88), Daple (dishevelled-associating protein with a high frequency of leucines), also known as Ccdc88c), and cysteine-rich protein Idax. The DVL2 PDZ domain has been shown to bind the nuclear export signal sequence of the DVL2 protein. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This DVL-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467201 [Multi-domain]  Cd Length: 87  Bit Score: 39.66  E-value: 5.04e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 320 NHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREM---RGSITFKI 376
Cdd:cd06717   26 GGIYVGSIMKGGAVAADGRIEPGDMILQVNDISFENMSNDDAVRVLREAvhkPGPITLTV 85
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
 2-91 5.21e-04

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271038 [Multi-domain]  Cd Length: 320  Bit Score: 42.95  E-value: 5.21e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSGCLPFY-------------------------------GTKERLF-------- 42
Cdd:cd14136  186 SPEVILGAGYGTPADIWSTACMAFELATGDYLFDphsgedysrdedhlaliiellgriprsiilsGKYSREFfnrkgelr 265

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983  43 ----------EGIIKGKYKMNPRQWSHISesakDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd14136  266 hisklkpwplEDVLVEKYKWSKEEAKEFA----SFLLPMLEYDPEKRATAAQCLQHPWL 320
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 1-91 5.25e-04

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: 42.42  E-value: 5.25e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYKMNPRQWshiSESAKDLVRRMLMLDPAER 79
Cdd:cd08223  169 MSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDmNSLVYKILEGKLPPMPKQY---SPELGELIKAMLHQDPEKR 245

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd08223  246 PSVKRILRQPYI 257
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
 2-89 5.59e-04

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: 42.35  E-value: 5.59e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVK-REPYGKPVDVWGCGVILFILLSGCLPF-YGTKERLFEGIIKgkykmnprqwshISESAKDLVRRMLMLDPAER 79
Cdd:cd14012  176 PPELAQgSKSPTRKTDVWDLGLLFLQMLFGLDVLeKYTSPNPVLVSLD------------LSASLQDFLSKCLSLDPKKR 243

                         90
                 ....*....|
gi 768035983  80 ITVYEALNHP 89
Cdd:cd14012  244 PTALELLPHE 253
PDZ_LIMK-like cd06754
PDZ domain of LIM Kinase (LIMK) family, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 297-367 5.77e-04

PDZ domain of LIM Kinase (LIMK) family, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the LIMK protein family, and related domains. The LIMK family is composed of LIMK1 and LIMK2, which are common downstream effectors of several signalization pathways and function as signaling nodes that control cytoskeleton dynamics through the phosphorylation of cofilin family proteins. They also control microtubule dynamics. The LIMK1 PDZ domain binds tubulin and nischarin. LIMK1 also binds a carboxy-terminal motif of membrane type 1-matrix metalloproteinase (MT1-MMP, also known as MMP14) having features of a PDZ domain-binding site; MT1-MMP is a major protease involved in dissemination of carcinoma cells during cancer progression. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LIMK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467236 [Multi-domain]  Cd Length: 92  Bit Score: 39.56  E-value: 5.77e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 297 VRLVQFQKNTDEPMGITLKMNE--LNHCIVARIMHGGMIHRQGT---LHVGDEIREINGISVANQTVEQLQKMLRE 367
Cdd:cd06754    4 VTLVSIPPTPEGKRGFSVSVEKgcSEHSHTVRVSELDPMHLSPDlksLHVGDRILEVNGTPVRDLSLEEIDDLIQS 79
PDZ_GIPC1 cd23077
PDZ domain of PDZ domain-containing protein GIPC1; PDZ (PSD-95 (Postsynaptic density protein ...
 306-374 5.78e-04

PDZ domain of PDZ domain-containing protein GIPC1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC1, and related domains. GIPC1 (also known as GIPC, GAIP/RGS19-interacting protein or Tax-interacting protein 2) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC1 functions as an adaptor molecule for loading PDZ-target cargoes on the MYO6 motor protein. The GIPC1 PDZ domain interacts with a variety of ligands, such as RGS19, NRP1, GLUT1, SEMA4C, SDC4 and IGF1R. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467290 [Multi-domain]  Cd Length: 94  Bit Score: 39.41  E-value: 5.78e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 306 TDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITF 374
Cdd:cd23077   14 SEDALGLTITDNGAGYAFIKRIKEGSVIDRIQLISVGDMIEAINGQSLLGCRHYEVARLLKELPRGRTF 82
PDZ_PICK1-like cd06722
PDZ domain of PICK1 (protein interacting with C-kinase 1) and similar domains; PDZ (PSD-95 ...
 334-373 6.08e-04

