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Conserved domains on  [gi|18150824|dbj|BAA81712|]
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protein tyrosine kinase [Ephydatia fluviatilis]

Protein Classification

tyrosine-protein kinase; tyrosine-protein kinase CSK( domain architecture ID 10185290)

tyrosine-protein kinase is a cytoplasmic (or nonreceptor) kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates; contains Src Homology 3 (SH3) and SH2 domains| tyrosine-protein kinase CSK is a cytoplasmic (or nonreceptor) kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates; it catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
219-478 0e+00

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 515.36  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKdekAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:cd05039   1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQKVAVKCLKDDST---AAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnVKQ 378
Cdd:cd05039  78 VTEYMAKGSLVDYLRSRGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEAS-SNQ 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCW 458
Cdd:cd05039 157 DGGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCW 236
                       250       260
                ....*....|....*....|
gi 18150824 459 EKDPSQRPNFTRIEKALESV 478
Cdd:cd05039 237 ELDPAKRPTFKQLREKLEHI 256
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
105-203 1.46e-61

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198190  Cd Length: 98  Bit Score: 195.97  E-value: 1.46e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEkGLVTVDDDEYFDNLIKLVEHY 184
Cdd:cd09937   1 SLMPWFHGKISREEAERLLQPPEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYRN-GKLTIDEEEYFENLIQLVEHY 79
                        90
                ....*....|....*....
gi 18150824 185 QKEADGLCTRLKAPVDKEG 203
Cdd:cd09937  80 TKDADGLCTRLVKPKVKEG 98
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
8-64 1.67e-35

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. 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: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 125.88  E-value: 1.67e-35
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824   8 GTECIGKYNFPGSSPHDLPFKKGDRLVIVAPSKDPNWYKARREDGLEGMIPFNYVQE 64
Cdd:cd11769   1 GTECIAKYNFNGASEEDLPFKKGDILTIVAVTKDPNWYKAKNKDGREGMIPANYVQK 57
 
Name Accession Description Interval E-value
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
219-478 0e+00

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 515.36  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKdekAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:cd05039   1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQKVAVKCLKDDST---AAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnVKQ 378
Cdd:cd05039  78 VTEYMAKGSLVDYLRSRGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEAS-SNQ 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCW 458
Cdd:cd05039 157 DGGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCW 236
                       250       260
                ....*....|....*....|
gi 18150824 459 EKDPSQRPNFTRIEKALESV 478
Cdd:cd05039 237 ELDPAKRPTFKQLREKLEHI 256
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
225-475 8.69e-128

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 371.50  E-value: 8.69e-128
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    225 SLLKKslIGKGEFGEVWLGDYEGKK------VAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:smart00221   2 TLGKK--LGEGAFGEVYKGTLKGKGdgkeveVAVKTLKED-ASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    299 ITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSN 375
Cdd:smart00221  79 VMEYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRdlyDDDY 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMM 455
Cdd:smart00221 159 YKVKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLML 238
                          250       260
                   ....*....|....*....|
gi 18150824    456 DCWEKDPSQRPNFTRIEKAL 475
Cdd:smart00221 239 QCWAEDPEDRPTFSELVEIL 258
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
232-475 1.67e-124

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 363.35  E-value: 1.67e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   232 IGKGEFGEVWLGDYEGK------KVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:pfam07714   7 LGEGAFGEVYKGTLKGEgentkiKVAVKTLKEG-ADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   306 GSLIDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSSNVKQEGA 381
Cdd:pfam07714  86 GDLLDFLRKHKRK-LTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRdiydDDYYRKRGGG 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   382 KLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:pfam07714 165 KLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYD 244
                         250
                  ....*....|....
gi 18150824   462 PSQRPNFTRIEKAL 475
Cdd:pfam07714 245 PEDRPTFSELVEDL 258
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
105-203 1.46e-61

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 195.97  E-value: 1.46e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEkGLVTVDDDEYFDNLIKLVEHY 184
Cdd:cd09937   1 SLMPWFHGKISREEAERLLQPPEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYRN-GKLTIDEEEYFENLIQLVEHY 79
                        90
                ....*....|....*....
gi 18150824 185 QKEADGLCTRLKAPVDKEG 203
Cdd:cd09937  80 TKDADGLCTRLVKPKVKEG 98
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
230-466 3.57e-40

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 150.93  E-value: 3.57e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYE--GKKVAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:COG0515  13 RLLGRGGMGVVYLARDLrlGRPVALKVLRPELaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGE 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAklp 384
Cdd:COG0515  93 SLADLLRRRGP--LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARalGGATLTQTGT--- 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWT----APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRM---ESPDGCPDQIYKIMMDC 457
Cdd:COG0515 168 VVGTpgymAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAIVLRA 246

                ....*....
gi 18150824 458 WEKDPSQRP 466
Cdd:COG0515 247 LAKDPEERY 255
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
8-64 1.67e-35

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. 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: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 125.88  E-value: 1.67e-35
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824   8 GTECIGKYNFPGSSPHDLPFKKGDRLVIVAPSKDPNWYKARREDGLEGMIPFNYVQE 64
Cdd:cd11769   1 GTECIAKYNFNGASEEDLPFKKGDILTIVAVTKDPNWYKAKNKDGREGMIPANYVQK 57
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
107-190 2.84e-33

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 120.80  E-value: 2.84e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    107 MPWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQK 186
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQK 80

                   ....
gi 18150824    187 EADG 190
Cdd:smart00252  81 NSLG 84
SH2 pfam00017
SH2 domain;
109-184 9.33e-28

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 105.38  E-value: 9.33e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824   109 WFHGRISREDAEKLLTP-PKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHY 184
Cdd:pfam00017   1 WYHGKISRQEAERLLLNgKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEHY 77
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
232-414 1.41e-19

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 89.49  E-value: 1.41e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  232 IGKGEFGEVWLGDYE--GKKVAMKSMKDH--LKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:PTZ00263  26 LGTGSFGRVRIAKHKgtGEYYAIKCLKKReiLK-MKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVGGE 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  308 LIDYLRSRGRavitkqnqidFARDVVK--------GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:PTZ00263 105 LFTHLRKAGR----------FPNDVAKfyhaelvlAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPDRTFT 174
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 18150824  380 GAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:PTZ00263 175 LCGTP-EYLAPEVIQSKGHGKAVDWWTMGVLLYEF 208
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
230-466 1.04e-17

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 85.62  E-value: 1.04e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  230 SLIGKGEFGEVWLG-D-YEGKKVAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVcliGIsLD---DNPI-YLITEF 302
Cdd:NF033483  13 ERIGRGGMAEVYLAkDtRLDRDVAVKVLRPDLaRDPEFVARFRREAQSAASLSHPNIV---SV-YDvgeDGGIpYIVMEY 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  303 MAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEG 380
Cdd:NF033483  89 VDGRTLKDYIREHGP--LSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARalSSTTMTQTN 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  381 AKL-PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-------------------PRVPVEDVANHVENgyrm 440
Cdd:NF033483 167 SVLgTVHYLSPEQARGGTVDARSDIYSLGIVLYEMLT-GRPPFdgdspvsvaykhvqedpppPSELNPGIPQSLDA---- 241
                        250       260
                 ....*....|....*....|....*.
gi 18150824  441 espdgcpdqiykIMMDCWEKDPSQRP 466
Cdd:NF033483 242 ------------VVLKATAKDPDDRY 255
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
7-63 3.10e-12

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: 61.40  E-value: 3.10e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824      7 VGTECIGKYNFPGSSPHDLPFKKGDRLVIVAPSkDPNWYKARREDGLEGMIPFNYVQ 63
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKS-DDGWWKGRLGRGKEGLFPSNYVE 56
 
Name Accession Description Interval E-value
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
219-478 0e+00

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 515.36  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKdekAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:cd05039   1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQKVAVKCLKDDST---AAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnVKQ 378
Cdd:cd05039  78 VTEYMAKGSLVDYLRSRGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEAS-SNQ 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCW 458
Cdd:cd05039 157 DGGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCW 236
                       250       260
                ....*....|....*....|
gi 18150824 459 EKDPSQRPNFTRIEKALESV 478
Cdd:cd05039 237 ELDPAKRPTFKQLREKLEHI 256
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
225-475 8.69e-128

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 371.50  E-value: 8.69e-128
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    225 SLLKKslIGKGEFGEVWLGDYEGKK------VAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:smart00221   2 TLGKK--LGEGAFGEVYKGTLKGKGdgkeveVAVKTLKED-ASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    299 ITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSN 375
Cdd:smart00221  79 VMEYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRdlyDDDY 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMM 455
Cdd:smart00221 159 YKVKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLML 238
                          250       260
                   ....*....|....*....|
gi 18150824    456 DCWEKDPSQRPNFTRIEKAL 475
Cdd:smart00221 239 QCWAEDPEDRPTFSELVEIL 258
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
219-478 1.25e-126

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 368.54  E-value: 1.25e-126
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKDhlkDEKAKTqFLAEASVMTTLRHPNLVCLIGISLDDN-PIY 297
Cdd:cd05082   1 WALNMKELKLLQTIGKGEFGDVMLGDYRGNKVAVKCIKN---DATAQA-FLAEASVMTQLRHSNLVQLLGVIVEEKgGLY 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVk 377
Cdd:cd05082  77 IVTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASST- 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDC 457
Cdd:cd05082 156 QDTGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVMKNC 235
                       250       260
                ....*....|....*....|.
gi 18150824 458 WEKDPSQRPNFTRIEKALESV 478
Cdd:cd05082 236 WHLDAAMRPSFLQLREQLEHI 256
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
225-475 8.32e-126

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 366.47  E-value: 8.32e-126
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    225 SLLKKslIGKGEFGEVWLGDYEGK------KVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:smart00219   2 TLGKK--LGEGAFGEVYKGKLKGKggkkkvEVAVKTLKED-ASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    299 ITEFMAKGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSN 375
Cdd:smart00219  79 VMEYMEGGDLLSYLRKN-RPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRdlyDDDY 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMM 455
Cdd:smart00219 158 YRKRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLML 237
                          250       260
                   ....*....|....*....|
gi 18150824    456 DCWEKDPSQRPNFTRIEKAL 475
Cdd:smart00219 238 QCWAEDPEDRPTFSELVEIL 257
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
232-476 2.49e-125

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 365.32  E-value: 2.49e-125
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK-----VAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd00192   3 LGEGAFGEVYKGKLKGGDgktvdVAVKTLKED-ASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSR-------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN---- 375
Cdd:cd00192  82 DLLDFLRKSrpvfpspEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDddyy 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMM 455
Cdd:cd00192 162 RKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELML 241
                       250       260
                ....*....|....*....|.
gi 18150824 456 DCWEKDPSQRPNFTRIEKALE 476
Cdd:cd00192 242 SCWQLDPEDRPTFSELVERLE 262
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
232-475 1.67e-124

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 363.35  E-value: 1.67e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   232 IGKGEFGEVWLGDYEGK------KVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:pfam07714   7 LGEGAFGEVYKGTLKGEgentkiKVAVKTLKEG-ADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   306 GSLIDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSSNVKQEGA 381
Cdd:pfam07714  86 GDLLDFLRKHKRK-LTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRdiydDDYYRKRGGG 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   382 KLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:pfam07714 165 KLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYD 244
                         250
                  ....*....|....
gi 18150824   462 PSQRPNFTRIEKAL 475
Cdd:pfam07714 245 PEDRPTFSELVEDL 258
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
232-468 4.60e-109

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 323.47  E-value: 4.60e-109
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd05034   3 LGAGQFGEVWMGVWNGTtKVAVKTLKPGTMSPEA---FLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRS-RGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN---VKQEGAKLPVK 386
Cdd:cd05034  80 YLRTgEGRA-LRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDdeyTAREGAKFPIK 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 WTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRP 466
Cdd:cd05034 159 WTAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERP 238

                ..
gi 18150824 467 NF 468
Cdd:cd05034 239 TF 240
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
219-477 7.19e-108

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 321.28  E-value: 7.19e-108
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd05068   3 WEIDRKSLKLLRKLGSGQFGEVWEGLWNNTtPVAVKTLKPGTMDPE---DFLREAQIMKKLRHPKLIQLYAVCTLEEPIY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSN 375
Cdd:cd05068  80 IITELMKHGSLLEYLQGKGRS-LQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARviKVED 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 V--KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd05068 159 EyeAREGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDI 238
                       250       260
                ....*....|....*....|....
gi 18150824 454 MMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05068 239 MLECWKADPMERPTFETLQWKLED 262
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
219-476 3.39e-103

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 308.73  E-value: 3.39e-103
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKdhlKDEKAKTqFLAEASVMTTLRHPNLVCLIGISLDdNPIYL 298
Cdd:cd05083   1 WLLNLQKLTLGEIIGEGEFGAVLQGEYMGQKVAVKNIK---CDVTAQA-FLEETAVMTKLQHKNLVRLLGVILH-NGLYI 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvKQ 378
Cdd:cd05083  76 VMELMSKGNLVNFLRSRGRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKVGSM-GV 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCW 458
Cdd:cd05083 155 DNSRLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSCW 234
                       250
                ....*....|....*...
gi 18150824 459 EKDPSQRPNFTRIEKALE 476
Cdd:cd05083 235 EAEPGKRPSFKKLREKLE 252
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
219-476 2.37e-94

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 286.62  E-value: 2.37e-94
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYE--GKKVAMKSMKDhlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPI 296
Cdd:cd05052   1 WEIERTDITMKHKLGGGQYGEVYEGVWKkyNLTVAVKTLKE---DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPF 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 297 YLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSS 373
Cdd:cd05052  78 YIITEFMPYGNLLDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSrlmTGD 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd05052 158 TYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYEL 237
                       250       260
                ....*....|....*....|...
gi 18150824 454 MMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05052 238 MRACWQWNPSDRPSFAEIHQALE 260
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
232-475 1.34e-93

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 283.95  E-value: 1.34e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDHLKDEKaKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd05041   3 IGRGNFGDVYRGVLKPDNteVAVKTCRETLPPDL-KRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGSLL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--------SSSNVKQega 381
Cdd:cd05041  82 TFLRKKGAR-LTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSReeedgeytVSDGLKQ--- 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 kLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:cd05041 158 -IPIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYD 236
                       250
                ....*....|....
gi 18150824 462 PSQRPNFTRIEKAL 475
Cdd:cd05041 237 PENRPSFSEIYNEL 250
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
231-476 2.28e-89

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 273.91  E-value: 2.28e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVW-------LGDYEGK-KVAMKSMKDHLKDEKaKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd05044   2 FLGSGAFGEVFegtakdiLGDGSGEtKVAVKTLRKGATDQE-KAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLR-----SRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE----DNVAKVSDFGLAK-- 371
Cdd:cd05044  81 MEGGDLLSYLRaarptAFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSkdyrERVVKIGDFGLARdi 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 -SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQ 449
Cdd:cd05044 161 yKNDYYRKEGeGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPDD 240
                       250       260
                ....*....|....*....|....*..
gi 18150824 450 IYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05044 241 LYELMLRCWSTDPEERPSFARILEQLQ 267
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
219-481 2.99e-88

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 270.99  E-value: 2.99e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-KKVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGIsLDDNPIY 297
Cdd:cd05067   2 WEVPRETLKLVERLGAGQFGEVWMGYYNGhTKVAIKSLKQGSMSPDA---FLAEANLMKQLQHQRLVRLYAV-VTQEPIY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSS 374
Cdd:cd05067  78 IITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLArliEDNE 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIM 454
Cdd:cd05067 158 YTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLM 237
                       250       260
                ....*....|....*....|....*..
gi 18150824 455 MDCWEKDPSQRPNFTRIEKALESVAVA 481
Cdd:cd05067 238 RLCWKERPEDRPTFEYLRSVLEDFFTA 264
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
232-475 5.53e-88

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 269.70  E-value: 5.53e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd05059  12 LGSGQFGVVHLGKWRGKiDVAIKMIKEGSMSED---DFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANGCLLN 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEGAKLPVKW 387
Cdd:cd05059  89 YLRER-RGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARyvlDDEYTSSVGTKFPVKW 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd05059 168 SPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPEERPT 247

                ....*...
gi 18150824 468 FTRIEKAL 475
Cdd:cd05059 248 FKILLSQL 255
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
219-481 8.11e-88

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 269.99  E-value: 8.11e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd05072   2 WEIPRESIKLVKKLGAGQFGEVWMGYYNNStKVAVKTLKPGTMSVQA---FLEEANLMKTLQHDKLVRLYAVVTKEEPIY 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSS 374
Cdd:cd05072  79 IITEYMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARvieDNE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIM 454
Cdd:cd05072 159 YTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIM 238
                       250       260
                ....*....|....*....|....*..
gi 18150824 455 MDCWEKDPSQRPNFTRIEKALESVAVA 481
Cdd:cd05072 239 KTCWKEKAEERPTFDYLQSVLDDFYTA 265
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
232-475 8.03e-86

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: 264.01  E-value: 8.03e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDY 311
Cdd:cd13999   1 IGSGSFGEVYKGKWRGTDVAIKKLKVEDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSLYDL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 312 LRSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsSSNVKQEGAKLPV---KWT 388
Cdd:cd13999  81 LHKKKI-PLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSR-IKNSTTEKMTGVVgtpRWM 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 389 APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHV-ENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd13999 159 APEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAVvQKGLRPPIPPDCPPELSKLIKRCWNEDPEKRPS 237

                ....*...
gi 18150824 468 FTRIEKAL 475
Cdd:cd13999 238 FSEIVKRL 245
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
219-478 8.39e-84

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 260.43  E-value: 8.39e-84
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG--------KKVAMKSMKDHlKDEKAKTQFLAEASVMTTL-RHPNLVCLIGI 289
Cdd:cd05053   7 WELPRDRLTLGKPLGEGAFGQVVKAEAVGldnkpnevVTVAVKMLKDD-ATEKDLSDLVSEMEMMKMIgKHKNIINLLGA 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 290 SLDDNPIYLITEFMAKGSLIDYLRSRgRAVITKQNQID---------------FARDVVKGMVYLESQNFVHRDLAARNV 354
Cdd:cd05053  86 CTQDGPLYVVVEYASKGNLREFLRAR-RPPGEEASPDDprvpeeqltqkdlvsFAYQVARGMEYLASKKCIHRDLAARNV 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 355 LIAEDNVAKVSDFGLAKSSSNV----KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDV 430
Cdd:cd05053 165 LVTEDNVMKIADFGLARDIHHIdyyrKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEEL 244
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 18150824 431 ANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05053 245 FKLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRI 292
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
219-478 1.58e-83

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 258.52  E-value: 1.58e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGK-KVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd05148   1 WERPREEFTLERKLGSGYFGEVWEGLWKNRvRVAIKILKS--DDLLKQQDFQKEVQALKRLRHKHLISLFAVCSVGEPVY 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK------ 371
Cdd:cd05148  79 IITELMEKGSLLAFLRSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARlikedv 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 -SSSNvkqegAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQI 450
Cdd:cd05148 159 yLSSD-----KKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEI 233
                       250       260
                ....*....|....*....|....*...
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05148 234 YKIMLECWAAEPEDRPSFKALREELDNI 261
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
231-477 1.93e-83

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 258.01  E-value: 1.93e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK-VAMKSMKDHLKDEkAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd05085   3 LLGKGNFGEVYKGTLKDKTpVAVKTCKEDLPQE-LKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-------SSSNVKQegak 382
Cdd:cd05085  82 SFLRKKKDELKTKQ-LVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRqeddgvySSSGLKQ---- 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd05085 157 IPIKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNP 236
                       250
                ....*....|....*
gi 18150824 463 SQRPNFTRIEKALES 477
Cdd:cd05085 237 ENRPKFSELQKELAA 251
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
232-472 6.83e-81

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 251.50  E-value: 6.83e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK-----VAMKSMK-DHLKDEKAktQFLAEASVMTTLRHPNLVCLIGISLDDnPIYLITEFMAK 305
Cdd:cd05060   3 LGHGNFGSVRKGVYLMKSgkeveVAVKTLKqEHEKAGKK--EFLREASVMAQLDHPCIVRLIGVCKGE-PLMLVMELAPL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS----SSNVK-QEG 380
Cdd:cd05060  80 GPLLKYLKKRR--EIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRAlgagSDYYRaTTA 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEK 460
Cdd:cd05060 158 GRWPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKY 237
                       250
                ....*....|..
gi 18150824 461 DPSQRPNFTRIE 472
Cdd:cd05060 238 RPEDRPTFSELE 249
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
232-476 6.98e-81

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 251.37  E-value: 6.98e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGIsLDDNPIYLITEFMAKGSLID 310
Cdd:cd14203   3 LGQGCFGEVWMGTWNGTtKVAIKTLKPGTMSPEA---FLEEAQIMKKLRHDKLVQLYAV-VSEEPIYIVTEFMSKGSLLD 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRS-RGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKQEGAKLPVK 386
Cdd:cd14203  79 FLKDgEGKYLKLPQ-LVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLArliEDNEYTARQGAKFPIK 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 WTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRP 466
Cdd:cd14203 158 WTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERP 237
                       250
                ....*....|
gi 18150824 467 NFTRIEKALE 476
Cdd:cd14203 238 TFEYLQSFLE 247
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
214-476 3.60e-80

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 250.33  E-value: 3.60e-80
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 214 FKEKGWAIPKASLLKKSLIGKGEFGEVWLGDY-EGKKVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGIsLD 292
Cdd:cd05073   1 WEKDAWEIPRESLKLEKKLGAGQFGEVWMATYnKHTKVAVKTMKPGSMSVEA---FLAEANVMKTLQHDKLVKLHAV-VT 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 293 DNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK- 371
Cdd:cd05073  77 KEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARv 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 --SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQ 449
Cdd:cd05073 157 ieDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEE 236
                       250       260
                ....*....|....*....|....*..
gi 18150824 450 IYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05073 237 LYNIMMRCWKNRPEERPTFEYIQSVLD 263
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
221-471 5.60e-80

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 250.00  E-value: 5.60e-80
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLGDYEGK-------KVAMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05036   3 VPRKNLTLIRALGQGAFGEVYEGTVSGMpgdpsplQVAVKTLPELCSEQDEM-DFLMEALIMSKFNHPNIVRCIGVCFQR 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLR-SRGRA----VITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA---EDNVAKVS 365
Cdd:cd05036  82 LPRFILLELMAGGDLKSFLReNRPRPeqpsSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTckgPGRVAKIG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 366 DFGLAK----SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRME 441
Cdd:cd05036 162 DFGMARdiyrADYYRKGGKAMLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGRMD 241
                       250       260       270
                ....*....|....*....|....*....|
gi 18150824 442 SPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05036 242 PPKNCPGPVYRIMTQCWQHIPEDRPNFSTI 271
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
232-471 7.91e-80

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 249.21  E-value: 7.91e-80
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKK---VAMKSMKDHLKDeKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05033  12 IGGGEFGEVCSGSLKlpGKKeidVAIKTLKSGYSD-KQRLDFLTEASIMGQFDHPNVIRLEGVVTKSRPVMIVTEYMENG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSSNVKQEGAK 382
Cdd:cd05033  91 SLDKFLR-ENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRrledSEATYTTKGGK 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd05033 170 IPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQLMLDCWQKDR 249

                ....*....
gi 18150824 463 SQRPNFTRI 471
Cdd:cd05033 250 NERPTFSQI 258
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
232-475 2.01e-77

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 242.53  E-value: 2.01e-77
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEkAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd05084   4 IGRGNFGEVFSGRLraDNTPVAVKSCRETLPPD-LKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDFL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--------SSSNVKQega 381
Cdd:cd05084  83 TFLRTEGPRLKVKE-LIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSReeedgvyaATGGMKQ--- 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 kLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:cd05084 159 -IPVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYD 237
                       250
                ....*....|....
gi 18150824 462 PSQRPNFTRIEKAL 475
Cdd:cd05084 238 PRKRPSFSTVHQDL 251
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
232-475 7.93e-77

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 241.39  E-value: 7.93e-77
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd05112  12 IGSGQFGLVHLGYWLNKdKVAIKTIREGAMSEE---DFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEGAKLPVKW 387
Cdd:cd05112  89 YLRTQ-RGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRfvlDDQYTSSTGTKFPVKW 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd05112 168 SSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKERPEDRPS 247

                ....*...
gi 18150824 468 FTRIEKAL 475
Cdd:cd05112 248 FSLLLRQL 255
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
218-481 9.79e-77

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 241.90  E-value: 9.79e-77
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 218 GWAIPKASLLKKSLIGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGIsLDDNPI 296
Cdd:cd05069   6 AWEIPRESLRLDVKLGQGCFGEVWMGTWNGTtKVAIKTLKPGTMMPEA---FLQEAQIMKKLRHDKLVPLYAV-VSEEPI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 297 YLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SS 373
Cdd:cd05069  82 YIVTEFMGKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARlieDN 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd05069 162 EYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHEL 241
                       250       260
                ....*....|....*....|....*...
gi 18150824 454 MMDCWEKDPSQRPNFTRIEKALESVAVA 481
Cdd:cd05069 242 MKLCWKKDPDERPTFEYIQSFLEDYFTA 269
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
219-483 6.59e-76

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 241.02  E-value: 6.59e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG---------KKVAMKSMKDHLKDeKAKTQFLAEASVMTTL-RHPNLVCLIG 288
Cdd:cd05099   7 WEFPRDRLVLGKPLGEGCFGQVVRAEAYGidksrpdqtVTVAVKMLKDNATD-KDLADLISEMELMKLIgKHKNIINLLG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSRGRAV------ITK--QNQIDF------ARDVVKGMVYLESQNFVHRDLAARNV 354
Cdd:cd05099  86 VCTQEGPLYVIVEYAAKGNLREFLRARRPPGpdytfdITKvpEEQLSFkdlvscAYQVARGMEYLESRRCIHRDLAARNV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 355 LIAEDNVAKVSDFGLAKSSSNV----KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDV 430
Cdd:cd05099 166 LVTEDNVMKIADFGLARGVHDIdyykKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEEL 245
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 18150824 431 ANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVAVAMS 483
Cdd:cd05099 246 FKLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVLAAVS 298
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
219-477 1.96e-75

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 238.40  E-value: 1.96e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLG-------DYEGKKVAMKSMKDHLKDEKaKTQFLAEASVMTTLRHPNLVCLIGISL 291
Cdd:cd05032   1 WELPREKITLIRELGQGSFGMVYEGlakgvvkGEPETRVAIKTVNENASMRE-RIEFLNEASVMKEFNCHHVVRLLGVVS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 292 DDNPIYLITEFMAKGSLIDYLRSR--------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAK 363
Cdd:cd05032  80 TGQPTLVVMELMAKGDLKSYLRSRrpeaennpGLGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 364 VSDFGLAKSSSNV----KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYR 439
Cdd:cd05032 160 IGDFGMTRDIYETdyyrKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGH 239
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18150824 440 MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05032 240 LDLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLKD 277
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
218-476 7.40e-75

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 236.89  E-value: 7.40e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 218 GWAIPKASLLKKSLIGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGIsLDDNPI 296
Cdd:cd05071   3 AWEIPRESLRLEVKLGQGCFGEVWMGTWNGTtRVAIKTLKPGTMSPEA---FLQEAQVMKKLRHEKLVQLYAV-VSEEPI 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 297 YLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SS 373
Cdd:cd05071  79 YIVTEYMSKGSLLDFLKGEMGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARlieDN 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd05071 159 EYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDL 238
                       250       260
                ....*....|....*....|...
gi 18150824 454 MMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05071 239 MCQCWRKEPEERPTFEYLQAFLE 261
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
221-468 1.77e-74

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 235.77  E-value: 1.77e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKK-SLIGKGEFGEV----WLGDYEGKK--VAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05057   3 IVKETELEKgKVLGSGAFGTVykgvWIPEGEKVKipVAIKVLREE-TGPKANEEILDEAYVMASVDHPHLVRLLGICLSS 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NpIYLITEFMAKGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-- 371
Cdd:cd05057  82 Q-VQLITQLMPLGCLLDYVRNH-RDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKll 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 --SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQ 449
Cdd:cd05057 160 dvDEKEYHAEGGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTID 239
                       250
                ....*....|....*....
gi 18150824 450 IYKIMMDCWEKDPSQRPNF 468
Cdd:cd05057 240 VYMVLVKCWMIDAESRPTF 258
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
232-471 2.93e-74

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 234.54  E-value: 2.93e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY---EGK--KVAMKSMK-DHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDdNPIYLITEFMAK 305
Cdd:cd05040   3 LGDGSFGVVRRGEWttpSGKviQVAVKCLKsDVLSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLS-SPLMMVTELAPL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRAVITkQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN-----VKQEG 380
Cdd:cd05040  82 GSLLDRLRKDQGHFLI-STLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQnedhyVMQEH 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQIYKIMMDCWE 459
Cdd:cd05040 161 RKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDkEGERLERPDDCPQDIYNVMLQCWA 240
                       250
                ....*....|..
gi 18150824 460 KDPSQRPNFTRI 471
Cdd:cd05040 241 HKPADRPTFVAL 252
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
219-481 5.31e-73

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 231.88  E-value: 5.31e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGK-KVAMKSMKdhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGIsLDDNPIY 297
Cdd:cd05070   4 WEIPRESLQLIKRLGNGQFGEVWMGTWNGNtKVAIKTLK---PGTMSPESFLEEAQIMKKLKHDKLVQLYAV-VSEEPIY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRS-RGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SS 373
Cdd:cd05070  80 IVTEYMSKGSLLDFLKDgEGRA-LKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARlieDN 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd05070 159 EYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHEL 238
                       250       260
                ....*....|....*....|....*...
gi 18150824 454 MMDCWEKDPSQRPNFTRIEKALESVAVA 481
Cdd:cd05070 239 MIHCWKKDPEERPTFEYLQGFLEDYFTA 266
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
229-478 1.04e-72

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 231.16  E-value: 1.04e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEGKK-----VAMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGIsLDDNPIYLITEFM 303
Cdd:cd05056  11 GRCIGEGQFGDVYQGVYMSPEnekiaVAVKTCKNCTSPSVRE-KFLQEAYIMRQFDHPHIVKLIGV-ITENPVWIVMELA 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEG 380
Cdd:cd05056  89 PLGELRSYLQVN-KYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRymeDESYYKASK 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEK 460
Cdd:cd05056 168 GKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAY 247
                       250
                ....*....|....*...
gi 18150824 461 DPSQRPNFTRIEKALESV 478
Cdd:cd05056 248 DPSKRPRFTELKAQLSDI 265
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
222-468 5.99e-72

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 228.61  E-value: 5.99e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLiGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd05113   3 PKDLTFLKEL-GTGQFGVVKYGKWRGQyDVAIKMIKEGSMSED---EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVK 377
Cdd:cd05113  79 EYMANGCLLNYLREMRKRFQTQQ-LLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRyvlDDEYTS 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDC 457
Cdd:cd05113 158 SVGSKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSC 237
                       250
                ....*....|.
gi 18150824 458 WEKDPSQRPNF 468
Cdd:cd05113 238 WHEKADERPTF 248
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
222-479 6.63e-72

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 229.58  E-value: 6.63e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLGDYE------GKKVAMKSMKdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD-- 293
Cdd:cd05038   2 EERHLKFIKQLGEGHFGSVELCRYDplgdntGEQVAVKSLQ-PSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPgr 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSS 373
Cdd:cd05038  81 RSLRLIMEYLPSGSLRDYLQ-RHRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SN------VKQEGaKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPY--PRVP------------VEDVANH 433
Cdd:cd05038 160 PEdkeyyyVKEPG-ESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQspPALFlrmigiaqgqmiVTRLLEL 238
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 434 VENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd05038 239 LKSGERLPRPPSCPDEVYDLMKECWEYEPQDRPSFSDLILIIDRLR 284
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
231-478 7.95e-71

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 226.29  E-value: 7.95e-71
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKK---VAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05066  11 VIGAGEFGEVCSGRLKlpGKReipVAIKTLKAGYT-EKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPVMIVTEYMEN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-----SSSNVKQEG 380
Cdd:cd05066  90 GSLDAFLR-KHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRvleddPEAAYTTRG 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEK 460
Cdd:cd05066 169 GKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQK 248
                       250
                ....*....|....*...
gi 18150824 461 DPSQRPNFTRIEKALESV 478
Cdd:cd05066 249 DRNERPKFEQIVSILDKL 266
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
219-479 1.00e-70

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 226.98  E-value: 1.00e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKD--HLKDEKAktqFLAEASVMTTL-RHPNLVCLIG 288
Cdd:cd05055  30 WEFPRNNLSFGKTLGAGAFGKVVEATAYGlsksdavMKVAVKMLKPtaHSSEREA---LMSELKIMSHLgNHENIVNLLG 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFG 368
Cdd:cd05055 107 ACTIGGPILVITEYCCYGDLLNFLRRKRESFLTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFG 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 369 LAK---SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPV-EDVANHVENGYRMESP 443
Cdd:cd05055 187 LARdimNDSNYVVKGnARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPVdSKFYKLIKEGYRMAQP 266
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 18150824 444 DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd05055 267 EHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIGKQL 302
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
231-478 5.88e-70

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 223.50  E-value: 5.88e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDY---EGKKV--AMKSMkDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT-EFMA 304
Cdd:cd05058   2 VIGKGHFGCVYHGTLidsDGQKIhcAVKSL-NRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSEGSPLVVlPYMK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRGRAVITKqNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS------SSNVKQ 378
Cdd:cd05058  81 HGDLRNFIRSETHNPTVK-DLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDiydkeyYSVHNH 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCW 458
Cdd:cd05058 160 TGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCW 239
                       250       260
                ....*....|....*....|
gi 18150824 459 EKDPSQRPNFTRIEKALESV 478
Cdd:cd05058 240 HPKPEMRPTFSELVSRISQI 259
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
231-476 6.38e-70

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 223.98  E-value: 6.38e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKK---VAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05065  11 VIGAGEFGEVCRGRLKlpGKReifVAIKTLKSGYT-EKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPVMIITEFMEN 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLR-SRGRAVITKQnqIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSSN---VK 377
Cdd:cd05065  90 GALDSFLRqNDGQFTVIQL--VGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDptyTS 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDC 457
Cdd:cd05065 168 SLGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQLMLDC 247
                       250
                ....*....|....*....
gi 18150824 458 WEKDPSQRPNFTRIEKALE 476
Cdd:cd05065 248 WQKDRNLRPKFGQIVNTLD 266
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
219-485 1.33e-69

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 224.12  E-value: 1.33e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG---------KKVAMKSMKDHlKDEKAKTQFLAEASVMTTL-RHPNLVCLIG 288
Cdd:cd05098   8 WELPRDRLVLGKPLGEGCFGQVVLAEAIGldkdkpnrvTKVAVKMLKSD-ATEKDLSDLISEMEMMKMIgKHKNIINLLG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSR--------------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNV 354
Cdd:cd05098  87 ACTQDGPLYVIVEYASKGNLREYLQARrppgmeycynpshnPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNV 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 355 LIAEDNVAKVSDFGLAKSSSNV----KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDV 430
Cdd:cd05098 167 LVTEDNVMKIADFGLARDIHHIdyykKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEEL 246
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 431 ANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVaVAMSSS 485
Cdd:cd05098 247 FKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI-VALTSN 300
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
232-477 1.86e-69

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 222.15  E-value: 1.86e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK----VAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNpIYLITEFMAKGS 307
Cdd:cd05116   3 LGSGNFGTVKKGYYQMKKvvktVAVKILKNEANDPALKDELLREANVMQQLDNPYIVRMIGICEAES-WMLVMEMAELGP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK-----QEGAK 382
Cdd:cd05116  82 LNKFLQKNRH--VTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADEnyykaQTHGK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd05116 160 WPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDV 239
                       250
                ....*....|....*
gi 18150824 463 SQRPNFTRIEKALES 477
Cdd:cd05116 240 DERPGFAAVELRLRN 254
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
232-479 6.52e-69

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 220.89  E-value: 6.52e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGK-KVAMKSMKDHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd05114  12 LGSGLFGVVRLGKWRAQyKVAIKAIREGAMSEE---DFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGCLLN 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEGAKLPVKW 387
Cdd:cd05114  89 YLRQR-RGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRyvlDDQYTSSSGAKFPVKW 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd05114 168 SPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPEGRPT 247
                       250
                ....*....|..
gi 18150824 468 FTRIEKALESVA 479
Cdd:cd05114 248 FADLLRTITEIA 259
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
221-477 1.43e-68

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 220.71  E-value: 1.43e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLG-------DYEGKKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05048   2 IPLSAVRFLEELGEGAFGKVYKGellgpssEESAISVAIKTLKEN-ASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRSR-----------GRAVITKQNQIDF---ARDVVKGMVYLESQNFVHRDLAARNVLIAED 359
Cdd:cd05048  81 QPQCMLFEYMAHGDLHEFLVRHsphsdvgvssdDDGTASSLDQSDFlhiAIQIAAGMEYLSSHHYVHRDLAARNCLVGDG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 360 NVAKVSDFGLAK---SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVE 435
Cdd:cd05048 161 LTVKISDFGLSRdiySSDYYRVQSkSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIR 240
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 18150824 436 NGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05048 241 SRQLLPCPEDCPARVYSLMVECWHEIPSRRPRFKEIHTRLRT 282
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
221-478 3.81e-68

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


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 219.07  E-value: 3.81e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLGDYE--GKK---VAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNP 295
Cdd:cd05063   2 IHPSHITKQKVIGAGEFGEVFRGILKmpGRKevaVAIKTLKPGYT-EKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKP 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 IYLITEFMAKGSLIDYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---- 371
Cdd:cd05063  81 AMIITEYMENGALDKYLRDHDGEFSSYQ-LVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRvled 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 -SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQI 450
Cdd:cd05063 160 dPEGTYTTSGGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAV 239
                       250       260
                ....*....|....*....|....*...
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05063 240 YQLMLQCWQQDRARRPRFVDIVNLLDKL 267
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
219-478 1.02e-66

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 217.19  E-value: 1.02e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDY---------EGKKVAMKSMKDHlKDEKAKTQFLAEASVMTTL-RHPNLVCLIG 288
Cdd:cd05101  19 WEFPRDKLTLGKPLGEGCFGQVVMAEAvgidkdkpkEAVTVAVKMLKDD-ATEKDLSDLVSEMEMMKMIgKHKNIINLLG 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSR--------------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNV 354
Cdd:cd05101  98 ACTQDGPLYVIVEYASKGNLREYLRARrppgmeysydinrvPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNV 177
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 355 LIAEDNVAKVSDFGLAKSSSNV----KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDV 430
Cdd:cd05101 178 LVTENNVMKIADFGLARDINNIdyykKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEEL 257
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 18150824 431 ANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05101 258 FKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 305
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
219-484 1.57e-66

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 217.20  E-value: 1.57e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG---------KKVAMKSMKDHLKDeKAKTQFLAEASVMTTL-RHPNLVCLIG 288
Cdd:cd05100   7 WELSRTRLTLGKPLGEGCFGQVVMAEAIGidkdkpnkpVTVAVKMLKDDATD-KDLSDLVSEMEMMKMIgKHKNIINLLG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSR--------------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNV 354
Cdd:cd05100  86 ACTQDGPLYVLVEYASKGNLREYLRARrppgmdysfdtcklPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 355 LIAEDNVAKVSDFGLAKSSSNV----KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDV 430
Cdd:cd05100 166 LVTEDNVMKIADFGLARDVHNIdyykKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEEL 245
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 18150824 431 ANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVAVAMSS 484
Cdd:cd05100 246 FKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTST 299
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
220-476 5.72e-66

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


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 213.87  E-value: 5.72e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 220 AIPKASLLKKSLIGKGEFGEVWLG-----DYEGKK--VAMKSMKdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLD 292
Cdd:cd05046   1 AFPRSNLQEITTLGRGEFGEVFLAkakgiEEEGGEtlVLVKALQ-KTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCRE 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 293 DNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQ-------IDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVS 365
Cdd:cd05046  80 AEPHYMILEYTDLGDLKQFLRATKSKDEKLKPPplstkqkVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVS 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 366 DFGLAK---SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENG-YRME 441
Cdd:cd05046 160 LLSLSKdvyNSEYYKLRNALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGkLELP 239
                       250       260       270
                ....*....|....*....|....*....|....*
gi 18150824 442 SPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05046 240 VPEGCPSRLYKLMTRCWAVNPKDRPSFSELVSALG 274
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
221-475 1.51e-65