PDZ domain of PICK1 (protein interacting with C-kinase 1) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PICK1, and related domains. PICK1 (also known as PRKCA-binding protein and protein kinase C-alpha-binding protein) plays a key role in regulating trafficking of binding partners by altering either their subcellular targeting and/or surface expression. PICK1 plays a role in synaptic plasticity by regulating the trafficking and internalization of amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors; the PICK1-PDZ domain binds the AMPA receptor subunits. The PICK1 PDZ domain also binds glutamate transporters, Eph receptors, metabotropic glutamate receptors, and ASICs (acid-sensing ion channels), among others. Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PICK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467205 [Multi-domain]  Cd Length: 84  Bit Score: 39.32  E-value: 6.08e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 768035983 334 HRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSIT 373
Cdd:cd06722   39 AKDGTLAAGDEIVGVNGKSVKGKTKVEVAKMIQAVKGEVT 78
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
 1-36 6.22e-04

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: 42.32  E-value: 6.22e-04
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG 36
Cdd:cd14147  177 MAPEVIKASTFSKGSDVWSFGVLLWELLTGEVPYRG 212
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
 2-90 6.60e-04

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: 42.49  E-value: 6.60e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVV-KREPYGKPVDVWGCGVILFILLSGCLPFYGTKE-----RLFEGI----------------IKGKYKMNPRQ-WS 58
Cdd:cd07860  168 APEILlGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEidqlfRIFRTLgtpdevvwpgvtsmpdYKPSFPKWARQdFS 247

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768035983  59 HI----SESAKDLVRRMLMLDPAERITVYEALNHPW 90
Cdd:cd07860  248 KVvpplDEDGRDLLSQMLHYDPNKRISAKAALAHPF 283
PDZ2_ZO1-like_ds cd06728
PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form ...
 296-377 6.66e-04

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467210 [Multi-domain]  Cd Length: 79  Bit Score: 39.13  E-value: 6.66e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 296 RVRLVQFQKNTDepMGITLKmnelNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFK 375
Cdd:cd06728    2 KVTLTKSRKNDE--YGLRLG----SRIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLV 75


                 ..
gi 768035983 376 IV 377
Cdd:cd06728   76 VL 77
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
 426-483 6.79e-04

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 38.17  E-value: 6.79e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 426 VRAQFEYDPAKDDLIPCKEagirfrvGDIIQIISKDDHNWWQGKLE---NSKNGTAGLIPS 483
Cdd:cd11773    2 YKALYDYEPQTEDELTIQE-------DDILYLLEKSDDDWWKVKLKvnsSDDDEPVGLVPA 55
PDZ3_Par3-like cd23059
PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 327-376 6.84e-04

PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par-3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467272 [Multi-domain]  Cd Length: 103  Bit Score: 39.57  E-value: 6.84e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768035983 327 IMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLR-------EMRGSITFKI 376
Cdd:cd23059   44 IIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMETLRramstegNIRGMIQLVV 100
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 1-91 6.97e-04

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: 42.25  E-value: 6.97e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-ERLFEGIIKGKYK-MNPrqwsHISESAKDLVRRMLMLDPAE 78
Cdd:cd08225  169 LSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNlHQLVLKICQGYFApISP----NFSRDLRSLISQLFKVSPRD 244

                         90
                 ....*....|...
gi 768035983  79 RITVYEALNHPWL 91
Cdd:cd08225  245 RPSITSILKRPFL 257
PDZ4_GRIP1-2-like cd06686
PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 323-376 7.21e-04

PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467174 [Multi-domain]  Cd Length: 99  Bit Score: 39.25  E-value: 7.21e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06686   39 LISFIEPDSPAERCGVLQVGDRVLSINGIPTEDRTLEEANQLLRDSASKVTLEI 92
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
 427-482 7.83e-04

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 38.01  E-value: 7.83e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 427 RAQFEYDPAKDDlipckEAGirFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11803    4 RALYDFEPENEG-----ELG--FKEGDIITLTNQIDENWYEGMV----NGQSGFFP 48
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
 425-483 7.88e-04

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 38.03  E-value: 7.88e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983 425 YVRAQFEYDPAKddliPCKEagIRFRVGDIIQIISKDD-----HNWWQGKlenSKNGTAGLIPS 483
Cdd:cd11771    1 FCRALYDFTPEN----PEME--LSLKKGDIVAVLSKTDplgrdSEWWKGR---TRDGRIGWFPS 55
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 1-91 7.88e-04

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: 41.72  E-value: 7.88e-04
                         10        20        30        40        50        60        70        80
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gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF-YGTKERLFEGIIKGKYKMNPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd08218  168 LSPEICENKPYNNKSDIWALGCVLYEMCTLKHAFeAGNMKNLVLKIIRGSYPPVP---SRYSYDLRSLVSQLFKRNPRDR 244

                         90
                 ....*....|..
gi 768035983  80 ITVYEALNHPWL 91
Cdd:cd08218  245 PSINSILEKPFI 256
PDZ2_GRIP1-2-like cd06681
PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 323-376 8.08e-04

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467169 [Multi-domain]  Cd Length: 89  Bit Score: 39.14  E-value: 8.08e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06681   33 TVTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSILKQCGQEATLLI 86
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
 1-86 8.14e-04

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: 41.99  E-value: 8.14e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIkgKYKMNPRQwSHISESA-----KDLVRRMLMLD 75
Cdd:cd13979  173 RAPELLKGERVTPKADIYSFGITLWQMLTRELPYAGLRQHVLYAVV--AKDLRPDL-SGLEDSEfgqrlRSLISRCWSAQ 249

                         90
                 ....*....|.
gi 768035983  76 PAERITVYEAL 86
Cdd:cd13979  250 PAERPNADESL 260
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
 426-483 8.21e-04

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 37.88  E-value: 8.21e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983 426 VRAQFEYDPAKDDlipckEAGirFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd11950    2 VRALYDFEALEDD-----ELG--FNSGDVIEVLDSSNPSWWKGRL----HGKLGLFPA 48
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
 427-487 8.23e-04

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 37.74  E-value: 8.23e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 427 RAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKlensKNGTAGLIPSPELQ 487
Cdd:cd11824    3 SVLYDYTAQEDDELS-------ISKGDVVAVIEKGEDGWWTVE----RNGQKGLVPGTYLE 52
PDZ2_APBA1_3-like cd06793
PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, ...
 323-378 8.26e-04

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This APBA1,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467255 [Multi-domain]  Cd Length: 78  Bit Score: 38.54  E-value: 8.26e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 323 IVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIVP 378
Cdd:cd06793   24 IICSLLRGGIAERGG-VRVGHRIIEINGQSVVATPHEKIVQLLSNSVGEIHMKTMP 78
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
 1-88 8.82e-04

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: 41.95  E-value: 8.82e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFygTKERLFEGIIK-GKYKMNPRQWSHISESAKDLVRRMLmLDPAER 79
Cdd:cd06652  176 MSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPW--AEFEAMAAIFKiATQPTNPQLPAHVSDHCRDFLKRIF-VEAKLR 252


                 ....*....
gi 768035983  80 ITVYEALNH 88
Cdd:cd06652  253 PSADELLRH 261
STKc_NDR2 cd05627
Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze ...
 1-95 9.19e-04

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270776 [Multi-domain]  Cd Length: 366  Bit Score: 42.35  E-value: 9.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRmLMLDPAER 79
Cdd:cd05627  204 IAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSeTPQETYRKVMNWKETLVFPPEVPISEKAKDLILR-FCTDAENR 282

                         90
                 ....*....|....*....
gi 768035983  80 I---TVYEALNHPWLKERD 95
Cdd:cd05627  283 IgsnGVEEIKSHPFFEGVD 301
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
 1-80 9.43e-04

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270740 [Multi-domain]  Cd Length: 328  Bit Score: 42.02  E-value: 9.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF----------YGTKERLFEGIIKGKYKMnPRQwshISESAKDLVRR 70
Cdd:cd05588  163 IAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPFdivgssdnpdQNTEDYLFQVILEKPIRI-PRS---LSVKAASVLKG 238

                         90
                 ....*....|
gi 768035983  71 MLMLDPAERI 80
Cdd:cd05588  239 FLNKNPAERL 248
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
 1-34 9.74e-04

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: 41.51  E-value: 9.74e-04
                         10        20        30
                 ....*....|....*....|....*....|....
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF 34
Cdd:cd14148  168 MAPEVIRLSLFSKSSDVWSFGVLLWELLTGEVPY 201
PDZ_syntrophin-like cd06801
PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), ...
 323-366 9.89e-04

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467262 [Multi-domain]  Cd Length: 83  Bit Score: 38.71  E-value: 9.89e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLR 366
Cdd:cd06801   28 LISKIFKGQAADQTGQLFVGDAILSVNGENLEDATHDEAVQALK 71
PDZ_RIM-like cd06714
PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ ...
 315-372 1.02e-03

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467198 [Multi-domain]  Cd Length: 95  Bit Score: 38.69  E-value: 1.02e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 315 KMNELNHC--IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSI 372
Cdd:cd06714   31 KMTESGRLgaYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQDIISQSKGEV 90
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
 11-72 1.03e-03

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.