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 212.71  E-value: 1.51e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLGDYEGKK-------VAMKSMKDhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05049   2 IKRDTIVLKRELGEGAFGKVFLGECYNLEpeqdkmlVAVKTLKD-ASSPDARKDFEREAELLTNLQHENIVKFYGVCTEG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRSRG-RAVITKQNQID-----------FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV 361
Cdd:cd05049  81 DPLLMVFEYMEHGDLNKFLRSHGpDAAFLASEDSApgeltlsqllhIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 362 AKVSDFGLAK---SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENG 437
Cdd:cd05049 161 VKIGDFGMSRdiySTDYYRVGGhTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQG 240
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18150824 438 YRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05049 241 RLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIHKRL 278
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
232-476 2.22e-65

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 212.77  E-value: 2.22e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW-------LGDYEGKKVAMKSMKDHLKDEkAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd05050  13 IGQGAFGRVFqarapglLPYEPFTMVAVKMLKEEASAD-MQADFQREAALMAEFDHPNIVKLLGVCAVGKPMCLLFEYMA 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSR--------------------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKV 364
Cdd:cd05050  92 YGDLNEFLRHRspraqcslshstssarkcglNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKI 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 365 SDFGLAK---SSSNVK-QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRM 440
Cdd:cd05050 172 ADFGLSRniySADYYKaSENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVIYYVRDGNVL 251
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 18150824 441 ESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05050 252 SCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQ 287
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
219-471 2.22e-64

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 210.42  E-value: 2.22e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKDHLKDEKAKtqflaeaSVMTTLR-------HPNLV 284
Cdd:cd05054   2 WEFPRDRLKLGKPLGRGAFGKVIQASAFGidksatcRTVAVKMLKEGATASEHK-------ALMTELKilihighHLNVV 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 285 CLIGISLDDN-PIYLITEFMAKGSLIDYLRSR------------------------GRAVITKQNQIDFARDVVKGMVYL 339
Cdd:cd05054  75 NLLGACTKPGgPLMVIVEFCKFGNLSNYLRSKreefvpyrdkgardveeeedddelYKEPLTLEDLICYSFQVARGMEFL 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 340 ESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIY 415
Cdd:cd05054 155 ASRKCIHRDLAARNILLSENNVVKICDFGLArdiyKDPDYVRKGDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIF 234
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 416 SYGRVPYPRVPV-EDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05054 235 SLGASPYPGVQMdEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSEL 291
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
232-480 1.26e-63

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 208.28  E-value: 1.26e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG---DYEGK----KVAMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd05045   8 LGEGEFGKVVKAtafRLKGRagytTVAVKMLKENASSSELR-DLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLR-SR---------------------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA 362
Cdd:cd05045  87 YGSLRSFLReSRkvgpsylgsdgnrnssyldnpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKM 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 363 KVSDFGLAK----SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGY 438
Cdd:cd05045 167 KISDFGLSRdvyeEDSYVKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFNLLKTGY 246
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 18150824 439 RMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVAV 480
Cdd:cd05045 247 RMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKMMV 288
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
231-478 1.82e-63

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 207.39  E-value: 1.82e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG-----DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDN-----PIYL-I 299
Cdd:cd05035   6 ILGEGEFGSVMEAqlkqdDGSQLKVAVKTMKVDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASdlnkpPSPMvI 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYL---RSRGRAV-ITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS--S 373
Cdd:cd05035  86 LPFMKHGDLHSYLlysRLGGLPEkLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRKiyS 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEG--AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIY 451
Cdd:cd05035 166 GDYYRQGriSKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVY 245
                       250       260
                ....*....|....*....|....*..
gi 18150824 452 KIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05035 246 FLMYFCWTVDPKDRPTFTKLREVLENI 272
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
221-478 2.75e-62

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 204.38  E-value: 2.75e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVW-----LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDN- 294
Cdd:cd05074   6 IQEQQFTLGRMLGKGEFGSVReaqlkSEDGSFQKVAVKMLKADIFSSSDIEEFLREAACMKEFDHPNVIKLIGVSLRSRa 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 295 ----PI-YLITEFMAKGSLIDYL-RSR-GRAVIT--KQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVS 365
Cdd:cd05074  86 kgrlPIpMVILPFMKHGDLHTFLlMSRiGEEPFTlpLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVA 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 366 DFGLAKS--SSNVKQEG--AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRME 441
Cdd:cd05074 166 DFGLSKKiySGDYYRQGcaSKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRLK 245
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 18150824 442 SPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05074 246 QPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQLELI 282
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
221-471 4.84e-62

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 204.11  E-value: 4.84e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLGDYEGKK------------------VAMKSMKDHLKDEkAKTQFLAEASVMTTLRHPN 282
Cdd:cd05051   2 FPREKLEFVEKLGEGQFGEVHLCEANGLSdltsddfigndnkdepvlVAVKMLRPDASKN-AREDFLKEVKIMSQLKDPN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 283 LVCLIGISLDDNPIYLITEFMAKGSLIDYLRSR----GRAVITKQNQIDF------ARDVVKGMVYLESQNFVHRDLAAR 352
Cdd:cd05051  81 IVRLLGVCTRDEPLCMIVEYMENGDLNQFLQKHeaetQGASATNSKTLSYgtllymATQIASGMKYLESLNFVHRDLATR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 353 NVLIAEDNVAKVSDFGLAKS--SSN-VKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRV-PYPRVPV 427
Cdd:cd05051 161 NCLVGPNYTIKIADFGMSRNlySGDyYRIEGrAVLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCKEqPYEHLTD 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 428 EDVANHVENGYR-------MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05051 241 EQVIENAGEFFRddgmevyLSRPPNCPKEIYELMLECWRRDEEDRPTFREI 291
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
231-478 8.95e-62

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 203.24  E-value: 8.95e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG-----DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL-----IT 300
Cdd:cd14204  14 VLGEGEFGSVMEGelqqpDGTNHKVAVKTMKLDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVCLEVGSQRIpkpmvIL 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYL-RSR---GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS--SS 374
Cdd:cd14204  94 PFMKYGDLHSFLlRSRlgsGPQHVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVADFGLSKKiySG 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEG--AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYK 452
Cdd:cd14204 174 DYYRQGriAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLKQPEDCLDELYD 253
                       250       260
                ....*....|....*....|....*.
gi 18150824 453 IMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14204 254 IMYSCWRSDPTDRPTFTQLRENLEKL 279
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
105-203 1.46e-61

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 195.97  E-value: 1.46e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEkGLVTVDDDEYFDNLIKLVEHY 184
Cdd:cd09937   1 SLMPWFHGKISREEAERLLQPPEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYRN-GKLTIDEEEYFENLIQLVEHY 79
                        90
                ....*....|....*....
gi 18150824 185 QKEADGLCTRLKAPVDKEG 203
Cdd:cd09937  80 TKDADGLCTRLVKPKVKEG 98
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
232-477 1.58e-60

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 199.40  E-value: 1.58e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK----VAMKSMKDhlKDEKAKT-QFLAEASVMTTLRHPNLVCLIGISLDDNpIYLITEFMAKG 306
Cdd:cd05115  12 LGSGNFGCVKKGVYKMRKkqidVAIKVLKQ--GNEKAVRdEMMREAQIMHQLDNPYIVRMIGVCEAEA-LMLVMEMASGG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-----SSNVKQEGA 381
Cdd:cd05115  89 PLNKFLSGK-KDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKAlgaddSYYKARSAG 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:cd05115 168 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYK 247
                       250
                ....*....|....*.
gi 18150824 462 PSQRPNFTRIEKALES 477
Cdd:cd05115 248 WEDRPNFLTVEQRMRT 263
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
231-475 6.89e-59

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 195.26  E-value: 6.89e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG--DYEGKKV--AMKSMKDHLKDEKAKtQFLAEASVMTTL-RHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05047   2 VIGEGNFGQVLKAriKKDGLRMdaAIKRMKEYASKDDHR-DFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPH 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLR-SR-------------GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK 371
Cdd:cd05047  81 GNLLDFLRkSRvletdpafaiansTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 SSS-NVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQI 450
Cdd:cd05047 161 GQEvYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEV 240
                       250       260
                ....*....|....*....|....*
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05047 241 YDLMRQCWREKPYERPSFAQILVSL 265
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
227-482 7.32e-59

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 195.23  E-value: 7.32e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLiGKGEFGEVWLG----DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD-------NP 295
Cdd:cd05075   4 LGKTL-GEGEFGSVMEGqlnqDDSVLKVAVKTMKIAICTRSEMEDFLSEAVCMKEFDHPNVMRLIGVCLQNtesegypSP 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 IyLITEFMAKGSLIDYL-RSR---GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK 371
Cdd:cd05075  83 V-VILPFMKHGDLHSFLlYSRlgdCPVYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSK 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 SSSN--VKQEG--AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCP 447
Cdd:cd05075 162 KIYNgdYYRQGriSKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPPDCL 241
                       250       260       270
                ....*....|....*....|....*....|....*
gi 18150824 448 DQIYKIMMDCWEKDPSQRPNFTRIEKALESVAVAM 482
Cdd:cd05075 242 DGLYELMSSCWLLNPKDRPSFETLRCELEKILKDL 276
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
224-475 9.72e-59

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 194.76  E-value: 9.72e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 224 ASLLKKSLIGKGEFGEVWLG--DYEGKK---VAMKSMKDHLKDeKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:cd05064   5 KSIKIERILGTGRFGELCRGclKLPSKRelpVAIHTLRAGCSD-KQRRGFLAEALTLGQFDHSNIVRLEGVITRGNTMMI 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSN 375
Cdd:cd05064  84 VTEYMSNGALDSFLR-KHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLqedKSEAI 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMM 455
Cdd:cd05064 163 YTTMSGKSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLML 242
                       250       260
                ....*....|....*....|
gi 18150824 456 DCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05064 243 DCWQKERGERPRFSQIHSIL 262
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
221-468 1.09e-58

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 196.01  E-value: 1.09e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKK-SLIGKGEFGEV----WLGDYEGKK--VAMKSMKDhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDd 293
Cdd:cd05108   3 ILKETEFKKiKVLGSGAFGTVykglWIPEGEKVKipVAIKELRE-ATSPKANKEILDEAYVMASVDNPHVCRLLGICLT- 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-- 371
Cdd:cd05108  81 STVQLITQLMPFGCLLDYVREH-KDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKll 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 --SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQ 449
Cdd:cd05108 160 gaEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTID 239
                       250
                ....*....|....*....
gi 18150824 450 IYKIMMDCWEKDPSQRPNF 468
Cdd:cd05108 240 VYMIMVKCWMIDADSRPKF 258
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
221-477 1.96e-58

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 194.41  E-value: 1.96e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLG-------DYEGKKVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05092   2 IKRRDIVLKWELGEGAFGKVFLAechnllpEQDKMLVAVKALKE--ATESARQDFQREAELLTVLQHQHIVRFYGVCTEG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRSRG-RAVITKQNQ------------IDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN 360
Cdd:cd05092  80 EPLIMVFEYMRHGDLNRFLRSHGpDAKILDGGEgqapgqltlgqmLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGL 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 361 VAKVSDFGLAKS--SSNVKQEGAK--LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVEN 436
Cdd:cd05092 160 VVKIGDFGMSRDiySTDYYRVGGRtmLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQ 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 18150824 437 GYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05092 240 GRELERPRTCPPEVYAIMQGCWQREPQQRHSIKDIHSRLQA 280
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
219-476 6.02e-58

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 193.26  E-value: 6.02e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIP--KASLLKKslIGKGEFGEVwlgdYEG-----------KKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVC 285
Cdd:cd05061   1 WEVSreKITLLRE--LGQGSFGMV----YEGnardiikgeaeTRVAVKTVNES-ASLRERIEFLNEASVMKGFTCHHVVR 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 286 LIGISLDDNPIYLITEFMAKGSLIDYLRS--------RGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA 357
Cdd:cd05061  74 LLGVVSKGQPTLVVMELMAHGDLKSYLRSlrpeaennPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVA 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 358 EDNVAKVSDFGLAKS--SSNVKQEGAK--LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANH 433
Cdd:cd05061 154 HDFTVKIGDFGMTRDiyETDYYRKGGKglLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKF 233
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 18150824 434 VENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05061 234 VMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLK 276
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
221-479 1.82e-57

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 191.78  E-value: 1.82e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKK-SLIGKGEFGEV----WLGDYEGKK--VAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05109   3 ILKETELKKvKVLGSGAFGTVykgiWIPDGENVKipVAIKVLREN-TSPKANKEILDEAYVMAGVGSPYVCRLLGICLTS 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NpIYLITEFMAKGSLIDYLR-SRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK- 371
Cdd:cd05109  82 T-VQLVTQLMPYGCLLDYVReNKDR--IGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARl 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 ---SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPD 448
Cdd:cd05109 159 ldiDETEYHADGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTI 238
                       250       260       270
                ....*....|....*....|....*....|.
gi 18150824 449 QIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd05109 239 DVYMIMVKCWMIDSECRPRFRELVDEFSRMA 269
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
228-476 7.59e-57

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 189.28  E-value: 7.59e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    228 KKSLIGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:smart00220   3 ILEKLGEGSFGKVYLARDkkTGKLVAIKVIKKKKIKKDRE-RILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEG 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    306 GSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsssnVKQEGAKLPV 385
Cdd:smart00220  82 GDLFDLLKKRGR--LSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLAR----QLDPGEKLTT 155
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    386 K-----WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYP-RVPVEDVANHVENGYR--MESPDGCPDQIYKIMMDC 457
Cdd:smart00220 156 FvgtpeYMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPgDDQLLELFKKIGKPKPpfPPPEWDISPEAKDLIRKL 234
                          250
                   ....*....|....*....
gi 18150824    458 WEKDPSQRPNftrIEKALE 476
Cdd:smart00220 235 LVKDPEKRLT---AEEALQ 250
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
229-475 3.55e-56

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


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 189.05  E-value: 3.55e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEV--WLGDYEGKKV--AMKSMKDHlKDEKAKTQFLAEASVMTTL-RHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd05089   7 EDVIGEGNFGQVikAMIKKDGLKMnaAIKMLKEF-ASENDHRDFAGELEVLCKLgHHPNIINLLGACENRGYLYIAIEYA 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLR-------------SRGRA-VITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL 369
Cdd:cd05089  86 PYGNLLDFLRksrvletdpafakEHGTAsTLTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIADFGL 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 370 AKSSS-NVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPD 448
Cdd:cd05089 166 SRGEEvYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEKPRNCDD 245
                       250       260
                ....*....|....*....|....*..
gi 18150824 449 QIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05089 246 EVYELMRQCWRDRPYERPPFSQISVQL 272
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
232-477 8.22e-56

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 187.53  E-value: 8.22e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEG-------KKVAMKSMKDhlKDEKA-KTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd05091  14 LGEDRFGKVYKGHLFGtapgeqtQAVAIKTLKD--KAEGPlREEFRHEAMLRSRLQHPNIVCLLGVVTKEQPMSMIFSYC 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRG-----------RAVITKQNQIDFARDVVK---GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL 369
Cdd:cd05091  92 SHGDLHEFLVMRSphsdvgstdddKTVKSTLEPADFLHIVTQiaaGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDLGL 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 370 AK---SSSNVKQEGAK-LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDG 445
Cdd:cd05091 172 FRevyAADYYKLMGNSlLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMIRNRQVLPCPDD 251
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 446 CPDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05091 252 CPAWVYTLMLECWNEFPSRRPRFKDIHSRLRT 283
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
232-477 1.97e-55

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 186.76  E-value: 1.97e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY------EGKKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05090  13 LGECAFGKIYKGHLylpgmdHAQLVAIKTLKDY-NNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEQPVCMLFEFMNQ 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRG---------------RAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA 370
Cdd:cd05090  92 GDLHEFLIMRSphsdvgcssdedgtvKSSLDHGDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQLHVKISDLGLS 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 371 KS--SSNVK--QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGC 446
Cdd:cd05090 172 REiySSDYYrvQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRQLLPCSEDC 251
                       250       260       270
                ....*....|....*....|....*....|.
gi 18150824 447 PDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05090 252 PPRMYSLMTECWQEIPSRRPRFKDIHARLRS 282
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
221-481 3.55e-55

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 186.01  E-value: 3.55e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLG-------DYEGKKVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05093   2 IKRHNIVLKRELGEGAFGKVFLAecynlcpEQDKILVAVKTLKD--ASDNARKDFHREAELLTNLQHEHIVKFYGVCVEG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRSRGRAVI-----------TKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA 362
Cdd:cd05093  80 DPLIMVFEYMKHGDLNKFLRAHGPDAVlmaegnrpaelTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 363 KVSDFGLAKS--SSNVKQEGAK--LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGY 438
Cdd:cd05093 160 KIGDFGMSRDvySTDYYRVGGHtmLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGR 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 18150824 439 RMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVAVA 481
Cdd:cd05093 240 VLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKA 282
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
231-478 7.64e-55

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 185.22  E-value: 7.64e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE------GKKVAMK----SMKDHLKDekaktqFLAEASVMTTLRHPNLVCLIGI--SLDDNPIYL 298
Cdd:cd14205  11 QLGKGNFGSVEMCRYDplqdntGEVVAVKklqhSTEEHLRD------FEREIEILKSLQHDNIVKYKGVcySAGRRNLRL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLrSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQ 378
Cdd:cd14205  85 IMEYLPYGSLRDYL-QKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKE 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 -----EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSY---GRVPyPRVPVEDVANH-------------VENG 437
Cdd:cd14205 164 yykvkEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYiekSKSP-PAEFMRMIGNDkqgqmivfhlielLKNN 242
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 18150824 438 YRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14205 243 GRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQI 283
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
219-475 8.71e-55

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 186.75  E-value: 8.71e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASL-LKKSLiGKGEFGEVWLGDYEGKK-------VAMKSMKDHLKDEKAKTqFLAEASVMTTL-RHPNLVCLIG- 288
Cdd:cd14207   2 WEFARERLkLGKSL-GRGAFGKVVQASAFGIKksptcrvVAVKMLKEGATASEYKA-LMTELKILIHIgHHLNVVNLLGa 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSR---------------------------GRAV---------------------- 319
Cdd:cd14207  80 CTKSGGPLMVIVEYCKYGNLSNYLKSKrdffvtnkdtslqeelikekkeaeptgGKKKrlesvtssesfassgfqedksl 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 320 -----------------ITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQ 378
Cdd:cd14207 160 sdveeeeedsgdfykrpLTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLArdiyKNPDYVRK 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPV-EDVANHVENGYRMESPDGCPDQIYKIMMDC 457
Cdd:cd14207 240 GDARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQIdEDFCSKLKEGIRMRAPEFATSEIYQIMLDC 319
                       330
                ....*....|....*...
gi 18150824 458 WEKDPSQRPNFTRIEKAL 475
Cdd:cd14207 320 WQGDPNERPRFSELVERL 337
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
219-475 7.58e-54

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 184.41  E-value: 7.58e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKDHLKDEKAKTqFLAEASVMTTL-RHPNLVCLIG-I 289
Cdd:cd05103   2 WEFPRDRLKLGKPLGRGAFGQVIEADAFGidktatcRTVAVKMLKEGATHSEHRA-LMSELKILIHIgHHLNVVNLLGaC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 290 SLDDNPIYLITEFMAKGSLIDYLRSR-----------GRAVITKQNQIDFARD--------------------------- 331
Cdd:cd05103  81 TKPGGPLMVIVEFCKFGNLSAYLRSKrsefvpyktkgARFRQGKDYVGDISVDlkrrldsitssqssassgfveekslsd 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 332 ---------------------------VVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQEG 380
Cdd:cd05103 161 veeeeagqedlykdfltledlicysfqVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLArdiyKDPDYVRKGD 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPV-EDVANHVENGYRMESPDGCPDQIYKIMMDCWE 459
Cdd:cd05103 241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320
                       330
                ....*....|....*.
gi 18150824 460 KDPSQRPNFTRIEKAL 475
Cdd:cd05103 321 GEPSQRPTFSELVEHL 336
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
219-478 7.95e-54

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 186.00  E-value: 7.95e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKDHLKDEKaKTQFLAEASVMTTL-RHPNLVCLIGIS 290
Cdd:cd05105  32 WEFPRDGLVLGRILGSGAFGKVVEGTAYGlsrsqpvMKVAVKMLKPTARSSE-KQALMSELKIMTHLgPHLNIVNLLGAC 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 291 LDDNPIYLITEFMAKGSLIDYLR-----------------------------SRGRAVITKQNQID-------------- 327
Cdd:cd05105 111 TKSGPIYIITEYCFYGDLVNYLHknrdnflsrhpekpkkdldifginpadesTRSYVILSFENKGDymdmkqadttqyvp 190
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 328 ---------------------------------------------------FARDVVKGMVYLESQNFVHRDLAARNVLI 356
Cdd:cd05105 191 mleikeaskysdiqrsnydrpasykgsndsevknllsddgseglttldllsFTYQVARGMEFLASKNCVHRDLAARNVLL 270
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 357 AEDNVAKVSDFGLAKS---SSNVKQEGAK-LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDV-A 431
Cdd:cd05105 271 AQGKIVKICDFGLARDimhDSNYVSKGSTfLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMIVDSTfY 350
                       330       340       350       360
                ....*....|....*....|....*....|....*....|....*..
gi 18150824 432 NHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05105 351 NKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVESL 397
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
221-481 2.00e-53

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 181.36  E-value: 2.00e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLGD-------YEGKKVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD 293
Cdd:cd05094   2 IKRRDIVLKRELGEGAFGKVFLAEcynlsptKDKMLVAVKTLKD--PTLAARKDFQREAELLTNLQHDHIVKFYGVCGDG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRSRG-RAVITKQNQ-------------IDFARDVVKGMVYLESQNFVHRDLAARNVLIAED 359
Cdd:cd05094  80 DPLIMVFEYMKHGDLNKFLRAHGpDAMILVDGQprqakgelglsqmLHIATQIASGMVYLASQHFVHRDLATRNCLVGAN 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 360 NVAKVSDFGLAKS--SSNVKQEGAK--LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVE 435
Cdd:cd05094 160 LLVKIGDFGMSRDvySTDYYRVGGHtmLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECIT 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 436 NGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVAVA 481
Cdd:cd05094 240 QGRVLERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHALGKA 285
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
230-478 3.34e-53

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 180.86  E-value: 3.34e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWL------GDYEGKKVAMKSMKDHLKDEKakTQFLAEASVMTTLRHPNLVCLIGISLDDN--PIYLITE 301
Cdd:cd05081  10 SQLGKGNFGSVELcrydplGDNTGALVAVKQLQHSGPDQQ--RDFQREIQILKALHSDFIVKYRGVSYGPGrrSLRLVME 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-----SSSNV 376
Cdd:cd05081  88 YLPSGCLRDFLQ-RHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKllpldKDYYV 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYG-----------RVPYPRVPVEDVANHVE---NGYRMES 442
Cdd:cd05081 167 VREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCdkscspsaeflRMMGCERDVPALCRLLElleEGQRLPA 246
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 18150824 443 PDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05081 247 PPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDML 282
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
222-475 6.39e-53

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 180.17  E-value: 6.39e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLGDYEGKK----------------VAMKSMKDHLkDEKAKTQFLAEASVMTTLRHPNLVC 285
Cdd:cd05097   3 PRQQLRLKEKLGEGQFGEVHLCEAEGLAeflgegapefdgqpvlVAVKMLRADV-TKTARNDFLKEIKIMSRLKNPNIIR 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 286 LIGISLDDNPIYLITEFMAKGSLIDYLRSRG-RAVITKQNQID---------FARDVVKGMVYLESQNFVHRDLAARNVL 355
Cdd:cd05097  82 LLGVCVSDDPLCMITEYMENGDLNQFLSQREiESTFTHANNIPsvsianllyMAVQIASGMKYLASLNFVHRDLATRNCL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 356 IAEDNVAKVSDFGLAK---SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGR-VPYPRVPVEDV 430
Cdd:cd05097 162 VGNHYTIKIADFGMSRnlySGDYYRIQGrAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLCKeQPYSLLSDEQV 241
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 18150824 431 ANHVENGYR-------MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05097 242 IENTGEFFRnqgrqiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
232-478 1.01e-52

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 179.35  E-value: 1.01e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL------GDYEGKKVAMKSMK-----DHLKDEKAKTQFLAEasvmttLRHPNLVCLIGISLDD--NPIYL 298
Cdd:cd05079  12 LGEGHFGKVELcrydpeGDNTGEQVAVKSLKpesggNHIADLKKEIEILRN------LYHENIVKYKGICTEDggNGIKL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLrSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK- 377
Cdd:cd05079  86 IMEFLPSGSLKEYL-PRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKe 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 ----QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYP--------------RVPVEDVANHVENGYR 439
Cdd:cd05079 165 yytvKDDLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSESSpmtlflkmigpthgQMTVTRLVRVLEEGKR 244
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 18150824 440 MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05079 245 LPRPPNCPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEAI 283
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
232-471 2.05e-52

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: 176.31  E-value: 2.05e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMkDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd00180   1 LGKGSFGKVYKArdKETGKKVAVKVI-PKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSSNVKQEGAKLPV 385
Cdd:cd00180  80 DLLKEN-KGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKdldsDDSLLKTTGGTTPP 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 KWTAPEALRENKFSNKTDVWSFGVLLWEIysygrvpyprvpvedvanhvengyrmespdgcpDQIYKIMMDCWEKDPSQR 465
Cdd:cd00180 159 YYAPPELLGGRYYGPKVDIWSLGVILYEL---------------------------------EELKDLIRRMLQYDPKKR 205

                ....*.
gi 18150824 466 PNFTRI 471
Cdd:cd00180 206 PSAKEL 211
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
219-471 2.92e-52

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 177.92  E-value: 2.92e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISL 291
Cdd:cd05062   1 WEVAREKITMSRELGQGSFGMVYEGIAKGvvkdepeTRVAIKTVNEA-ASMRERIEFLNEASVMKEFNCHHVVRLLGVVS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 292 DDNPIYLITEFMAKGSLIDYLRS--------RGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAK 363
Cdd:cd05062  80 QGQPTLVIMELMTRGDLKSYLRSlrpemennPVQAPPSLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 364 VSDFGLAKS--SSNVKQEGAK--LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYR 439
Cdd:cd05062 160 IGDFGMTRDiyETDYYRKGGKglLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGL 239
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 440 MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05062 240 LDKPDNCPDMLFELMRMCWQYNPKMRPSFLEI 271
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
220-475 4.23e-52

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


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 177.64  E-value: 4.23e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 220 AIPKASLLKKSLIGKGEFGEVWLGDY-----EGKKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD- 293
Cdd:cd05043   2 AVSRERVTLSDLLQEGTFGRIFHGILrdekgKEEEVLVKTVKDH-ASEIQVTMLLQESSLLYGLSHQNLLPILHVCIEDg 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAKGSLIDYLRS------RGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDF 367
Cdd:cd05043  81 EKPMVLYPYMNWGNLKLFLQQcrlseaNNPQALSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDN 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 368 GLAK----SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESP 443
Cdd:cd05043 161 ALSRdlfpMDYHCLGDNENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQP 240
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 444 DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05043 241 INCPDELFAVMACCWALDPEERPSFQQLVQCL 272
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
221-479 1.28e-51

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 177.18  E-value: 1.28e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKK-SLIGKGEFGEVWLGDY--EGKKVAMK---SMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDN 294
Cdd:cd05110   3 ILKETELKRvKVLGSGAFGTVYKGIWvpEGETVKIPvaiKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPT 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 295 pIYLITEFMAKGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--- 371
Cdd:cd05110  83 -IQLVTQLMPHGCLLDYVHEH-KDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARlle 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 -SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQI 450
Cdd:cd05110 161 gDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDV 240
                       250       260
                ....*....|....*....|....*....
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd05110 241 YMVMVKCWMIDADSRPKFKELAAEFSRMA 269
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
229-471 1.29e-51

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 177.11  E-value: 1.29e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLG----DYEGKKVAMKSMKDHLKDEKAKtQFLAEASVMTTL-RHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd05088  12 QDVIGEGNFGQVLKArikkDGLRMDAAIKRMKEYASKDDHR-DFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYA 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLR--------------SRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL 369
Cdd:cd05088  91 PHGNLLDFLRksrvletdpafaiaNSTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGL 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 370 AKSSS-NVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCPD 448
Cdd:cd05088 171 SRGQEvYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDD 250
                       250       260
                ....*....|....*....|...
gi 18150824 449 QIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05088 251 EVYDLMRQCWREKPYERPSFAQI 273
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
222-477 2.19e-51

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 176.34  E-value: 2.19e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLGDYEGKK------------------VAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNL 283
Cdd:cd05095   3 PRKLLTFKEKLGEGQFGEVHLCEAEGMEkfmdkdfalevsenqpvlVAVKMLRAD-ANKNARNDFLKEIKIMSRLKDPNI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 284 VCLIGISLDDNPIYLITEFMAKGSLIDYLrSRGRA-----------VITKQNQIDFARDVVKGMVYLESQNFVHRDLAAR 352
Cdd:cd05095  82 IRLLAVCITDDPLCMITEYMENGDLNQFL-SRQQPegqlalpsnalTVSYSDLRFMAAQIASGMKYLSSLNFVHRDLATR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 353 NVLIAEDNVAKVSDFGLAK---SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGR-VPYPRVPV 427
Cdd:cd05095 161 NCLVGKNYTIKIADFGMSRnlySGDYYRIQGrAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFCReQPYSQLSD 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 428 EDVANHVENGYR-------MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05095 241 EQVIENTGEFFRdqgrqtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHTLLQE 297
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
231-478 8.05e-51

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: 173.73  E-value: 8.05e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKT--QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14061   1 VIGVGGFGKVYRGIWRGEEVAVKAARQDPDEDISVTleNVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGAL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRgraVITKQNQIDFARDVVKGMVYLESQNFV---HRDLAARNVLIAE--------DNVAKVSDFGLAKSSSNVK 377
Cdd:cd14061  81 NRVLAGR---KIPPHVLVDWAIQIARGMNYLHNEAPVpiiHRDLKSSNILILEaienedleNKTLKITDFGLAREWHKTT 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQIYKIMMD 456
Cdd:cd14061 158 RMSAAGTYAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDGLAVAYGVAvNKLTLPIPSTCPEPFAQLMKD 236
                       250       260
                ....*....|....*....|..
gi 18150824 457 CWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14061 237 CWQPDPHDRPSFADILKQLENI 258
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
199-471 4.32e-50

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 175.97  E-value: 4.32e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 199 VDKEGQHLFVVDVNDFK-EKGWAIPKASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKA------KTQFLAE 271
Cdd:cd05107  11 VSSDGHEYIYVDPMQLPyDSAWEMPRDNLVLGRTLGSGAFGRVVEATAHGLSHSQSTMKVAVKMLKStarsseKQALMSE 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 272 ASVMTTL-RHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLR------------------------------------- 313
Cdd:cd05107  91 LKIMSHLgPHLNIVNLLGACTKGGPIYIITEYCRYGDLVDYLHrnkhtflqyyldknrddgslisggstplsqrkshvsl 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 314 ---------------------------------------------------SRGR--------AVITKQNQIDFARDVVK 334
Cdd:cd05107 171 gsesdggymdmskdesadyvpmqdmkgtvkyadiessnyespydqylpsapERTRrdtlinesPALSYMDLVGFSYQVAN 250
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 335 GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS---SSNVKQEGAK-LPVKWTAPEALRENKFSNKTDVWSFGVL 410
Cdd:cd05107 251 GMEFLASKNCVHRDLAARNVLICEGKLVKICDFGLARDimrDSNYISKGSTfLPLKWMAPESIFNNLYTTLSDVWSFGIL 330
                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18150824 411 LWEIYSYGRVPYPRVPV-EDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05107 331 LWEIFTLGGTPYPELPMnEQFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQL 392
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
223-478 5.17e-50

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 172.39  E-value: 5.17e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 223 KASLLKKSLIGKGEFGEVWLGDYE------GKKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLD--DN 294
Cdd:cd05080   3 KRYLKKIRDLGEGHFGKVSLYCYDptndgtGEMVAVKALKAD-CGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEqgGK 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 295 PIYLITEFMAKGSLIDYLRsrgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS 374
Cdd:cd05080  82 SLQLIMEYVPLGSLRDYLP---KHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVP 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 N------VKQEGAKlPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRvPY--PRVPVED-------------VANH 433
Cdd:cd05080 159 EgheyyrVREDGDS-PVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCD-SSqsPPTKFLEmigiaqgqmtvvrLIEL 236
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 18150824 434 VENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd05080 237 LERGERLPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
221-477 1.07e-49

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 172.04  E-value: 1.07e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKKSLIGKGEFGEVWLGDYEGKK------------------VAMKSMK-DHLKDekAKTQFLAEASVMTTLRHP 281
Cdd:cd05096   2 FPRGHLLFKEKLGEGQFGEVHLCEVVNPQdlptlqfpfnvrkgrpllVAVKILRpDANKN--ARNDFLKEVKILSRLKDP 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 282 NLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSR-------------GRA----VITKQNQIDFARDVVKGMVYLESQNF 344
Cdd:cd05096  80 NIIRLLGVCVDEDPLCMITEYMENGDLNQFLSSHhlddkeengndavPPAhclpAISYSSLLHVALQIASGMKYLSSLNF 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 345 VHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEG-AKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRV 420
Cdd:cd05096 160 VHRDLATRNCLVGENLTIKIADFGMSRnlyAGDYYRIQGrAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLCKE 239
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 421 -PYPRVPVEDVANHVENGYR-------MESPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd05096 240 qPYGELTDEQVIENAGEFFRdqgrqvyLFRPPPCPQGLYELMLQCWSRDCRERPSFSDIHAFLTE 304
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
219-475 1.12e-49

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 172.86  E-value: 1.12e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKDHLKDEKAKTqFLAEASVMTTL-RHPNLVCLIGIS 290
Cdd:cd05102   2 WEFPRDRLRLGKVLGHGAFGKVVEASAFGidkssscETVAVKMLKEGATASEHKA-LMSELKILIHIgNHLNVVNLLGAC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 291 LDDN-PIYLITEFMAKGSLIDYLR-----------------SRGRAVI-------------------------------- 320
Cdd:cd05102  81 TKPNgPLMVIVEFCKYGNLSNFLRakregfspyrersprtrSQVRSMVeavradrrsrqgsdrvasftestsstnqprqe 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 321 ---------TKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQEGAKLPVKW 387
Cdd:cd05102 161 vddlwqsplTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLArdiyKDPDYVRKGSARLPLKW 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPV-EDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRP 466
Cdd:cd05102 241 MAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQInEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERP 320

                ....*....
gi 18150824 467 NFTRIEKAL 475
Cdd:cd05102 321 TFSDLVEIL 329
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
214-476 5.47e-49

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 172.34  E-value: 5.47e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 214 FKEKgWAIPKASLLKKSLIGKGEFGEV------WLGDYEGK-KVAMKSMKD--HLKDEKAktqFLAEASVMTTL-RHPNL 283
Cdd:cd05106  29 YNEK-WEFPRDNLQFGKTLGAGAFGKVveatafGLGKEDNVlRVAVKMLKAsaHTDEREA---LMSELKILSHLgQHKNI 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 284 VCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQID------------------------------------ 327
Cdd:cd05106 105 VNLLGACTHGGPVLVITEYCCYGDLLNFLRKKAETFLNFVMALPeisetssdyknitlekkyirsdsgfssqgsdtyvem 184
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 328 --------------------------------FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS--- 372
Cdd:cd05106 185 rpvsssssqssdskdeedtedswpldlddllrFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDimn 264
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 -SSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVED-VANHVENGYRMESPDGCPDQI 450
Cdd:cd05106 265 dSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILVNSkFYKMVKRGYQMSRPDFAPPEI 344
                       330       340
                ....*....|....*....|....*.
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05106 345 YSIMKMCWNLEPTERPTFSQISQLIQ 370
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
219-476 6.69e-49

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 172.01  E-value: 6.69e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEG-------KKVAMKSMKD--HLKDEKAktqFLAEASVMTTL-RHPNLVCLIG 288
Cdd:cd05104  30 WEFPRDRLRFGKTLGAGAFGKVVEATAYGlakadsaMTVAVKMLKPsaHSTEREA---LMSELKVLSYLgNHINIVNLLG 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 289 ISLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQ------------------------------------------- 325
Cdd:cd05104 107 ACTVGGPTLVITEYCCYGDLLNFLRRKRDSFICPKFEdlaeaalyrnllhqremacdslneymdmkpsvsyvvptkadkr 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 326 ------------------------------IDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS--- 372
Cdd:cd05104 187 rgvrsgsyvdqdvtseileedelaldtedlLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARDirn 266
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 -SSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVED-VANHVENGYRMESPDGCPDQI 450
Cdd:cd05104 267 dSNYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPVDSkFYKMIKEGYRMDSPEFAPSEM 346
                       330       340
                ....*....|....*....|....*.
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd05104 347 YDIMRSCWDADPLKRPTFKQIVQLIE 372
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
230-466 5.24e-48

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: 166.22  E-value: 5.24e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLG--DYEGKKVAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14014   6 RLLGRGGMGEVYRArdTLLGRPVAIKVLRPELaEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEGG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPV- 385
Cdd:cd14014  86 SLADLLRERGP--LPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLg 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 --KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPR-VPVEDVANHVENGYRMESPD--GCPDQIYKIMMDCWEK 460
Cdd:cd14014 164 tpAYMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGdSPAAVLAKHLQEAPPPPSPLnpDVPPALDAIILRALAK 242

                ....*.
gi 18150824 461 DPSQRP 466
Cdd:cd14014 243 DPEERP 248
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
221-479 1.23e-47

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 165.90  E-value: 1.23e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 221 IPKASLLKK-SLIGKGEFGEV----WLGDYEGKK--VAMKSMKDhlkdeKAKTQFLAEAS----VMTTLRHPNLVCLIGI 289
Cdd:cd05111   3 IFKETELRKlKVLGSGVFGTVhkgiWIPEGDSIKipVAIKVIQD-----RSGRQSFQAVTdhmlAIGSLDHAYIVRLLGI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 290 SlDDNPIYLITEFMAKGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL 369
Cdd:cd05111  78 C-PGASLQLVTQLLPLGSLLDHVRQH-RGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGV 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 370 AK----SSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDG 445
Cdd:cd05111 156 ADllypDDKKYFYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQI 235
                       250       260       270
                ....*....|....*....|....*....|....
gi 18150824 446 CPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd05111 236 CTIDVYMVMVKCWMIDENIRPTFKELANEFTRMA 269
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
231-478 6.02e-47

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: 163.67  E-value: 6.02e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMK-DHLKDEKAKTQFL-AEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14146   1 IIGVGGFGKVYRATWKGQEVAVKAARqDPDEDIKATAESVrQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQ-------IDFARDVVKGMVYLESQNFV---HRDLAARNVLIAE----DNVA----KVSDFGLA 370
Cdd:cd14146  81 NRALAAANAAPGPRRARripphilVNWAVQIARGMLYLHEEAVVpilHRDLKSSNILLLEkiehDDICnktlKITDFGLA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 371 KSSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQ 449
Cdd:cd14146 161 REWHRTTKMSAAGTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAvNKLTLPIPSTCPEP 239
                       250       260
                ....*....|....*....|....*....
gi 18150824 450 IYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14146 240 FAKLMKECWEQDPHIRPSFALILEQLTAI 268
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
231-478 1.67e-46

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: 162.08  E-value: 1.67e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKT--QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14148   1 IIGVGGFGKVYKGLWRGEEVAVKAARQDPDEDIAVTaeNVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGAL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGravITKQNQIDFARDVVKGMVYLESQNFV---HRDLAARNVLIAE--------DNVAKVSDFGLAKSSSNVK 377
Cdd:cd14148  81 NRALAGKK---VPPHVLVNWAVQIARGMNYLHNEAIVpiiHRDLKSSNILILEpienddlsGKTLKITDFGLAREWHKTT 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQIYKIMMD 456
Cdd:cd14148 158 KMSAAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAmNKLTLPIPSTCPEPFARLLEE 236
                       250       260
                ....*....|....*....|..
gi 18150824 457 CWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14148 237 CWDPDPHGRPDFGSILKRLEDI 258
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
231-467 1.88e-46