Pssm-ID: 270774 [Multi-domain]  Cd Length: 409  Bit Score: 42.30  E-value: 1.03e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983  11 YGKPVDVWGCGVILFILLSGCLPFYGtkERLFEgiIKGKYkMN-------PRQWSHISESAKDLVRRML 72
Cdd:cd05624  256 YGPECDWWSLGVCMYEMLYGETPFYA--ESLVE--TYGKI-MNheerfqfPSHVTDVSEEAKDLIQRLI 319
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
 443-487 1.08e-03

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 37.59  E-value: 1.08e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 768035983 443 KEAG-IRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPSPELQ 487
Cdd:cd11928   12 KEPGdLKFNKGDIIILRRKVDENWYHGEL----NGCHGFLPASYIQ 53
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
 426-476 1.28e-03

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 37.49  E-value: 1.28e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDHNWWQGKLENSKNG 476
Cdd:cd11812    2 VVALYDYTANRSD-------ELTIHRGDIIRVLYKDNDNWWFGSLVNGQQG 45
SH3_9 pfam14604
Variant SH3 domain;
428-483 1.32e-03

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 37.21  E-value: 1.32e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983  428 AQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:pfam14604   1 ALYPYEPKDDDELS-------LQRGDVITVIEESEDGWWEGIN----TGRTGLVPA 45
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
 449-483 1.46e-03

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212775  Cd Length: 54  Bit Score: 37.37  E-value: 1.46e-03
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 768035983 449 FRVGDIIQIISKDD--HNWWQGKLenskNGTAGLIPS 483
Cdd:cd11841   18 FQAGDRITVLTRTDsqFDWWEGRL----RGRVGIFPA 50
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
 1-92 1.61e-03

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: 41.15  E-value: 1.61e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERI 80
Cdd:cd14201  180 MAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPFQANSPQDLRMFYEKNKNLQPSIPRETSPYLADLLLGLLQRNQKDRM 259

                         90
                 ....*....|..
gi 768035983  81 TVYEALNHPWLK 92
Cdd:cd14201  260 DFEAFFSHPFLE 271
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
 1-73 1.61e-03

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: 41.16  E-value: 1.61e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983   1 MAPEVVKRE---PYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPrQWSHISESAKDLVRRMLM 73
Cdd:cd14150  165 MAPEVIRMQdtnPYSFQSDVYAYGVVLYELMSGTLPYSNINNRDQIIFMVGRGYLSP-DLSKLSSNCPKAMKRLLI 239
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
 1-95 1.63e-03

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 41.50  E-value: 1.63e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTK-----ERLFEGIIkgkykMNPRqwsHISESAKDLVRRMLMLD 75
Cdd:PTZ00426 195 IAPEILLNVGHGKAADWWTLGIFIYEILVGCPPFYANEplliyQKILEGII-----YFPK---FLDNNCKHLMKKLLSHD 266

                         90       100
                 ....*....|....*....|....*
gi 768035983  76 PAERI-----TVYEALNHPWLKERD 95
Cdd:PTZ00426 267 LTKRYgnlkkGAQNVKEHPWFGNID 291
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
 2-30 1.68e-03

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 41.52  E-value: 1.68e-03
                         10        20
                 ....*....|....*....|....*....
gi 768035983   2 APEVVKREPYGKPVDVWGCGVILFILLSG 30
Cdd:PHA03212 251 APELLARDPYGPAVDIWSAGIVLFEMATC 279
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
 432-482 1.72e-03

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 37.30  E-value: 1.72e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768035983 432 YDPAKDdlipcKEAGIRFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11972    9 YDYTKD-----KEDELSFQEGAIIYVIKKNDDGWYEGVM----NGVTGLFP 50
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
 424-483 1.88e-03

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. 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). However, Brk lacks the N-terminal myristoylation sites. 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, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 36.79  E-value: 1.88e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983 424 IYVrAQFEYDP-AKDDLipckeagiRFRVGDIIQIISKDDHNWWqgKLENSKNGTAGLIPS 483
Cdd:cd11845    1 IYV-ALYDYEArTDDDL--------SFKKGDRLQILDDSDGDWW--LARHLSTGKEGYIPS 50
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
 426-476 1.99e-03

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 36.96  E-value: 1.99e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768035983 426 VRAQFEYDPAKDDlipckeaGIRFRVGDIIQIISKDDhNWWQGKLENSKNG 476
Cdd:cd11837    2 ATALYPWRAKKEN-------HLSFAKGDIITVLEQQE-MWWFGELEGGEEG 44
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
 1-34 2.00e-03

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 40.57  E-value: 2.00e-03
                         10        20        30
                 ....*....|....*....|....*....|....
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPF 34
Cdd:cd13991  171 MAPEVVLGKPCDAKVDVWSSCCMMLHMLNGCHPW 204
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 3-79 2.09e-03

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: 40.73  E-value: 2.09e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768035983   3 PEVVKREPYGKPVDVWGCGVILFILLSGCLPFY-GTKERLFEGIIKGKYKMNPrqwSHISESAKDLVRRMLMLDPAER 79
Cdd:cd08219  169 PEIWENMPYNNKSDIWSLGCILYELCTLKHPFQaNSWKNLILKVCQGSYKPLP---SHYSYELRSLIKQMFKRNPRSR 243
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
 1-40 2.11e-03

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: 40.45  E-value: 2.11e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 768035983   1 MAPEVVK---REPYGKPVDVWGCGVILFILLSGCLPFYGTKER 40
Cdd:cd14062  158 MAPEVIRmqdENPYSFQSDVYAFGIVLYELLTGQLPYSHINNR 200
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 1-92 2.37e-03

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: 40.54  E-value: 2.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKR-EPYGKPVDVWGCGVILFILLSGCLPFygTKERLFEGIIKGKYKMNPR-QWSHISESAKDLVRRMLMLDPAE 78
Cdd:cd06917  168 MAPEVITEgKYYDTKADIWSLGITTYEMATGNPPY--SDVDALRAVMLIPKSKPPRlEGNGYSPLLKEFVAACLDEEPKD 245

                         90
                 ....*....|....
gi 768035983  79 RITVYEALNHPWLK 92
Cdd:cd06917  246 RLSADELLKSKWIK 259
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
 2-88 2.40e-03

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: 40.74  E-value: 2.40e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   2 APEVVKREPYG---KPVDVWGCGVILFILLSGCLPF---YGTKERLFEGIIKGKYKMnPRQwSHISESAKDLVRRMLMLD 75
Cdd:cd13986  186 APELFDVKSHCtidEKTDIWSLGCTLYALMYGESPFeriFQKGDSLALAVLSGNYSF-PDN-SRYSEELHQLVKSMLVVN 263

                         90
                 ....*....|...
gi 768035983  76 PAERITVYEALNH 88
Cdd:cd13986  264 PAERPSIDDLLSR 276
STKc_NDR_like_fungal cd05629
Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs ...
 1-92 2.42e-03

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270778 [Multi-domain]  Cd Length: 377  Bit Score: 40.99  E-value: 2.42e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRmLMLDPAER 79
Cdd:cd05629  215 IAPEIFLQQGYGQECDWWSLGAIMFECLIGWPPFCSeNSHETYRKIINWRETLYFPDDIHLSVEAEDLIRR-LITNAENR 293

                         90
                 ....*....|....*.
gi 768035983  80 ITVY---EALNHPWLK 92
Cdd:cd05629  294 LGRGgahEIKSHPFFR 309
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
 443-483 2.44e-03

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212822  Cd Length: 53  Bit Score: 36.71  E-value: 2.44e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 768035983 443 KEAGIRFRVGDIIQIISKDDHNWWQGKLENskNGTAGLIPS 483
Cdd:cd11889   12 TEGDLGFLEGDLIEVLSIGDGSWWSGKLRR--NGAEGIFPS 50
PDZ2_PDZD2-like cd06758
PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 ...
 323-367 2.47e-03

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467239 [Multi-domain]  Cd Length: 88  Bit Score: 37.72  E-value: 2.47e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLRE 367
Cdd:cd06758   32 FVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRS 76
PDZ2_LNX1_2-like cd06678
PDZ domain 2 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ ...
 300-360 2.75e-03