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 161.92  E-value: 1.88e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd06606   7 LLGKGSFGSVYLALNLdtGELMAVKEVELSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGSL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGR---AVITKqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPV 385
Cdd:cd06606  87 ASLLKKFGKlpePVVRK-----YTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTKSL 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 K----WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPrvpveDVANHVENGYRM-------ESPDGCPDQIYKIM 454
Cdd:cd06606 162 RgtpyWMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWS-----ELGNPVAALFKIgssgeppPIPEHLSEEAKDFL 235
                       250
                ....*....|...
gi 18150824 455 MDCWEKDPSQRPN 467
Cdd:cd06606 236 RKCLQRDPKKRPT 248
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
229-478 1.24e-45

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: 160.19  E-value: 1.24e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKT--QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14147   8 EEVIGIGGFGKVYRGSWRGELVAVKAARQDPDEDISVTaeSVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAGG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGravITKQNQIDFARDVVKGMVYLESQNFV---HRDLAARNVLIA--------EDNVAKVSDFGLAKSSSN 375
Cdd:cd14147  88 PLSRALAGRR---VPPHVLVNWAVQIARGMHYLHCEALVpviHRDLKSNNILLLqpienddmEHKTLKITDFGLAREWHK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQIYKIM 454
Cdd:cd14147 165 TTQMSAAGTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAvNKLTLPIPSTCPEPFAQLM 243
                       250       260
                ....*....|....*....|....
gi 18150824 455 MDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14147 244 ADCWAQDPHRRPDFASILQQLEAL 267
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
224-478 9.57e-45

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: 157.90  E-value: 9.57e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 224 ASLLKKSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKT--QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd14145   6 SELVLEEIIGIGGFGKVYRAIWIGDEVAVKAARHDPDEDISQTieNVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVME 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRSRGravITKQNQIDFARDVVKGMVYLESQNFV---HRDLAARNVLIAE--------DNVAKVSDFGLA 370
Cdd:cd14145  86 FARGGPLNRVLSGKR---IPPDILVNWAVQIARGMNYLHCEAIVpviHRDLKSSNILILEkvengdlsNKILKITDFGLA 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 371 KSSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQ 449
Cdd:cd14145 163 REWHRTTKMSAAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAmNKLSLPIPSTCPEP 241
                       250       260
                ....*....|....*....|....*....
gi 18150824 450 IYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14145 242 FARLMEDCWNPDPHSRPPFTNILDQLTAI 270
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
232-471 2.84e-44

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: 155.73  E-value: 2.84e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDhLKDEKAKTqflaeasvMTTLRHPNLVCLIGISLDdNPIY-LITEFMAKGSLID 310
Cdd:cd14059   1 LGSGAQGAVFLGKFRGEEVAVKKVRD-EKETDIKH--------LRKLNHPNIIKFKGVCTQ-APCYcILMEYCPYGQLYE 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSrGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKlPVKWT 388
Cdd:cd14059  71 VLRA-GR-EITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKelSEKSTKMSFAG-TVAWM 147
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 389 APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHV-ENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd14059 148 APEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGFKLLMKQCWNSKPRNRPS 226

                ....
gi 18150824 468 FTRI 471
Cdd:cd14059 227 FRQI 230
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
232-475 7.03e-43

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 152.26  E-value: 7.03e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY-EGKKVAMKSMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14065   1 LGKGFFGEVYKVTHrETGKVMVMKELKRFDEQRS---FLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEE 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAK---VSDFGLAK----SSSNVKQEGAKL 383
Cdd:cd14065  78 LLKSMDEQLPWSQ-RVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRnavVADFGLARempdEKTKKPDRKKRL 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PV----KWTAPEALRENKFSNKTDVWSFGVLLWEIysYGRVP-----YPRvpVEDVANHVEnGYRMESPDGCPDQIYKIM 454
Cdd:cd14065 157 TVvgspYWMAPEMLRGESYDEKVDVFSFGIVLCEI--IGRVPadpdyLPR--TMDFGLDVR-AFRTLYVPDCPPSFLPLA 231
                       250       260
                ....*....|....*....|.
gi 18150824 455 MDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd14065 232 IRCCQLDPEKRPSFVELEHHL 252
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
228-466 1.33e-42

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: 151.59  E-value: 1.33e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDY--EGKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05122   4 ILEKIGKGGFGVVYKARHkkTGQIVAIKKIN--LESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRaVITKQnQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE----G 380
Cdd:cd05122  82 GSLKDLLKNTNK-TLTEQ-QIAYvCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRntfvG 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLpvkWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVP----VEDVANHVENGYRmeSPDGCPDQIYKIMMD 456
Cdd:cd05122 160 TPY---WMAPEVIQGKPYGFKADIWSLGITAIEM-AEGKPPYSELPpmkaLFLIATNGPPGLR--NPKKWSKEFKDFLKK 233
                       250
                ....*....|
gi 18150824 457 CWEKDPSQRP 466
Cdd:cd05122 234 CLQKDPEKRP 243
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
232-479 1.68e-42

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 151.89  E-value: 1.68e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMkdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14154   1 LGKGFFGQAIKVTHRetGEVMVMKEL--IRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGTLK 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-------SSNVKQEGAK 382
Cdd:cd14154  79 DVLKDMAR-PLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLiveerlpSGNMSPSETL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVK---------------WTAPEALRENKFSNKTDVWSFGVLLWEIysYGRVP-----YPRvpVEDVANHVEnGYRMES 442
Cdd:cd14154 158 RHLKspdrkkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEI--IGRVEadpdyLPR--TKDFGLNVD-SFREKF 232
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 18150824 443 PDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd14154 233 CAGCPPPFFKLAFLCCDLDPEKRPPFETLEEWLEALY 269
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
232-476 2.10e-42

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 151.66  E-value: 2.10e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE-GKKVAMKSMKDhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14066   1 IGSGGFGTVYKGVLEnGTVVAVKRLNE-MNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLED 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLR-SRGRAVITKQNQIDFARDVVKGMVYLESQNF---VHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVK 386
Cdd:cd14066  80 RLHcHKGSPPLPWPQRLKIAKGIARGLEYLHEECPppiIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKTSAVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 ----WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVED-VANHVENgYRMESPDGCPD------------- 448
Cdd:cd14066 160 gtigYLAPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAVDENRENAsRKDLVEW-VESKGKEELEDildkrlvdddgve 237
                       250       260       270
                ....*....|....*....|....*....|...
gi 18150824 449 -----QIYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd14066 238 eeeveALLRLALLCTRSDPSLRPSMKEVVQMLE 270
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
232-476 2.50e-42

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 151.05  E-value: 2.50e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKsMKDHLKDEKAktqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDY 311
Cdd:cd14058   1 VGRGSFGVVCKARWRNQIVAVK-IIESESEKKA---FEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNV 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 312 LRSRGRAVI-TKQNQIDFARDVVKGMVYLES---QNFVHRDLAARNVLI-AEDNVAKVSDFGLAKSSSNVKQEGaKLPVK 386
Cdd:cd14058  77 LHGKEPKPIyTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLtNGGTVLKICDFGTACDISTHMTNN-KGSAA 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 WTAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPYPRV--PVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQ 464
Cdd:cd14058 156 WMAPEVFEGSKYSEKCDVFSWGIILWEVITR-RKPFDHIggPAFRIMWAVHNGERPPLIKNCPKPIESLMTRCWSKDPEK 234
                       250
                ....*....|..
gi 18150824 465 RPNFTRIEKALE 476
Cdd:cd14058 235 RPSMKEIVKIMS 246
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
233-478 1.31e-41

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 148.57  E-value: 1.31e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 233 GKGEFGEVWLGDY--EGKKVAMKSMkdhLKDEKaktqflaEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14060   2 GGGSFGSVYRAIWvsQDKEVAVKKL---LKIEK-------EAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFD 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRAVITKQNQIDFARDVVKGMVYLESQ---NFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVKW 387
Cdd:cd14060  72 YLNSNESEEMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVGTFPW 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPYPRVPVEDVA-NHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRP 466
Cdd:cd14060 152 MAPEVIQSLPVSETCDTYSYGVVLWEMLTR-EVPFKGLEGLQVAwLVVEKNERPTIPSSCPRSFAELMRRCWEADVKERP 230
                       250
                ....*....|..
gi 18150824 467 NFTRIEKALESV 478
Cdd:cd14060 231 SFKQIIGILESM 242
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
230-466 3.57e-40

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 150.93  E-value: 3.57e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYE--GKKVAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:COG0515  13 RLLGRGGMGVVYLARDLrlGRPVALKVLRPELaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGE 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAklp 384
Cdd:COG0515  93 SLADLLRRRGP--LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARalGGATLTQTGT--- 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWT----APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRM---ESPDGCPDQIYKIMMDC 457
Cdd:COG0515 168 VVGTpgymAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAIVLRA 246

                ....*....
gi 18150824 458 WEKDPSQRP 466
Cdd:COG0515 247 LAKDPEERY 255
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
230-473 2.00e-39

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: 143.04  E-value: 2.00e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14003   6 KTLGEGSFGKVKLARHKltGEKVAIKIIdKSKLKEEIEE-KIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYASGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEGAKL--- 383
Cdd:cd14003  85 ELFDYIVNNGR--LSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGL----SNEFRGGSLLktf 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 ---PVkWTAPEALRENKFSN-KTDVWSFGVLLweiYS--YGRVPYPRVPVEDVANHVENG-YRMES--PDGCPDQIYKIM 454
Cdd:cd14003 159 cgtPA-YAAPEVLLGRKYDGpKADVWSLGVIL---YAmlTGYLPFDDDNDSKLFRKILKGkYPIPShlSPDARDLIRRML 234
                       250
                ....*....|....*....
gi 18150824 455 mdcwEKDPSQRPNFTRIEK 473
Cdd:cd14003 235 ----VVDPSKRITIEEILN 249
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
232-476 1.54e-38

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 140.74  E-value: 1.54e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIY-LITEFMAKGSLI 309
Cdd:cd14064   1 IGSGSFGKVYKGRCRNKIVAIKRYRANTYCSKSDVDmFCREVSILCRLNHPCVIQFVGACLDDPSQFaIVTQYVSGGSLF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRaVITKQNQIDFARDVVKGMVYLE--SQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEG-AKLP-- 384
Cdd:cd14064  81 SLLHEQKR-VIDLQSKLIIAVDVAKGMEYLHnlTQPIIHRDLNSHNILLYEDGHAVVADFGESRFLQSLDEDNmTKQPgn 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWTAPEALREN-KFSNKTDVWSFGVLLWEIYSyGRVPYPRV-PVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd14064 160 LRWMAPEVFTQCtRYSIKADVFSYALCLWELLT-GEIPFAHLkPAAAAADMAYHHIRPPIGYSIPKPISSLLMRGWNAEP 238
                       250
                ....*....|....
gi 18150824 463 SQRPNFTRIEKALE 476
Cdd:cd14064 239 ESRPSFVEIVALLE 252
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
231-467 2.88e-37

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: 137.36  E-value: 2.88e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG-DYE-GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd06627   7 LIGRGAFGSVYKGlNLNtGEFVAIKQISLEKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENGSL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGR------AVITKQnqidfardVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-KSSSNVKQEGa 381
Cdd:cd06627  87 ASIIKKFGKfpeslvAVYIYQ--------VLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVAtKLNEVEKDEN- 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 kLPV---KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-PRVPVEDVANHVENGYrMESPDGCPDQIYKIMMDC 457
Cdd:cd06627 158 -SVVgtpYWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPYyDLQPMAALFRIVQDDH-PPLPENISPELRDFLLQC 234
                       250
                ....*....|
gi 18150824 458 WEKDPSQRPN 467
Cdd:cd06627 235 FQKDPTLRPS 244
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
232-480 5.99e-37

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 137.00  E-value: 5.99e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMkSMKDHLK-DEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14222   1 LGKGFFGQAIKVTHKATGKVM-VMKELIRcDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLPVK-- 386
Cdd:cd14222  80 FLRADDP--FPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRliVEEKKKPPPDKPTTKkr 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 ------------------WTAPEALRENKFSNKTDVWSFGVLLWEIysYGRV---P--YPRvpVEDVANHVENGYRMESP 443
Cdd:cd14222 158 tlrkndrkkrytvvgnpyWMAPEMLNGKSYDEKVDIFSFGIVLCEI--IGQVyadPdcLPR--TLDFGLNVRLFWEKFVP 233
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 18150824 444 DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVAV 480
Cdd:cd14222 234 KDCPPAFFPLAAICCRLEPDSRPAFSKLEDSFEALSL 270
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
232-466 1.79e-36

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 135.79  E-value: 1.79e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG----DYEGKKVAMKSMKDHlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05042   3 IGNGWFGKVLLGeiysGTSVAQVVVKELKAS-ANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDLGD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIDFAR---DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN----VKQEG 380
Cdd:cd05042  82 LKAYLRSEREHERGDSDTRTLQRmacEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKedyiETDDK 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRE----------NKFSNktdVWSFGVLLWEIYSYGRVPYPRVPVEDVANHV--ENGYRMESPD---G 445
Cdd:cd05042 162 LWFPLRWTAPELVTEfhdrllvvdqTKYSN---IWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPQlelP 238
                       250       260
                ....*....|....*....|.
gi 18150824 446 CPDQIYKIMMDCWeKDPSQRP 466
Cdd:cd05042 239 YSDRWYEVLQFCW-LSPEQRP 258
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
8-64 1.67e-35

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. 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: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 125.88  E-value: 1.67e-35
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824   8 GTECIGKYNFPGSSPHDLPFKKGDRLVIVAPSKDPNWYKARREDGLEGMIPFNYVQE 64
Cdd:cd11769   1 GTECIAKYNFNGASEEDLPFKKGDILTIVAVTKDPNWYKAKNKDGREGMIPANYVQK 57
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
232-478 3.86e-35

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 132.00  E-value: 3.86e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGE-VWLGDYEGKKVAMksMKDHLK-DEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14221   1 LGKGCFGQaIKVTHRETGEVMV--MKELIRfDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLR 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA------KSSSNVKQEGAKL 383
Cdd:cd14221  79 GIIKSMDSHYPWSQ-RVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLArlmvdeKTQPEGLRSLKKP 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PVK----------WTAPEALRENKFSNKTDVWSFGVLLWEIysYGRVP-----YPRvpVEDVANHVENGYRMESPDGCPD 448
Cdd:cd14221 158 DRKkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEI--IGRVNadpdyLPR--TMDFGLNVRGFLDRYCPPNCPP 233
                       250       260       270
                ....*....|....*....|....*....|
gi 18150824 449 QIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14221 234 SFFPIAVLCCDLDPEKRPSFSKLEHWLETL 263
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
232-468 9.72e-35

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 130.65  E-value: 9.72e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd13978   1 LGSGGFGTVSKARHVSWFgmVAIKCLHSSPNCIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSLK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRS---------RGRavitkqnqidFARDVVKGMVYLESQN--FVHRDLAARNVLIAEDNVAKVSDFGLAK----SSS 374
Cdd:cd13978  81 SLLEReiqdvpwslRFR----------IIHEIALGMNFLHNMDppLLHHDLKPENILLDNHFHVKISDFGLSKlgmkSIS 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKL---PVKWTAPEALRE--NKFSNKTDVWSFGVLLWEIYSyGRVPYPrvpveDVANH------VENGYRMESP 443
Cdd:cd13978 151 ANRRRGTENlggTPIYMAPEAFDDfnKKPTSKSDVYSFAIVIWAVLT-RKEPFE-----NAINPllimqiVSKGDRPSLD 224
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 444 DGCPDQ-------IYKIMMDCWEKDPSQRPNF 468
Cdd:cd13978 225 DIGRLKqienvqeLISLMIRCWDGNPDARPTF 256
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
232-477 1.55e-34

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


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 130.46  E-value: 1.55e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG----DYEGKKVAMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd14206   5 IGNGWFGKVILGeifsDYTPAQVVVKELRVSAGPLEQR-KFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEFCQLGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRA-----------VITKQNqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakSSSNV 376
Cdd:cd14206  84 LKRYLRAQRKAdgmtpdlptrdLRTLQR---MAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGL--SHNNY 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQ------EGAKLPVKWTAPEALRENKF-------SNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHV--ENGYRME 441
Cdd:cd14206 159 KEdyyltpDRLWIPLRWVAPELLDELHGnlivvdqSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVvrEQQMKLA 238
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 18150824 442 SPD---GCPDQIYKIMMDCWeKDPSQRPNFTRIEKALES 477
Cdd:cd14206 239 KPRlklPYADYWYEIMQSCW-LPPSQRPSVEELHLQLSY 276
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
219-479 2.60e-34

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 129.80  E-value: 2.60e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKkVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNpIYL 298
Cdd:cd14151   3 WEIPDGQITVGQRIGSGSFGTVYKGKWHGD-VAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ-LAI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRsrgrAVITK---QNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----K 371
Cdd:cd14151  81 VTQWCEGSSLYHHLH----IIETKfemIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLAtvksR 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 SSSNVKQEGAKLPVKWTAPEALR---ENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVED-VANHVENGYRmeSPD--- 444
Cdd:cd14151 157 WSGSHQFEQLSGSILWMAPEVIRmqdKNPYSFQSDVYAFGIVLYELMT-GQLPYSNINNRDqIIFMVGRGYL--SPDlsk 233
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18150824 445 ---GCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd14151 234 vrsNCPKAMKRLMAECLKKKRDERPLFPQILASIELLA 271
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
231-478 1.77e-33

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 128.00  E-value: 1.77e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKD--HLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14158  22 KLGEGGFGVVFKGYINDKNVAVKKLAAmvDISTEDLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMPNGSL 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSR-GRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSS----SNVKQEGAKL 383
Cdd:cd14158 102 LDRLACLnDTPPLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASekfsQTIMTERIVG 181
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PVKWTAPEALReNKFSNKTDVWSFGVLLWEIYS-YGRVPYPRVP---------VEDVANHVENGYRMESPDGCPDQI--- 450
Cdd:cd14158 182 TTAYMAPEALR-GEITPKSDIFSFGVVLLEIITgLPPVDENRDPqllldikeeIEDEEKTIEDYVDKKMGDWDSTSIeam 260
                       250       260
                ....*....|....*....|....*...
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14158 261 YSVASQCLNDKKNRRPDIAKVQQLLQEL 288
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
232-476 2.78e-33

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: 126.35  E-value: 2.78e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKkVAMKSMKdhLKDEKAkTQFLA---EASVMTTLRHPNLVCLIGISLDDNpIYLITEFMAKGSL 308
Cdd:cd14062   1 IGSGSFGTVYKGRWHGD-VAVKKLN--VTDPTP-SQLQAfknEVAVLRKTRHVNILLFMGYMTKPQ-LAIVTQWCEGSSL 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRsrgraVI-TK---QNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQEG 380
Cdd:cd14062  76 YKHLH-----VLeTKfemLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLAtvktRWSGSQQFEQ 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALR---ENKFSNKTDVWSFGVLLWEIYSyGRVPYPRV-PVEDVANHVENGYRmeSPD------GCPDQI 450
Cdd:cd14062 151 PTGSILWMAPEVIRmqdENPYSFQSDVYAFGIVLYELLT-GQLPYSHInNRDQILFMVGRGYL--RPDlskvrsDTPKAL 227
                       250       260
                ....*....|....*....|....*.
gi 18150824 451 YKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd14062 228 RRLMEDCIKFQRDERPLFPQILASLE 253
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
107-190 2.84e-33

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 120.80  E-value: 2.84e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824    107 MPWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQK 186
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQK 80

                   ....
gi 18150824    187 EADG 190
Cdd:smart00252  81 NSLG 84
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
232-466 5.07e-33

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: 125.79  E-value: 5.07e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKdhLKDEKAKTqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd06614   8 IGEGASGEVYKATDraTGKEVAIKKMR--LRKQNKEL-IINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGGSLT 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRsrGRAVITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKL---PV 385
Cdd:cd06614  85 DIIT--QNPVRMNESQIAYvCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSKRNSVvgtPY 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 kWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRV-PVEDVANHVENGY-RMESPDGCPDQIYKIMMDCWEKDPS 463
Cdd:cd06614 163 -WMAPEVIKRKDYGPKVDIWSLGIMCIEM-AEGEPPYLEEpPLRALFLITTKGIpPLKNPEKWSPEFKDFLNKCLVKDPE 240

                ...
gi 18150824 464 QRP 466
Cdd:cd06614 241 KRP 243
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
226-476 6.76e-33

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 125.92  E-value: 6.76e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKKSLIGKGEFGEVWLGDYEGKkVAMKSMK-DHLKDEKAKTqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd14063   2 LEIKEVIGKGRFGRVHRGRWHGD-VAIKLLNiDYLNEEQLEA-FKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSLCK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIaEDNVAKVSDFGLAkSSSNVKQEGA--- 381
Cdd:cd14063  80 GRTLYSLIHER-KEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFL-ENGRVVITDFGLF-SLSGLLQPGRred 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 --KLPVKWT---APE---ALRENK-------FSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPD-G 445
Cdd:cd14063 157 tlVIPNGWLcylAPEiirALSPDLdfeeslpFTKASDVYAFGTVWYELLA-GRWPFKEQPAESIIWQVGCGKKQSLSQlD 235
                       250       260       270
                ....*....|....*....|....*....|.
gi 18150824 446 CPDQIYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd14063 236 IGREVKDILMQCWAYDPEKRPTFSDLLRMLE 266
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
232-468 7.27e-33

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: 125.41  E-value: 7.27e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14009   1 IGRGSFATVWKGRHKqtGEVVAIKEISRKKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRA--VITKqnqiDFARDVVKGMVYLESQNFVHRDLAARNVLIA---EDNVAKVSDFGLAKSSSNVKQE----G 380
Cdd:cd14009  81 QYIRKRGRLpeAVAR----HFMQQLASGLKFLRSKNIIHRDLKPQNLLLStsgDDPVLKIADFGFARSLQPASMAetlcG 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLpvkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYprvpveDVANHVE--------------NGYRMESPDgC 446
Cdd:cd14009 157 SPL---YMAPEILQFQKYDAKADLWSVGAILFEMLV-GKPPF------RGSNHVQllrniersdavipfPIAAQLSPD-C 225
                       250       260
                ....*....|....*....|..
gi 18150824 447 PDQIYKIMmdcwEKDPSQRPNF 468
Cdd:cd14009 226 KDLLRRLL----RRDPAERISF 243
Pkinase pfam00069
Protein kinase domain;
228-471 8.56e-33

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 123.89  E-value: 8.56e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   228 KKSLIGKGEFGEVWLGdYE---GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:pfam00069   3 VLRKLGSGSFGTVYKA-KHrdtGKIVAIKKIKKEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYVE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   305 KGSLIDYLRSRGraVITKQNQIDFARDVVKGMvylesqnfvhrdlaarnvliaEDNVAKVSDFGlaksSSNvkqegaklp 384
Cdd:pfam00069  82 GGSLFDLLSEKG--AFSEREAKFIMKQILEGL---------------------ESGSSLTTFVG----TPW--------- 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   385 vkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENG--YRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:pfam00069 126 --YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEIYELIIDQpyAFPELPSNLSEEAKDLLKKLLKKDP 202

                  ....*....
gi 18150824   463 SQRPNFTRI 471
Cdd:pfam00069 203 SKRLTATQA 211
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
242-478 8.97e-33

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 125.79  E-value: 8.97e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 242 LGDYEGKKVAMKS-MKDHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSrgravi 320
Cdd:cd14042  25 TGYYKGNLVAIKKvNKKRIDLTR---EVLKELKHMRDLQHDNLTRFIGACVDPPNICILTEYCPKGSLQDILEN------ 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 321 tkqNQID--------FARDVVKGMVYLESQNFV-HRDLAARNVLIaeDN--VAKVSDFGLA---KSSSNVKQEGAKLPVK 386
Cdd:cd14042  96 ---EDIKldwmfrysLIHDIVKGMHYLHDSEIKsHGNLKSSNCVV--DSrfVLKITDFGLHsfrSGQEPPDDSHAYYAKL 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 -WTAPEALRENKFSN----KTDVWSFGVLLWEIYS----YGRVPYPRVPVEDVANHVENG----YRME-SPDGCPDQIYK 452
Cdd:cd14042 171 lWTAPELLRDPNPPPpgtqKGDVYSFGIILQEIATrqgpFYEEGPDLSPKEIIKKKVRNGekppFRPSlDELECPDEVLS 250
                       250       260
                ....*....|....*....|....*.
gi 18150824 453 IMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14042 251 LMQRCWAEDPEERPDFSTLRNKLKKL 276
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
232-476 1.56e-32

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: 124.80  E-value: 1.56e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVmTTLRHPNLVCLIGIS--LDDNPIYLIT-EFMAKGSL 308
Cdd:cd13979  11 LGSGGFGSVYKATYKGETVAVKIVRRRRKNRASRQSFWAELNA-ARLRHENIVRVLAAEtgTDFASLGLIImEYCGNGTL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 ---IDylrsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKl 383
Cdd:cd13979  90 qqlIY----EGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVklGEGNEVGTPRS- 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PVKWT----APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESP---DGCPDQIYKIMMD 456
Cdd:cd13979 165 HIGGTytyrAPELLKGERVTPKADIYSFGITLWQMLT-RELPYAGLRQHVLYAVVAKDLRPDLSgleDSEFGQRLRSLIS 243
                       250       260
                ....*....|....*....|..
gi 18150824 457 -CWEKDPSQRPN-FTRIEKALE 476
Cdd:cd13979 244 rCWSAQPAERPNaDESLLKSLE 265
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
231-475 3.42e-32

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 124.47  E-value: 3.42e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKsmkdhLKDEKAKTQFLAEASVMTT--LRHPNLVCLIGISLDDNP----IYLITEFMA 304
Cdd:cd13998   2 VIGKGRFGEVWKASLKNEPVAVK-----IFSSRDKQSWFREKEIYRTpmLKHENILQFIAADERDTAlrteLWLVTAFHP 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRsrgRAVITKQNQIDFARDVVKGMVYLESQNF---------VHRDLAARNVLIAEDNVAKVSDFGLA--KSS 373
Cdd:cd13998  77 NGSL*DYLS---LHTIDWVSLCRLALSVARGLAHLHSEIPgctqgkpaiAHRDLKSKNILVKNDGTCCIADFGLAvrLSP 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEGAKLP----VKWTAPEALREN-KFSN-----KTDVWSFGVLLWEIYS-----YGRVPYPRVPVED-VANH---- 433
Cdd:cd13998 154 STGEEDNANNGqvgtKRYMAPEVLEGAiNLRDfesfkRVDIYAMGLVLWEMASrctdlFGIVEEYKPPFYSeVPNHpsfe 233
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 18150824 434 ------VENGYRMESPDG---CPD--QIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd13998 234 dmqevvVRDKQRPNIPNRwlsHPGlqSLAETIEECWDHDAEARLTAQCIEERL 286
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
232-467 5.94e-32

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 123.56  E-value: 5.94e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEG----KKVAMKSMKDHLKDEKaKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05087   5 IGHGWFGKVFLGEVNSglssTQVVVKELKASASVQD-QMQFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCPLGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRS-RGRAVITKQNQI--DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQEG 380
Cdd:cd05087  84 LKGYLRScRAAESMAPDPLTlqRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLShckyKEDYFVTADQ 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPEALRE----------NKFSNktdVWSFGVLLWEIYSYGRVPYPRVPVEDVANHV--ENGYRMESPD---G 445
Cdd:cd05087 164 LWVPLRWIAPELVDEvhgnllvvdqTKQSN---VWSLGVTIWELFELGNQPYRHYSDRQVLTYTvrEQQLKLPKPQlklS 240
                       250       260
                ....*....|....*....|..
gi 18150824 446 CPDQIYKIMMDCWEKdPSQRPN 467
Cdd:cd05087 241 LAERWYEVMQFCWLQ-PEQRPT 261
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
232-471 6.80e-32

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


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 122.58  E-value: 6.80e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14007   8 LGKGKFGNVYLAREkkSGFIVALKVIsKSQLQKSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILEYAPNGEL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGR------AVITKQnqidfardVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNVKQega 381
Cdd:cd14007  88 YKELKKQKRfdekeaAKYIYQ--------LALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWsVHAPSNRRK--- 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 klpvkwT--------APEALRENKFSNKTDVWSFGVLLWEIYsYGRVP-YPRVPVEDVANHVENGYRMES--PDGCPDQI 450
Cdd:cd14007 157 ------TfcgtldylPPEMVEGKEYDYKVDIWSLGVLCYELL-VGKPPfESKSHQETYKRIQNVDIKFPSsvSPEAKDLI 229
                       250       260
                ....*....|....*....|.
gi 18150824 451 YKIMmdcwEKDPSQRPNFTRI 471
Cdd:cd14007 230 SKLL----QKDPSKRLSLEQV 246
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
232-478 7.64e-32

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 122.58  E-value: 7.64e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTqfLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDY 311
Cdd:cd14155   1 IGSGFFSEVYKVRHRTSGQVMALKMNTLSSNRANM--LREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 312 LRSRgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLAKSSSNVKQEGAKLPV--- 385
Cdd:cd14155  79 LDSN--EPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIKRDEngyTAVVGDFGLAEKIPDYSDGKEKLAVvgs 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 -KWTAPEALRENKFSNKTDVWSFGVLLWEIYSygrvpypRVPVE-DVANHVEN------GYRMESPDgCPDQIYKIMMDC 457
Cdd:cd14155 157 pYWMAPEVLRGEPYNEKADVFSYGIILCEIIA-------RIQADpDYLPRTEDfgldydAFQHMVGD-CPPDFLQLAFNC 228
                       250       260
                ....*....|....*....|.
gi 18150824 458 WEKDPSQRPNFTRIEKALESV 478
Cdd:cd14155 229 CNMDPKSRPSFHDIVKTLEEI 249
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
235-472 2.72e-31

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 121.45  E-value: 2.72e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 235 GEFGEVWLGDYEGKK-VAMKSM-KDHLKDEKAKTqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYL 312
Cdd:cd14027   4 GGFGKVSLCFHRTQGlVVLKTVyTGPNCIEHNEA-LLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 313 RSRGRAVITKQNqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSS--SNVKQEGAKLPVKWT-- 388
Cdd:cd14027  83 KKVSVPLSVKGR---IILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKmwSKLTKEEHNEQREVDgt 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 389 -----------APEALRE--NKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANH-VENGYR---MESPDGCPDQIY 451
Cdd:cd14027 160 akknagtlyymAPEHLNDvnAKPTEKSDVYSFAIVLWAIFA-NKEPYENAINEDQIIMcIKSGNRpdvDDITEYCPREII 238
                       250       260
                ....*....|....*....|.
gi 18150824 452 KIMMDCWEKDPSQRPNFTRIE 472
Cdd:cd14027 239 DLMKLCWEANPEARPTFPGIE 259
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
231-467 3.51e-31

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: 120.65  E-value: 3.51e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd08215   7 VIGKGSFGSAYLvrRKSDGKLYVLKEIDLSNMSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYADGGDL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVIT-KQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvKQEGAKlpvk 386
Cdd:cd08215  87 AQKIKKQKKKGQPfPEEQIlDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLES-TTDLAK---- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 wT--------APEALRENKFSNKTDVWSFGVLLWE----------------IYSYGRVPYPRVPvedvanhveNGYrmes 442
Cdd:cd08215 162 -TvvgtpyylSPELCENKPYNYKSDIWALGCVLYElctlkhpfeannlpalVYKIVKGQYPPIP---------SQY---- 227
                       250       260
                ....*....|....*....|....*
gi 18150824 443 pdgcPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd08215 228 ----SSELRDLVNSMLQKDPEKRPS 248
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
232-476 4.43e-31

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: 120.66  E-value: 4.43e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd05117   8 LGRGSFGVVRLAVHkkTGEEYAVKIIDKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELCTGGELF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGR------AVITKQnqidfardVVKGMVYLESQNFVHRDLAARNVLIAEDNVA---KVSDFGLAKsssnVKQEG 380
Cdd:cd05117  88 DRIVKKGSfsereaAKIMKQ--------ILSAVAYLHSQGIVHRDLKPENILLASKDPDspiKIIDFGLAK----IFEEG 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLpvkWT--------APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENG-YRMESP------DG 445
Cdd:cd05117 156 EKL---KTvcgtpyyvAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYGETEQELFEKILKGkYSFDSPewknvsEE 231
                       250       260       270
                ....*....|....*....|....*....|.
gi 18150824 446 CPDQIYKimmdCWEKDPSQRPNftrIEKALE 476
Cdd:cd05117 232 AKDLIKR----LLVVDPKKRLT---AAEALN 255
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
232-479 4.69e-31

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 120.32  E-value: 4.69e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKaktqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14156   1 IGSGFFSKVYkvTHGATGKVMVVKIYKNDVDQHK----IVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLrSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI---AEDNVAKVSDFGLAKSSSNV--KQEGAKLP 384
Cdd:cd14156  77 ELL-AREELPLSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIrvtPRGREAVVTDFGLAREVGEMpaNDPERKLS 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VK----WTAPEALRENKFSNKTDVWSFGVLLWEIysYGRVP-----YPRvpVEDVANHVEnGYRMESPdGCPDQIYKIMM 455
Cdd:cd14156 156 LVgsafWMAPEMLRGEPYDRKVDVFSFGIVLCEI--LARIPadpevLPR--TGDFGLDVQ-AFKEMVP-GCPEPFLDLAA 229
                       250       260
                ....*....|....*....|....
gi 18150824 456 DCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd14156 230 SCCRMDAFKRPSFAELLDELEDIA 253
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
231-477 6.48e-31

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 120.80  E-value: 6.48e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMK----------------SMKDHLKDE---KAKTQFLAEASVMTTLRHPNLVCLIGISL 291
Cdd:cd14000   1 LLGDGGFGSVYRASYKGEPVAVKifnkhtssnfanvpadTMLRHLRATdamKNFRLLRQELTVLSHLHHPSIVYLLGIGI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 292 ddNPIYLITEFMAKGSLIDYLR--SRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV-----AKV 364
Cdd:cd14000  81 --HPLMLVLELAPLGSLDHLLQqdSRSFASLGRTLQQRIALQVADGLRYLHSAMIIYRDLKSHNVLVWTLYPnsaiiIKI 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 365 SDFGLAKSSSNVKQEGAKLPVKWTAPEALREN-KFSNKTDVWSFGVLLWEIYSYGRvpyPRVPVEDVANHVENGYRMESP 443
Cdd:cd14000 159 ADYGISRQCCRMGAKGSEGTPGFRAPEIARGNvIYNEKVDVFSFGMLLYEILSGGA---PMVGHLKFPNEFDIHGGLRPP 235
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 18150824 444 DGCPDQIY-----KIMMDCWEKDPSQRPNFTRIEKALES 477
Cdd:cd14000 236 LKQYECAPwpeveVLMKKCWKENPQQRPTAVTVVSILNS 274
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
223-478 1.08e-30

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: 119.74  E-value: 1.08e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 223 KASLLKKslIGKGEFGEVWLGDYEGKkVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNpIYLITEF 302
Cdd:cd14150   1 EVSMLKR--IGTGSFGTVFRGKWHGD-VAVKILKVTEPTPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPN-FAIITQW 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA------KSSSNV 376
Cdd:cd14150  77 CEGSSLYRHLHVTETRFDTMQ-LIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLAtvktrwSGSQQV 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKlpVKWTAPEALR---ENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVED-VANHVENGYRmeSPD------GC 446
Cdd:cd14150 156 EQPSGS--ILWMAPEVIRmqdTNPYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDqIIFMVGRGYL--SPDlsklssNC 230
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 447 PDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14150 231 PKAMKRLLIDCLKFKREERPLFPQILVSIELL 262
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
228-466 1.41e-30

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: 119.04  E-value: 1.41e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLG--DYEGKKVAMKSMKDHLKDEKAK---TQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd06632   4 KGQLLGSGSFGSVYEGfnGDTGDFFAVKEVSLVDDDKKSResvKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEY 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRaviTKQNQID-FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVkqeGA 381
Cdd:cd06632  84 VPGGSIHKLLQRYGA---FEEPVIRlYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAF---SF 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVK----WTAPEALRE--NKFSNKTDVWSFGVLLWEIYSyGRVPYPRV-PVEDVANHVENGYRMESPDGCPDQIYKIM 454
Cdd:cd06632 158 AKSFKgspyWMAPEVIMQknSGYGLAVDIWSLGCTVLEMAT-GKPPWSQYeGVAAIFKIGNSGELPPIPDHLSPDAKDFI 236
                       250
                ....*....|..
gi 18150824 455 MDCWEKDPSQRP 466
Cdd:cd06632 237 RLCLQRDPEDRP 248
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
232-475 1.60e-30

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


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 119.68  E-value: 1.60e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMkdHLKDEKAktqFLAEASVMTT--LRHPNLVCLIGISLDDN----PIYLITEFMAK 305
Cdd:cd14056   3 IGKGRYGEVWLGKYRGEKVAVKIF--SSRDEDS---WFRETEIYQTvmLRHENILGFIAADIKSTgswtQLWLITEYHEH 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRsrgRAVITKQNQIDFARDVVKGMVYLESQNF--------VHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK 377
Cdd:cd14056  78 GSLYDYLQ---RNTLDTEEALRLAYSAASGLAHLHTEIVgtqgkpaiAHRDLKSKNILVKRDGTCCIADLGLAVRYDSDT 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLP------VKWTAPEALRE----NKFSN--KTDVWSFGVLLWEI---------YSYGRVPY----PRVP-VEDVA 431
Cdd:cd14056 155 NTIDIPPnprvgtKRYMAPEVLDDsinpKSFESfkMADIYSFGLVLWEIarrceiggiAEEYQLPYfgmvPSDPsFEEMR 234
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 18150824 432 NHV-ENGYRMESP-----DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd14056 235 KVVcVEKLRPPIPnrwksDPVLRSMVKLMQECWSENPHARLTALRVKKTL 284
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
219-476 2.10e-30

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 119.37  E-value: 2.10e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLKKSLIGKGEFGEVWLGDYEGKkVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNpIYL 298
Cdd:cd14149   7 WEIEASEVMLSTRIGSGSFGTVYKGKWHGD-VAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDN-LAI 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSRGRAVITKQnQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSS 374
Cdd:cd14149  85 VTQWCEGSSLYKHLHVQETKFQMFQ-LIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLAtvksRWSG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKLPVKWTAPEALR---ENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVED-VANHVENGYrmESPD------ 444
Cdd:cd14149 164 SQQVEQPTGSILWMAPEVIRmqdNNPFSFQSDVYSYGIVLYELMT-GELPYSHINNRDqIIFMVGRGY--ASPDlsklyk 240
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 445 GCPDQIYKIMMDCWEKDPSQRPNFTRIEKALE 476
Cdd:cd14149 241 NCPKAMKRLVADCIKKVKEERPLFPQILSSIE 272
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
228-471 1.11e-29

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: 116.50  E-value: 1.11e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLG--DYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd14099   5 RGKFLGKGGFAKCYEVtdMSTGKVYAGKVVpKSSLTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAkssSNVKQEGAKlp 384
Cdd:cd14099  85 NGSLMELLKRRKA--LTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLA---ARLEYDGER-- 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 vKWT--------APEALRENK-FSNKTDVWSFGVLLweiYS--YGRVPYPRVPVEDVANHV-ENGYRMESPDGCPDQIYK 452
Cdd:cd14099 158 -KKTlcgtpnyiAPEVLEKKKgHSFEVDIWSLGVIL---YTllVGKPPFETSDVKETYKRIkKNEYSFPSHLSISDEAKD 233
                       250
                ....*....|....*....
gi 18150824 453 IMMDCWEKDPSQRPNFTRI 471
Cdd:cd14099 234 LIRSMLQPDPTKRPSLDEI 252
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
232-475 1.61e-29