PDZ domain 2 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467166 [Multi-domain]  Cd Length: 82  Bit Score: 37.23  E-value: 2.75e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 300 VQFQKNTDEPMGITL--KMNELNHCIVaRIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQ 360
Cdd:cd06678    3 VTLNKRDGEQLGIKLvrKKDEPGVFIL-DLLEGGLAARDGRLKSDDRVLAINGQDLRHGTPEQ 64
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
 1-95 2.77e-03

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 40.37  E-value: 2.77e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEV------VKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRmLM 73
Cdd:cd05601  170 IAPEVltsmngGSKGTYGVECDWWSLGIVAYEMLYGKTPFTEdTVIKTYSNIMNFKKFLKFPEDPKVSESAVDLIKG-LL 248

                         90       100
                 ....*....|....*....|...
gi 768035983  74 LDPAERITvYEAL-NHPWLKERD 95
Cdd:cd05601  249 TDAKERLG-YEGLcCHPFFSGID 270
SH3_SH3RF_C cd11785
C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), ...
 441-483 3.19e-03

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212719  Cd Length: 55  Bit Score: 36.29  E-value: 3.19e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 768035983 441 PCKEAGIRFRVGDIIQIISKDDHNWWQGKLEnsKNGTAGLIPS 483
Cdd:cd11785   10 PQSEAELELKEGDIVFVHKKREDGWFKGTLQ--RTGKTGLFPG 50
SH3_RIM-BP_3 cd12013
Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs ...
 427-488 3.23e-03

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212946  Cd Length: 61  Bit Score: 36.59  E-value: 3.23e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768035983 427 RAQFEYDPAKDDLIPCKEAGIRFRVGDIIQII-SKDDHNWWQGKLenskNGTAGLIPSPELQE 488
Cdd:cd12013    3 VALFDYDPRESSPNVDAEVELSFRAGDIITVFgEMDEDGFYYGEL----NGQRGLVPSNFLEE 61
PDZ_SHANK1_3-like cd06746
PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and ...
 330-377 3.24e-03

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467228 [Multi-domain]  Cd Length: 101  Bit Score: 37.57  E-value: 3.24e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 768035983 330 GGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06746   52 GGVADKAG-LKKGDFLLEINGEDVVKASHEQVVNLIRQSGNTLVLKVV 98
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
 449-488 3.49e-03

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 36.14  E-value: 3.49e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 768035983 449 FRVGDIIQIISKDDHNWWQGklENSKnGTAGLIPSPELQE 488
Cdd:cd11770   18 FKKGEVLRIISKRADGWWLA--ENSK-GNRGLVPKTYLKV 54
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
 449-482 3.50e-03

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 36.36  E-value: 3.50e-03
                         10        20        30
                 ....*....|....*....|....*....|....
gi 768035983 449 FRVGDIIQIISKDDHNWWQGKLenskNGTAGLIP 482
Cdd:cd11956   20 FKRGDVLLLHSKASSDWWRGEH----NGMRGLIP 49
STKc_PINK1 cd14018
Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze ...
 1-87 3.72e-03

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: 40.17  E-value: 3.72e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP-------YGKpVDVWGCGVILFILLSGCLPFYGTKERLFEgiiKGKYKMN--PRQWSHISESAKDLVRRM 71
Cdd:cd14018  215 MAPEVSTAVPgpgvvinYSK-ADAWAVGAIAYEIFGLSNPFYGLGDTMLE---SRSYQESqlPALPSAVPPDVRQVVKDL 290

                         90
                 ....*....|....*.
gi 768035983  72 LMLDPAERITVYEALN 87
Cdd:cd14018  291 LQRDPNKRVSARVAAN 306
PDZ11_MUPP1-PDZ9_PATJ-like cd06674
PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ ...
 300-376 3.82e-03

PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 11 of MUPP1, PDZ domain 9 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ11 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467162 [Multi-domain]  Cd Length: 87  Bit Score: 36.88  E-value: 3.82e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 300 VQFQKNTDEPMGITL--KMNELNhCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06674    6 VELQKKPGRGLGLSIvgKRNDTG-VFVSDIVKGGAADADGRLMQGDQILSVNGEDVRNASQEAAAALLKCAQGKVRLEV 83
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 1-92 3.84e-03

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 40.37  E-value: 3.84e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP----YGKPVDVWGCGVILFILLSGCLPFY-----GTkerlFEGIIKGKYKMNPRQWSHISESAKDLVRRM 71
Cdd:cd05621  219 ISPEVLKSQGgdgyYGRECDWWSVGVFLFEMLVGDTPFYadslvGT----YSKIMDHKNSLNFPDDVEISKHAKNLICAF 294

                         90       100
                 ....*....|....*....|....
gi 768035983  72 LMlDPAERI---TVYEALNHPWLK 92
Cdd:cd05621  295 LT-DREVRLgrnGVEEIKQHPFFR 317
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
 1-80 3.99e-03

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: 39.86  E-value: 3.99e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWS-HISESAKDLVRRMLMLDPAER 79
Cdd:cd05608  172 MAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPFRARGEKVENKELKQRILNDSVTYSeKFSPASKSICEALLAKDPEKR 251


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gi 768035983  80 I 80
Cdd:cd05608  252 L 252
PDZ0_MAGI-1_3-like cd06730
PDZ domain 0 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 322-377 4.14e-03

PDZ domain 0 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 0 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ0 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467212 [Multi-domain]  Cd Length: 85  Bit Score: 36.79  E-value: 4.14e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768035983 322 CIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06730   29 PYLGEVKEDKVVYKSGKLHPGELLLEVNGTPVSGLTLRDVLAVIKHCKEPVRLKTV 84
SH3_RIM-BP cd11851
Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding ...
 426-488 4.34e-03

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212785  Cd Length: 62  Bit Score: 36.14  E-value: 4.34e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768035983 426 VRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQII-SKDDHNWWQGKLENSKNgtaGLIPSPELQE 488
Cdd:cd11851    2 MVALYDYNPETMSPNDDPEEELSFHAGDVVRVYgPMDEDGFYYGELEGGRK---GLVPSNFVQE 62
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
 425-483 4.54e-03

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 35.93  E-value: 4.54e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768035983 425 YVRAQFEYDPAKDDLIPckeagirFRVGDIIQIISKDDHNWWQGKLenskNGTAGLIPS 483
Cdd:cd12046    1 QVVALFSYEASQPEDLE-------FQKGDVILVLSKVNEDWLEGQC----KGKIGIFPS 48
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
 61-91 4.57e-03

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 40.07  E-value: 4.57e-03
                         10        20        30
                 ....*....|....*....|....*....|.
gi 768035983  61 SESAKDLVRRMLMLDPAERITVYEALNHPWL 91
Cdd:cd07874  284 ASQARDLLSKMLVIDPAKRISVDEALQHPYI 314
PDZ2_MUPP1-like cd06667
PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 323-376 4.61e-03

PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467155 [Multi-domain]  Cd Length: 80  Bit Score: 36.49  E-value: 4.61e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06667   25 VVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQCGSHVRLVV 78
PDZ_SNX27-like cd23070
PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density ...
 319-378 5.12e-03

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467283 [Multi-domain]  Cd Length: 93  Bit Score: 37.00  E-value: 5.12e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 319 LNHciVARIMHGGMIHRQGtLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIVP 378
Cdd:cd23070   37 LQH--VSAVLEGGAADKAG-VRKGDRILEVNGVNVEGATHKQVVDLIKSGGDELTLTVIS 93
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
 1-89 5.31e-03

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: 39.29  E-value: 5.31e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP-YGKPVDVWGCGVILFILLSGC-LPFYGTkerLFEGIIKGKYKMNPRqwSHISESAKDLVRRMLMLDPAE 78
Cdd:cd13997  167 LAPELLNENYtHLPKADIFSLGVTVYEAATGEpLPRNGQ---QWQQLRQGKLPLPPG--LVLSQELTRLLKVMLDPDPTR 241

                         90
                 ....*....|.
gi 768035983  79 RITVYEALNHP 89
Cdd:cd13997  242 RPTADQLLAHD 252
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 1-72 5.32e-03

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270747 [Multi-domain]  Cd Length: 352  Bit Score: 39.67  E-value: 5.32e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP----YGKPVDVWGCGVILFILLSGCLPFY-----GTkerlFEGIIKGKYKMNPRQWSHISESAKDLVRRM 71
Cdd:cd05596  193 ISPEVLKSQGgdgvYGRECDWWSVGVFLYEMLVGDTPFYadslvGT----YGKIMNHKNSLQFPDDVEISKDAKSLICAF 268


                 .
gi 768035983  72 L 72
Cdd:cd05596  269 L 269
PDZ2_Dlg1-2-4-like cd06724
PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg) ...
 324-377 5.55e-03