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 116.50  E-value: 1.61e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD-YEGKKVAMKSMKDhLK---DEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05086   5 IGNGWFGKVLLGEiYTGTSVARVVVKE-LKasaNPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFEFCDLGD 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIDFAR---DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA----KSSSNVKQEG 380
Cdd:cd05086  84 LKTYLANQQEKLRGDSQIMLLQRmacEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGfsryKEDYIETDDK 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPVKWTAPE----------ALRENKFSNktdVWSFGVLLWEIYSYGRVPYPRVPVEDVANHV--ENGYRMESPD---G 445
Cdd:cd05086 164 KYAPLRWTAPElvtsfqdgllAAEQTKYSN---IWSLGVTLWELFENAAQPYSDLSDREVLNHVikERQVKLFKPHleqP 240
                       250       260       270
                ....*....|....*....|....*....|
gi 18150824 446 CPDQIYKIMMDCWeKDPSQRPNFTRIEKAL 475
Cdd:cd05086 241 YSDRWYEVLQFCW-LSPEKRPTAEEVHRLL 269
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
232-465 2.66e-29

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: 115.73  E-value: 2.66e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSM-KDHLK--------DEKAKTQFLA---EASVMTTLRHPNLVCLIGIsLDD---N 294
Cdd:cd14008   1 LGRGSFGKVKLAldTETGQLYAIKIFnKSRLRkrregkndRGKIKNALDDvrrEIAIMKKLDHPNIVRLYEV-IDDpesD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 295 PIYLITEFMAKGSLIDYLRSRGRAVITKQ--NQIdfARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS 372
Cdd:cd14008  80 KLYLVLEYCEGGPVMELDSGDRVPPLPEEtaRKY--FRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEM 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 SSNVKQEGAKLP--VKWTAPEALRENKFSN---KTDVWSFGVLLWEIYsYGRVPYPRVPVEDVANHVENGYRMES-PDGC 446
Cdd:cd14008 158 FEDGNDTLQKTAgtPAFLAPELCDGDSKTYsgkAADIWALGVTLYCLV-FGRLPFNGDNILELYEAIQNQNDEFPiPPEL 236
                       250
                ....*....|....*....
gi 18150824 447 PDQIYKIMMDCWEKDPSQR 465
Cdd:cd14008 237 SPELKDLLRRMLEKDPEKR 255
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
243-475 6.33e-29

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 114.79  E-value: 6.33e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 243 GDYEGKKVAMKsmkdHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGraviT 321
Cdd:cd13992  21 GVYGGRTVAIK----HItFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNRE----I 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 322 KQN---QIDFARDVVKGMVYLESQNF-VHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKQEGAKLPVK--WTAPEA 392
Cdd:cd13992  93 KMDwmfKSSFIKDIVKGMNYLHSSSIgYHGRLKSSNCLVDSRWVVKLTDFGLRnllEEQTNHQLDEDAQHKKllWTAPEL 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 393 LRENKF----SNKTDVWSFGVLLWEIYSYGRvPYP----RVPVEDVANhveNGYRMESP------DGCPDQIYKIMMDCW 458
Cdd:cd13992 173 LRGSLLevrgTQKGDVYSFAIILYEILFRSD-PFAlereVAIVEKVIS---GGNKPFRPelavllDEFPPRLVLLVKQCW 248
                       250
                ....*....|....*..
gi 18150824 459 EKDPSQRPNFTRIEKAL 475
Cdd:cd13992 249 AENPEKRPSFKQIKKTL 265
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
232-471 1.06e-28

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 114.11  E-value: 1.06e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDekAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIyLITEFMAKGSLIDY 311
Cdd:cd05037  15 IYDGILREVGDGRVQEVEVLLKVLDSDHRD--ISESFFETASLMSQISHKHLVKLYGVCVADENI-MVQEYVRYGPLDKY 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 312 LRSRGRAViTKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV------AKVSDFGLakSSSNVKQEGAKLPV 385
Cdd:cd05037  92 LRRMGNNV-PLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLAREGLdgyppfIKLSDPGV--PITVLSREERVDRI 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 KWTAPEALRE--NKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDgCPdQIYKIMMDCWEKDPS 463
Cdd:cd05037 169 PWIAPECLRNlqANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAPD-CA-ELAELIMQCWTYEPT 246

                ....*...
gi 18150824 464 QRPNFTRI 471
Cdd:cd05037 247 KRPSFRAI 254
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
232-465 1.22e-28

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 113.38  E-value: 1.22e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL----GDyeGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05123   1 LGKGSFGKVLLvrkkDT--GKLYAMKVLrKKEIIKRKEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPGG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvkqEGAKLpv 385
Cdd:cd05123  79 ELFSHLSKEGR---FPEERARFyAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSS---DGDRT-- 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 kWT--------APEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYPRVPVEDV-ANHVENGYRMesPDGCPDQIYKIMMD 456
Cdd:cd05123 151 -YTfcgtpeylAPEVLLGKGYGKAVDWWSLGVLLYEML-TGKPPFYAENRKEIyEKILKSPLKF--PEYVSPEAKSLISG 226

                ....*....
gi 18150824 457 CWEKDPSQR 465
Cdd:cd05123 227 LLQKDPTKR 235
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
228-466 1.55e-28

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: 114.02  E-value: 1.55e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLG-------DYEGKKVAMKSMKDHLKDEKAKTQFLA---EASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd06629   5 KGELIGKGTYGRVYLAmnattgeMLAVKQVELPKTSSDRADSRQKTVVDAlksEIDTLKDLDHPNIVQYLGFEETEDYFS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK 377
Cdd:cd06629  85 IFLEYVPGGSIGSCLRKYGK--FEEDLVRFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKKSDDIY 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVK----WTAPEALRENK--FSNKTDVWSFGVLLWEIYSyGRVPYPrvPVEDVANHVENGYRMESPDGCPD-QI 450
Cdd:cd06629 163 GNNGATSMQgsvfWMAPEVIHSQGqgYSAKVDIWSLGCVVLEMLA-GRRPWS--DDEAIAAMFKLGNKRSAPPVPEDvNL 239
                       250       260
                ....*....|....*....|
gi 18150824 451 YKI----MMDCWEKDPSQRP 466
Cdd:cd06629 240 SPEaldfLNACFAIDPRDRP 259
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
108-198 4.48e-28

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 107.09  E-value: 4.48e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQKE 187
Cdd:cd09935   4 SWYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVHHHSKN 83
                        90
                ....*....|.
gi 18150824 188 ADGLCTRLKAP 198
Cdd:cd09935  84 ADGLITTLRYP 94
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
227-466 4.57e-28

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: 112.63  E-value: 4.57e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLIGKGEFGEVWLG--DYEGKKVAMKSMK---DHLKDEKAKTQFLA----EASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd06628   3 IKGALIGSGSFGSVYLGmnASSGELMAVKQVElpsVSAENKDRKKSMLDalqrEIALLRELQHENIVQYLGSSSDANHLN 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRG---RAVITkqnqiDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--- 371
Cdd:cd06628  83 IFLEYVPGGSVATLLNNYGafeESLVR-----NFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKkle 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 -SSSNVKQEGAKL----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPDGC 446
Cdd:cd06628 158 aNSLSTKNNGARPslqgSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNI 236
                       250       260
                ....*....|....*....|
gi 18150824 447 PDQIYKIMMDCWEKDPSQRP 466
Cdd:cd06628 237 SSEARDFLEKTFEIDHNKRP 256
SH2 pfam00017
SH2 domain;
109-184 9.33e-28

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 105.38  E-value: 9.33e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824   109 WFHGRISREDAEKLLTP-PKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHY 184
Cdd:pfam00017   1 WYHGKISRQEAERLLLNgKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEHY 77
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
226-465 4.77e-27

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 109.27  E-value: 4.77e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKKSLiGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd14081   4 RLGKTL-GKGQTGLVKLAKHCvtGQKVAIKIVnKEKLSKESVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVLEY 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAksssNVKQEGAK 382
Cdd:cd14081  83 VSGGELFDYLVKKGR--LTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMA----SLQPEGSL 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 L------PvKWTAPEALRENKFSN-KTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENG-YRMES--PDGCPDQIYK 452
Cdd:cd14081 157 LetscgsP-HYACPEVIKGEKYDGrKADIWSCGVILYALLV-GALPFDDDNLRQLLEKVKRGvFHIPHfiSPDAQDLLRR 234
                       250
                ....*....|...
gi 18150824 453 IMmdcwEKDPSQR 465
Cdd:cd14081 235 ML----EVNPEKR 243
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
230-422 1.61e-26

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: 107.72  E-value: 1.61e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLG--DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFmAKGS 307
Cdd:cd14002   7 ELIGEGSFGKVYKGrrKYTGQVVALKFIPKRGKSEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEY-AQGE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIdfARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-SSN------VKqeG 380
Cdd:cd14002  86 LFQILEDDGTLPEEEVRSI--AKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAmSCNtlvltsIK--G 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 18150824 381 AKLpvkWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd14002 162 TPL---YMAPELVQEQPYDHTADLWSLGCILYELF-VGQPPF 199
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
231-479 1.97e-26

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


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 108.68  E-value: 1.97e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKDhlKDEKAktqFLAEASVMTT--LRHPNLVCLIGISL----DDNPIYLITEFMA 304
Cdd:cd14142  12 CIGKGRYGEVWRGQWQGESVAVKIFSS--RDEKS---WFRETEIYNTvlLRHENILGFIASDMtsrnSCTQLWLITHYHE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRsrgRAVITKQNQIDFARDVVKGMVYLESQNF--------VHRDLAARNVLIAEDNVAKVSDFGLAKSSSnv 376
Cdd:cd14142  87 NGSLYDYLQ---RTTLDHQEMLRLALSAASGLVHLHTEIFgtqgkpaiAHRDLKSKNILVKSNGQCCIADLGLAVTHS-- 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 kQEGAKLPV---------KWTAPEALRE----NKFS--NKTDVWSFGVLLWEI----YSYGRVPYPRVPVEDVANH---- 433
Cdd:cd14142 162 -QETNQLDVgnnprvgtkRYMAPEVLDEtintDCFEsyKRVDIYAFGLVLWEVarrcVSGGIVEEYKPPFYDVVPSdpsf 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 434 -------VENGYRMESP-----DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd14142 241 edmrkvvCVDQQRPNIPnrwssDPTLTAMAKLMKECWYQNPSARLTALRIKKTLLKIL 298
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
231-477 2.49e-26

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 107.35  E-value: 2.49e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKDHlkdekAKTQFL-AEASVMTTLRHPNLVCLIGISLddNPIYLITEFMAKGSLi 309
Cdd:cd14068   1 LLGDGGFGSVYRAVYRGEDVAVKIFNKH-----TSFRLLrQELVVLSHLHHPSLVALLAAGT--APRMLVMELAPKGSL- 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE-----DNVAKVSDFGLAKSSSNVKQEGAKLP 384
Cdd:cd14068  73 DALLQQDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTlypncAIIAKIADYGIAQYCCRMGIKTSEGT 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWTAPEALREN-KFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESP---DGCP--DQIYKIMMDCW 458
Cdd:cd14068 153 PGFRAPEVARGNvIYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPvkeYGCApwPGVEALIKDCL 232
                       250
                ....*....|....*....
gi 18150824 459 EKDPSQRPNFTRIEKALES 477
Cdd:cd14068 233 KENPQCRPTSAQVFDILNS 251
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
230-471 3.05e-26

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: 107.09  E-value: 3.05e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVW----LGDyeGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd08530   6 KKLGKGSYGSVYkvkrLSD--NQVYALKEVNLGSLSQKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPF 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRG--RAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN---VKQEG 380
Cdd:cd08530  84 GDLSKLISKRKkkRRLFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKnlaKTQIG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLpvkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEK 460
Cdd:cd08530 164 TPL---YAAPEVWKGRPYDYKSDIWSLGCLLYEMAT-FRPPFEARTMQELRYKVCRGKFPPIPPVYSQDLQQIIRSLLQV 239
                       250
                ....*....|.
gi 18150824 461 DPSQRPNFTRI 471
Cdd:cd08530 240 NPKKRPSCDKL 250
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
232-466 3.76e-26

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 106.93  E-value: 3.76e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIG--ISLDDNPIYLITEFMAKGS 307
Cdd:cd13983   9 LGRGSFKTVYRAfdTEEGIEVAWNEIKLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDswESKSKKEVIFITELMTSGT 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGR---AVITKqnqidFARDVVKGMVYLESQN--FVHRDLAARNVLI-AEDNVAKVSDFGLAKSssnvKQEGA 381
Cdd:cd13983  89 LKQYLKRFKRlklKVIKS-----WCRQILEGLNYLHTRDppIIHRDLKCDNIFInGNTGEVKIGDLGLATL----LRQSF 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVKWT----APEaLRENKFSNKTDVWSFGVLLWEIYSyGRVPYprvpVE-----DVANHVENGYRMESPDGCPDQ-IY 451
Cdd:cd13983 160 AKSVIGTpefmAPE-MYEEHYDEKVDIYAFGMCLLEMAT-GEYPY----SEctnaaQIYKKVTSGIKPESLSKVKDPeLK 233
                       250
                ....*....|....*
gi 18150824 452 KIMMDCWEKdPSQRP 466
Cdd:cd13983 234 DFIEKCLKP-PDERP 247
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
228-466 5.59e-26

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 106.75  E-value: 5.59e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLG-DYEGKKVAMKSMKDHLKD-EKAKTQFLA---EASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd06631   5 KGNVLGKGAYGTVYCGlTSTGQLIAVKQVELDTSDkEKAEKEYEKlqeEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEF 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRG---RAVITKqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-------- 371
Cdd:cd06631  85 VPGGSIASILARFGaleEPVFCR-----YTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKrlcinlss 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 -SSSNVKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVenGYRMESPDGCPDQI 450
Cdd:cd06631 160 gSQSQLLKSMRGTPY-WMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMNPMAAIFAI--GSGRKPVPRLPDKF 235
                       250       260
                ....*....|....*....|
gi 18150824 451 YKIMMD----CWEKDPSQRP 466
Cdd:cd06631 236 SPEARDfvhaCLTRDQDERP 255
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
232-478 8.27e-26

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 106.04  E-value: 8.27e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDhlKDEKAKTQFLAEASVMTTL-RHPNLVCLIGISLDDN-------PIYLITE 301
Cdd:cd13975   8 LGRGQYGVVYACDSWGGHfpCALKSVVP--PDDKHWNDLALEFHYTRSLpKHERIVSLHGSVIDYSygggssiAVLLIME 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGslidyLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGA 381
Cdd:cd13975  86 RLHRD-----LYTGIKAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCKPEAMMSGSIV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVKwTAPEaLRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRV-----PVEDVANHVENGYRMESPDGCPDQIYKIMMD 456
Cdd:cd13975 161 GTPIH-MAPE-LFSGKYDNSVDVYAFGILFWYLCA-GHVKLPEAfeqcaSKDHLWNNVRKGVRPERLPVFDEECWNLMEA 237
                       250       260
                ....*....|....*....|..
gi 18150824 457 CWEKDPSQRPNFTRIEKALESV 478
Cdd:cd13975 238 CWSGDPSQRPLLGIVQPKLQGI 259
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
232-467 1.18e-25

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 105.90  E-value: 1.18e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDhlkdEKAKTQF---LAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd06610   9 IGSGATAVVYAAYCLpkKEKVAIKRIDL----EKCQTSMdelRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKQNQIDFA-RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-------SSNVKQ 378
Cdd:cd06610  85 SLLDIMKSSYPRGGLDEAIIATVlKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASlatggdrTRKVRK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVkWTAPEALRENK-FSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDV----ANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd06610 165 TFVGTPC-WMAPEVMEQVRgYDFKADIWSFGITAIEL-ATGAAPYSKYPPMKVlmltLQNDPPSLETGADYKKYSKSFRK 242
                       250
                ....*....|....*
gi 18150824 454 MMD-CWEKDPSQRPN 467
Cdd:cd06610 243 MISlCLQKDPSKRPT 257
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
231-475 1.34e-25

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


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 106.02  E-value: 1.34e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKDHlkdEKAktQFLAEASVMTT--LRHPNLVCLIGISLDDN----PIYLITEFMA 304
Cdd:cd14144   2 SVGKGRYGEVWKGKWRGEKVAVKIFFTT---EEA--SWFRETEIYQTvlMRHENILGFIAADIKGTgswtQLYLITDYHE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSrgrAVITKQNQIDFARDVVKGMVYLESQNF--------VHRDLAARNVLIAEDNVAKVSDFGLA---KSS 373
Cdd:cd14144  77 NGSLYDFLRG---NTLDTQSMLKLAYSAACGLAHLHTEIFgtqgkpaiAHRDIKSKNILVKKNGTCCIADLGLAvkfISE 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNV------KQEGAKlpvKWTAPEALRE----NKFS--NKTDVWSFGVLLWEI----YSYGRVPYPRVPVEDVANH---- 433
Cdd:cd14144 154 TNEvdlppnTRVGTK---RYMAPEVLDEslnrNHFDayKMADMYSFGLVLWEIarrcISGGIVEEYQLPYYDAVPSdpsy 230
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 18150824 434 -------VENGYRMESP-----DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd14144 231 edmrrvvCVERRRPSIPnrwssDEVLRTMSKLMSECWAHNPAARLTALRVKKTL 284
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
223-473 1.71e-25

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: 104.91  E-value: 1.71e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 223 KASLLKKslIGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd14072   1 NYRLLKT--IGKGNFAKVKLARHvlTGREVAIKIIDKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGRaVITKQNQIDFaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEG 380
Cdd:cd14072  79 EYASGGEVFDYLVAHGR-MKEKEARAKF-RQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGF----SNEFTPG 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPV-----KWTAPEALRENKFSN-KTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENG-YRME---SPDgCPDQI 450
Cdd:cd14072 153 NKLDTfcgspPYAAPELFQGKKYDGpEVDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLRGkYRIPfymSTD-CENLL 230
                       250       260
                ....*....|....*....|...
gi 18150824 451 YKIMMdcweKDPSQRPNFTRIEK 473
Cdd:cd14072 231 KKFLV----LNPSKRGTLEQIMK 249
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
232-446 1.76e-25

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: 105.04  E-value: 1.76e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14161  11 LGKGTYGRVKKArDSSGRLVAIKSIrKDRIKDEQDLLHIRREIEIMSSLNHPHIISVYEVFENSSKIVIVMEYASRGDLY 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEGAKL------ 383
Cdd:cd14161  91 DYISERQR--LSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGL----SNLYNQDKFLqtycgs 164
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 384 PVkWTAPEALRENKFSN-KTDVWSFGVLLWeIYSYGRVPYPRVPVEDVANHVENGYRMESP---DGC 446
Cdd:cd14161 165 PL-YASPEIVNGRPYIGpEVDSWSLGVLLY-ILVHGTMPFDGHDYKILVKQISSGAYREPTkpsDAC 229
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
228-414 2.50e-25

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: 105.02  E-value: 2.50e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDYE--GKKVAMKSMK-DHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd06609   5 LLERIGKGSFGEVYKGIDKrtNQVVAIKVIDlEEAEDEIEDIQ--QEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRgravITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKQEG 380
Cdd:cd06609  83 GGSVLDLLKPG----PLDETYIAFiLREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSgqlTSTMSKRNTF 158
                       170       180       190
                ....*....|....*....|....*....|....
gi 18150824 381 AKLPVkWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06609 159 VGTPF-WMAPEVIKQSGYDEKADIWSLGITAIEL 191
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
250-468 2.53e-25

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: 104.29  E-value: 2.53e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 250 VAMKSM-KDHLKdeKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRaviTKQNQID 327
Cdd:cd14121  24 VAVKCVsKSSLN--KASTEnLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRSRRT---LPESTVR 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 328 -FARDVVKGMVYLESQNFVHRDLAARNVLI--AEDNVAKVSDFGLAKSSSNVKQE----GAKLpvkWTAPEALRENKFSN 400
Cdd:cd14121  99 rFLQQLASALQFLREHNISHMDLKPQNLLLssRYNPVLKLADFGFAQHLKPNDEAhslrGSPL---YMAPEMILKKKYDA 175
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18150824 401 KTDVWSFGVLLWEIYsYGRVPYPRVPVEDVANHVENGYRMESPDG------CPDQIYKIMmdcwEKDPSQRPNF 468
Cdd:cd14121 176 RVDLWSVGVILYECL-FGRAPFASRSFEELEEKIRSSKPIEIPTRpelsadCRDLLLRLL----QRDPDRRISF 244
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
226-471 2.69e-25

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: 104.42  E-value: 2.69e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKKslIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd08529   4 ILNK--LGKGSFGVVYkvVRKVDGRVYALKQIDISRMSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRS-RGRAVitKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS---SSNVKQ 378
Cdd:cd08529  82 ENGDLHSLIKSqRGRPL--PEDQIwKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKIlsdTTNFAQ 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYprvpveDVANHVE------NGYRMESPDGCPDQIYK 452
Cdd:cd08529 160 TIVGTPY-YLSPELCEDKPYNEKSDVWALGCVLYELCT-GKHPF------EAQNQGAlilkivRGKYPPISASYSQDLSQ 231
                       250
                ....*....|....*....
gi 18150824 453 IMMDCWEKDPSQRPNFTRI 471
Cdd:cd08529 232 LIDSCLTKDYRQRPDTTEL 250
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
231-478 3.06e-25

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 104.71  E-value: 3.06e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKkVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14153   7 LIGKGRFGQVYHGRWHGE-VAIRLIDIERDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRAV-ITKQNQIdfARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAkVSDFGLAkSSSNVKQEGAK-----LP 384
Cdd:cd14153  86 VVRDAKVVLdVNKTRQI--AQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLF-TISGVLQAGRRedklrIQ 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKW---TAPEALR-------ENK--FSNKTDVWSFGVLLWEIYSYgRVPYPRVPVEDVANHVENGYR-MESPDGCPDQIY 451
Cdd:cd14153 162 SGWlchLAPEIIRqlspeteEDKlpFSKHSDVFAFGTIWYELHAR-EWPFKTQPAEAIIWQVGSGMKpNLSQIGMGKEIS 240
                       250       260
                ....*....|....*....|....*..
gi 18150824 452 KIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14153 241 DILLFCWAYEQEERPTFSKLMEMLEKL 267
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
231-478 5.04e-25

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


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 104.28  E-value: 5.04e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKkVAMKSM------KDHLKdekaktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd14152   7 LIGQGRWGKVHRGRWHGE-VAIRLLeidgnnQDHLK------LFKKEVMNYRQTRHENVVLFMGACMHPPHLAIITSFCK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLR-SRGRAVITKQNQIdfARDVVKGMVYLESQNFVHRDLAARNVLIaEDNVAKVSDFGLAkSSSNVKQEGA-- 381
Cdd:cd14152  80 GRTLYSFVRdPKTSLDINKTRQI--AQEIIKGMGYLHAKGIVHKDLKSKNVFY-DNGKVVITDFGLF-GISGVVQEGRre 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 ---KLPVKWT---APEALRENK---------FSNKTDVWSFGVLLWEIYSYGRvPYPRVPVEDVANHVENGYRME---SP 443
Cdd:cd14152 156 nelKLPHDWLcylAPEIVREMTpgkdedclpFSKAADVYAFGTIWYELQARDW-PLKNQPAEALIWQIGSGEGMKqvlTT 234
                       250       260       270
                ....*....|....*....|....*....|....*
gi 18150824 444 DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14152 235 ISLGKEVTEILSACWAFDLEERPSFTLLMDMLEKL 269
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
243-478 5.33e-25

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 103.81  E-value: 5.33e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 243 GDYEGKKVAMKSMK--DHLKDEKAKTqflaEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSR----G 316
Cdd:cd14044  27 GKYDKKVVILKDLKnnEGNFTEKQKI----ELNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVLNDKisypD 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 317 RAVITKQNQIDFARDVVKGMVYLESQNF-VHRDLAARNVLIAEDNVAKVSDFGlaksSSNVKQEGAKLpvkWTAPEALRE 395
Cdd:cd14044 103 GTFMDWEFKISVMYDIAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFG----CNSILPPSKDL---WTAPEHLRQ 175
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 396 NKFSNKTDVWSFGVLLWEIYSYGRVPYprvpVEDVANHVENGYRMESPDGC----PD-----------QIYKIMMDCWEK 460
Cdd:cd14044 176 AGTSQKGDVYSYGIIAQEIILRKETFY----TAACSDRKEKIYRVQNPKGMkpfrPDlnlesagererEVYGLVKNCWEE 251
                       250
                ....*....|....*...
gi 18150824 461 DPSQRPNFTRIEKALESV 478
Cdd:cd14044 252 DPEKRPDFKKIENTLAKI 269
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
231-426 5.97e-25

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 103.50  E-value: 5.97e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMK--SMKDHLKD-EKaktqflaEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd06612  10 KLGEGSYGSVYKAIHKetGQVVAIKvvPVEEDLQEiIK-------EISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCGA 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQE---G 380
Cdd:cd06612  83 GSVSDIMKITNKTLTEEEIAA-ILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGqlTDTMAKRNtviG 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 381 AKLpvkWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVP 426
Cdd:cd06612 162 TPF---WMAPEVIQEIGYNNKADIWSLGITAIEM-AEGKPPYSDIH 203
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
231-465 6.60e-25

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 103.25  E-value: 6.60e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDY--EGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd14663   7 TLGEGTFAKVKFARNtkTGESVAIKIIdKEQVAREGMVEQIKREIAIMKLLRHPNIVELHEVMATKTKIFFVMELVTGGE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPV-- 385
Cdd:cd14663  87 LFSKIAKNGR--LKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSALSEQFRQDGLLHTTcg 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 --KWTAPEALRENKFSN-KTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGyRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd14663 165 tpNYVAPEVLARRGYDGaKADIWSCGVILFVLLA-GYLPFDDENLMALYRKIMKG-EFEYPRWFSPGAKSLIKRILDPNP 242

                ...
gi 18150824 463 SQR 465
Cdd:cd14663 243 STR 245
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
232-475 6.74e-25

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


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 103.97  E-value: 6.74e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMkdhLKDEKAktQFLAEASVMTT--LRHPNLVCLIGISLDDN----PIYLITEFMAK 305
Cdd:cd14220   3 IGKGRYGEVWMGKWRGEKVAVKVF---FTTEEA--SWFRETEIYQTvlMRHENILGFIAADIKGTgswtQLYLITDYHEN 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSrgrAVITKQNQIDFARDVVKGMVYLESQNF--------VHRDLAARNVLIAEDNVAKVSDFGLA-KSSSNV 376
Cdd:cd14220  78 GSLYDFLKC---TTLDTRALLKLAYSAACGLCHLHTEIYgtqgkpaiAHRDLKSKNILIKKNGTCCIADLGLAvKFNSDT 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKLPVK-----WTAPEALRENKFSNK------TDVWSFGVLLWE---------IYSYGRVPY----PRVP------ 426
Cdd:cd14220 155 NEVDVPLNTRvgtkrYMAPEVLDESLNKNHfqayimADIYSFGLIIWEmarrcvtggIVEEYQLPYydmvPSDPsyedmr 234
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 18150824 427 ----VEDVANHVENGYrmeSPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd14220 235 evvcVKRLRPTVSNRW---NSDECLRAVLKLMSECWAHNPASRLTALRIKKTL 284
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
231-465 7.26e-25

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


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 103.95  E-value: 7.26e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKdhlkdEKAKTQFLAEASVMTT--LRHPNLVCLIGIS---LDDNPIY-LITEFMA 304
Cdd:cd14053   2 IKARGRFGAVWKAQYLNRLVAVKIFP-----LQEKQSWLTEREIYSLpgMKHENILQFIGAEkhgESLEAEYwLITEFHE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRgraVITKQNQIDFARDVVKGMVYLESQ----------NFVHRDLAARNVLIAEDNVAKVSDFGLA-KSS 373
Cdd:cd14053  77 RGSLCDYLKGN---VISWNELCKIAESMARGLAYLHEDipatngghkpSIAHRDFKSKNVLLKSDLTACIADFGLAlKFE 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEGAKLPV---KWTAPEAL------RENKFSnKTDVWSFGVLLWEIYS-----------YgRVPY-----PRVPVE 428
Cdd:cd14053 154 PGKSCGDTHGQVgtrRYMAPEVLegainfTRDAFL-RIDMYAMGLVLWELLSrcsvhdgpvdeY-QLPFeeevgQHPTLE 231
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 18150824 429 DVANHVENgyRMESPDGCPD--------QIYKIMMDCWEKDPSQR 465
Cdd:cd14053 232 DMQECVVH--KKLRPQIRDEwrkhpglaQLCETIEECWDHDAEAR 274
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
232-479 7.45e-25

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


Pssm-ID: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 104.36  E-value: 7.45e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMkdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDD----NPIYLITEFMAKGS 307
Cdd:cd14219  13 IGKGRYGEVWMGKWRGEKVAVKVF---FTTEEASWFRETEIYQTVLMRHENILGFIAADIKGtgswTQLYLITDYHENGS 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSrgrAVITKQNQIDFARDVVKGMVYLESQNF--------VHRDLAARNVLIAEDNVAKVSDFGLA-KSSSNVKQ 378
Cdd:cd14219  90 LYDYLKS---TTLDTKAMLKLAYSSVSGLCHLHTEIFstqgkpaiAHRDLKSKNILVKKNGTCCIADLGLAvKFISDTNE 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPV-----KWTAPEALRE----NKFSN--KTDVWSFGVLLWEI----YSYGRVPYPRVPVEDvanHVENGYRME-- 441
Cdd:cd14219 167 VDIPPNTrvgtkRYMPPEVLDEslnrNHFQSyiMADMYSFGLILWEVarrcVSGGIVEEYQLPYHD---LVPSDPSYEdm 243
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 442 -----------------SPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd14219 244 reivcikrlrpsfpnrwSSDECLRQMGKLMTECWAHNPASRLTALRVKKTLAKMS 298
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
231-466 8.12e-25

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: 103.32  E-value: 8.12e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG-DYEGKKV-AMKS-MKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14098   7 RLGSGTFAEVKKAvEVETGKMrAIKQiVKRKVAGNDKNLQlFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN--VAKVSDFGLAKsssnVKQEGAKL- 383
Cdd:cd14098  87 DLMDFIMAWG--AIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLAK----VIHTGTFLv 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 ----PVKWTAPEALR------ENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPD---GCPDQI 450
Cdd:cd14098 161 tfcgTMAYLAPEILMskeqnlQGGYSNLVDMWSVGCLVYVMLT-GALPFDGSSQLPVEKRIRKGRYTQPPLvdfNISEEA 239
                       250
                ....*....|....*.
gi 18150824 451 YKIMMDCWEKDPSQRP 466
Cdd:cd14098 240 IDFILRLLDVDPEKRM 255
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
224-466 9.30e-25

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: 103.06  E-value: 9.30e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 224 ASLLKKSLIGKGEFGEVWLGDY--EGKKVAMKSMkdHLKDEKAKT-QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd06623   1 SDLERVKVLGQGSSGVVYKVRHkpTGKIYALKKI--HVDGDEEFRkQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGR------AVITKQnqidfardVVKGMVYLESQ-NFVHRDLAARNVLIAEDNVAKVSDFGLAKSS 373
Cdd:cd06623  79 EYMDGGSLADLLKKVGKipepvlAYIARQ--------ILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGISKVL 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQE-----GAklpVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPDgCPD 448
Cdd:cd06623 151 ENTLDQcntfvGT---VTYMSPERIQGESYSYAADIWSLGLTLLECAL-GKFPFLPPGQPSFFELMQAICDGPPPS-LPA 225
                       250       260
                ....*....|....*....|...
gi 18150824 449 QIYKIMMD-----CWEKDPSQRP 466
Cdd:cd06623 226 EEFSPEFRdfisaCLQKDPKKRP 248
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
232-466 1.85e-24

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: 102.51  E-value: 1.85e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd06611  13 LGDGAFGKVYKAQHkeTGLFAAAKIIQ--IESEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGALD 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAVitKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKL---PV 385
Cdd:cd06611  91 SIMLELERGL--TEPQIRYvCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKSTLQKRDTFigtPY 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 kWTAPEAL-----RENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHVENGY--RMESPDGCPDQIYKIMMDCW 458
Cdd:cd06611 169 -WMAPEVVacetfKDNPYDYKADIWSLGITLIEL-AQMEPPHHELNPMRVLLKILKSEppTLDQPSKWSSSFNDFLKSCL 246

                ....*...
gi 18150824 459 EKDPSQRP 466
Cdd:cd06611 247 VKDPDDRP 254
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
229-476 1.98e-24

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: 102.06  E-value: 1.98e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd14083   8 KEVLGTGAFSEVVLAEDKatGKLVAIKCIdKKALKGKEDSLE--NEIAVLRKIKHPNIVQLLDIYESKSHLYLVMELVTG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI---AEDNVAKVSDFGLAKSSSNVKQEGAK 382
Cdd:cd14083  86 GELFDRIVEKG--SYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLYyspDEDSKIMISDFGLSKMEDSGVMSTAC 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVKWTAPEALRENKFSNKTDVWSFGVLLWeIYSYGrvpYPRVPVEDVANHVEN----GYRMESP------DGCPDQIYK 452
Cdd:cd14083 164 GTPGYVAPEVLAQKPYGKAVDCWSIGVISY-ILLCG---YPPFYDENDSKLFAQilkaEYEFDSPywddisDSAKDFIRH 239
                       250       260
                ....*....|....*....|....
gi 18150824 453 IMmdcwEKDPSQRpnFTrIEKALE 476
Cdd:cd14083 240 LM----EKDPNKR--YT-CEQALE 256
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
238-476 2.33e-24

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 101.80  E-value: 2.33e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 238 GEVWLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGR 317
Cdd:cd14057   9 GELWKGRWQGNDIVAKILKVRDVTTRISRDFNEEYPRLRIFSHPNVLPVLGACNSPPNLVVISQYMPYGSLYNVLHEGTG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 318 AVITKQNQIDFARDVVKGMVYLES-QNFVHR-DLAARNVLIAEDNVAKVSdfgLAKSSSNVKQEGAKLPVKWTAPEALR- 394
Cdd:cd14057  89 VVVDQSQAVKFALDIARGMAFLHTlEPLIPRhHLNSKHVMIDEDMTARIN---MADVKFSFQEPGKMYNPAWMAPEALQk 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 395 --ENKFSNKTDVWSFGVLLWEIYSYgRVPYPRVPVEDVANHVE-NGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd14057 166 kpEDINRRSADMWSFAILLWELVTR-EVPFADLSNMEIGMKIAlEGLRVTIPPGISPHMCKLMKICMNEDPGKRPKFDMI 244

                ....*
gi 18150824 472 EKALE 476
Cdd:cd14057 245 VPILE 249
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
232-466 3.71e-24

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 101.61  E-value: 3.71e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG---DyEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd06626   8 IGEGTFGKVYTAvnlD-TGELMAMKEIRFQDNDPKTIKEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSrGR----AVITKqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLP 384
Cdd:cd06626  87 EELLRH-GRildeAVIRV-----YTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPGE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VK-------WTAPEALRENKFSNK---TDVWSFGVLLWEIYSyGRVPYPRVPVE-DVANHVENGYRMESPDgcPDQIYKI 453
Cdd:cd06626 161 VNslvgtpaYMAPEVITGNKGEGHgraADIWSLGCVVLEMAT-GKRPWSELDNEwAIMYHVGMGHKPPIPD--SLQLSPE 237
                       250
                ....*....|....*..
gi 18150824 454 MMD----CWEKDPSQRP 466
Cdd:cd06626 238 GKDflsrCLESDPKKRP 254
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
225-422 3.93e-24

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: 100.93  E-value: 3.93e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKslIGKGEFGEVWLGdYE---GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd14073   4 ELLET--LGKGTYGKVKLA-IEratGREVAIKSIkKDKIEDEQDMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVM 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEG 380
Cdd:cd14073  81 EYASGGELYDYISERRR--LPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGL----SNLYSKD 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 18150824 381 AKL------PVkWTAPEALRENKFSN-KTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd14073 155 KLLqtfcgsPL-YASPEIVNGTPYQGpEVDCWSLGVLLYTLV-YGTMPF 201
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
230-467 4.05e-24

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: 101.60  E-value: 4.05e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDY--EGKKVAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd13996  12 ELLGSGGFGSVYKVRNkvDGVTYAIKKIRLTEK-SSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGT 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRavITKQNQ---IDFARDVVKGMVYLESQNFVHRDLAARNVLIA-EDNVAKVSDFGLAKSSSNVKQEG--- 380
Cdd:cd13996  91 LRDWIDRRNS--SSKNDRklaLELFKQILKGVSYIHSKGIVHRDLKPSNIFLDnDDLQVKIGDFGLATSIGNQKRELnnl 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 --------AKLPVK-----WTAPEALRENKFSNKTDVWSFGVLLWEIYsygrvpYPRVPVEDVANHVENGYRMESPDGC- 446
Cdd:cd13996 169 nnnnngntSNNSVGigtplYASPEQLDGENYNEKADIYSLGIILFEML------HPFKTAMERSTILTDLRNGILPESFk 242
                       250       260
                ....*....|....*....|...
gi 18150824 447 --PDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd13996 243 akHPKEADLIQSLLSKNPEERPS 265
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
108-184 4.13e-24

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 95.60  E-value: 4.13e-24
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 108 PWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYD-GRVENYRVRRNEKG-LVTVDDDEYFDNLIKLVEHY 184
Cdd:cd00173   1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRSGdGKVKHYLIERNEGGyYLLGGSGRTFPSLPELVEHY 79
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
232-422 4.17e-24

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: 101.22  E-value: 4.17e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLA-EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14162   8 LGHGSYAVVKKAYSTkhKCKVAIKIVSKKKAPEDYLQKFLPrEIEVIKGLKHPNLICFYEAIETTSRVYIIMELAENGDL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGrAVITKQNQIDFaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKL----- 383
Cdd:cd14162  88 LDYIRKNG-ALPEPQARRWF-RQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFARGVMKTKDGKPKLsetyc 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18150824 384 -PVKWTAPEALR----ENKFSnktDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd14162 166 gSYAYASPEILRgipyDPFLS---DIWSMGVVLYTMV-YGRLPF 205
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
232-473 4.80e-24

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: 101.11  E-value: 4.80e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE----GKKVA------MKSMKDHLKdekaktQFLA-EASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd14080   8 IGEGSYSKVKLAEYTksglKEKVAckiidkKKAPKDFLE------KFLPrELEILRKLRHPNIIQVYSIFERGSKVFIFM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGrAVITKQNQIDFaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvKQEG 380
Cdd:cd14080  82 EYAEHGDLLEYIQKRG-ALSESQARIWF-RQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCP--DDDG 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKL------PVKWTAPEALRENKFSNKT-DVWSFGVLLWeIYSYGRVPY--------PRVPVEDVANHVENgYRMESPDg 445
Cdd:cd14080 158 DVLsktfcgSAAYAAPEILQGIPYDPKKyDIWSLGVILY-IMLCGSMPFddsnikkmLKDQQNRKVRFPSS-VKKLSPE- 234
                       250       260
                ....*....|....*....|....*...
gi 18150824 446 CPDQIYKIMmdcwEKDPSQRPNFTRIEK 473
Cdd:cd14080 235 CKDLIDQLL----EPDPTKRATIEEILN 258
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
230-465 8.12e-24

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


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 101.28  E-value: 8.12e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDekaktQFLAEASVMTT--LRHPNLVCLIGIS----LDDNPIYLIT-EF 302
Cdd:cd14054   1 QLIGQGRYGTVWKGSLDERPVAVKVFPARHRQ-----NFQNEKDIYELplMEHSNILRFIGADerptADGRMEYLLVlEY 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRsrgravitkQNQIDF------ARDVVKGMVYLES------QN---FVHRDLAARNVLIAEDNVAKVSDF 367
Cdd:cd14054  76 APKGSLCSYLR---------ENTLDWmsscrmALSLTRGLAYLHTdlrrgdQYkpaIAHRDLNSRNVLVKADGSCVICDF 146
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 368 GLA---KSSSNVK-----QEGAKL----PVKWTAPEA------LRENKFSNK-TDVWSFGVLLWEI-------YSYGRVP 421
Cdd:cd14054 147 GLAmvlRGSSLVRgrpgaAENASIsevgTLRYMAPEVlegavnLRDCESALKqVDVYALGLVLWEIamrcsdlYPGESVP 226
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18150824 422 YPRVPVE-DVANHV----------ENGYRMESPDG------CPDQIYKIMMDCWEKDPSQR 465
Cdd:cd14054 227 PYQMPYEaELGNHPtfedmqllvsREKARPKFPDAwkenslAVRSLKETIEDCWDQDAEAR 287
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
232-478 1.04e-23