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467207 [Multi-domain]  Cd Length: 85  Bit Score: 36.48  E-value: 5.55e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983 324 VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06724   32 VTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTHEEAVAALKNTSDVVYLKVA 85
PDZ5_GRIP1-2-like cd06682
PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 323-376 5.69e-03

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467170 [Multi-domain]  Cd Length: 85  Bit Score: 36.55  E-value: 5.69e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983 323 IVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKI 376
Cdd:cd06682   30 IISDVKKGSVAHRTGTLEPGDKLLAIDNIRLDNCSMEDAAQILQQAEDIVKLKI 83
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
 425-483 5.70e-03

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 35.48  E-value: 5.70e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768035983 425 YVRAQFEYDPA-KDDLipckeagiRFRVGDIIQIISK-DDHN-WWQGKLenskNGTAGLIPS 483
Cdd:cd11842    1 KAVALYDFAGEqPGDL--------AFQKGDIITILKKsDSQNdWWTGRI----GGREGIFPA 50
PDZ13_MUPP1-like cd06676
PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 ...
 324-377 5.95e-03

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ13 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467164 [Multi-domain]  Cd Length: 83  Bit Score: 36.55  E-value: 5.95e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 768035983 324 VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIV 377
Cdd:cd06676   30 VKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKTKGTVTLTVL 83
PDZ2-PDZRN4-like cd06716
PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related ...
 289-374 6.86e-03

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467200 [Multi-domain]  Cd Length: 88  Bit Score: 36.48  E-value: 6.86e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983 289 MDMENVTRVRlvqfqKNTDEPMGITL---KMNELNHCI-VARIMHGGMIHRQGTLHVGDEIREINGISVANQtvEQLQKM 364
Cdd:cd06716    1 IEYEEVTLKR-----SNSQEKLGLTLcyrTDDEEDTGIyVSEVDPNSIAAKDGRIREGDQILQINGVDVQNR--EEAIAL 73

                         90
                 ....*....|
gi 768035983 365 LREMRGSITF 374
Cdd:cd06716   74 LSEEEKSITL 83
PDZ2_Par3-like cd23058
PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 324-369 7.40e-03

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467271 [Multi-domain]  Cd Length: 93  Bit Score: 36.47  E-value: 7.40e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 768035983 324 VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMR 369
Cdd:cd23058   36 IKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRSTK 81
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
 1-107 7.62e-03

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: 39.22  E-value: 7.62e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPEVVKREP----YGKPVDVWGCGVILFILLSGCLPFY-----GTkerlFEGIIKGKYKMNPRQWSHISESAKDLVRRM 71
Cdd:cd05622  240 ISPEVLKSQGgdgyYGRECDWWSVGVFLYEMLVGDTPFYadslvGT----YSKIMNHKNSLTFPDDNDISKEAKNLICAF 315

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 768035983  72 LMlDPAERI---TVYEALNHPWLKErDRYAYKiHLPETV 107
Cdd:cd05622  316 LT-DREVRLgrnGVEEIKRHLFFKN-DQWAWE-TLRDTV 351
STKc_NDR1 cd05628
Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze ...
 1-70 8.06e-03

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270777 [Multi-domain]  Cd Length: 376  Bit Score: 39.25  E-value: 8.06e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768035983   1 MAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYG-TKERLFEGIIKGKYKMNPRQWSHISESAKDLVRR 70
Cdd:cd05628  203 IAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSeTPQETYKKVMNWKETLIFPPEVPISEKAKDLILR 273
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
 1-91 9.24e-03

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: 38.88  E-value: 9.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768035983   1 MAPE--VVKREP--YGKPVDVWGCGVILFILLSGCLPF---YGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLM 73
Cdd:cd14040  189 LPPEcfVVGKEPpkISNKVDVWSVGVIFFQCLYGRKPFghnQSQQDILQENTILKATEVQFPVKPVVSNEAKAFIRRCLA 268

                         90
                 ....*....|....*...
gi 768035983  74 LDPAERITVYEALNHPWL 91
Cdd:cd14040  269 YRKEDRFDVHQLASDPYL 286
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
 449-482 9.34e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 34.83  E-value: 9.34e-03
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                 ....*....|....*....|....*....|....*.
gi 768035983 449 FRVGDIIQIISKDDH--NWWQGKLenskNGTAGLIP 482
Cdd:cd12044   18 FQRGDLIYILSKEYNmyGWWVGEL----NGIVGIVP 49
 
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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