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 100.26  E-value: 1.04e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY-EGKKVAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14664   1 IGRGGAGTVYKGVMpNGTLVAVKRLKGEGT-QGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGE 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRavitKQNQIDF------ARDVVKGMVYLE---SQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--------SS 373
Cdd:cd14664  80 LLHSRPE----SQPPLDWetrqriALGSARGLAYLHhdcSPLIIHRDVKSNNILLDEEFEAHVADFGLAKlmddkdshVM 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNVKQEgaklpVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPDGC-----PD 448
Cdd:cd14664 156 SSVAGS-----YGYIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFDEAFLDDGVDIVDWVRGLLEEKKVealvdPD 229
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 18150824 449 -----------QIYKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14664 230 lqgvykleeveQVFQVALLCTQSSPMERPTMREVVRMLEGD 270
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
222-473 1.87e-23

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 99.76  E-value: 1.87e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLG-DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd06641   2 PEELFTKLEKIGKGSFGEVFKGiDNRTQKVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSrgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQ 378
Cdd:cd06641  82 EYLGGGSALDLLEP---GPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGqlTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCW 458
Cdd:cd06641 159 N*FVGTPFWMAPEVIKQSAYDSKADIWSLGITAIEL-ARGEPPHSELHPMKVLFLIPKNNPPTLEGNYSKPLKEFVEACL 237
                       250
                ....*....|....*
gi 18150824 459 EKDPSQRPNFTRIEK 473
Cdd:cd06641 238 NKEPSFRPTAKELLK 252
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
231-479 2.43e-23

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


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 99.82  E-value: 2.43e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKVAMKSMKDhlKDEKAktqFLAEASVMTT--LRHPNLVCLIGISLDDN----PIYLITEFMA 304
Cdd:cd14143   2 SIGKGRFGEVWRGRWRGEDVAVKIFSS--REERS---WFREAEIYQTvmLRHENILGFIAADNKDNgtwtQLWLVSDYHE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLrsrGRAVITKQNQIDFARDVVKGMVYLESQ--------NFVHRDLAARNVLIAEDNVAKVSDFGLA---KSS 373
Cdd:cd14143  77 HGSLFDYL---NRYTVTVEGMIKLALSIASGLAHLHMEivgtqgkpAIAHRDLKSKNILVKKNGTCCIADLGLAvrhDSA 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 SNV------KQEGAKlpvKWTAPEALRE----NKFSN--KTDVWSFGVLLWEIY---SYGRVP-------YPRVP----V 427
Cdd:cd14143 154 TDTidiapnHRVGTK---RYMAPEVLDDtinmKHFESfkRADIYALGLVFWEIArrcSIGGIHedyqlpyYDLVPsdpsI 230
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 428 EDVANHV-ENGYRMESP-----DGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd14143 231 EEMRKVVcEQKLRPNIPnrwqsCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
107-201 2.47e-23

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 94.19  E-value: 2.47e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 107 MPWFHGRISREDAEKLL--TPPKNGRFLVRESQNYpGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHY 184
Cdd:cd10401   3 MPWFHGKISREESEQILliGSKTNGKFLIRERDNN-GSYALCLLHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLVEHY 81
                        90
                ....*....|....*..
gi 18150824 185 QKEADGLCTRLKAPVDK 201
Cdd:cd10401  82 SYKPDGLLRVLTEPCPR 98
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
243-478 3.03e-23

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 98.78  E-value: 3.03e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 243 GDYEGKKVAMKS-MKDHLKDEKAKTQflaEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRgRAVIT 321
Cdd:cd14045  26 GIYDGRTVAIKKiAKKSFTLSKRIRK---EVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLNE-DIPLN 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 322 KQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-----KSSSNVKQEGAKLPVKWTAPEALREN 396
Cdd:cd14045 102 WGFRFSFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTtyrkeDGSENASGYQQRLMQVYLPPENHSNT 181
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 397 KF--SNKTDVWSFGVLLWEIYSYGRvpyprvPVEDVANHVENGYRMESPD----------GCPDQIYKIMMDCWEKDPSQ 464
Cdd:cd14045 182 DTepTQATDVYSYAIILLEIATRND------PVPEDDYSLDEAWCPPLPElisgktenscPCPADYVELIRRCRKNNPAQ 255
                       250
                ....*....|....
gi 18150824 465 RPNFTRIEKALESV 478
Cdd:cd14045 256 RPTFEQIKKTLHKI 269
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
108-198 3.85e-23

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 93.42  E-value: 3.85e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-----SYDGRVENYRVRRnekglvtVDDDEY------- 173
Cdd:cd09933   4 EWFFGKIKRKDAEKLLLAPGNprGTFLIRESETTPGAYSLSVrdgddARGDTVKHYRIRK-------LDNGGYyittrat 76
                        90       100
                ....*....|....*....|....*
gi 18150824 174 FDNLIKLVEHYQKEADGLCTRLKAP 198
Cdd:cd09933  77 FPTLQELVQHYSKDADGLCCRLTVP 101
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
231-467 9.45e-23

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: 97.43  E-value: 9.45e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGdYE---GKKVAMKSMK-DHLKDEKAK--TQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd06625   7 LLGQGAFGQVYLC-YDadtGRELAVKQVEiDPINTEASKevKALECEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMP 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRG---RAVITKqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGA 381
Cdd:cd06625  86 GGSVKDEIKAYGaltENVTRK-----YTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQTICSSTG 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVK----WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY----PRVPVEDVANHVENgyrMESPDGCPDQIYKI 453
Cdd:cd06625 161 MKSVTgtpyWMSPEVINGEGYGRKADIWSVGCTVVEMLT-TKPPWaefePMAAIFKIATQPTN---PQLPPHVSEDARDF 236
                       250
                ....*....|....
gi 18150824 454 MMDCWEKDPSQRPN 467
Cdd:cd06625 237 LSLIFVRNKKQRPS 250
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
232-466 9.72e-23

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: 97.34  E-value: 9.72e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14116  13 LGKGKFGNVYLAREKQSKfiLALKVLfKAQLEKAGVEHQLRREVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTV 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVKWT 388
Cdd:cd14116  93 YRELQKLSK--FDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAPSSRRTTLCGTLDYL 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 389 APEALRENKFSNKTDVWSFGVLLWEiYSYGRVPYPRVPVEDV---ANHVENGYRMESPDGCPDQIYKIMmdcwEKDPSQR 465
Cdd:cd14116 171 PPEMIEGRMHDEKVDLWSLGVLCYE-FLVGKPPFEANTYQETykrISRVEFTFPDFVTEGARDLISRLL----KHNPSQR 245

                .
gi 18150824 466 P 466
Cdd:cd14116 246 P 246
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
232-412 1.25e-22

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: 97.07  E-value: 1.25e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSM-KDHLKDEKAKTQFLAEAsvMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14078  11 IGSGGFAKVKLATHilTGEKVAIKIMdKKALGDDLPRVKTEIEA--LKNLSHQHICRLYHVIETDNKIFMVLEYCPGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNVKQE-----GAk 382
Cdd:cd14078  89 FDYIVAKDR--LSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLcAKPKGGMDHHletccGS- 165
                       170       180       190
                ....*....|....*....|....*....|.
gi 18150824 383 lPVkWTAPEALRENKF-SNKTDVWSFGVLLW 412
Cdd:cd14078 166 -PA-YAAPELIQGKPYiGSEADVWSMGVLLY 194
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
229-481 1.88e-22

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: 96.64  E-value: 1.88e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEG--KKVAMKSMKDHLKDEKaKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14167   8 REVLGTGAFSEVVLAEEKRtqKLVAIKCIAKKALEGK-ETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVL---IAEDNVAKVSDFGLAK--SSSNVKQEGA 381
Cdd:cd14167  87 ELFDRIVEKG--FYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKieGSGSVMSTAC 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPvKWTAPEALRENKFSNKTDVWSFGVLLWeIYSYGrvpYPRVPVEDVANHVEN----GYRMESP--DGCPDQIYKIMM 455
Cdd:cd14167 165 GTP-GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCG---YPPFYDENDAKLFEQilkaEYEFDSPywDDISDSAKDFIQ 239
                       250       260
                ....*....|....*....|....*.
gi 18150824 456 DCWEKDPSQRpnFTrIEKALESVAVA 481
Cdd:cd14167 240 HLMEKDPEKR--FT-CEQALQHPWIA 262
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
245-471 1.89e-22

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 96.71  E-value: 1.89e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 245 YEGKKVAMKSM---KDHLKDEKAKTQFlaeaSVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRgravit 321
Cdd:cd14043  21 YEGDWVWLKKFpggSHTELRPSTKNVF----SKLRELRHENVNLFLGLFVDCGILAIVSEHCSRGSLEDLLRND------ 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 322 kQNQIDFA------RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKQEGAKLPVKWTAPEA 392
Cdd:cd14043  91 -DMKLDWMfkssllLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNeilEAQNLPLPEPAPEELLWTAPEL 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 393 LRE----NKFSNKTDVWSFGVLLWEIYSYGrVPY------PRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd14043 170 LRDprleRRGTFPGDVFSFAIIMQEVIVRG-APYcmlglsPEEIIEKVRSPPPLCRPSVSMDQAPLECIQLMKQCWSEAP 248

                ....*....
gi 18150824 463 SQRPNFTRI 471
Cdd:cd14043 249 ERRPTFDQI 257
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
232-422 2.45e-22

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: 96.36  E-value: 2.45e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMK------------SMKDHLKDEKAKTQFLA-EASVMTTLRHPNLVCLIGISLDDNPI 296
Cdd:cd14077   9 IGAGSMGKVKLAKhiRTGEKCAIKiiprasnaglkkEREKRLEKEISRDIRTIrEAALSSLLNHPHICRLRDFLRTPNHY 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 297 YLITEFMAKGSLIDYLRSRGRaVITKQNQiDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNV 376
Cdd:cd14077  89 YMLFEYVDGGQLLDYIISHGK-LKEKQAR-KFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGL----SNL 162
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 18150824 377 KQEGAKL-----PVKWTAPEALRENKFSN-KTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14077 163 YDPRRLLrtfcgSLYFAAPELLQAQPYTGpEVDVWSFGVVLYVLVC-GKVPF 213
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
232-478 2.70e-22

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 96.82  E-value: 2.70e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKD--HLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14159   1 IGEGGFGCVYQAVMRNTEYAVKRLKEdsELDWSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLPNGSLE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAV-ITKQNQIDFARDVVKGMVYL--ESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVK 386
Cdd:cd14159  81 DRLHCQVSCPcLSWSQRLHVLLGTARAIQYLhsDSPSLIHGDVKSSNILLDAALNPKLGDFGLARFSRRPKQPGMSSTLA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 WTA----------PEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY------PRVPVEDVANHVENGYRMESPDG----- 445
Cdd:cd14159 161 RTQtvrgtlaylpEEYVKTGTLSVEIDVYSFGVVLLELLT-GRRAMevdscsPTKYLKDLVKEEEEAQHTPTTMThsaea 239
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 446 ----CPDQIYKIMMD--------------------CWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14159 240 qaaqLATSICQKHLDpqagpcppelgieisqlacrCLHRRAKKRPPMTEVFQELERL 296
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
231-422 4.10e-22

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: 97.00  E-value: 4.10e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSMKDHL---KDEKAKTqfLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05595   2 LLGKGTFGKVILvrEKATGRYYAMKILRKEViiaKDEVAHT--VTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLrSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvkqEGAKLPV 385
Cdd:cd05595  80 GELFFHL-SRER-VFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGIT---DGATMKT 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 18150824 386 -----KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05595 155 fcgtpEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 195
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
231-414 4.65e-22

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 96.11  E-value: 4.65e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMK----------DHLKDEKaktqflaeaSVMTTLRHPNLVCLIGISLDDNPIYL 298
Cdd:cd05580   8 TLGTGSFGRVRLVKHKdsGKYYALKILKkakiiklkqvEHVLNEK---------RILSEVRHPFIVNLLGSFQDDRNLYM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsssnvk 377
Cdd:cd05580  79 VMEYVPGGELFSLLRRSGR---FPNDVAKFyAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAK------ 149
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18150824 378 qegaKLPVK-WT--------APEALReNKFSNKT-DVWSFGVLLWEI 414
Cdd:cd05580 150 ----RVKDRtYTlcgtpeylAPEIIL-SKGHGKAvDWWALGILIYEM 191
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
225-429 5.69e-22

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 95.11  E-value: 5.69e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVWLGD--YEGKKVAMKSM-KDHL----KDEKAKTQFLAEASVMTTL-RHPNLVCLIGISLDDNPI 296
Cdd:cd13993   1 RYQLISPIGEGAYGVVYLAVdlRTGRKYAIKCLyKSGPnskdGNDFQKLPQLREIDLHRRVsRHPNIITLHDVFETEVAI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 297 YLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAED-NVAKVSDFGLAkSSSN 375
Cdd:cd13993  81 YIVLEYCPNGDLFEAITENRIYVGKTELIKNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDeGTVKLCDFGLA-TTEK 159
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVKWTAPEALRENKFSNKT------DVWSFGVLLWEIySYGRVPYPRVPVED 429
Cdd:cd13993 160 ISMDFGVGSEFYMAPECFDEVGRSLKGypcaagDIWSLGIILLNL-TFGRNPWKIASESD 218
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
232-475 6.31e-22

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 94.97  E-value: 6.31e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG------DYEGKK--VAMKSMKDHLKDekAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIyLITEFM 303
Cdd:cd14208   7 LGKGSFTKIYRGlrtdeeDDERCEteVLLKVMDPTHGN--CQESFLEAASIMSQISHKHLVLLHGVCVGKDSI-MVQEFV 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRG-RAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA------KVSDFGLAKSSSNV 376
Cdd:cd14208  84 CHGALDLYLKKQQqKGPVAISWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLSREGDKgsppfiKLSDPGVSIKVLDE 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKLPvkWTAPEALRE-NKFSNKTDVWSFGVLLWEIYSYGRVPyprVPVEDVANHVE-NGYRMESPDGCPDQIYKIM 454
Cdd:cd14208 164 ELLAERIP--WVAPECLSDpQNLALEADKWGFGATLWEIFSGGHMP---LSALDPSKKLQfYNDRKQLPAPHWIELASLI 238
                       250       260
                ....*....|....*....|.
gi 18150824 455 MDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd14208 239 QQCMSYNPLLRPSFRAIIRDL 259
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
225-423 7.36e-22

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: 94.72  E-value: 7.36e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd06605   2 DLEYLGELGEGNGGVVSKVRHRpsGQIMAVKVIRLEIDEALQK-QILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQ-NFVHRDLAARNVLIAEDNVAKVSDFGLaksSSNVKQEGA 381
Cdd:cd06605  81 MDGGSLDKILKEVGR--IPERILGKIAVAVVKGLIYLHEKhKIIHRDVKPSNILVNSRGQVKLCDFGV---SGQLVDSLA 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 382 KLPV---KWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYP 423
Cdd:cd06605 156 KTFVgtrSYMAPERISGGKYTVKSDIWSLGLSLVEL-ATGRFPYP 199
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
232-410 9.32e-22

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: 9.32e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKdhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14006   1 LGRGRFGVVKRCIEKatGREFAAKFIP---KRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELL 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE--DNVAKVSDFGLAKsssNVKQEGAKLPVKW 387
Cdd:cd14006  78 DRLAERG--SLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADrpSPQIKIIDFGLAR---KLNPGEELKEIFG 152
                       170       180
                ....*....|....*....|....*..
gi 18150824 388 T----APEALRENKFSNKTDVWSFGVL 410
Cdd:cd14006 153 TpefvAPEIVNGEPVSLATDMWSIGVL 179
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
229-475 9.55e-22

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: 95.06  E-value: 9.55e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYE--GKKVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14166   8 MEVLGSGAFSEVYLVKQRstGKLYALKCIKK--SPLSRDSSLENEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSGG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVL-IAEDNVAK--VSDFGLAKSSSNVKQEGAKL 383
Cdd:cd14166  86 ELFDRILERG--VYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLyLTPDENSKimITDFGLSKMEQNGIMSTACG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PVKWTAPEALRENKFSNKTDVWSFGVLLWeIYSYGRVPYPRVPVEDVANHVENG-YRMESP--DGCPDQIYKIMMDCWEK 460
Cdd:cd14166 164 TPGYVAPEVLAQKPYSKAVDCWSIGVITY-ILLCGYPPFYEETESRLFEKIKEGyYEFESPfwDDISESAKDFIRHLLEK 242
                       250
                ....*....|....*
gi 18150824 461 DPSQRPNftrIEKAL 475
Cdd:cd14166 243 NPSKRYT---CEKAL 254
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
232-422 1.13e-21

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 94.21  E-value: 1.13e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL--GDYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd05572   1 LGVGGFGRVELvqLKSKGRTFALKCVkKRHIVQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGEL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavitkqnqidFARD--------VVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsssnVKQEG 380
Cdd:cd05572  81 WTILRDRGL----------FDEYtarfytacVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAK----KLGSG 146
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKlpvKWT--------APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05572 147 RK---TWTfcgtpeyvAPEIILNKGYDFSVDYWSLGILLYELLT-GRPPF 192
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
268-475 1.25e-21

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 94.59  E-value: 1.25e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 268 FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHR 347
Cdd:cd05076  62 FFETASLMSQVSHTHLVFVHGVCVRGSENIMVEEFVEHGPLDVWLR-KEKGHVPMAWKFVVARQLASALSYLENKNLVHG 140
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 348 DLAARNVLIAEDNVA-------KVSDFGLAKSSSNVKQEGAKLPvkWTAPEALRE-NKFSNKTDVWSFGVLLWEIYSYGR 419
Cdd:cd05076 141 NVCAKNILLARLGLEegtspfiKLSDPGVGLGVLSREERVERIP--WIAPECVPGgNSLSTAADKWGFGATLLEICFNGE 218
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824 420 VPYPRVPVEDVANHVENGYRMESPDgCPdQIYKIMMDCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05076 219 APLQSRTPSEKERFYQRQHRLPEPS-CP-ELATLISQCLTYEPTQRPSFRTILRDL 272
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
108-198 1.42e-21

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 89.10  E-value: 1.42e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQ 185
Cdd:cd10370   4 PWYFGKIKRIEAEKKLLLPENehGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQLDEGGFFIARRTTFRTLQELVEHYS 83
                        90
                ....*....|...
gi 18150824 186 KEADGLCTRLKAP 198
Cdd:cd10370  84 KDSDGLCVNLRKP 96
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
222-466 2.16e-21

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 93.97  E-value: 2.16e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLG-DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd06642   2 PEELFTKLERIGKGSFGEVYKGiDNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSrgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQ 378
Cdd:cd06642  82 EYLGGGSALDLLKP---GPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGqlTDTQIKR 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHVENgyrmESPDGCPDQIYKIMMD-- 456
Cdd:cd06642 159 NTFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIEL-AKGEPPNSDLHPMRVLFLIPK----NSPPTLEGQHSKPFKEfv 233
                       250
                ....*....|..
gi 18150824 457 --CWEKDPSQRP 466
Cdd:cd06642 234 eaCLNKDPRFRP 245
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
230-414 2.27e-21

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 93.64  E-value: 2.27e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVW---LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLR---HPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd14052   6 ELIGSGEFSQVYkvsERVPTGKVYAVKKLKPNYAGAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTELC 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRavitkQNQIDFAR------DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS---SS 374
Cdd:cd14052  86 ENGSLDVFLSELGL-----LGRLDEFRvwkilvELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVwplIR 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKlpvKWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd14052 161 GIEREGDR---EYIAPEILSEHMYDKPADIFSLGLILLEA 197
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
227-472 2.45e-21

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: 93.25  E-value: 2.45e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLiGKGEFGEVWLGD--YEGKKVAMKSMkDHLK-DEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd14074   7 LEETL-GRGHFAVVKLARhvFTGEKVAVKVI-DKTKlDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILELG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRAVITKQNQIDFaRDVVKGMVYLESQNFVHRDLAARNVLIAEDN-VAKVSDFGLakssSNVKQEGAK 382
Cdd:cd14074  85 DGGDMYDYIMKHENGLNEDLARKYF-RQIVSAISYCHKLHVVHRDLKPENVVFFEKQgLVKLTDFGF----SNKFQPGEK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 L-----PVKWTAPEALRENKF-SNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGyRMESPD----GCPDQIYK 452
Cdd:cd14074 160 LetscgSLAYSAPEILLGDEYdAPAVDIWSLGVILYMLVC-GQPPFQEANDSETLTMIMDC-KYTVPAhvspECKDLIRR 237
                       250       260
                ....*....|....*....|
gi 18150824 453 IMMdcweKDPSQRPNFTRIE 472
Cdd:cd14074 238 MLI----RDPKKRASLEEIE 253
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
242-471 2.62e-21

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 93.46  E-value: 2.62e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 242 LGDYEGK-KVAMKSMKDHLKDekAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLiDYLRSRGRAVI 320
Cdd:cd05077  30 GYSYEKEiKVILKVLDPSHRD--ISLAFFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPL-DLFMHRKSDVL 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 321 TKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV-------AKVSDFGLAKSSSNVKQEGAKLPvkWTAPEAL 393
Cdd:cd05077 107 TTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdgecgpfIKLSDPGIPITVLSRQECVERIP--WIAPECV 184
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 394 RENK-FSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDgCpDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd05077 185 EDSKnLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEKERFYEGQCMLVTPS-C-KELADLMTHCMNYDPNQRPFFRAI 261
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
231-479 2.63e-21

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: 93.55  E-value: 2.63e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG--DYEGKKVAMKSMkdHLKDEKAKTQFLAEASVMTTL-RHPNLVCLIGISLDDNP----IYLITEFm 303
Cdd:cd13985   7 QLGEGGFSYVYLAhdVNTGRRYALKRM--YFNDEEQLRVAIKEIEIMKRLcGHPNIVQYYDSAILSSEgrkeVLLLMEY- 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQN--FVHRDLAARNVLIAEDNVAKVSDFGLA---------KS 372
Cdd:cd13985  84 CPGSLVDILEKSPPSPLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFGSAttehyplerAE 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 SSNVKQEGAKlpvKWT-----APEALreNKFSN-----KTDVWSFGVLLWEIySYGRVPY-PRVPVEDVANHvengYRME 441
Cdd:cd13985 164 EVNIIEEEIQ---KNTtpmyrAPEMI--DLYSKkpigeKADIWALGCLLYKL-CFFKLPFdESSKLAIVAGK----YSIP 233
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18150824 442 SPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEKALESVA 479
Cdd:cd13985 234 EQPRYSPELHDLIRHMLTPDPAERPDIFQVINIITKDT 271
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
232-416 2.83e-21

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: 93.75  E-value: 2.83e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDHLK--DEKAKtqfLAEA-SVMTTLRHPNLVCLIGISLDDNPIYLITEFMaKG 306
Cdd:cd07830   7 LGDGTFGSVYLARNkeTGELVAIKKMKKKFYswEECMN---LREVkSLRKLNEHPNIVKLKEVFRENDELYFVFEYM-EG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKqNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPV 385
Cdd:cd07830  83 NLYQLMKDRKGKPFSE-SVIrSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSRPPYTDYVST 161
                       170       180       190
                ....*....|....*....|....*....|...
gi 18150824 386 KW-TAPEA-LRENKFSNKTDVWSFGVLLWEIYS 416
Cdd:cd07830 162 RWyRAPEIlLRSTSYSSPVDIWALGCIMAELYT 194
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
108-201 3.52e-21

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 88.27  E-value: 3.52e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPP-KNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDE-----YFDNLIKLV 181
Cdd:cd10343   4 PWYHGNITRSKAEELLSKAgKDGSFLVRDSESVSGAYALCVLYQNCVHTYRILPNAEDKLSVQASEgvpvrFFTTLPELI 83
                        90       100
                ....*....|....*....|
gi 18150824 182 EHYQKEADGLCTRLKAPVDK 201
Cdd:cd10343  84 EFYQKENMGLVTHLLYPVER 103
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
232-471 3.71e-21

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: 92.87  E-value: 3.71e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL-------GDYEGKKVAMKSMKDHLKDEKAktQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd08222   8 LGSGNFGTVYLvsdlkatADEELKVLKEISVGELQPDETV--DANREAKLLSKLDHPAIVKFHDSFVEKESFCIVTEYCE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRS-RGRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIaEDNVAKVSDFGLAK---SSSNVKQE 379
Cdd:cd08222  86 GGDLDDKISEyKKSGTTIDENQIlDWFIQLLLAVQYMHERRILHRDLKAKNIFL-KNNVIKVGDFGISRilmGTSDLATT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 380 GAKLPVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSYgrvpyprvpvedvaNHVENGYRMES-------------PDGC 446
Cdd:cd08222 165 FTGTPY-YMSPEVLKHEGYNSKSDIWSLGCILYEMCCL--------------KHAFDGQNLLSvmykivegetpslPDKY 229
                       250       260
                ....*....|....*....|....*
gi 18150824 447 PDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd08222 230 SKELNAIYSRMLNKDPALRPSAAEI 254
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
232-465 5.16e-21

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 92.32  E-value: 5.16e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY-EGKKV-AMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd05578   8 IGKGSFGKVCIVQKkDTKKMfAMKYMNKQKCIEKDSVRnVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDLLLGGDL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLrsrGRAVITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA--KSSSNVKQEGAKLPV 385
Cdd:cd05578  88 RYHL---QQKVKFSEETVKFyICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIAtkLTDGTLATSTSGTKP 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 kWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYP---RVPVEDVAnHVENGYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd05578 165 -YMAPEVFMRAGYSFAVDWWSLGVTAYEML-RGKRPYEihsRTSIEEIR-AKFETASVLYPAGWSEEAIDLINKLLERDP 241

                ...
gi 18150824 463 SQR 465
Cdd:cd05578 242 QKR 244
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
109-199 5.18e-21

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 87.72  E-value: 5.18e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTP-PKNGRFLVRESQNYPGDYTLCVsydgRVENYRVR----RNEKGLVTVDDDEYFDNLIKLVEH 183
Cdd:cd09931   2 WFHGHLSGKEAEKLLLEkGKPGSFLVRESQSKPGDFVLSV----RTDDDKVThimiRCQGGKYDVGGGEEFDSLTDLVEH 77
                        90       100
                ....*....|....*....|
gi 18150824 184 YQK----EADGLCTRLKAPV 199
Cdd:cd09931  78 YKKnpmvETSGTVVHLKQPL 97
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
232-471 5.78e-21

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: 92.33  E-value: 5.78e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMK-DHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG-- 306
Cdd:cd08224   8 IGKGQFSVVYRArcLLDGRLVALKKVQiFEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLELADAGdl 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 -SLIDYLRSRGRAVITKQNQIDFARdVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvKQEGAKLPV 385
Cdd:cd08224  88 sRLIKHFKKQKRLIPERTIWKYFVQ-LCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSS-KTTAAHSLV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 K---WTAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPY--PRVPVEDVANHVENG-YRMESPDGCPDQIYKIMMDCWE 459
Cdd:cd08224 166 GtpyYMSPERIREQGYDFKSDIWSLGCLLYEMAAL-QSPFygEKMNLYSLCKKIEKCeYPPLPADLYSQELRDLVAACIQ 244
                       250
                ....*....|..
gi 18150824 460 KDPSQRPNFTRI 471
Cdd:cd08224 245 PDPEKRPDISYV 256
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
230-422 7.46e-21

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: 92.50  E-value: 7.46e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYE--GKKVAMKSMK----------DHLKDEKaktqflaeaSVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd05612   7 KTIGTGTFGRVHLVRDRisEHYYALKVMAipevirlkqeQHVHNEK---------RVLKEVSHPFIIRLFWTEHDQRFLY 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK 377
Cdd:cd05612  78 MLMEYVPGGELFSYLRNSGR--FSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKLRDRT 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 378 QEGAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05612 156 WTLCGTP-EYLAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPF 198
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
222-466 9.69e-21

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 92.04  E-value: 9.69e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLG-DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd06640   2 PEELFTKLERIGKGSFGEVFKGiDNRTQQVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIM 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRsrgrAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVK 377
Cdd:cd06640  82 EYLGGGSALDLLR----AGPFDEFQIaTMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGqlTDTQIK 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHVENgYRMESPDGCPDQIYKIMMD- 456
Cdd:cd06640 158 RNTFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIEL-AKGEPPNSDMHPMRVLFLIPK-NNPPTLVGDFSKPFKEFIDa 235
                       250
                ....*....|
gi 18150824 457 CWEKDPSQRP 466
Cdd:cd06640 236 CLNKDPSFRP 245
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
228-408 1.10e-20

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: 91.77  E-value: 1.10e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLG-D-YEGKKVAMKSMK-DHLKDEKAKTQfLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd07829   3 KLEKLGEGTYGVVYKAkDkKTGEIVALKKIRlDNEEEGIPSTA-LREISLLKELKHPNIVKLLDVIHTENKLYLVFEYCD 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KgSLIDYLRSRGRAVitKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkqegakL 383
Cdd:cd07829  82 Q-DLKKYLDKRPGPL--PPNLIkSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFG--------I 150
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 18150824 384 PVK---------W-TAPEAL-RENKFSNKTDVWSFG 408
Cdd:cd07829 151 PLRtythevvtlWyRAPEILlGSKHYSTAVDIWSVG 186
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
230-466 1.15e-20

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: 91.29  E-value: 1.15e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTL-RHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd13997   6 EQIGSGSFSEVFkvRSKVDGCLYAVKKSKKPFRGPKERARALREVEAHAALgQHPNIVRYYSSWEEGGHLYIQMELCENG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKl 383
Cdd:cd13997  86 SLQDALEELSPISKLSEAEVwDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATrlETSGDVEEGDS- 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 pvKWTAPEALRENK-FSNKTDVWSFGVLLWEIYSYGRVPYPRvpveDVANHVENGYRMESP-DGCPDQIYKIMMDCWEKD 461
Cdd:cd13997 165 --RYLAPELLNENYtHLPKADIFSLGVTVYEAATGEPLPRNG----QQWQQLRQGKLPLPPgLVLSQELTRLLKVMLDPD 238

                ....*
gi 18150824 462 PSQRP 466
Cdd:cd13997 239 PTRRP 243
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
232-475 1.29e-20

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 91.16  E-value: 1.29e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW------LGDYEGKKVAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd05078   7 LGQGTFTKIFkgirreVGDYGQLHETEVLLKVLDKAHRNYSEsFFEAASMMSQLSHKHLVLNYGVCVCGDENILVQEYVK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI--AEDNVA------KVSDFGLakSSSNV 376
Cdd:cd05078  87 FGSLDTYLK-KNKNCINILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLirEEDRKTgnppfiKLSDPGI--SITVL 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKLPVKWTAPEALRENK-FSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDGCpdQIYKIMM 455
Cdd:cd05078 164 PKDILLERIPWVPPECIENPKnLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWT--ELANLIN 241
                       250       260
                ....*....|....*....|
gi 18150824 456 DCWEKDPSQRPNFTRIEKAL 475
Cdd:cd05078 242 NCMDYEPDHRPSFRAIIRDL 261
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
232-414 1.41e-20

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 92.41  E-value: 1.41e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFmAKGSL 308
Cdd:cd06633  29 IGHGSFGAVYFAtnSHTNEVVAIKKMSYSGKQTNEKWQdIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEY-CLGSA 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVitkqNQIDFA---RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVkQEGAKLPV 385
Cdd:cd06633 108 SDLLEVHKKPL----QEVEIAaitHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASPA-NSFVGTPY 182
                       170       180       190
                ....*....|....*....|....*....|..
gi 18150824 386 kWTAPE---ALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06633 183 -WMAPEvilAMDEGQYDGKVDIWSLGITCIEL 213
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
232-412 1.44e-20

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: 90.91  E-value: 1.44e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSM-KDHLKDEKAKTQFlAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14071   8 IGKGNFAVVKLARHRITKteVAIKIIdKSQLDEENLKKIY-REVQIMKMLNHPHIIKLYQVMETKDMLYLVTEYASNGEI 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGR----AVITKQNQIDFARDvvkgmvYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEGAKLP 384
Cdd:cd14071  87 FDYLAQHGRmsekEARKKFWQILSAVE------YCHKRHIVHRDLKAENLLLDANMNIKIADFGF----SNFFKPGELLK 156
                       170       180       190
                ....*....|....*....|....*....|....
gi 18150824 385 V-----KWTAPEALRENKFSN-KTDVWSFGVLLW 412
Cdd:cd14071 157 TwcgspPYAAPEVFEGKEYEGpQLDIWSLGVVLY 190
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
222-422 1.91e-20

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 90.76  E-value: 1.91e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLG--DYEGKKVAMKSMkdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06647   5 PKKKYTRFEKIGQGASGTVYTAidVATGQEVAIKQM--NLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDylrsrgraVITK----QNQID-FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS 374
Cdd:cd06647  83 MEYLAGGSLTD--------VVTEtcmdEGQIAaVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQIT 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 375 NVKQEGAKL---PVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd06647 155 PEQSKRSTMvgtPY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 203
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
232-422 2.11e-20

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: 91.12  E-value: 2.11e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYE-GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd05581   9 LGEGSYSTVVLAkEKEtGKEYAIKVLdKRHIIKEKKVKYVTIEKEVLSRLAHPGIVKLYYTFQDESKLYFVLEYAPNGDL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAvitkqNQID---FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-------SSSNVKQ 378
Cdd:cd05581  89 LEYIRKYGSL-----DEKCtrfYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKvlgpdssPESTKGD 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824 379 EGAKLPVKW--------TA----PEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd05581 164 ADSQIAYNQaraasfvgTAeyvsPELLNEKPAGKSSDLWALGCIIYQML-TGKPPF 218
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
230-464 2.17e-20

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 91.22  E-value: 2.17e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgS 307
Cdd:cd07833   7 GVVGEGAYGVVLKCRNKatGEIVAIKKFKESEDDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYVER-T 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYL-RSRGRAVITKQNQIDFarDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-----KSSSNVKQEGA 381
Cdd:cd07833  86 LLELLeASPGGLPPDAVRSYIW--QLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFAraltaRPASPLTDYVA 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 klpVKW-TAPEAL-RENKFSNKTDVWSFGVLLWEIYSyGRvpyPRVPVEdvaNHVengyrmespdgcpDQIYKIMMDCWE 459
Cdd:cd07833 164 ---TRWyRAPELLvGDTNYGKPVDVWAIGCIMAELLD-GE---PLFPGD---SDI-------------DQLYLIQKCLGP 220

                ....*
gi 18150824 460 KDPSQ 464
Cdd:cd07833 221 LPPSH 225
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
232-465 2.76e-20

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: 90.43  E-value: 2.76e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEG--KKVAMKSMkdhlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14010   8 IGRGKHSVVYKGRRKGtiEFVAIKCV-----DKSKRPEVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTGGDLE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--------------SSSN 375
Cdd:cd14010  83 TLLRQDGN--LPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARregeilkelfgqfsDEGN 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVK----WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP----VEDVANHVENGYRMESPDGCP 447
Cdd:cd14010 161 VNKVSKKQAKRgtpyYMAPELFQGGVHSFASDLWALGCVLYEMFT-GKPPFVAESftelVEKILNEDPPPPPPKVSSKPS 239
                       250
                ....*....|....*...
gi 18150824 448 DQIYKIMMDCWEKDPSQR 465
Cdd:cd14010 240 PDFKSLLKGLLEKDPAKR 257
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
224-467 2.90e-20

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: 90.47  E-value: 2.90e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 224 ASLLKKSLIGKGEFGEVWLGD--YEGKKVAMKSMKD-HLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd08228   2 ANFQIEKKIGRGQFSEVYRATclLDRKPVALKKVQIfEMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSL---IDYLRSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSN 375
Cdd:cd08228  82 ELADAGDLsqmIKYFKKQKR-LIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRffSSKT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPYprvpVEDVANHVENGYRMESPDGCP-------D 448
Cdd:cd08228 161 TAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPF----YGDKMNLFSLCQKIEQCDYPPlptehysE 235
                       250
                ....*....|....*....
gi 18150824 449 QIYKIMMDCWEKDPSQRPN 467
Cdd:cd08228 236 KLRELVSMCIYPDPDQRPD 254
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
222-426 4.83e-20

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: 89.42  E-value: 4.83e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLG-DYE-GKKVAMKSMkDHLKDEKAKTQFlAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06648   5 PRSDLDNFVKIGEGSTGIVCIAtDKStGRQVAVKKM-DLRKQQRRELLF-NEVVIMRDYQHPNIVEMYSSYLVGDELWVV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLrSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNVKQ 378
Cdd:cd06648  83 MEFLEGGALTDIV-THTR--MNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFcAQVSKEVPR 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 18150824 379 EGAKLPVK-WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP 426
Cdd:cd06648 160 RKSLVGTPyWMAPEVISRLPYGTEVDIWSLGIMVIEMVD-GEPPYFNEP 207
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
232-477 4.93e-20

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: 89.67  E-value: 4.93e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD----YEGKKVAMK---SMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNP-IYLITEFM 303
Cdd:cd13994   1 IGKGATSVVRIVTkknpRSGVLYAVKeyrRRDDESKRKDYVKRLTSEYIISSKLHHPNIVKVLDLCQDLHGkWCLVMEYC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGlakSSSNVKQEGAKL 383
Cdd:cd13994  81 PGGDLFTLIEKADS--LSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFG---TAEVFGMPAEKE 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 -PVK--------WTAPEALRENKFSNK-TDVWSFGVLLWEIYSyGRVPYpRVPV-EDVA-----------NHVENGYRME 441
Cdd:cd13994 156 sPMSaglcgsepYMAPEVFTSGSYDGRaVDVWSCGIVLFALFT-GRFPW-RSAKkSDSAykayeksgdftNGPYEPIENL 233
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 18150824 442 SPDGCPDQIYKIMMdcweKDPSQRPnftRIEKALES 477
Cdd:cd13994 234 LPSECRRLIYRMLH----PDPEKRI---TIDEALND 262
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
228-426 6.18e-20

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: 89.46  E-value: 6.18e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDY--EGKKVAMKSMK-DHLKDEKAKTQflAEASVMTTLRH---PNLVCLIGISLDDNPIYLITE 301
Cdd:cd06917   5 RLELVGRGSYGAVYRGYHvkTGRVVALKVLNlDTDDDDVSDIQ--KEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRS-----RGRAVITkqnqidfaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSS 373
Cdd:cd06917  83 YCEGGSIRTLMRAgpiaeRYIAVIM--------REVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAaslNQN 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 18150824 374 SNVKQEGAKLPVkWTAPEALRENKFSN-KTDVWSFGVLLWEIySYGRVPYPRVP 426
Cdd:cd06917 155 SSKRSTFVGTPY-WMAPEVITEGKYYDtKADIWSLGITTYEM-ATGNPPYSDVD 206
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
228-471 6.43e-20

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: 89.02  E-value: 6.43e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDY--EGKKVAMK--SMKDHLKDEKakTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd08220   4 KIRVVGRGAYGTVYLCRRkdDNKLVIIKqiPVEQMTKEER--QAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI-AEDNVAKVSDFGLAKS-SSNVKQEGA 381
Cdd:cd08220  82 PGGTLFEYIQQRKGSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLnKKRTVVKIGDFGISKIlSSKSKAYTV 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRvpyprvpVEDVAN------HVENGYRMESPDGCPDQIYKIMM 455
Cdd:cd08220 162 VGTPCYISPELCEGKPYNQKSDIWALGCVLYELASLKR-------AFEAANlpalvlKIMRGTFAPISDRYSEELRHLIL 234
                       250
                ....*....|....*.
gi 18150824 456 DCWEKDPSQRPNFTRI 471
Cdd:cd08220 235 SMLHLDPNKRPTLSEI 250
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
225-467 6.69e-20

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: 89.11  E-value: 6.69e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVWLGDY--EGKKVAMKSM--KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd14070   3 SYLIGRKLGEGSFAKVREGLHavTGEKVAIKVIdkKKAKKDSYVTKNLRREGRIQQMIRHPNITQLLDILETENSYYLVM 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLaksSSNVKQEG 380
Cdd:cd14070  83 ELCPGGNLMHRIYDKKR--LEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGL---SNCAGILG 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPV-------KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVE--NGYRMESPDGCPDQIY 451
Cdd:cd14070 158 YSDPFstqcgspAYAAPELLARKKYGPKVDVWSIGVNMYAMLT-GTLPFTVEPFSLRALHQKmvDKEMNPLPTDLSPGAI 236
                       250
                ....*....|....*.
gi 18150824 452 KIMMDCWEKDPSQRPN 467
Cdd:cd14070 237 SFLRSLLEPDPLKRPN 252
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
230-422 7.57e-20

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: 90.81  E-value: 7.57e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWL--GDYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05573   7 KVIGRGAFGEVWLvrDKDTGQVYAMKILrKSDMLKREQIAHVRAERDILADADSPWIVRLHYAFQDEDHLYLVMEYMPGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGraVITKqnqiDFARDVVKGMV----YLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----------- 371
Cdd:cd05573  87 DLMNLLIKYD--VFPE----ETARFYIAELVlaldSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCTkmnksgdresy 160
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18150824 372 --------SSSNVKQEGAKLPVK------------WTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd05573 161 lndsvntlFQDNVLARRRPHKQRrvraysavgtpdYIAPEVLRGTGYGPECDWWSLGVILYEML-YGFPPF 230
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
232-466 7.92e-20

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 89.25  E-value: 7.92e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV-WLGDYEGKKVAMK----------------SMKDHLKDEKAK---TQFLAEASVMTTLRHPNLVCLIGISL 291
Cdd:cd14067   1 LGQGGSGTViYRARYQGQPVAVKrfhikkckkrtdgsadTMLKHLRAADAMknfSEFRQEASMLHSLQHPCIVYLIGISI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 292 ddNPIYLITEFMAKGSLIDYL--RSRGRAVITKQNQIDF--ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV-----A 362
Cdd:cd14067  81 --HPLCFALELAPLGSLNTVLeeNHKGSSFMPLGHMLTFkiAYQIAAGLAYLHKKNIIFCDLKSDNILVWSLDVqehinI 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 363 KVSDFGLAKSSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYR--M 440
Cdd:cd14067 159 KLSDYGISRQSFHEGALGVEGTPGYQAPEIRPRIVYDEKVDMFSYGMVLYELLS-GQRPSLGHHQLQIAKKLSKGIRpvL 237
                       250       260
                ....*....|....*....|....*....
gi 18150824 441 ESPDGCpdQIYK---IMMDCWEKDPSQRP 466
Cdd:cd14067 238 GQPEEV--QFFRlqaLMMECWDTKPEKRP 264
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
230-411 8.67e-20

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: 88.99  E-value: 8.67e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGdYEG---KKVAMKSMKDHL-----KDEKAKT-QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd14084  12 RTLGSGACGEVKLA-YDKstcKKVAIKIINKRKftigsRREINKPrNIETEIEILKKLSHPCIIKIEDFFDAEDDYYIVL 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRS--RGRAVITKQnqidFARDVVKGMVYLESQNFVHRDLAARNVLI---AEDNVAKVSDFGLAKSSSN 375
Cdd:cd14084  91 ELMEGGELFDRVVSnkRLKEAICKL----YFYQMLLAVKYLHSNGIIHRDLKPENVLLssqEEECLIKITDFGLSKILGE 166
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 376 VK-QEGAKLPVKWTAPEALR---ENKFSNKTDVWSFGVLL 411
Cdd:cd14084 167 TSlMKTLCGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVIL 206
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
232-476 8.81e-20

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: 88.60  E-value: 8.81e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDH-------LKDEKAKTQFLaEASVMTTLR---HPNLVCLIGISLDDNPIYLI 299
Cdd:cd14004   8 MGEGAYGQVNLAIYksKGKEVVIKFIFKErilvdtwVRDRKLGTVPL-EIHILDTLNkrsHPNIVKLLDFFEDDEFYYLV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKG-SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQ 378
Cdd:cd14004  87 MEKHGSGmDLFDFIERKPN--MDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAYIKSGPF 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNK-TDVWSFGVLLWEIYsYGRVPYprVPVEDVANHVENGYRMESPDgCPDQIYKIMmdc 457
Cdd:cd14004 165 DTFVGTIDYAAPEVLRGNPYGGKeQDIWALGVLLYTLV-FKENPF--YNIEEILEADLRIPYAVSED-LIDLISRML--- 237
                       250
                ....*....|....*....
gi 18150824 458 wEKDPSQRPNftrIEKALE 476
Cdd:cd14004 238 -NRDVGDRPT---IEELLT 252
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
232-412 8.86e-20

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: 88.55  E-value: 8.86e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSM-KDHLkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14075  10 LGSGNFSQVKLGihQLTKEKVAIKILdKTKL-DQKTQRLLSREISSMEKLHHPNIIRLYEVVETLSKLHLVMEYASGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRaVITKQNQIDFARdVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEGAKL----- 383
Cdd:cd14075  89 YTKISTEGK-LSESEAKPLFAQ-IVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGF----STHAKRGETLntfcg 162
                       170       180       190
                ....*....|....*....|....*....|..
gi 18150824 384 --PvkWTAPEALR-ENKFSNKTDVWSFGVLLW 412
Cdd:cd14075 163 spP--YAAPELFKdEHYIGIYVDIWALGVLLY 192
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
107-198 9.08e-20

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 84.37  E-value: 9.08e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 107 MPWFHGRISREDAEKLL--TPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHY 184
Cdd:cd09938   1 LPFFYGSITREEAEEYLklAGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELCEYH 80
                        90
                ....*....|....
gi 18150824 185 QKEADGLCTRLKAP 198
Cdd:cd09938  81 STDLDGLVCLLRKP 94
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
230-471 1.08e-19

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: 88.38  E-value: 1.08e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14186   7 NLLGKGSFACVYRARslHTGLEVAIKMIDKKAMQKAGMVQrVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAkssSNVKQEGAK---- 382
Cdd:cd14186  87 EMSRYLKNRKKP-FTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLA---TQLKMPHEKhftm 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 --LPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENG-YRMesPDGCPDQIYKIMMDCWE 459
Cdd:cd14186 163 cgTP-NYISPEIATRSAHGLESDVWSLGCMFYTLLV-GRPPFDTDTVKNTLNKVVLAdYEM--PAFLSREAQDLIHQLLR 238
                       250
                ....*....|..
gi 18150824 460 KDPSQRPNFTRI 471
Cdd:cd14186 239 KNPADRLSLSSV 250
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
228-422 1.11e-19

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: 88.53  E-value: 1.11e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDYEGK---KVAMKSMKdhlKDEKAKTQFL--AEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd14202   6 RKDLIGHGAFAVVFKGRHKEKhdlEVAVKCIN---KKNLAKSQTLlgKEIKILKELKHENIVALYDFQEIANSVYLVMEY 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA--------EDNV-AKVSDFGLAKSS 373
Cdd:cd14202  83 CNGGDLADYLHTMR--TLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnPNNIrIKIADFGFARYL 160
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 18150824 374 SNvKQEGAKL---PVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14202 161 QN-NMMAATLcgsPM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPF 209
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
108-198 1.20e-19

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 83.77  E-value: 1.20e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQ 185
Cdd:cd10369   4 PWFFGAIKRADAEKQLLYSENqtGAFLIRESESQKGEFSLSVLDGGVVKHYRIRRLDEGGFFLTRRKTFSTLNEFVNYYT 83
                        90
                ....*....|...
gi 18150824 186 KEADGLCTRLKAP 198
Cdd:cd10369  84 TTSDGLCVKLGKP 96
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
228-422 1.30e-19

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: 88.53  E-value: 1.30e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDYEGK---KVAMKSMKdhlKDEKAKTQFL--AEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd14201  10 RKDLVGHGAFAVVFKGRHRKKtdwEVAIKSIN---KKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVMEY 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA-----EDNVA----KVSDFGLAKS- 372
Cdd:cd14201  87 CNGGDLADYLQAKG--TLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSyasrkKSSVSgiriKIADFGFARYl 164
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 SSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd14201 165 QSNMMAATLCGSPMYMAPEVIMSQHYDAKADLWSIGTVIYQCL-VGKPPF 213
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
232-414 1.41e-19

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 89.49  E-value: 1.41e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  232 IGKGEFGEVWLGDYE--GKKVAMKSMKDH--LKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:PTZ00263  26 LGTGSFGRVRIAKHKgtGEYYAIKCLKKReiLK-MKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVGGE 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  308 LIDYLRSRGRavitkqnqidFARDVVK--------GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:PTZ00263 105 LFTHLRKAGR----------FPNDVAKfyhaelvlAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPDRTFT 174
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 18150824  380 GAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:PTZ00263 175 LCGTP-EYLAPEVIQSKGHGKAVDWWTMGVLLYEF 208
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
232-414 1.63e-19

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 88.55  E-value: 1.63e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDY 311
Cdd:cd06643  13 LGDGAFGKVYKAQNKETGILAAAKVIDTKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGAVDAV 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 312 LRSRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNVKQEGAKLPVK-WTA 389
Cdd:cd06643  93 MLELERPLTEPQIRV-VCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVsAKNTRTLQRRDSFIGTPyWMA 171
                       170       180       190
                ....*....|....*....|....*....|
gi 18150824 390 PEAL-----RENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06643 172 PEVVmcetsKDRPYDYKADVWSLGVTLIEM 201
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
231-465 1.79e-19

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 89.23  E-value: 1.79e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK--VAMKSMKDH--LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05620   2 VLGKGSFGKVLLAELKGKGeyFAVKALKKDvvLIDDDVECTMVEKRVLALAWENPFLTHLYCTFQTKEHLFFVMEFLNGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKQNQidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSS---SNVKQEGAKL 383
Cdd:cd05620  82 DLMFHIQDKGRFDLYRATF--YAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENvfgDNRASTFCGT 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYPrvpvEDVANHVENGYRMESPDgCPDQIYK----IMMDCWE 459
Cdd:cd05620 160 P-DYIAPEILQGLKYTFSVDWWSFGVLLYEML-IGQSPFH----GDDEDELFESIRVDTPH-YPRWITKeskdILEKLFE 232

                ....*.
gi 18150824 460 KDPSQR 465
Cdd:cd05620 233 RDPTRR 238
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
232-465 2.07e-19

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: 88.00  E-value: 2.07e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14117  14 LGKGKFGNVYLAREKQSKfiVALKVLfKSQIEKEGVEHQLRREIEIQSHLRHPNILRLYNYFHDRKRIYLILEYAPRGEL 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVKWT 388
Cdd:cd14117  94 YKELQKHGR--FDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWSVHAPSLRRRTMCGTLDYL 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 389 APEALRENKFSNKTDVWSFGVLLWEIYsygrVPYPrvPVEDvANHVENGYRMES---------PDGCPDQIYKIMmdcwE 459
Cdd:cd14117 172 PPEMIEGRTHDEKVDLWCIGVLCYELL----VGMP--PFES-ASHTETYRRIVKvdlkfppflSDGSRDLISKLL----R 240

                ....*.
gi 18150824 460 KDPSQR 465
Cdd:cd14117 241 YHPSER 246
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
223-473 2.19e-19

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 87.71  E-value: 2.19e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 223 KASLLKKslIGKGEFGEVWL--GDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLIT 300
Cdd:cd08225   1 RYEIIKK--IGEGSFGKIYLakAKSDSEHCVIKEIDLTKMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENGRLFIVM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLrSRGRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN-VAKVSDFGLAKS---SSN 375
Cdd:cd08225  79 EYCDGGDLMKRI-NRQRGVLFSEDQIlSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGmVAKLGDFGIARQlndSME 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 376 VKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMM 455
Cdd:cd08225 158 LAYTCVGTPY-YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSLIS 235
                       250
                ....*....|....*...
gi 18150824 456 DCWEKDPSQRPNFTRIEK 473
Cdd:cd08225 236 QLFKVSPRDRPSITSILK 253
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
105-198 2.51e-19

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 83.00  E-value: 2.51e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYDGR----VENYRVRRNEKGLVTVDDDEYFDNL 177
Cdd:cd10362   1 EPEPWFFKNLSRNDAERQLLAPGNthGSFLIRESETTAGSFSLSVrDFDQNqgevVKHYKIRNLDNGGFYISPRITFPGL 80
                        90       100
                ....*....|....*....|.
gi 18150824 178 IKLVEHYQKEADGLCTRLKAP 198
Cdd:cd10362  81 HELVRHYTNASDGLCTRLSRP 101
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
230-466 2.74e-19

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 86.98  E-value: 2.74e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVW----LGDyeGKKVAMKSMKDHLKDEKAKTQFLAEA-SVMTTLRHPNLVCLIGISLDDNPIYLITEfMA 304
Cdd:cd14050   7 SKLGEGSFGEVFkvrsRED--GKLYAVKRSRSRFRGEKDRKRKLEEVeRHEKLGEHPNCVRFIKAWEEKGILYIQTE-LC 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRGRaviTKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL----AKSSSNVKQE 379
Cdd:cd14050  84 DTSLQQYCEETHS---LPESEVwNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLvvelDKEDIHDAQE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 380 GAKlpvKWTAPEALReNKFSNKTDVWSFGVLLWEIYSygrvpYPRVPVEDVANH-VENGY-RMESPDGCPDQ---IYKIM 454
Cdd:cd14050 161 GDP---RYMAPELLQ-GSFTKAADIFSLGITILELAC-----NLELPSGGDGWHqLRQGYlPEEFTAGLSPElrsIIKLM 231
                       250
                ....*....|..
gi 18150824 455 MDcweKDPSQRP 466
Cdd:cd14050 232 MD---PDPERRP 240
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
232-412 2.75e-19

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: 87.32  E-value: 2.75e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14079  10 LGVGSFGKVKLAEHEltGHKVAVKILnRQKIKSLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVMEYVSGGEL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLakssSNVKQEGAKL----- 383
Cdd:cd14079  90 FDYIVQKGR--LSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGL----SNIMRDGEFLktscg 163
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 18150824 384 -PvKWTAPEALrenkfSNK------TDVWSFGVLLW 412
Cdd:cd14079 164 sP-NYAAPEVI-----SGKlyagpeVDVWSCGVILY 193
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
232-414 3.27e-19

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 87.86  E-value: 3.27e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSLI 309
Cdd:cd07861   8 IGEGTYGVVYKGRNKktGQIVAMKKIRLESEEEGVPSTAIREISLLKELQHPNIVCLEDVLMQENRLYLVFEFLSM-DLK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSrgravITKQNQID------FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkqegakL 383
Cdd:cd07861  87 KYLDS-----LPKGKYMDaelvksYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFG--------I 153
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 18150824 384 PVK----------WTAPEALR-ENKFSNKTDVWSFGVLLWEI 414
Cdd:cd07861 154 PVRvythevvtlwYRAPEVLLgSPRYSTPVDIWSIGTIFAEM 195
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
107-184 3.47e-19

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 81.66  E-value: 3.47e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 107 MPWFHGRISREDAEKLLTP--PKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEY-FDNLIKLVEH 183
Cdd:cd10347   1 LRWYHGKISREVAEALLLRegGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRHGEDAFFSDDGPLiFHGLDTLIEH 80

                .
gi 18150824 184 Y 184
Cdd:cd10347  81 Y 81
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
231-471 3.72e-19

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 87.16  E-value: 3.72e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK--VAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDdnPIYLITEFMAKGSL 308
Cdd:cd14025   3 KVGSGGFGQVYKVRHKHWKtwLAIKCPPSLHVDDSERMELLEEAKKMEMAKFRHILPVYGICSE--PVGLVMEYMETGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRS-------RGRAVitkqnqidfaRDVVKGMVYLESQN--FVHRDLAARNVLIAEDNVAKVSDFGLAK-----SSS 374
Cdd:cd14025  81 EKLLASeplpwelRFRII----------HETAVGMNFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKwnglsHSH 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKLPVKWTAPEALRENK--FSNKTDVWSFGVLLWEIYSygrvpyPRVPVEDVAN------HVENGYRME----- 441
Cdd:cd14025 151 DLSRDGLRGTIAYLPPERFKEKNrcPDTKHDVYSFAIVIWGILT------QKKPFAGENNilhimvKVVKGHRPSlspip 224
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 442 --SPDGCpDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd14025 225 rqRPSEC-QQMICLMKRCWDQDPRKRPTFQDI 255
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
228-422 4.55e-19

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: 87.63  E-value: 4.55e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDYE--GKKVAMKSMK-DHLKDEKAKTQFLA--EASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd07841   4 KGKKLGEGTYAVVYKARDKetGRIVAIKKIKlGERKEAKDGINFTAlrEIKLLQELKHPNIIGLLDVFGHKSNINLVFEF 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAkGSLidylrsrgRAVItKQNQIDFARDVVK--------GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-- 372
Cdd:cd07841  84 ME-TDL--------EKVI-KDKSIVLTPADIKsymlmtlrGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSfg 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 18150824 373 SSNVKQeGAKLPVKW-TAPEAL-RENKFSNKTDVWSFGVLLWEIYSygRVPY 422
Cdd:cd07841 154 SPNRKM-THQVVTRWyRAPELLfGARHYGVGVDMWSVGCIFAELLL--RVPF 202
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
271-465 5.98e-19

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: 86.64  E-value: 5.98e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGIsLDD---NPIYLITEFMAKGSLIDylrsrgraVIT------KQNQIDFaRDVVKGMVYLES 341
Cdd:cd14118  64 EIAILKKLDHPNVVKLVEV-LDDpneDNLYMVFELVDKGAVME--------VPTdnplseETARSYF-RDIVLGIEYLHY 133
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 342 QNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLPVKWTAPEALRE--NKFSNK-TDVWSFGVLLWeIYS 416
Cdd:cd14118 134 QKIIHRDIKPSNLLLGDDGHVKIADFGVSNefEGDDALLSSTAGTPAFMAPEALSEsrKKFSGKaLDIWAMGVTLY-CFV 212
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 417 YGRVPYPRVPVEDVANHVENGyRMESPDGC------PDQIYKIMmdcwEKDPSQR 465
Cdd:cd14118 213 FGRCPFEDDHILGLHEKIKTD-PVVFPDDPvvseqlKDLILRML----DKNPSER 262
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
232-471 6.92e-19

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 87.01  E-value: 6.92e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKD-HLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd08229  32 IGRGQFSEVYRATCllDGVPVALKKVQIfDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAGDL 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLR--SRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLP 384
Cdd:cd08229 112 SRMIKhfKKQKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRffSSKTTAAHSLVGT 191
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPY-PRVPVEDVANHVEN-GYRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd08229 192 PYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYgDKMNLYSLCKKIEQcDYPPLPSDHYSEELRQLVNMCINPDP 271

                ....*....
gi 18150824 463 SQRPNFTRI 471
Cdd:cd08229 272 EKRPDITYV 280
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
231-422 7.79e-19

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 87.83  E-value: 7.79e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSMKDHL---KDEKAKTqfLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05593  22 LLGKGTFGKVILvrEKASGKYYAMKILKKEViiaKDEVAHT--LTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNG 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLrSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEGAK 382
Cdd:cd05593 100 GELFFHL-SRER-VFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKegiTDAATMKTFCG 177
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 383 LPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05593 178 TP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 215
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
232-473 9.44e-19

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: 86.17  E-value: 9.44e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGE-VWLGDYEGKKVAMKSM-KDHLKdekaktqfLAEASVmTTLR----HPNLVCLIGISLDDNPIYLITEFMAk 305
Cdd:cd13982   9 LGYGSEGTiVFRGTFDGRPVAVKRLlPEFFD--------FADREV-QLLResdeHPNVIRYFCTEKDRQFLYIALELCA- 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRAVITKQNQID---FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV-----AKVSDFGLAKS----- 372
Cdd:cd13982  79 ASLQDLVESPRESKLFLRPGLEpvrLLRQIASGLAHLHSLNIVHRDLKPQNILISTPNAhgnvrAMISDFGLCKKldvgr 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 SSNVKQEGAKLPVKWTAPEALRENKFSNKT---DVWSFGVLLWEIYSYGRVPYPRvPVEDVANHVENGYRMESPDG---C 446
Cdd:cd13982 159 SSFSRRSGVAGTSGWIAPEMLSGSTKRRQTravDIFSLGCVFYYVLSGGSHPFGD-KLEREANILKGKYSLDKLLSlgeH 237
                       250       260
                ....*....|....*....|....*..
gi 18150824 447 PDQIYKIMMDCWEKDPSQRPNFTRIEK 473
Cdd:cd13982 238 GPEAQDLIERMIDFDPEKRPSAEEVLN 264
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
231-411 9.76e-19

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: 85.85  E-value: 9.76e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG--DYEGKKVAMK--SMKDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14069   8 TLGEGAFGEVFLAvnRNTEEAVAVKfvDMKRAPGDCPENIK--KEVCIQKMLSHKNVVRFYGHRREGEFQYLFLEYASGG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYlrsrgravITKQNQID------FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-------KSS 373
Cdd:cd14069  86 ELFDK--------IEPDVGMPedvaqfYFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLAtvfrykgKER 157
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 374 SNVKQEGAkLPvkWTAPEALRENKF-SNKTDVWSFGVLL 411
Cdd:cd14069 158 LLNKMCGT-LP--YVAPELLAKKKYrAEPVDVWSCGIVL 193
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
232-414 1.07e-18

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 86.23  E-value: 1.07e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYE-GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLR-HPNLVCLIGISLDDNPIYLITEFMAkGSL 308
Cdd:cd07832   8 IGEGAHGIVFKAkDREtGETVALKKVALRKLEGGIPNQALREIKALQACQgHPYVVKLRDVFPHGTGFVLVFEYML-SSL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQiDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvkqEGAKLP---- 384
Cdd:cd07832  87 SEVLRDEERPLTEAQVK-RYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSE---EDPRLYshqv 162
                       170       180       190
                ....*....|....*....|....*....|...
gi 18150824 385 -VKW-TAPEALR-ENKFSNKTDVWSFGVLLWEI 414
Cdd:cd07832 163 aTRWyRAPELLYgSRKYDEGVDLWAVGCIFAEL 195
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
232-472 1.12e-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: 1.12e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd05579   1 ISRGAYGRVYLAkkKSTGDLYAIKVIkKRDMIRKNQVDSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGR------AVITKQnqidfardVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAK 382
Cdd:cd05579  81 YSLLENVGAldedvaRIYIAE--------IVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVGLVRRQIKLS 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVK-----------------WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGyRMESPDG 445
Cdd:cd05579 153 IQKKsngapekedrrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLV-GIPPFHAETPEEIFQNILNG-KIEWPED 230
                       250       260       270
                ....*....|....*....|....*....|...
gi 18150824 446 ------CPDQIYKIMmdcwEKDPSQRPNFTRIE 472
Cdd:cd05579 231 pevsdeAKDLISKLL----TPDPEKRLGAKGIE 259
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
278-411 1.18e-18

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 85.49  E-value: 1.18e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 278 LRHPNLVCLIGISLDDNP------IYLITEFMAKGSLIDYLrSRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAA 351
Cdd:cd14012  55 LRHPNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELL-DSVGSVPLDTARR-WTLQLLEALEYLHRNGVVHKSLHA 132
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 352 RNVLI---AEDNVAKVSDFGLAKSSSNVKQEGAKLPVK---WTAPEALRENK-FSNKTDVWSFGVLL 411
Cdd:cd14012 133 GNVLLdrdAGTGIVKLTDYSLGKTLLDMCSRGSLDEFKqtyWLPPELAQGSKsPTRKTDVWDLGLLF 199
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
108-210 1.22e-18

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 80.78  E-value: 1.22e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPPKN-GRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKG---LVTVDddeyFDNLIKLVEH 183
Cdd:cd09941   4 PWFHGKISRAEAEEILMNQRPdGAFLIRESESSPGDFSLSVKFGNDVQHFKVLRDGAGkyfLWVVK----FNSLNELVDY 79
                        90       100
                ....*....|....*....|....*..
gi 18150824 184 YQkeadglctrlKAPVDKEgQHLFVVD 210
Cdd:cd09941  80 HR----------TTSVSRN-QQIFLRD 95
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
222-478 1.29e-18

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 86.31  E-value: 1.29e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVW--LGDYEGKKVAMKSMkdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06656  17 PKKKYTRFEKIGQGASGTVYtaIDIATGQEVAIKQM--NLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSrgraVITKQNQID-FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQ 378
Cdd:cd06656  95 MEYLAGGSLTDVVTE----TCMDEGQIAaVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKL--PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-PRVPVEDVANHVENGY-RMESPDGCPDQIYKIM 454
Cdd:cd06656 171 KRSTMvgTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPYlNENPLRALYLIATNGTpELQNPERLSAVFRDFL 249
                       250       260       270
                ....*....|....*....|....*....|..
gi 18150824 455 MDCWEKDPSQRPN--------FTRIEKALESV 478
Cdd:cd06656 250 NRCLEMDVDRRGSakellqhpFLKLAKPLSSL 281
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
230-473 1.58e-18

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: 85.23  E-value: 1.58e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLG-------DYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd14076   7 RTLGEGEFGKVKLGwplpkanHRSGVQVAIKLIrRDTQQENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIGIVLE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRSRgRAVITKQNQIDFARdVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSSNVK 377
Cdd:cd14076  87 FVSGGELFDYILAR-RRLKDSVACRLFAQ-LISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANtfdhFNGDLM 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKLPVkWTAPEALRENKF--SNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYR--MESPDGCPDQIYKI 453
Cdd:cd14076 165 STSCGSPC-YAAPELVVSDSMyaGRKADIWSCGVILYAMLA-GYLPFDDDPHNPNGDNVPRLYRyiCNTPLIFPEYVTPK 242
                       250       260
                ....*....|....*....|....
gi 18150824 454 MMDCWEK----DPSQRPNFTRIEK 473
Cdd:cd14076 243 ARDLLRRilvpNPRKRIRLSAIMR 266
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
232-414 1.78e-18

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 85.85  E-value: 1.78e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDY 311
Cdd:cd06644  20 LGDGAFGKVYKAKNKETGALAAAKVIETKSEEELEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFCPGGAVDAI 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 312 LRSRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNVKQEGAKLPVK-WTA 389
Cdd:cd06644 100 MLELDRGLTEPQIQV-ICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVsAKNVKTLQRRDSFIGTPyWMA 178
                       170       180       190
                ....*....|....*....|....*....|
gi 18150824 390 P-----EALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06644 179 PevvmcETMKDTPYDYKADIWSLGITLIEM 208
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
230-421 2.11e-18

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: 85.40  E-value: 2.11e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQFLAEASVM---TTLRHPNLVCLIGISL---DDNP--IYLI 299
Cdd:cd07838   5 AEIGEGAYGTVYKARdlQDGRFVALKKVRVPLSEEGIPLSTIREIALLkqlESFEHPNVVRLLDVCHgprTDRElkLTLV 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKgSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvkqE 379
Cdd:cd07838  85 FEHVDQ-DLATYLDKCPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIYSF---E 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 380 GAKLPVKWT----APEALRENKFSNKTDVWSFGVLLWEIYSygRVP 421
Cdd:cd07838 161 MALTSVVVTlwyrAPEVLLQSSYATPVDMWSVGCIFAELFN--RRP 204
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
231-414 2.16e-18

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 85.08  E-value: 2.16e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGdYE---GKKVAMKSMK---DHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLD--DNPIYLITEF 302
Cdd:cd06653   9 LLGRGAFGEVYLC-YDadtGRELAVKQVPfdpDSQETSKEVNALECEIQLLKNLRHDRIVQYYGCLRDpeEKKLSIFVEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAK 382
Cdd:cd06653  88 MPGGSVKDQLKAYG--ALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMSGTG 165
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 18150824 383 LPV-----KWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06653 166 IKSvtgtpYWMSPEVISGEGYGRKADVWSVACTVVEM 202
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
105-198 2.41e-18

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 80.39  E-value: 2.41e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYDGR----VENYRVRRNEKGLVTVDDDEYFDNL 177
Cdd:cd10363   1 ETEEWFFKGISRKDAERQLLAPGNmlGSFMIRDSETTKGSYSLSVrDYDPQhgdtVKHYKIRTLDNGGFYISPRSTFSTL 80
                        90       100
                ....*....|....*....|.
gi 18150824 178 IKLVEHYQKEADGLCTRLKAP 198
Cdd:cd10363  81 QELVDHYKKGNDGLCQKLSVP 101
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
231-467 2.74e-18

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: 84.86  E-value: 2.74e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL---GDYEGKKVAMKSMKDHL----KDEKAKTQ----FLAEASVM-TTLRHPNLVCLIGISLDDNPIYL 298
Cdd:cd08528   7 LLGSGAFGCVYKvrkKSNGQTLLALKEINMTNpafgRTEQERDKsvgdIISEVNIIkEQLRHPNIVRYYKTFLENDRLYI 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMAKGSLIDYLRSrgraviTKQNQIDFARDVVKGMV--------YLESQN-FVHRDLAARNVLIAEDNVAKVSDFGL 369
Cdd:cd08528  87 VMELIEGAPLGEHFSS------LKEKNEHFTEDRIWNIFvqmvlalrYLHKEKqIVHRDLKPNNIMLGEDDKVTITDFGL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 370 A--KSSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPYPRVPVEDVANHVENGYRMESPDGC- 446
Cdd:cd08528 161 AkqKGPESSKMTSVVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTL-QPPFYSTNMLTLATKIVEAEYEPLPEGMy 239
                       250       260
                ....*....|....*....|.
gi 18150824 447 PDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd08528 240 SDDITFVIRSCLTPDPEARPD 260
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
222-485 2.84e-18

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: 85.16  E-value: 2.84e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVW--LGDYEGKKVAMKSMkdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06654  18 PKKKYTRFEKIGQGASGTVYtaMDVATGQEVAIRQM--NLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSrgraVITKQNQID-FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQ 378
Cdd:cd06654  96 MEYLAGGSLTDVVTE----TCMDEGQIAaVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQS 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKL--PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-PRVPVEDVANHVENGY-RMESPDGCPDQIYKIM 454
Cdd:cd06654 172 KRSTMvgTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPYlNENPLRALYLIATNGTpELQNPEKLSAIFRDFL 250
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 18150824 455 MDCWEKDPSQRPN--------FTRIEKALESVAVAMSSS 485
Cdd:cd06654 251 NRCLEMDVEKRGSakellqhqFLKIAKPLSSLTPLIAAA 289
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
222-478 3.34e-18

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: 85.16  E-value: 3.34e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLGD--YEGKKVAMKSMkdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06655  17 PKKKYTRYEKIGQGASGTVFTAIdvATGQEVAIKQI--NLQKQPKKELIINEILVMKELKNPNIVNFLDSFLVGDELFVV 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRsrgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:cd06655  95 MEYLAGGSLTDVVT---ETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSK 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 380 GAKL--PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-PRVPVEDVANHVENGY-RMESPDGCPDQIYKIMM 455
Cdd:cd06655 172 RSTMvgTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPYlNENPLRALYLIATNGTpELQNPEKLSPIFRDFLN 250
                       250       260       270
                ....*....|....*....|....*....|.
gi 18150824 456 DCWEKDPSQRPN--------FTRIEKALESV 478
Cdd:cd06655 251 RCLEMDVEKRGSakellqhpFLKLAKPLSSL 281
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
109-195 4.07e-18

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 79.71  E-value: 4.07e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCVS-YDG----RVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10365   5 WYFGKITRRESERLLLNAENprGTFLVRESETTKGAYCLSVSdFDNakglNVKHYKIRKLDSGGFYITSRTQFNSLQQLV 84
                        90
                ....*....|....
gi 18150824 182 EHYQKEADGLCTRL 195
Cdd:cd10365  85 AYYSKHADGLCHRL 98
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
232-471 4.12e-18

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: 84.03  E-value: 4.12e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSM---KDHLKDEKAKTQflaEASVMTTLRHPNLVCL-IGISLDDNPIYLITEFMAK 305
Cdd:cd08223   8 IGKGSYGEVWLVRHkrDRKQYVIKKLnlkNASKRERKAAEQ---EAKLLSKLKHPNIVSYkESFEGEDGFLYIVMGFCEG 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEGAK 382
Cdd:cd08223  85 GDLYTRLKEQKGVLLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARvleSSSDMATTLIG 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVkWTAPEALRENKFSNKTDVWSFGVLLWEI----------------YSYGRVPYPRVPvedvanhvengyRMESPDGC 446
Cdd:cd08223 165 TPY-YMSPELFSNKPYNHKSDVWALGCCVYEMatlkhafnakdmnslvYKILEGKLPPMP------------KQYSPELG 231
                       250       260
                ....*....|....*....|....*
gi 18150824 447 pdQIYKIMMDcweKDPSQRPNFTRI 471
Cdd:cd08223 232 --ELIKAMLH---QDPEKRPSVKRI 251
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
229-476 6.42e-18

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: 83.79  E-value: 6.42e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEG--KKVAMKSM-KDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd14169   8 KEKLGEGAFSEVVLAQERGsqRLVALKCIpKKALRGKEAMVE--NEIAVLRRINHENIVSLEDIYESPTHLYLAMELVTG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA---EDNVAKVSDFGLAK-SSSNVKQEGA 381
Cdd:cd14169  86 GELFDRIIERGS--YTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYAtpfEDSKIMISDFGLSKiEAQGMLSTAC 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPvKWTAPEALRENKFSNKTDVWSFGVLLWeIYSYGRVP-YPRVPVEDVANHVENGYRMESP--DGCPDQIYKIMMDCW 458
Cdd:cd14169 164 GTP-GYVAPELLEQKPYGKAVDVWAIGVISY-ILLCGYPPfYDENDSELFNQILKAEYEFDSPywDDISESAKDFIRHLL 241
                       250
                ....*....|....*...
gi 18150824 459 EKDPSQRPNftrIEKALE 476
Cdd:cd14169 242 ERDPEKRFT---CEQALQ 256
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
225-466 6.54e-18

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 84.03  E-value: 6.54e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVWLGDYE--GKKVAMKSMkdHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNP-IYLIT 300
Cdd:cd06620   6 DLETLKDLGAGNGGSVSKVLHIptGTIMAKKVI--HIdAKSSVRKQILRELQILHECHSPYIVSFYGAFLNENNnIIICM 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGRAVITKQNQIDFArdVVKGMVYLESQ-NFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:cd06620  84 EYMDCGSLDKILKKKGPFPEEVLGKIAVA--VLEGLTYLYNVhRIIHRDIKPSNILVNSKGQIKLCDFGVSGELINSIAD 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 380 GAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPyprvpvedVANHVENGYRMESPDGCPDQIYKIMMDCWE 459
Cdd:cd06620 162 TFVGTSTYMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFP--------FAGSNDDDDGYNGPMGILDLLQRIVNEPPP 232

                ....*..
gi 18150824 460 KDPSQRP 466
Cdd:cd06620 233 RLPKDRI 239
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
229-442 6.97e-18

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: 83.99  E-value: 6.97e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEGKK--VAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd14209   6 IKTLGTGSFGRVMLVRHKETGnyYAMKILdKQKVVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEYVPG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsssNVKQEGAKL-- 383
Cdd:cd14209  86 GEMFSHLRRIGR--FSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAK---RVKGRTWTLcg 160
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18150824 384 -PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVP-YPRVPVEDVANHVENGYRMES 442
Cdd:cd14209 161 tP-EYLAPEIILSKGYNKAVDWWALGVLIYEMAA-GYPPfFADQPIQIYEKIVSGKVRFPS 219
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
108-187 7.48e-18

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 78.55  E-value: 7.48e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRIS--REDAEKLLT---PPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVR-RNEKGLVT--VDDDEYFDNLIK 179
Cdd:cd10341   5 PWFHGKLGdgRDEAEKLLLeycEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRsRQENGEKKyyLTDNLVFDSLYE 84

                ....*...
gi 18150824 180 LVEHYQKE 187
Cdd:cd10341  85 LIDYYRQN 92
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
208-422 8.06e-18

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: 83.88  E-value: 8.06e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 208 VVDVNDfkekgwaiPKASLLKKSLIGKGEFGEVWLG--DYEGKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVC 285
Cdd:cd06659  13 VVDQGD--------PRQLLENYVKIGEGSTGVVCIAreKHSGRQVAVKMMD--LRKQQRRELLFNEVVIMRDYQHPNVVE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 286 LIGISLDDNPIYLITEFMAKGSLIDYLrSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVS 365
Cdd:cd06659  83 MYKSYLVGEELWVLMEYLQGGALTDIV-SQTR--LNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLS 159
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 366 DFGL-AKSSSNVKQEGAKLPVK-WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd06659 160 DFGFcAQISKDVPKRKSLVGTPyWMAPEVISRCPYGTEVDIWSLGIMVIEMVD-GEPPY 217
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
232-413 8.06e-18

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: 83.49  E-value: 8.06e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF--MAKGS 307
Cdd:cd07835   7 IGEGTYGVVYkaRDKLTGEIVALKKIRLETEDEGVPSTAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEFldLDLKK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LID--YLRSRGRAVITKqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkqegakLPV 385
Cdd:cd07835  87 YMDssPLTGLDPPLIKS-----YLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAFG--------VPV 153
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 386 K---------W-TAPEALRENK-FSNKTDVWSFGVLLWE 413
Cdd:cd07835 154 RtythevvtlWyRAPEILLGSKhYSTPVDIWSVGCIFAE 192
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
231-465 1.00e-17

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


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 83.58  E-value: 1.00e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG----DYEGKK--VAMKSMKDH-LKDEKAKTQFLAEASvmttLRHPNLVCLIG----ISLDDNPIYLI 299
Cdd:cd14055   2 LVGKGRFAEVWKAklkqNASGQYetVAVKIFPYEeYASWKNEKDIFTDAS----LKHENILQFLTaeerGVGLDRQYWLI 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSRgraVITKQNQIDFARDVVKGMVYLESQNF---------VHRDLAARNVLIAEDNVAKVSDFGLA 370
Cdd:cd14055  78 TAYHENGSLQDYLTRH---ILSWEDLCKMAGSLARGLAHLHSDRTpcgrpkipiAHRDLKSSNILVKNDGTCVLADFGLA 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 371 ---------KSSSNVKQEGAKlpvKWTAPEALR-----ENKFSNK-TDVWSFGVLLWEIYS----YGRVPYPRVPVEDVA 431
Cdd:cd14055 155 lrldpslsvDELANSGQVGTA---RYMAPEALEsrvnlEDLESFKqIDVYSMALVLWEMASrceaSGEVKPYELPFGSKV 231
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 432 NHVENGYRM--------ESPDgCPDQ---------IYKIMMDCWEKDPSQR 465
Cdd:cd14055 232 RERPCVESMkdlvlrdrGRPE-IPDSwlthqgmcvLCDTITECWDHDPEAR 281
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
230-466 1.04e-17

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 85.62  E-value: 1.04e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  230 SLIGKGEFGEVWLG-D-YEGKKVAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVcliGIsLD---DNPI-YLITEF 302
Cdd:NF033483  13 ERIGRGGMAEVYLAkDtRLDRDVAVKVLRPDLaRDPEFVARFRREAQSAASLSHPNIV---SV-YDvgeDGGIpYIVMEY 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  303 MAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEG 380
Cdd:NF033483  89 VDGRTLKDYIREHGP--LSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARalSSTTMTQTN 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  381 AKL-PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-------------------PRVPVEDVANHVENgyrm 440
Cdd:NF033483 167 SVLgTVHYLSPEQARGGTVDARSDIYSLGIVLYEMLT-GRPPFdgdspvsvaykhvqedpppPSELNPGIPQSLDA---- 241
                        250       260
                 ....*....|....*....|....*.
gi 18150824  441 espdgcpdqiykIMMDCWEKDPSQRP 466
Cdd:NF033483 242 ------------VVLKATAKDPDDRY 255
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
232-467 1.18e-17

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: 82.59  E-value: 1.18e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL----GDyeGKKVAMKSMkDHLK-DEKAKTQFLAEASVMTTLRHPNLVCLIG--ISLDDNPIYLITEFMA 304
Cdd:cd08217   8 IGKGSFGTVRKvrrkSD--GKILVWKEI-DYGKmSEKEKQQLVSEVNILRELKHPNIVRYYDriVDRANTTLYIVMEYCE 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRgraviTKQNQI---DFARDVVKGMV---------YLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS 372
Cdd:cd08217  85 GGDLAQLIKKC-----KKENQYipeEFIWKIFTQLLlalyechnrSVGGGKILHRDLKPANIFLDSDNNVKLGDFGLARV 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 SSNvKQEGAKLPVK---WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYprvpveDVANHVE------NGYRMESP 443
Cdd:cd08217 160 LSH-DSSFAKTYVGtpyYMSPELLNEQSYDEKSDIWSLGCLIYELCA-LHPPF------QAANQLElakkikEGKFPRIP 231
                       250       260
                ....*....|....*....|....
gi 18150824 444 DGCPDQIYKIMMDCWEKDPSQRPN 467
Cdd:cd08217 232 SRYSSELNEVIKSMLNVDPDKRPS 255
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
232-413 1.22e-17

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 82.35  E-value: 1.22e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd06613   8 IGSGTYGDVYKARNiaTGELAAVKVIKLEPGDDFEIIQ--QEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGGGSLQ 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 D-YLRSRGraviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKQEGAKLP 384
Cdd:cd06613  86 DiYQVTGP----LSELQIAYvCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSaqlTATIAKRKSFIGTP 161
                       170       180       190
                ....*....|....*....|....*....|..
gi 18150824 385 VkWTAPEALRENK---FSNKTDVWSFGVLLWE 413
Cdd:cd06613 162 Y-WMAPEVAAVERkggYDGKCDIWALGITAIE 192
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
231-412 1.28e-17

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: 82.37  E-value: 1.28e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVwlgdYE------GKKVAMKSM-------KDHLKDEkaktqflaEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd14095   7 VIGDGNFAVV----KEcrdkatDKEYALKIIdkakckgKEHMIEN--------EVAILRRVKHPNIVQLIEEYDTDTELY 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA----KVSDFGLAKSS 373
Cdd:cd14095  75 LVMELVKGGDLFDAITSSTK--FTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEDGskslKLADFGLATEV 152
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 374 SNVKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14095 153 KEPLFTVCGTPT-YVAPEILAETGYGLKVDIWAAGVITY 190
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
225-422 1.36e-17

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: 82.67  E-value: 1.36e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVW-LGDYEGK-----KVAMKSM--KDHLKDEKAktqflAEASVMTTLRHPNLVCLIGISLDDNPI 296
Cdd:cd14187   8 RYVRGRFLGKGGFAKCYeITDADTKevfagKIVPKSLllKPHQKEKMS-----MEIAIHRSLAHQHVVGFHGFFEDNDFV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 297 YLITEFMAKGSLIDyLRSRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAkssSNV 376
Cdd:cd14187  83 YVVLELCRRRSLLE-LHKRRKALTEPEARY-YLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLA---TKV 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 377 KQEGAKLPV-----KWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd14187 158 EYDGERKKTlcgtpNYIAPEVLSKKGHSFEVDIWSIGCIMYTLL-VGKPPF 207
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
232-466 1.39e-17

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 82.50  E-value: 1.39e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAkGSL 308
Cdd:cd06607   9 IGHGSFGAVYYARNKRTSevVAIKKMSYSGKQSTEKWQdIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEYCL-GSA 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVitKQNQID-FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAkSSSNVKQEGAKLPVkW 387
Cdd:cd06607  88 SDIVEVHKKPL--QEVEIAaICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSA-SLVCPANSFVGTPY-W 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPE---ALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHV-ENGYRMESPDGCPDQIYKIMMDCWEKDPS 463
Cdd:cd06607 164 MAPEvilAMDEGQYDGKVDVWSLGITCIEL-AERKPPLFNMNAMSALYHIaQNDSPTLSSGEWSDDFRNFVDSCLQKIPQ 242

                ...
gi 18150824 464 QRP 466
Cdd:cd06607 243 DRP 245
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
230-467 1.48e-17

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: 82.86  E-value: 1.48e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEV-WLGDYEGKKV-AMKSMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLD--DNPIYLITEFMAK 305
Cdd:cd06621   7 SSLGEGAGGSVtKCRLRNTKTIfALKTITTDPNPDVQK-QILRELEINKSCASPYIVKYYGAFLDeqDSSIGIAMEYCEG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSL---IDYLRSRG----RAVITKqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLaksSSNVKQ 378
Cdd:cd06621  86 GSLdsiYKKVKKKGgrigEKVLGK-----IAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGV---SGELVN 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVK---WTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPR------VPVEdVANHVENGYRMESPDgCPD- 448
Cdd:cd06621 158 SLAGTFTGtsyYMAPERIQGGPYSITSDVWSLGLTLLEV-AQNRFPFPPegepplGPIE-LLSYIVNMPNPELKD-EPEn 234
                       250       260
                ....*....|....*....|....*
gi 18150824 449 -----QIYKIMMD-CWEKDPSQRPN 467
Cdd:cd06621 235 gikwsESFKDFIEkCLEKDGTRRPG 259
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
232-465 1.56e-17

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: 83.42  E-value: 1.56e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDHL---KDEKAKTqfLAEASVM-TTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05570   3 LGKGSFGKVMLAERKKTDelYAIKVLKKEViieDDDVECT--MTEKRVLaLANRHPFLTGLHACFQTEDRLYFVMEYVNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsssnvkqEGAKLP 384
Cdd:cd05570  81 GDLMFHIQRARR---FTEERARFyAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK-------EGIWGG 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWT---------APEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGyRMESPDGCPDQIYKIMM 455
Cdd:cd05570 151 NTTStfcgtpdyiAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPFEGDDEDELFEAILND-EVLYPRWLSREAVSILK 228
                       250
                ....*....|
gi 18150824 456 DCWEKDPSQR 465
Cdd:cd05570 229 GLLTKDPARR 238
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
107-201 1.57e-17

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198263  Cd Length: 103  Bit Score: 77.96  E-value: 1.57e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 107 MPWFHGRISREDAEKLL-TPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVD-----DDEYFDNLIKL 180
Cdd:cd10400   3 VAVYHGKISRETGEKLLlAAGLDGSYLLRDSESVPGVYCLCVLYKGYVYTYRVSQTETGSWSAEtapgvHKRLFRKVKNL 82
                        90       100
                ....*....|....*....|.
gi 18150824 181 VEHYQKEADGLCTRLKAPVDK 201
Cdd:cd10400  83 ISAFQKPDQGIVTPLQYPVEK 103
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
232-416 1.69e-17

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 83.66  E-value: 1.69e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  232 IGKGEFGEVWLG--DYEGKKVAMKSMK--DHLKDEKAKTQF----------LAEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:PTZ00024  17 LGEGTYGKVEKAydTLTGKIVAIKKVKiiEISNDVTKDRQLvgmcgihfttLRELKIMNEIKHENIMGLVDVYVEGDFIN 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  298 LITEFMAkGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN-- 375
Cdd:PTZ00024  97 LVMDIMA-SDLKKVVDRKIR--LTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARRYGYpp 173
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824  376 -----VKQEGAKLPVKWT---------APEALR-ENKFSNKTDVWSFGVLLWEIYS 416
Cdd:PTZ00024 174 ysdtlSKDETMQRREEMTskvvtlwyrAPELLMgAEKYHFAVDMWSVGCIFAELLT 229
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
231-465 1.76e-17

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: 83.47  E-value: 1.76e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSM-KDHLKDEKAKTQFLAEASVM-TTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05604   3 VIGKGSFGKVLLakRKRDGKYYAVKVLqKKVILNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDFVNGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRsRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVKQEGAKL 383
Cdd:cd05604  83 ELFFHLQ-RERSFPEPRARF-YAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKegiSNSDTTTTFCGT 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVP-YPRvpveDVANHVENGYRME--SPDGCPDQIYKIMMDCWEK 460
Cdd:cd05604 161 P-EYLAPEVIRKQPYDNTVDWWCLGSVLYEML-YGLPPfYCR----DTAEMYENILHKPlvLRPGISLTAWSILEELLEK 234

                ....*
gi 18150824 461 DPSQR 465
Cdd:cd05604 235 DRQLR 239
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
232-414 1.92e-17

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 82.50  E-value: 1.92e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVC-------LIGISLDDNPIyLITE 301
Cdd:cd13989   1 LGSGGFGYVtlWKHQDTGEYVAIKKCRQELsPSDKNRERWCLEVQIMKKLNHPNVVSardvppeLEKLSPNDLPL-LAME 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRSRGRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLAK----SS 373
Cdd:cd13989  80 YCSGGDLRKVLNQPENCCGLKESEVrTLLSDISSAISYLHENRIIHRDLKPENIVLQQGGgrvIYKLIDLGYAKeldqGS 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 18150824 374 SNVKQEGAklpVKWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd13989 160 LCTSFVGT---LQYLAPELFESKKYTCTVDYWSFGTLAFEC 197
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
231-422 2.08e-17

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: 83.54  E-value: 2.08e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDHL---KDEKAKTqfLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05594  32 LLGKGTFGKVILVKEKatGRYYAMKILKKEVivaKDEVAHT--LTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANG 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLrSRGRaVITKQNQIDFARDVVKGMVYLESQ-NFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkQEGAKLP 384
Cdd:cd05594 110 GELFFHL-SRER-VFSEDRARFYGAEIVSALDYLHSEkNVVYRDLKLENLMLDKDGHIKITDFGLCKEGI---KDGATMK 184
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 18150824 385 V-----KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05594 185 TfcgtpEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 226
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
229-465 2.38e-17

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: 82.40  E-value: 2.38e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd14168  15 KEVLGTGAFSEVVLAEERatGKLFAVKCIpKKALKGKESSIE--NEIAVLRKIKHENIVALEDIYESPNHLYLVMQLVSG 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVL-IAEDNVAK--VSDFGLAK--SSSNVKQEG 380
Cdd:cd14168  93 GELFDRIVEKG--FYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLyFSQDEESKimISDFGLSKmeGKGDVMSTA 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsygrVPYPRVPVEDVANHVEN----GYRMESP--DGCPDQIYKIM 454
Cdd:cd14168 171 CGTP-GYVAPEVLAQKPYSKAVDCWSIGVIAYILL----CGYPPFYDENDSKLFEQilkaDYEFDSPywDDISDSAKDFI 245
                       250
                ....*....|.
gi 18150824 455 MDCWEKDPSQR 465
Cdd:cd14168 246 RNLMEKDPNKR 256
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
232-409 2.46e-17

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: 81.50  E-value: 2.46e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVwlgdYE------GKKVAMKSMKDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd14103   1 LGRGKFGTV----YRcvekatGKELAAKFIKCRKAKDREDVR--NEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAG 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDylrsrgRAV-----ITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA--EDNVAKVSDFGLAKsssnvKQ 378
Cdd:cd14103  75 GELFE------RVVdddfeLTERDCILFMRQICEGVQYMHKQGILHLDLKPENILCVsrTGNQIKIIDFGLAR-----KY 143
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 18150824 379 EG-AKLPVKW-----TAPEALRENKFSNKTDVWSFGV 409
Cdd:cd14103 144 DPdKKLKVLFgtpefVAPEVVNYEPISYATDMWSVGV 180
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
267-465 2.47e-17

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: 82.32  E-value: 2.47e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 267 QFLAEASVMTTLRHPNLVCLIGIsLDD---NPIYLITEFMAKGSLIDYLRSRGRAvitkQNQIDFA-RDVVKGMVYLESQ 342
Cdd:cd14199  71 RVYQEIAILKKLDHPNVVKLVEV-LDDpseDHLYMVFELVKQGPVMEVPTLKPLS----EDQARFYfQDLIKGIEYLHYQ 145
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 343 NFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKQEGAKLPVkWTAPEALRENK--FSNKT-DVWSFGVLLWeIYS 416
Cdd:cd14199 146 KIIHRDVKPSNLLVGEDGHIKIADFGVSnefEGSDALLTNTVGTPA-FMAPETLSETRkiFSGKAlDVWAMGVTLY-CFV 223
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 417 YGRVPYPRVPVEDVANHVENgyrmeSPDGCPDQ------IYKIMMDCWEKDPSQR 465
Cdd:cd14199 224 FGQCPFMDERILSLHSKIKT-----QPLEFPDQpdisddLKDLLFRMLDKNPESR 273
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
232-420 2.48e-17

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 81.85  E-value: 2.48e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAK--TQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14160   1 IGEGEIFEVYRVRIGNRSYAVKLFKQEKKMQWKKhwKRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNGTLF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLR-SRGRAVITKQNQIDFARDVVKGMVYLESQN---FVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPV 385
Cdd:cd14160  81 DRLQcHGVTKPLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLDDQMQPKLTDFALAHFRPHLEDQSCTINM 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 18150824 386 K-------WTAPEA-LRENKFSNKTDVWSFGVLLWEIYSYGRV 420
Cdd:cd14160 161 TtalhkhlWYMPEEyIRQGKLSVKTDVYSFGIVIMEVLTGCKV 203
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
105-199 2.59e-17

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 77.46  E-value: 2.59e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPP--KNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKG---LVTVDDDEY-FDNLI 178
Cdd:cd09944   3 RSQPWFHGGISRDEAARLIRQQglVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDEgqwYFTLDDGVTkFYDLL 82
                        90       100
                ....*....|....*....|.
gi 18150824 179 KLVEHYQKEADGLCTRLKAPV 199
Cdd:cd09944  83 QLVEFYQLNAGSLPTRLKHYC 103
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
232-423 2.92e-17

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: 82.23  E-value: 2.92e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMKSMK-DHLKDEKAKTqFLAEASVMTTLRHPNLVCLIGISLDDNP------IYLITEF 302
Cdd:cd07840   7 IGEGTYGQVYKARnkKTGELVALKKIRmENEKEGFPIT-AIREIKLLQKLDHPNVVRLKEIVTSKGSakykgsIYMVFEY 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MakgsliDY-----LRSRGraVITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNV 376
Cdd:cd07840  86 M------DHdltglLDNPE--VKFTESQIKCyMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKE 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 377 KqegaklPVKWT---------APEALR-ENKFSNKTDVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07840 158 N------NADYTnrvitlwyrPPELLLgATRYGPEVDMWSVGCILAELFT-GKPIFQ 207
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
222-426 3.11e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 82.01  E-value: 3.11e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLG--DYEGKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06658  20 PREYLDSFIKIGEGSTGIVCIAteKHTGKQVAVKKMD--LRKQQRRELLFNEVVIMRDYHHENVVDMYNSYLVGDELWVV 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSrgraviTKQNQIDFAR---DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSN 375
Cdd:cd06658  98 MEFLEGGALTDIVTH------TRMNEEQIATvclSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFcAQVSKE 171
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 18150824 376 VKQEGAKLPVK-WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP 426
Cdd:cd06658 172 VPKRKSLVGTPyWMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPYFNEP 222
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
225-429 3.35e-17

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 81.97  E-value: 3.35e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVwlgdYEGKK------VAMKSMK-DHlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd07873   3 TYIKLDKLGEGTYATV----YKGRSkltdnlVALKEIRlEH--EEGAPCTAIREVSLLKDLKHANIVTLHDIIHTEKSLT 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKgSLIDYLRSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS-NV 376
Cdd:cd07873  77 LVFEYLDK-DLKQYLDDCGN-SINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSiPT 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 377 KQEGAKLPVKWTAPE--ALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVED 429
Cdd:cd07873 155 KTYSNEVVTLWYRPPdiLLGSTDYSTQIDMWGVGCIFYEM-STGRPLFPGSTVEE 208
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
231-436 4.95e-17

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: 81.94  E-value: 4.95e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDY--EGKKVAMKSM-KDHLKDEKAKTQFLAEASVM-TTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05603   2 VIGKGSFGKVLLAKRkcDGKFYAVKVLqKKTILKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDYVNGG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRsRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSsnVKQEGAKLPV- 385
Cdd:cd05603  82 ELFFHLQ-RERCFLEPRARF-YAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCKEG--MEPEETTSTFc 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 386 ---KWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVP-YPRvpveDVANHVEN 436
Cdd:cd05603 158 gtpEYLAPEVLRKEPYDRTVDWWCLGAVLYEML-YGLPPfYSR----DVSQMYDN 207
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
225-429 5.96e-17

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 81.58  E-value: 5.96e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVWLGDYEGKK--VAMKSMK-DHlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd07872   7 TYIKLEKLGEGTYATVFKGRSKLTEnlVALKEIRlEH--EEGAPCTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFE 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKgSLIDYLRSRGrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS-NVKQEG 380
Cdd:cd07872  85 YLDK-DLKQYMDDCG-NIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSvPTKTYS 162
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 381 AKLPVKWTAPE--ALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVED 429
Cdd:cd07872 163 NEVVTLWYRPPdvLLGSSEYSTQIDMWGVGCIFFEMAS-GRPLFPGSTVED 212
pknD PRK13184
serine/threonine-protein kinase PknD;
231-465 6.26e-17

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 84.05  E-value: 6.26e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  231 LIGKGEFGEVWLGdYE---GKKVAMKSMKDHLKD-EKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:PRK13184   9 LIGKGGMGEVYLA-YDpvcSRRVALKKIREDLSEnPLLKKRFLREAKIAADLIHPGIVPVYSICSDGDPVYYTMPYIEGY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  307 SLIDYLRS-RGRAVITKQNQID-----FAR---DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS----- 372
Cdd:PRK13184  88 TLKSLLKSvWQKESLSKELAEKtsvgaFLSifhKICATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIFkklee 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  373 ----SSNVKQEGA-----KLPVK------WTAPEALRENKFSNKTDVWSFGVLLWEIYSYgRVPYPR------------V 425
Cdd:PRK13184 168 edllDIDVDERNIcyssmTIPGKivgtpdYMAPERLLGVPASESTDIYALGVILYQMLTL-SFPYRRkkgrkisyrdviL 246
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 18150824  426 PVEDVANHVEngyrmespdgCPDQIYKIMMDCWEKDPSQR 465
Cdd:PRK13184 247 SPIEVAPYRE----------IPPFLSQIAMKALAVDPAER 276
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
229-465 6.28e-17

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: 81.15  E-value: 6.28e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLG--DYEGKKVAMK--SMKDHLKD-----------------EKAKT-----QFLAEASVMTTLRHPN 282
Cdd:cd14200   5 QSEIGKGSYGVVKLAynESDDKYYAMKvlSKKKLLKQygfprrppprgskaaqgEQAKPlapleRVYQEIAILKKLDHVN 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 283 LVCLIGIsLDD---NPIYLITEFMAKGSLIDYlrSRGRAVITKQNQIDFaRDVVKGMVYLESQNFVHRDLAARNVLIAED 359
Cdd:cd14200  85 IVKLIEV-LDDpaeDNLYMVFDLLRKGPVMEV--PSDKPFSEDQARLYF-RDIVLGIEYLHYQKIVHRDIKPSNLLLGDD 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 360 NVAKVSDFGLA---KSSSNVKQEGAKLPVkWTAPEALRENK--FSNKT-DVWSFGVLLWeIYSYGRVPYPRVPVEDVANH 433
Cdd:cd14200 161 GHVKIADFGVSnqfEGNDALLSSTAGTPA-FMAPETLSDSGqsFSGKAlDVWAMGVTLY-CFVYGKCPFIDEFILALHNK 238
                       250       260       270
                ....*....|....*....|....*....|....
gi 18150824 434 VENGyRMESPDG--CPDQIYKIMMDCWEKDPSQR 465
Cdd:cd14200 239 IKNK-PVEFPEEpeISEELKDLILKMLDKNPETR 271
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
232-412 6.29e-17

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: 80.38  E-value: 6.29e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSM-KDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14185   8 IGDGNFAVVKECRHwnENQEYAMKIIdKSKLKGKEDMIE--SEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAED----NVAKVSDFGLAKSSSNVKQEGAKLP 384
Cdd:cd14185  86 FDAIIESVK--FTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHNpdksTTLKLADFGLAKYVTGPIFTVCGTP 163
                       170       180
                ....*....|....*....|....*...
gi 18150824 385 VkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14185 164 T-YVAPEILSEKGYGLEVDMWAAGVILY 190
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
229-415 6.83e-17

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: 81.42  E-value: 6.83e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYE--GKKVAMKSMK---DHLKDEKaktQFLAEASVMTTLRHPNLVCLIGISLDDNP-----IYL 298
Cdd:cd07834   5 LKPIGSGAYGVVCSAYDKrtGRKVAIKKISnvfDDLIDAK---RILREIKILRHLKHENIIGLLDILRPPSPeefndVYI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 299 ITEFMakgslidylRSRGRAVITKQNQID------FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS 372
Cdd:cd07834  82 VTELM---------ETDLHKVIKSPQPLTddhiqyFLYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARG 152
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 18150824 373 ssnvkQEGAKLPVKWT---------APEA-LRENKFSNKTDVWSFGVLLWEIY 415
Cdd:cd07834 153 -----VDPDEDKGFLTeyvvtrwyrAPELlLSSKKYTKAIDIWSVGCIFAELL 200
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
271-466 7.00e-17

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: 80.55  E-value: 7.00e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd06630  53 EIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVASLLSKYG--AFSENVIINYTLQILRGLAYLHDNQIIHRDLK 130
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 351 ARNVLI-AEDNVAKVSDFGLAkSSSNVKQEGAKL-------PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd06630 131 GANLLVdSTGQRLRIADFGAA-ARLASKGTGAGEfqgqllgTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMAT-AKPPW 208
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 423 prvPVEDVANHVENGYRMESPDGCPD-------QIYKIMMDCWEKDPSQRP 466
Cdd:cd06630 209 ---NAEKISNHLALIFKIASATTPPPipehlspGLRDVTLRCLELQPEDRP 256
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
232-477 8.45e-17

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: 80.17  E-value: 8.45e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLgdY----EGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd08221   8 LGRGAFGEAVL--YrkteDNSLVVWKEVNLSRLSEKERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCNGGN 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLPV 385
Cdd:cd08221  86 LHDKIAQQKNQLFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKvlDSESSMAESIVGTP 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 KWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENGYRMESPDgCPDQIYKIMMDCWEKDPSQR 465
Cdd:cd08221 166 YYMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTFDATNPLRLAVKIVQGEYEDIDEQ-YSEEIIQLVHDCLHQDPEDR 244
                       250
                ....*....|..
gi 18150824 466 PNftrIEKALES 477
Cdd:cd08221 245 PT---AEELLER 253
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
230-422 9.70e-17

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: 80.44  E-value: 9.70e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLG-D-YEGKKVAMK------SMKDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGI-SLDDNPIYLIT 300
Cdd:cd13990   6 NLLGKGGFSEVYKAfDlVEQRYVACKihqlnkDWSEEKKQNYIK-HALREYEIHKSLDHPRIVKLYDVfEIDTDSFCTVL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLE--SQNFVHRDLAARNVLIAEDNVA---KVSDFGLAK--SS 373
Cdd:cd13990  85 EYCDGNDLDFYLKQHKS--IPEREARSIIMQVVSALKYLNeiKPPIIHYDLKPGNILLHSGNVSgeiKITDFGLSKimDD 162
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 374 SNVKQEGAKLPVK-----W-TAPEALREN----KFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd13990 163 ESYNSDGMELTSQgagtyWyLPPECFVVGktppKISSKVDVWSVGVIFYQML-YGRKPF 220
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
232-468 1.04e-16

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: 80.28  E-value: 1.04e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW--LGDYEGKKVAMKSMKDHLkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLi 309
Cdd:cd06622   9 LGKGNYGSVYkvLHRPTGVTMAMKEIRLEL-DESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAGSL- 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAV-ITKQNQIDF-ARDVVKGMVYL-ESQNFVHRDLAARNVLIAEDNVAKVSDFGLaksSSNVKQEGAKLPV- 385
Cdd:cd06622  87 DKLYAGGVATeGIPEDVLRRiTYAVVKGLKFLkEEHNIIHRDVKPTNVLVNGNGQVKLCDFGV---SGNLVASLAKTNIg 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 --KWTAPEALREN------KFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHVE---NGYRMESPDGCPDQIYKIM 454
Cdd:cd06622 164 cqSYMAPERIKSGgpnqnpTYTVQSDVWSLGLSILEM-ALGRYPYPPETYANIFAQLSaivDGDPPTLPSGYSDDAQDFV 242
                       250
                ....*....|....
gi 18150824 455 MDCWEKDPSQRPNF 468
Cdd:cd06622 243 AKCLNKIPNRRPTY 256
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
231-471 1.24e-16

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 80.04  E-value: 1.24e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMkDHLKDEKakTQFLAEASVMTTL-RHPNLVCLIGISLDDNP------IYLITE 301
Cdd:cd06608  13 VIGEGTYGKVYKARHKktGQLAAIKIM-DIIEDEE--EEIKLEINILRKFsNHPNIATFYGAFIKKDPpggddqLWLVME 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDY---LRSRGRAVitKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSS 374
Cdd:cd06608  90 YCGGGSVTDLvkgLRKKGKRL--KEEWIAYiLRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSaqlDSTL 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVKQEGAKLPVkWTAPEAL-----RENKFSNKTDVWSFGVLLWEIySYGRVPY------------PRVPVEdvanhveng 437
Cdd:cd06608 168 GRRNTFIGTPY-WMAPEVIacdqqPDASYDARCDVWSLGITAIEL-ADGKPPLcdmhpmralfkiPRNPPP--------- 236
                       250       260       270
                ....*....|....*....|....*....|....
gi 18150824 438 yRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:cd06608 237 -TLKSPEKWSKEFNDFISECLIKNYEQRPFTEEL 269
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
232-478 1.31e-16

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 79.96  E-value: 1.31e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14026   5 LSRGAFGTVSRARHADWRvtVAIKCLKLDSpVGDSERNCLLKEAEILHKARFSYILPILGICNEPEFLGIVTEYMTNGSL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGR-AVITKQNQIDFARDVVKGMVYLESQN--FVHRDLAARNVLIAEDNVAKVSDFGLAK---------SSSNV 376
Cdd:cd14026  85 NELLHEKDIyPDVAWPLRLRILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSKwrqlsisqsRSSKS 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKlpVKWTAPEAL---RENKFSNKTDVWSFGVLLWEIYSYgrvpypRVPVEDVAN------HVENGYRME-SPDGC 446
Cdd:cd14026 165 APEGGT--IIYMPPEEYepsQKRRASVKHDIYSYAIIMWEVLSR------KIPFEEVTNplqimySVSQGHRPDtGEDSL 236
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18150824 447 PDQI------YKIMMDCWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14026 237 PVDIphratlINLIESGWAQNPDERPSFLKCLIELEPV 274
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
226-414 1.41e-16

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 80.17  E-value: 1.41e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKKslIGKGEFGEVWLGDYE---GKKVAMK-----SMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd14096   5 LINK--IGEGAFSNVYKAVPLrntGKPVAIKvvrkaDLSSDNLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYY 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLID-------YLRSRGRAVITKqnqidfardVVKGMVYLESQNFVHRDLAARNVLI-------------- 356
Cdd:cd14096  83 IVLELADGGEIFHqivrltyFSEDLSRHVITQ---------VASAVKYLHEIGVVHRDIKPENLLFepipfipsivklrk 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 357 AEDNVAKV-------------------SDFGLAKSssnVKQEGAKLP---VKWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd14096 154 ADDDETKVdegefipgvggggigivklADFGLSKQ---VWDSNTKTPcgtVGYTAPEVVKDERYSKKVDMWALGCVLYTL 230
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
231-443 1.53e-16

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: 80.74  E-value: 1.53e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK--VAMKSMKDH--LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05619  12 MLGKGSFGKVFLAELKGTNqfFAIKALKKDvvLMDDDVECTMVEKRVLSLAWEHPFLTHLFCTFQTKENLFFVMEYLNGG 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKQNQidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSS--SNVKQEGAKLP 384
Cdd:cd05619  92 DLMFHIQSCHKFDLPRATF--YAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENmlGDAKTSTFCGT 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 385 VKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYPRVPVEDVANHVengyRMESP 443
Cdd:cd05619 170 PDYIAPEILLGQKYNTSVDWWSFGVLLYEML-IGQSPFHGQDEEELFQSI----RMDNP 223
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
228-471 1.66e-16

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: 79.29  E-value: 1.66e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVW-LGDYEGKKVAMKSMKDHLKDEKA--KTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd14188   5 RGKVLGKGGFAKCYeMTDLTTNKVYAAKIIPHSRVSKPhqREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCS 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKL- 383
Cdd:cd14188  85 RRSMAHILKAR--KVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRRTIc 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 -PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYPRVPVEDVANHVENGyRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd14188 163 gTPNYLSPEVLNKQGHGCESDIWALGCVMYTML-LGRPPFETTNLKETYRCIREA-RYSLPSSLLAPAKHLIASMLSKNP 240

                ....*....
gi 18150824 463 SQRPNFTRI 471
Cdd:cd14188 241 EDRPSLDEI 249
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
232-416 1.69e-16

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: 78.82  E-value: 1.69e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYE-GKKVAMKSMKdhlKDEKAKTQFLAEASVMTTLR----HPNLVCLIGISLD--DNPIYLITEFM 303
Cdd:cd05118   7 IGEGAFGTVWLArDKVtGEKVAIKKIK---NDFRHPKAALREIKLLKHLNdvegHPNIVKLLDVFEHrgGNHLCLVFELM 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 aKGSLIDYLRSRGRAVitKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN-VAKVSDFGLAKS--SSNVKQE 379
Cdd:cd05118  84 -GMNLYELIKDYPRGL--PLDLIkSYLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLARSftSPPYTPY 160
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 380 GAKLPvkWTAPEALRENKFSNKT-DVWSFGVLLWEIYS 416
Cdd:cd05118 161 VATRW--YRAPEVLLGAKPYGSSiDIWSLGCILAELLT 196
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
229-466 1.84e-16

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 79.37  E-value: 1.84e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLG-DYEGK-KVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd06624  13 RVVLGKGTFGVVYAArDLSTQvRIAIKEIPE--RDSREVQPLHEEIALHSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGG 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLI-AEDNVAKVSDFGLAK--SSSNVKQEGAK 382
Cdd:cd06624  91 SLSALLRSKWGPLKDNENTIGYyTKQILEGLKYLHDNKIVHRDIKGDNVLVnTYSGVVKISDFGTSKrlAGINPCTETFT 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 LPVKWTAPEALRENK--FSNKTDVWSFGVLLWEIySYGRVPY-----PRVPVEDVANhvengYRM--ESPDGCPDQIYKI 453
Cdd:cd06624 171 GTLQYMAPEVIDKGQrgYGPPADIWSLGCTIIEM-ATGKPPFielgePQAAMFKVGM-----FKIhpEIPESLSEEAKSF 244
                       250
                ....*....|...
gi 18150824 454 MMDCWEKDPSQRP 466
Cdd:cd06624 245 ILRCFEPDPDKRA 257
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
230-475 1.85e-16

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 79.46  E-value: 1.85e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDY--EGKKVAMKSMKdhLKDEKAKTqflaEASVMTTLRHPNLV----CLIGISLDDNP-------- 295
Cdd:cd14047  12 ELIGSGGFGQVFKAKHriDGKTYAIKRVK--LNNEKAER----EVKALAKLDHPNIVryngCWDGFDYDPETsssnssrs 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 ----IYLITEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK 371
Cdd:cd14047  86 ktkcLFIQMEFCEKGTLESWIEKRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGLVT 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 SSSN-VKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRvpvEDVANHVENGyrmESPDGCpDQI 450
Cdd:cd14047 166 SLKNdGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELLHVCDSAFEK---SKFWTDLRNG---ILPDIF-DKR 238
                       250       260
                ....*....|....*....|....*....
gi 18150824 451 YKIMMDCWEK----DPSQRPNFTRIEKAL 475
Cdd:cd14047 239 YKIEKTIIKKmlskKPEDRPNASEILRTL 267
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
232-465 2.02e-16

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: 79.49  E-value: 2.02e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd05577   1 LGRGGFGEVCACQVKatGKMYACKKLdKKRIKKKKGETMALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGGDL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-KSSSNVKQEGAKLPVKW 387
Cdd:cd05577  81 KYHIYNVGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAvEFKGGKKIKGRVGTHGY 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALR-ENKFSNKTDVWSFGVLLWEIYSyGRVPYpRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWE----KDP 462
Cdd:cd05577 161 MAPEVLQkEVAYDFSVDWFALGCMLYEMIA-GRSPF-RQRKEKVDKEELKRRTLEMAVEYPDSFSPEARSLCEgllqKDP 238

                ...
gi 18150824 463 SQR 465
Cdd:cd05577 239 ERR 241
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
232-414 2.04e-16

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: 79.47  E-value: 2.04e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSLI 309
Cdd:cd07860   8 IGEGTYGVVYKARNKltGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQ-DLK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkqegakLPVK--- 386
Cdd:cd07860  87 KFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFG--------VPVRtyt 158
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 18150824 387 -------WTAPEALRENKF-SNKTDVWSFGVLLWEI 414
Cdd:cd07860 159 hevvtlwYRAPEILLGCKYySTAVDIWSLGCIFAEM 194
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
103-186 2.19e-16

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 74.10  E-value: 2.19e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 103 QLKTMPWFHGRISREDAEKLLTppKNGRFLVRESQ---NYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEyFDNLIK 179
Cdd:cd10361   2 DLENEPYYHGLLPREDAEELLK--NDGDFLVRKTEpkgGGKRKLVLSVRWDGKIRHFVINRDDGGKYYIEGKS-FKSISE 78

                ....*..
gi 18150824 180 LVEHYQK 186
Cdd:cd10361  79 LINYYQK 85
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
232-414 2.61e-16

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 79.68  E-value: 2.61e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFmAKGSL 308
Cdd:cd06634  23 IGHGSFGAVYFARdvRNNEVVAIKKMSYSGKQSNEKWQdIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEY-CLGSA 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVitkqNQIDFA---RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGlakSSSNVKQEGAKLPV 385
Cdd:cd06634 102 SDLLEVHKKPL----QEVEIAaitHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFG---SASIMAPANSFVGT 174
                       170       180       190
                ....*....|....*....|....*....|...
gi 18150824 386 K-WTAPE---ALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06634 175 PyWMAPEvilAMDEGQYDGKVDVWSLGITCIEL 207
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
229-418 2.67e-16

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: 79.15  E-value: 2.67e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVW-------LGDYEGKKVAMKSmkdhlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNP------ 295
Cdd:cd14048  11 IQCLGRGGFGVVFeaknkvdDCNYAVKRIRLPN------NELAREKVLREVRALAKLDHPGIVRYFNAWLERPPegwqek 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 -----IYLITEFMAKGSLIDYLRSR----GRAVITKQNQIdfaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSD 366
Cdd:cd14048  85 mdevyLYIQMQLCRKENLKDWMNRRctmeSRELFVCLNIF---KQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGD 161
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 367 FGLA-----------------KSSSNVKQEGAKLpvkWTAPEALRENKFSNKTDVWSFGVLLWE-IYSYG 418
Cdd:cd14048 162 FGLVtamdqgepeqtvltpmpAYAKHTGQVGTRL---YMSPEQIHGNQYSEKVDIFALGLILFElIYSFS 228
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
229-422 2.72e-16

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: 78.73  E-value: 2.72e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEGKK--VAMKSMKdhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14087   6 KALIGRGSFSRVVRVEHRVTRqpYAIKMIE---TKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE---DNVAKVSDFGLA----KSSSNVKQE 379
Cdd:cd14087  83 ELFDRIIAKGS--FTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYYHpgpDSKIMITDFGLAstrkKGPNCLMKT 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 18150824 380 GAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14087 161 TCGTP-EYIAPEILLRKPYTQSVDMWAVGVIAYILLS-GTMPF 201
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
231-416 2.88e-16

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 78.55  E-value: 2.88e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGdYE---GKKVAMKSMK---DHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLD--DNPIYLITEF 302
Cdd:cd06652   9 LLGQGAFGRVYLC-YDadtGRELAVKQVQfdpESPETSKEVNALECEIQLLKNLLHERIVQYYGCLRDpqERTLSIFMEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAK 382
Cdd:cd06652  88 MPGGSIKDQLKSYG--ALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLSGTG 165
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 383 LPV-----KWTAPEALRENKFSNKTDVWSFGVLLWEIYS 416
Cdd:cd06652 166 MKSvtgtpYWMSPEVISGEGYGRKADIWSVGCTVVEMLT 204
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
232-466 3.51e-16

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: 78.83  E-value: 3.51e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLaeasvmttLR---HPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14091   8 IGKGSYSVCKRCIHKatGKEYAVKIIDKSKRDPSEEIEIL--------LRygqHPNIITLRDVYDDGNSVYLVTELLRGG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA----KVSDFGLAKsssNVKQEGAK 382
Cdd:cd14091  80 ELLDRILRQKF--FSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADESGDpeslRICDFGFAK---QLRAENGL 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 L--P---VKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP---VEDVANHVENG-YRMESP------DGCP 447
Cdd:cd14091 155 LmtPcytANFVAPEVLKKQGYDAACDIWSLGVLLYTMLA-GYTPFASGPndtPEVILARIGSGkIDLSGGnwdhvsDSAK 233
                       250
                ....*....|....*....
gi 18150824 448 DQIYKiMMDCwekDPSQRP 466
Cdd:cd14091 234 DLVRK-MLHV---DPSQRP 248
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
231-465 3.57e-16

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: 78.91  E-value: 3.57e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05630   7 VLGKGGFGEVCACQVRatGKMYACKKLeKKRIKKRKGEAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLMNGGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKqeGAKLP 384
Cdd:cd05630  87 LKFHIYHMGQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAvhvPEGQTIK--GRVGT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY-------PRVPVEDVANHVENGYRME-SPDGcpdQIYKIMMD 456
Cdd:cd05630 165 VGYMAPEVVKNERYTFSPDWWALGCLLYEMIA-GQSPFqqrkkkiKREEVERLVKEVPEEYSEKfSPQA---RSLCSMLL 240

                ....*....
gi 18150824 457 CweKDPSQR 465
Cdd:cd05630 241 C--KDPAER 247
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
225-429 3.75e-16

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 78.90  E-value: 3.75e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVWLGDYE--GKKVAMKSMK-DHlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd07871   6 TYVKLDKLGEGTYATVFKGRSKltENLVALKEIRlEH--EEGAPCTAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFE 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMaKGSLIDYLRSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS-NVKQEG 380
Cdd:cd07871  84 YL-DSDLKQYLDNCGN-LMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARAKSvPTKTYS 161
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 381 AKLPVKWTAPE--ALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVED 429
Cdd:cd07871 162 NEVVTLWYRPPdvLLGSTEYSTPIDMWGVGCILYEMAT-GRPMFPGSTVKE 211
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
279-465 4.57e-16

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: 78.53  E-value: 4.57e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 279 RHPNLVCLIGISLDDNPIYLITEFMAKGSLID-YLRSRgraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA 357
Cdd:cd14175  53 QHPNIITLKDVYDDGKHVYLVTELMRGGELLDkILRQK---FFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYV 129
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 358 EDN----VAKVSDFGLAKsssNVKQEGAKL-----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPV- 427
Cdd:cd14175 130 DESgnpeSLRICDFGFAK---QLRAENGLLmtpcyTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPFANGPSd 205
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18150824 428 --EDVANHVENGyRMESPDGCPDQIYKIMMDCWEK----DPSQR 465
Cdd:cd14175 206 tpEEILTRIGSG-KFTLSGGNWNTVSDAAKDLVSKmlhvDPHQR 248
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
105-198 4.68e-16

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 73.48  E-value: 4.68e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYDGR----VENYRVRRNEKGLVTVDDDEYFDNL 177
Cdd:cd10364   1 ETEEWFFKDITRKDAERQLLAPGNsaGAFLIRESETLKGSYSLSVrDYDPQhgdvIKHYKIRSLDNGGYYISPRITFPCI 80
                        90       100
                ....*....|....*....|.
gi 18150824 178 IKLVEHYQKEADGLCTRLKAP 198
Cdd:cd10364  81 SDMIKHYQKQSDGLCRRLEKA 101
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
232-471 4.74e-16

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: 77.90  E-value: 4.74e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMKSMKDHLKDEKAKTQFLA-EASVMTTLRHPNLVCLIGI-SLDDNPIYLITEFMAKGS 307
Cdd:cd14165   9 LGEGSYAKVksAYSERLKCNVAIKIIDKKKAPDDFVEKFLPrELEILARLNHKSIIKTYEIfETSDGKVYIVMELGVQGD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGrAVITKQNQIDFaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSsnVKQEGAKLPVKW 387
Cdd:cd14165  89 LLEFIKLRG-ALPEDVARKMF-HQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRC--LRDENGRIVLSK 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 T--------APEALRENKFSNKT-DVWSFGVLLWeIYSYGRVPYPRVPV-----EDVANHVENGYRMESPDGCPDQIYKI 453
Cdd:cd14165 165 TfcgsaayaAPEVLQGIPYDPRIyDIWSLGVILY-IMVCGSMPYDDSNVkkmlkIQKEHRVRFPRSKNLTSECKDLIYRL 243
                       250
                ....*....|....*...
gi 18150824 454 MmdcwEKDPSQRPNFTRI 471
Cdd:cd14165 244 L----QPDVSQRLCIDEV 257
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
229-467 5.45e-16

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 78.49  E-value: 5.45e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEGKK----VAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd08216   3 LYEIGKCFKGGGVVHLAKHKPtntlVAVKKINLESDSKEDLKFLQQEILTSRQLQHPNILPYVTSFVVDNDLYVVTPLMA 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLR---SRG--RAVITkqnQIdfARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSdfGLAKSSSNVKQE 379
Cdd:cd08216  83 YGSCRDLLKthfPEGlpELAIA---FI--LRDVLNALEYIHSKGYIHRSVKASHILISGDGKVVLS--GLRYAYSMVKHG 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 380 GAKLPV-----------KWTAPEALREN--KFSNKTDVWSFGVLLWEIYSyGRVPYPRVP-------------------- 426
Cdd:cd08216 156 KRQRVVhdfpksseknlPWLSPEVLQQNllGYNEKSDIYSVGITACELAN-GVVPFSDMPatqmllekvrgttpqlldcs 234
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 427 ----VEDVANHVENGYRMESPDGCPDQIY----------KIMMDCWEKDPSQRPN 467
Cdd:cd08216 235 typlEEDSMSQSEDSSTEHPNNRDTRDIPyqrtfseafhQFVELCLQRDPELRPS 289
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
107-198 5.66e-16

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 73.42  E-value: 5.66e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 107 MPWFHGRISREDAEKLL--TPPKNGRFLVRESQNYpGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHY 184
Cdd:cd10402  10 MPWYHGSIARDEAERRLysGAQPDGKFLLRERKES-GTYALSLVYGKTVYHYRIDQDKSGKYSIPEGTKFDTLWQLVEYL 88
                        90
                ....*....|....
gi 18150824 185 QKEADGLCTRLKAP 198
Cdd:cd10402  89 KLKPDGLIFVLRES 102
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
232-467 6.56e-16

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 78.55  E-value: 6.56e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQ-FLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFmAKGSL 308
Cdd:cd06635  33 IGHGSFGAVYFARdvRTSEVVAIKKMSYSGKQSNEKWQdIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEY-CLGSA 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVitkqNQIDFA---RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVkQEGAKLPV 385
Cdd:cd06635 112 SDLLEVHKKPL----QEIEIAaitHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASPA-NSFVGTPY 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 kWTAPE---ALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRVPVEDVANHVENGyrmESP----DGCPDQIYKIMMDCW 458
Cdd:cd06635 187 -WMAPEvilAMDEGQYDGKVDVWSLGITCIEL-AERKPPLFNMNAMSALYHIAQN---ESPtlqsNEWSDYFRNFVDSCL 261

                ....*....
gi 18150824 459 EKDPSQRPN 467
Cdd:cd06635 262 QKIPQDRPT 270
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
231-422 7.53e-16

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: 78.50  E-value: 7.53e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK--VAMKSMKDH--LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05616   7 VLGKGSFGKVMLAERKGTDelYAVKILKKDvvIQDDDVECTMVEKRVLALSGKPPFLTQLHSCFQTMDRLYFVMEYVNGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSS--SNVKQEGAKLP 384
Cdd:cd05616  87 DLMYHIQQVGR--FKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENiwDGVTTKTFCGT 164
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 385 VKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05616 165 PDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPF 201
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
280-422 8.56e-16

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: 77.99  E-value: 8.56e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 280 HPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQIdfARDVVKGMVYLESQNFVHRDLAARNVLIAED 359
Cdd:cd14180  60 HPNIVALHEVLHDQYHTYLVMELLRGGELLDRIKKKARFSESEASQL--MRSLVSAVSFMHEAGVVHRDLKPENILYADE 137
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18150824 360 N---VAKVSDFGLAKsssnVKQEGAK------LPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14180 138 SdgaVLKVIDFGFAR----LRPQGSRplqtpcFTLQYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPF 204
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
228-416 8.78e-16

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: 78.18  E-value: 8.78e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGD--YEGKKVAMKSmkdhLKDEKAKTQF----LAEASVMTTLRHPNLVCLIGI--------SLDD 293
Cdd:cd07865  16 KLAKIGQGTFGEVFKARhrKTGQIVALKK----VLMENEKEGFpitaLREIKILQLLKHENVVNLIEIcrtkatpyNRYK 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 294 NPIYLITEFMAkgslidylrsRGRAVITKQNQIDFARDVVK--------GMVYLESQNFVHRDLAARNVLIAEDNVAKVS 365
Cdd:cd07865  92 GSIYLVFEFCE----------HDLAGLLSNKNVKFTLSEIKkvmkmllnGLYYIHRNKILHRDMKAANILITKDGVLKLA 161
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18150824 366 DFGLAKSSSNVKQEGaklPVKWT---------APEA-LRENKFSNKTDVWSFGVLLWEIYS 416
Cdd:cd07865 162 DFGLARAFSLAKNSQ---PNRYTnrvvtlwyrPPELlLGERDYGPPIDMWGAGCIMAEMWT 219
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
231-439 9.02e-16

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 77.37  E-value: 9.02e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDyEGKKVAMKSMKDHLKDEKAKTQFLA--EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14088   8 VIKTEEFCEIFRAK-DKTTGKLYTCKKFLKRDGRKVRKAAknEINILKMVKHPNILQLVDVFETRKEYFIFLELATGREV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI---AEDNVAKVSDFGLAKSSSNVKQEGAKLPv 385
Cdd:cd14088  87 FDWILDQG--YYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVYynrLKNSKIVISDFHLAKLENGLIKEPCGTP- 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 386 KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVP-YPRVPVEDVANHVENGYR 439
Cdd:cd14088 164 EYLAPEVVGRQRYGRPVDCWAIGVIMYILLS-GNPPfYDEAEEDDYENHDKNLFR 217
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
232-414 9.22e-16

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 78.48  E-value: 9.22e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  232 IGKGEFGEVWLGDYEGKK---VAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:PTZ00426  38 LGTGSFGRVILATYKNEDfppVAIKRFeKSKIIKQKQVDHVFSERKILNYINHPFCVNLYGSFKDESYLYLVLEFVIGGE 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  308 LIDYLRSRGRAvitkQNQID--FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPv 385
Cdd:PTZ00426 118 FFTFLRRNKRF----PNDVGcfYAAQIVLIFEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVDTRTYTLCGTP- 192
                        170       180
                 ....*....|....*....|....*....
gi 18150824  386 KWTAPEALRENKFSNKTDVWSFGVLLWEI 414
Cdd:PTZ00426 193 EYIAPEILLNVGHGKAADWWTLGIFIYEI 221
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
225-422 1.14e-15

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: 76.88  E-value: 1.14e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEV--WLGDYEGKKVAMKSMKDhlKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd14190   5 SIHSKEVLGGGKFGKVhtCTEKRTGLKLAAKVINK--QNSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEY 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI--AEDNVAKVSDFGLAKSSsnvkQEG 380
Cdd:cd14190  83 VEGGELFERIVDEDYH-LTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARRY----NPR 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18150824 381 AKLPV-----KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14190 158 EKLKVnfgtpEFLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPF 203
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
231-466 1.26e-15

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: 76.87  E-value: 1.26e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKV-AMKSMKDHLKDEKAKTQFLAEASVMTTLRH-PNLVCLIG--ISLDDNPIYLITEFmAKG 306
Cdd:cd14131   8 QLGKGGSSKVYKVLNPKKKIyALKRVDLEGADEQTLQSYKNEIELLKKLKGsDRIIQLYDyeVTDEDDYLYMVMEC-GEI 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVItkqnQIDFARDVVKGMV----YLESQNFVHRDLAARNVLIAEDNVaKVSDFGLAKS----SSNVKQ 378
Cdd:cd14131  87 DLATILKKKRPKPI----DPNFIRYYWKQMLeavhTIHEEGIVHSDLKPANFLLVKGRL-KLIDFGIAKAiqndTTSIVR 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSN----------KTDVWSFGVLLWEIySYGRVPYPRV--PVEDVANHVENGYRMESPDGC 446
Cdd:cd14131 162 DSQVGTLNYMSPEAIKDTSASGegkpkskigrPSDVWSLGCILYQM-VYGKTPFQHItnPIAKLQAIIDPNHEIEFPDIP 240
                       250       260
                ....*....|....*....|
gi 18150824 447 PDQIYKIMMDCWEKDPSQRP 466
Cdd:cd14131 241 NPDLIDVMKRCLQRDPKKRP 260
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
231-422 1.26e-15

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: 77.78  E-value: 1.26e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDHL---KDEKAKTqfLAEASVMTTLRHPNLvcligISLD---DNPIYL--IT 300
Cdd:cd05571   2 VLGKGTFGKVILCREKatGELYAIKILKKEViiaKDEVAHT--LTENRVLQNTRHPFL-----TSLKysfQTNDRLcfVM 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKGSLIDYLrSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK---SSSNVK 377
Cdd:cd05571  75 EYVNGGELFFHL-SRER-VFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCKeeiSYGATT 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 378 QEGAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05571 153 KTFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPF 195
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
228-416 1.31e-15

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: 77.04  E-value: 1.31e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGdYE---GKKVAMKSMK---DHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLD--DNPIYLI 299
Cdd:cd06651  11 RGKLLGQGAFGRVYLC-YDvdtGRELAAKQVQfdpESPETSKEVSALECEIQLLKNLQHERIVQYYGCLRDraEKTLTIF 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:cd06651  90 MEYMPGGSVKDQLKAYG--ALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICMS 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 18150824 380 GAKL-----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYS 416
Cdd:cd06651 168 GTGIrsvtgTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLT 209
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
231-422 1.42e-15

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: 77.28  E-value: 1.42e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKV--AMKSM--KDHLKDEKAKtQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05574   8 LLGKGDVGRVYLVRLKGTGKlfAMKVLdkEEMIKRNKVK-RVLTEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPGG 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQ-------- 378
Cdd:cd05574  87 ELFRLLQKQPGKRLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILLHESGHIMLTDFDLSKQSSVTPPpvrkslrk 166
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 379 ----EGAKLPVKWT-------------------APEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd05574 167 gsrrSSVKSIEKETfvaepsarsnsfvgteeyiAPEVIKGDGHGSAVDWWTLGILLYEML-YGTTPF 232
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
232-422 1.64e-15

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: 76.25  E-value: 1.64e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK---VAMKSMkdhLKDEKAKTQFL--AEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd14120   1 IGHGAFAVVFKGRHRKKPdlpVAIKCI---TKKNLSKSQNLlgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGG 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---------VAKVSDFGLAKsssnVK 377
Cdd:cd14120  78 DLADYLQAKG--TLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSgrkpspndiRLKIADFGFAR----FL 151
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 378 QEG---AKL---PVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14120 152 QDGmmaATLcgsPM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPF 200
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
231-471 1.69e-15

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: 76.17  E-value: 1.69e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQfLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd08219   7 VVGEGSFGRALLVQHVnsDQKYAMKEIRLPKSSSAVEDS-RKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCDGGDL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSN-VKQEGAKLPVKW 387
Cdd:cd08219  86 MQKIKLQRGKLFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSpGAYACTYVGTPY 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 388 TAPEALREN-KFSNKTDVWSFGVLLWEIYSYgRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRP 466
Cdd:cd08219 166 YVPPEIWENmPYNNKSDIWSLGCILYELCTL-KHPFQANSWKNLILKVCQGSYKPLPSHYSYELRSLIKQMFKRNPRSRP 244

                ....*
gi 18150824 467 NFTRI 471
Cdd:cd08219 245 SATTI 249
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
279-465 1.85e-15

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: 76.98  E-value: 1.85e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 279 RHPNLVCLIGISLDDNPIYLITEFMAKGSLID-YLRSRgraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA 357
Cdd:cd14178  55 QHPNIITLKDVYDDGKFVYLVMELMRGGELLDrILRQK---CFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYM 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 358 EDN----VAKVSDFGLAKsssNVKQEGAKL-----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP-- 426
Cdd:cd14178 132 DESgnpeSIRICDFGFAK---QLRAENGLLmtpcyTANFVAPEVLKRQGYDAACDIWSLGILLYTMLA-GFTPFANGPdd 207
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 18150824 427 -VEDVANHVENG-YRMESP--DGCPDQIYKIMMDCWEKDPSQR 465
Cdd:cd14178 208 tPEEILARIGSGkYALSGGnwDSISDAAKDIVSKMLHVDPHQR 250
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
109-198 2.09e-15

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 71.86  E-value: 2.09e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-----SYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10367   5 WYFGKIGRKDAERQLLSPGNprGAFLIRESETTKGAYSLSIrdwdqNRGDHVKHYKIRKLDTGGYYITTRAQFDTVQELV 84
                        90
                ....*....|....*..
gi 18150824 182 EHYQKEADGLCTRLKAP 198
Cdd:cd10367  85 QHYMEVNDGLCYLLTAP 101
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
106-202 2.30e-15

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 71.91  E-value: 2.30e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 106 TMPWFHGRISREDAEKLL-TPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRnEKGLVTVDDDEyFDNLIKLVEHY 184
Cdd:cd09932   3 SKEWFHANLTREQAEEMLmRVPRDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQ-EGRLFVIGTSQ-FESLVELVSYY 80
                        90
                ....*....|....*...
gi 18150824 185 QKEADGLCTRLKAPVDKE 202
Cdd:cd09932  81 EKHPLYRKIKLRYPVNEE 98
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
232-423 2.41e-15

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 77.17  E-value: 2.41e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  232 IGKGEFGEVWLGDYE--GKKVAMKSM-KDHlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:PLN00034  82 IGSGAGGTVYKVIHRptGRLYALKVIyGNH--EDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGSL 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  309 idylrsRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--------SSSNVKQeg 380
Cdd:PLN00034 160 ------EGTHIADEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRilaqtmdpCNSSVGT-- 231
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 18150824  381 aklpVKWTAPEalRENKFSNK-------TDVWSFGVLLWEIYsYGRVPYP 423
Cdd:PLN00034 232 ----IAYMSPE--RINTDLNHgaydgyaGDIWSLGVSILEFY-LGRFPFG 274
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
232-429 2.66e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 76.32  E-value: 2.66e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSLI 309
Cdd:cd07839   8 IGEGTYGTVFKAknRETHEIVALKRVRLDDDDEGVPSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYCDQ-DLK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSrGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-SSNVKQEGAKLPVKW- 387
Cdd:cd07839  87 KYFDS-CNGDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARAfGIPVRCYSAEVVTLWy 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 18150824 388 TAPEALRENK-FSNKTDVWSFGVLLWEIYSYGRVPYPRVPVED 429
Cdd:cd07839 166 RPPDVLFGAKlYSTSIDMWSAGCIFAELANAGRPLFPGNDVDD 208
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
110-193 2.72e-15

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 71.24  E-value: 2.72e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 110 FHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVehyqkeAD 189
Cdd:cd10352   9 YHGLISREEAEQLLSGASDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKNHYHYVGEKRFDTIHDLV------AD 82

                ....
gi 18150824 190 GLCT 193
Cdd:cd10352  83 GLIT 86
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
271-422 2.73e-15

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: 75.83  E-value: 2.73e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSrgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd14194  58 EVSILKEIQHPNVITLHEVYENKTDVILILELVAGGELFDFLAE--KESLTEEEATEFLKQILNGVYYLHSLQIAHFDLK 135
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 351 ARNVLIAEDNVA----KVSDFGLAK--SSSNVKQEGAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14194 136 PENIMLLDRNVPkpriKIIDFGLAHkiDFGNEFKNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
108-199 2.87e-15

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 71.56  E-value: 2.87e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQ-- 185
Cdd:cd09940   6 LWFVGEMERDTAENRLENRPDGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQRSDGLYYLSESRHFKSLVELVNYYErn 85
                        90
                ....*....|....*..
gi 18150824 186 --KEA-DGLCTRLKAPV 199
Cdd:cd09940  86 slGENfAGLDTTLKWPY 102
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
232-368 3.35e-15

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


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 72.47  E-value: 3.35e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL--GDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd13968   1 MGEGASAKVFWaeGECTTIGVAVKIGDDVNNEEGEDLESEMDILRRLKGLELNIPKVLVTEDVDGPNILLMELVKGGTLI 80
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18150824 310 DYLRsrgravITKQNQID---FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFG 368
Cdd:cd13968  81 AYTQ------EEELDEKDvesIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
232-422 3.55e-15

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: 76.27  E-value: 3.55e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKV--AMKSMKDH--LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05592   3 LGKGSFGKVMLAELKGTNQyfAIKALKKDvvLEDDDVECTMIERRVLALASQHPFLTHLFCTFQTESHLFFVMEYLNGGD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKL--- 383
Cdd:cd05592  83 LMFHIQQSGR---FDEDRARFyGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKENIYGENKASTFcgt 159
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 384 PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd05592 160 P-DYIAPEILKGQKYNQSVDWWSFGVLLYEML-IGQSPF 196
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
230-423 3.61e-15

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: 76.19  E-value: 3.61e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYE--GKKVAMKSMK----------DHLKDEKAKTQflaeasVMTTLRHPNLVCLIGISLDDNPIY 297
Cdd:cd05589   5 AVLGRGHFGKVLLAEYKptGELFAIKALKkgdiiardevESLMCEKRIFE------TVNSARHPFLVNLFACFQTPEHVC 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRgraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK 377
Cdd:cd05589  79 FVMEYAAGGDLMMHIHED---VFSEPRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKEGMGFG 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 18150824 378 QEGAKL---PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYP 423
Cdd:cd05589 156 DRTSTFcgtP-EFLAPEVLTDTSYTRAVDWWGLGVLIYEML-VGESPFP 202
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
232-416 3.85e-15

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: 75.59  E-value: 3.85e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMkdHL-KDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSL 308
Cdd:cd07836   8 LGEGTYATVYKGrnRTTGEIVALKEI--HLdAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDK-DL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS--------SSNVkqe 379
Cdd:cd07836  85 KKYMDTHGVRGALDPNTVkSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAfgipvntfSNEV--- 161
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 380 gakLPVKWTAPEALRENK-FSNKTDVWSFGVLLWEIYS 416
Cdd:cd07836 162 ---VTLWYRAPDVLLGSRtYSTSIDIWSVGCIMAEMIT 196
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
279-465 4.05e-15

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: 76.60  E-value: 4.05e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 279 RHPNLVCLIGISLDDNPIYLITEFMAKGSLID-YLRSRgraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA 357
Cdd:cd14176  71 QHPNIITLKDVYDDGKYVYVVTELMKGGELLDkILRQK---FFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYV 147
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 358 EDN----VAKVSDFGLAKsssNVKQEGAKL-----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPvE 428
Cdd:cd14176 148 DESgnpeSIRICDFGFAK---QLRAENGLLmtpcyTANFVAPEVLERQGYDAACDIWSLGVLLYTMLT-GYTPFANGP-D 222
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 18150824 429 DVANHV-----------ENGYRMESPDGCPDQIYKIMmdcwEKDPSQR 465
Cdd:cd14176 223 DTPEEIlarigsgkfslSGGYWNSVSDTAKDLVSKML----HVDPHQR 266
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
109-198 4.10e-15

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 70.82  E-value: 4.10e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV---SYDGRV-ENYRVRRNEKGLVTVDDDEYFDNLIKLVE 182
Cdd:cd10371   5 WFFRTISRKDAERQLLAPMNkaGSFLIRESESNKGAFSLSVkdvTTQGEVvKHYKIRSLDNGGYYISPRITFPTLQALVQ 84
                        90
                ....*....|....*.
gi 18150824 183 HYQKEADGLCTRLKAP 198
Cdd:cd10371  85 HYSKKGDGLCQKLTLP 100
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
109-195 4.98e-15

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 70.82  E-value: 4.98e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYD----GRVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10366   5 WYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIrDWDevrgDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 84
                        90
                ....*....|....
gi 18150824 182 EHYQKEADGLCTRL 195
Cdd:cd10366  85 KHYTEHADGLCHKL 98
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
223-471 5.17e-15

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: 74.85  E-value: 5.17e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 223 KASLLKKslIGKGEFGEVWL-------GDYEGKKVAMKSMKDHLKDEKAKtqflaEASVMTTLRHPNLVCLIGISLDDNP 295
Cdd:cd08218   1 KYVRIKK--IGEGSFGKALLvkskedgKQYVIKEINISKMSPKEREESRK-----EVAVLSKMKHPNIVQYQESFEENGN 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 IYLITEFMAKGSLIDYLRSRgRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS 374
Cdd:cd08218  74 LYIVMDYCDGGDLYKRINAQ-RGVLFPEDQIlDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLN 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 375 NVkQEGAKLPVK---WTAPEALRENKFSNKTDVWSFGVLLWEI------YSYG----------RVPYPRVPVedvanHVE 435
Cdd:cd08218 153 ST-VELARTCIGtpyYLSPEICENKPYNNKSDIWALGCVLYEMctlkhaFEAGnmknlvlkiiRGSYPPVPS-----RYS 226
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 18150824 436 NGYRMespdgcpdqiykIMMDCWEKDPSQRPNFTRI 471
Cdd:cd08218 227 YDLRS------------LVSQLFKRNPRDRPSINSI 250
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
222-426 5.20e-15

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 75.44  E-value: 5.20e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSLIGKGEFGEVWLGDYE--GKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd06657  18 PRTYLDNFIKIGEGSTGIVCIATVKssGKLVAVKKMD--LRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVV 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSrgraviTKQNQIDFAR---DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSN 375
Cdd:cd06657  96 MEFLEGGALTDIVTH------TRMNEEQIAAvclAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFcAQVSKE 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 18150824 376 VKQEGAKLPVK-WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP 426
Cdd:cd06657 170 VPRRKSLVGTPyWMAPELISRLPYGPEVDIWSLGIMVIEMVD-GEPPYFNEP 220
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
227-422 5.93e-15

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: 75.46  E-value: 5.93e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLIGKGEFG--EVWLGDYEGKKVAMKSMKdhlKDEKAKTQflAEASVMTTLR-HPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd14179  10 LKDKPLGEGSFSicRKCLHKKTNQEYAVKIVS---KRMEANTQ--REIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRAVITKQNQIdfARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLA--KSSSNVKQ 378
Cdd:cd14179  85 KGGELLERIKKKQHFSETEASHI--MRKLVSAVSHMHDVGVVHRDLKPENLLFTDESdnsEIKIIDFGFArlKPPDNQPL 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14179 163 KTPCFTLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPF 205
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
271-422 6.35e-15

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: 74.54  E-value: 6.35e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRaVITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd14114  49 EIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLSGGELFERIAAEHY-KMSEAEVINYMRQVCEGLCHMHENNIVHLDIK 127
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 351 ARNVLIA--EDNVAKVSDFGLA-----KSSSNVKQEGAklpvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14114 128 PENIMCTtkRSNEVKLIDFGLAthldpKESVKVTTGTA----EFAAPEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPF 201
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
231-444 7.19e-15

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


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 74.37  E-value: 7.19e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMaKGSL 308
Cdd:cd14082  10 VLGSGQFGIVYGGKHRktGRDVAIKVIDKLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKL-HGDM 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLAK--SSSNVKQEGAKL 383
Cdd:cd14082  89 LEMILSSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARiiGEKSFRRSVVGT 168
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18150824 384 PVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRvpVEDVANHVENGYRMESPD 444
Cdd:cd14082 169 PA-YLAPEVLRNKGYNRSLDMWSVGVIIYVSLS-GTFPFNE--DEDINDQIQNAAFMYPPN 225
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
228-466 7.21e-15

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 75.48  E-value: 7.21e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKA-KTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd06650   9 KISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAiRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYL-ESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPV 385
Cdd:cd06650  89 SLDQVLKKAGR--IPEQILGKVSIAVIKGLTYLrEKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTR 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 KWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYPRvpvedvanhvENGYRMESPDGCPdqiykIMMDCWEKDPSQR 465
Cdd:cd06650 167 SYMSPERLQGTHYSVQSDIWSMGLSLVEM-AVGRYPIPP----------PDAKELELMFGCQ-----VEGDAAETPPRPR 230

                .
gi 18150824 466 P 466
Cdd:cd06650 231 T 231
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
233-462 7.48e-15

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


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 75.08  E-value: 7.48e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 233 GKGEFGEVWLGDYEGKKVAMKSMKDHlkdEKAKTQFLAEASVMTTLRHPNLVCLIGI----SLDDNPIYLITEFMAKGSL 308
Cdd:cd14141   4 ARGRFGCVWKAQLLNEYVAVKIFPIQ---DKLSWQNEYEIYSLPGMKHENILQFIGAekrgTNLDVDLWLITAFHEKGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRgraVITKQNQIDFARDVVKGMVYLESQ----------NFVHRDLAARNVLIAEDNVAKVSDFGLA------KS 372
Cdd:cd14141  81 TDYLKAN---VVSWNELCHIAQTMARGLAYLHEDipglkdghkpAIAHRDIKSKNVLLKNNLTACIADFGLAlkfeagKS 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 373 SSNVK-QEGAKlpvKWTAPEAL------RENKFSnKTDVWSFGVLLWEIYSY-----GRVPYPRVPVEDvanhvENGYRM 440
Cdd:cd14141 158 AGDTHgQVGTR---RYMAPEVLegainfQRDAFL-RIDMYAMGLVLWELASRctasdGPVDEYMLPFEE-----EVGQHP 228
                       250       260
                ....*....|....*....|....*.
gi 18150824 441 ESPDGCPDQIYK----IMMDCWEKDP 462
Cdd:cd14141 229 SLEDMQEVVVHKkkrpVLRECWQKHA 254
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
109-194 7.94e-15

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 70.21  E-value: 7.94e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-----SYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10344  12 WLFEGLSREKAEELLMLPGNqvGSFLIRESETRRGCYSLSVrhrgsQSRDSVKHYRIFRLDNGWFYISPRLTFQCLEDMV 91
                        90
                ....*....|...
gi 18150824 182 EHYQKEADGLCTR 194
Cdd:cd10344  92 NHYSESADGLCCV 104
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
232-413 8.59e-15

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 74.57  E-value: 8.59e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLkDEKAKTQFLAEASVMTTLRHPNLV--CLI----GISLDDNPIyLITEFM 303
Cdd:cd14039   1 LGTGGFGNVCLYQNQetGEKIAIKSCRLEL-SVKNKDRWCHEIQIMKKLNHPNVVkaCDVpeemNFLVNDVPL-LAMEYC 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRAVITKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLAKS------- 372
Cdd:cd14039  79 SGGDLRKLLNKPENCCGLKESQVlSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEINgkiVHKIIDLGYAKDldqgslc 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 18150824 373 SSNVKQegaklpVKWTAPEALRENKFSNKTDVWSFGVLLWE 413
Cdd:cd14039 159 TSFVGT------LQYLAPELFENKSYTVTVDYWSFGTMVFE 193
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
109-198 9.40e-15

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 70.03  E-value: 9.40e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYD----GRVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10418   5 WYFGKLGRKDAERQLLSFGNprGTFLIRESETTKGAYSLSIrDWDdmkgDHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....*..
gi 18150824 182 EHYQKEADGLCTRLKAP 198
Cdd:cd10418  85 QHYSERAAGLCCRLVVP 101
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
232-416 9.55e-15

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: 75.55  E-value: 9.55e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW-LGD-YEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNP-----IYLITEFMa 304
Cdd:cd07853   8 IGYGAFGVVWsVTDpRDGKRVALKKMPNVFQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIdpfeeIYVVTELM- 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 kgslidylRSRGRAVITKQNQID------FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK-----SS 373
Cdd:cd07853  87 --------QSDLHKIIVSPQPLSsdhvkvFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARveepdES 158
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18150824 374 SNVKQEgaKLPVKWTAPEALRENK-FSNKTDVWSFGVLLWEIYS 416
Cdd:cd07853 159 KHMTQE--VVTQYYRAPEILMGSRhYTSAVDIWSVGCIFAELLG 200
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
230-416 9.61e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 74.84  E-value: 9.61e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLG--DYEGKKVAMKSMKdhLKDEKAKTQFLA--EASVMTTLRHPNLVCLIGISLDDNP---------- 295
Cdd:cd07864  13 GIIGEGTYGQVYKAkdKDTGELVALKKVR--LDNEKEGFPITAirEIKILRQLNHRSVVNLKEIVTDKQDaldfkkdkga 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 IYLITEFMAKgSLIDYLRSrGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SS 373
Cdd:cd07864  91 FYLVFEYMDH-DLMGLLES-GLVHFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLARlyNS 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 374 SNVKQEGAKLPVKWTAPEALR--ENKFSNKTDVWSFGVLLWEIYS 416
Cdd:cd07864 169 EESRPYTNKVITLWYRPPELLlgEERYGPAIDVWSCGCILGELFT 213
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
231-422 9.72e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 75.44  E-value: 9.72e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKKV--AMKSM-KDHLKDEKAKTQFLAEASVM-TTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05602  14 VIGKGSFGKVLLARHKSDEKfyAVKVLqKKAILKKKEEKHIMSERNVLlKNVKHPFLVGLHFSFQTTDKLYFVLDYINGG 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRsRGRAVITKQNQIdFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKssSNVKQEGAKLPV- 385
Cdd:cd05602  94 ELFYHLQ-RERCFLEPRARF-YAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCK--ENIEPNGTTSTFc 169
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 386 ---KWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPY 422
Cdd:cd05602 170 gtpEYLAPEVLHKQPYDRTVDWWCLGAVLYEML-YGLPPF 208
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
229-410 1.33e-14

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: 73.77  E-value: 1.33e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYEGKKVAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14107   7 KEEIGRGTFGFVKRVTHKGNGECCAAKFIPLR-SSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSSEEL 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA----EDnvAKVSDFGLAKSSSNVKQEGAKLP 384
Cdd:cd14107  86 LDRLFLKG--VVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVsptrED--IKICDFGFAQEITPSEHQFSKYG 161
                       170       180
                ....*....|....*....|....*..
gi 18150824 385 V-KWTAPEALRENKFSNKTDVWSFGVL 410
Cdd:cd14107 162 SpEFVAPEIVHQEPVSAATDIWALGVI 188
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
226-465 1.36e-14

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: 74.27  E-value: 1.36e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKksLIGKGEFGEVWL-----GDYEGKKVAMKSMKDHLKDEKAKT--QFLAEASVMTTLRH-PNLVCLIGISLDDNPIY 297
Cdd:cd05613   4 LLK--VLGTGAYGKVFLvrkvsGHDAGKLYAMKVLKKATIVQKAKTaeHTRTERQVLEHIRQsPFLVTLHYAFQTDTKLH 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK 377
Cdd:cd05613  82 LILDYINGGELFTHLSQRER--FTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDE 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKL---PVKWTAPEALR--ENKFSNKTDVWSFGVLLWEIYSyGRVPYP----RVPVEDVANHV---ENGYRMESPDG 445
Cdd:cd05613 160 NERAYSfcgTIEYMAPEIVRggDSGHDKAVDWWSLGVLMYELLT-GASPFTvdgeKNSQAEISRRIlksEPPYPQEMSAL 238
                       250       260
                ....*....|....*....|
gi 18150824 446 CPDQIYKIMMdcweKDPSQR 465
Cdd:cd05613 239 AKDIIQRLLM----KDPKKR 254
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
230-423 1.36e-14

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 74.82  E-value: 1.36e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVW--LGDYEGKKVAMKSMKD---HLKDekaKTQFLAEASVMTTLRHPNLVCLIGISLDDNP-----IYLI 299
Cdd:cd07859   6 EVIGKGSYGVVCsaIDTHTGEKVAIKKINDvfeHVSD---ATRILREIKLLRLLRHPDIVEIKHIMLPPSRrefkdIYVV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMaKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvkqe 379
Cdd:cd07859  83 FELM-ESDLHQVIKANDD--LTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVAFN---- 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 380 GAKLPVKWT---------APEALRE--NKFSNKTDVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07859 156 DTPTAIFWTdyvatrwyrAPELCGSffSKYTPAIDIWSIGCIFAEVLT-GKPLFP 209
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
232-411 1.39e-14

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: 73.51  E-value: 1.39e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKdhlKDEKAKTQFLAEASVMTTLR-HPNLVCLIGISLDDNPIYLIT-EFMAKGS 307
Cdd:cd13987   1 LGEGTYGKVLLAVHKgsGTKMALKFVP---KPSTKLKDFLREYNISLELSvHPHIIKTYDVAFETEDYYVFAqEYAPYGD 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LidylrsrgRAVITKQNQIDfaRDVVKGMV--------YLESQNFVHRDLAARNVLI--AEDNVAKVSDFGLA-KSSSNV 376
Cdd:cd13987  78 L--------FSIIPPQVGLP--EERVKRCAaqlasaldFMHSKNLVHRDIKPENVLLfdKDCRRVKLCDFGLTrRVGSTV 147
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKLPvkWTAPE---ALRENKFS--NKTDVWSFGVLL 411
Cdd:cd13987 148 KRVSGTIP--YTAPEvceAKKNEGFVvdPSIDVWAFGVLL 185
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
234-416 1.45e-14

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


Pssm-ID: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 74.30  E-value: 1.45e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 234 KGEFGEVWLGDYEGKKVAMKSMKdhLKDekaKTQFLAEASVMTT--LRHPNLVCLI-----GISLDDNpIYLITEFMAKG 306
Cdd:cd14140   5 RGRFGCVWKAQLMNEYVAVKIFP--IQD---KQSWQSEREIFSTpgMKHENLLQFIaaekrGSNLEME-LWLITAFHDKG 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRgraVITKQNQIDFARDVVKGMVYLESQ-----------NFVHRDLAARNVLIAEDNVAKVSDFGLAksssn 375
Cdd:cd14140  79 SLTDYLKGN---IVSWNELCHIAETMARGLSYLHEDvprckgeghkpAIAHRDFKSKNVLLKNDLTAVLADFGLA----- 150
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824 376 VKQEGAKLP---------VKWTAPEAL------RENKFSnKTDVWSFGVLLWEIYS 416
Cdd:cd14140 151 VRFEPGKPPgdthgqvgtRRYMAPEVLegainfQRDSFL-RIDMYAMGLVLWELVS 205
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
232-466 1.48e-14

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: 73.47  E-value: 1.48e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKK--VAMKSMKDHLKDekaKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14113  15 LGRGRFSVVKKCDQRGTKraVATKFVNKKLMK---RDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRLL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLA---KSSSNVKQEGAKl 383
Cdd:cd14113  92 DYVVRWGN--LTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQSLskpTIKLADFGDAvqlNTTYYIHQLLGS- 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 pVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVAnhvENGYRMES--PD----GCPDQIYKIMMDC 457
Cdd:cd14113 169 -PEFAAPEIILGNPVSLTSDLWSIGVLTYVLLS-GVSPFLDESVEETC---LNICRLDFsfPDdyfkGVSQKAKDFVCFL 243

                ....*....
gi 18150824 458 WEKDPSQRP 466
Cdd:cd14113 244 LQMDPAKRP 252
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
223-465 1.63e-14

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: 74.24  E-value: 1.63e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 223 KASLLKKSLIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLI 299
Cdd:cd05632   1 KNTFRQYRVLGKGGFGEVCACQVRatGKMYACKRLeKKRIKKRKGESMALNEKQILEKVNSQFVVNLAYAYETKDALCLV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-KSSSNVKQ 378
Cdd:cd05632  81 LTIMNGGDLKFHIYNMGNPGFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAvKIPEGESI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 379 EGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY----PRVPVEDVANHVENGYRMESPDGCPD--QIYK 452
Cdd:cd05632 161 RGRVGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE-GQSPFrgrkEKVKREEVDRRVLETEEVYSAKFSEEakSICK 239
                       250
                ....*....|...
gi 18150824 453 IMMdcwEKDPSQR 465
Cdd:cd05632 240 MLL---TKDPKQR 249
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
279-426 1.69e-14

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: 73.90  E-value: 1.69e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 279 RHPNLVCLIGISLDDNPIYLITEFMAKGSLIDylRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE 358
Cdd:cd14177  56 QHPNIITLKDVYDDGRYVYLVTELMKGGELLD--RILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYMD 133
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 359 DNVA----KVSDFGLAKsssNVKQEGAKL-----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVP 426
Cdd:cd14177 134 DSANadsiRICDFGFAK---QLRGENGLLltpcyTANFVAPEVLMRQGYDAACDIWSLGVLLYTMLA-GYTPFANGP 206
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
228-422 1.88e-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: 73.41  E-value: 1.88e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 228 KKSLIGKGEFGEVWLGDYE--GKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd14193   8 KEEILGGGRFGQVHKCEEKssGLKLAAKIIK--ARSQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDG 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA--EDNVAKVSDFGLAKSSsnvkQEGAKL 383
Cdd:cd14193  86 GELFDRIIDENYN-LTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVsrEANQVKIIDFGLARRY----KPREKL 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18150824 384 PV-----KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14193 161 RVnfgtpEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPF 203
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
232-422 1.91e-14

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 76.31  E-value: 1.91e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   232 IGKGEFGEVWLGDYEG-------KKVAMKSMKdhlkdEKAKTQFLAEASVMTTLRHPNLVCLIGISLD--DNPIYLITEF 302
Cdd:PTZ00266   21 IGNGRFGEVFLVKHKRtqeffcwKAISYRGLK-----EREKSQLVIEVNVMRELKHKNIVRYIDRFLNkaNQKLYILMEF 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824   303 MAKGSLIDYLRS--RGRAVITKQNQIDFARDVVKGMVYLES-------QNFVHRDLAARNVLI-----------AEDN-- 360
Cdd:PTZ00266   96 CDAGDLSRNIQKcyKMFGKIEEHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIFLstgirhigkitAQANnl 175
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824   361 ----VAKVSDFGLAKS--SSNVKQEGAKLPVKWTAPEALRENK-FSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:PTZ00266  176 ngrpIAKIGDFGLSKNigIESMAHSCVGTPYYWSPELLLHETKsYDDKSDMWALGCIIYELCS-GKTPF 243
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
232-422 1.95e-14

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: 73.97  E-value: 1.95e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL-----GDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05582   3 LGQGSFGKVFLvrkitGPDAGTLYAMKVLKKATLKVRDRVRTKMERDILADVNHPFIVKLHYAFQTEGKLYLILDFLRGG 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLrsrgravitkQNQIDFARDVVK--------GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQ 378
Cdd:cd05582  83 DLFTRL----------SKEVMFTEEDVKfylaelalALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEK 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 379 EGAKL--PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05582 153 KAYSFcgTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPF 197
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
232-422 2.05e-14

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: 73.11  E-value: 2.05e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW-LGDYEGKKV-AMKSMKDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14191  10 LGSGKFGQVFrLVEKKTKKVwAGKFFKAYSAKEKENIR--QEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSGGELF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVS--DFGLAKSSSNvkqeGAKLPV-- 385
Cdd:cd14191  88 ERIIDEDFE-LTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTKIKliDFGLARRLEN----AGSLKVlf 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 386 ---KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14191 163 gtpEFVAPEVINYEPIGYATDMWSIGVICYILVS-GLSPF 201
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
280-422 2.32e-14

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: 73.87  E-value: 2.32e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 280 HPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA-- 357
Cdd:cd14092  58 HPNIVKLHEVFQDELHTYLVMELLRGGELLERIRKKKR--FTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTde 135
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 358 -EDNVAKVSDFGLAKsssnVKQEGAKL--P---VKWTAPEALR----ENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14092 136 dDDAEIKIVDFGFAR----LKPENQPLktPcftLPYAAPEVLKqalsTQGYDESCDLWSLGVILYTMLS-GQVPF 205
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
232-416 2.39e-14

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: 73.46  E-value: 2.39e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEKAKTQfLAEASVMTTLR-HPNLVCLIGISLDDNP--IYLITEFMaKG 306
Cdd:cd07831   7 IGEGTFSEVLKAQSrkTGKYYAIKCMKKHFKSLEQVNN-LREIQALRRLSpHPNILRLIEVLFDRKTgrLALVFELM-DM 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRAVitKQNQI-DFARDVVKGMVYLESQNFVHRDLAARNVLIaEDNVAKVSDFGLAKSSSnvkqegAKLP- 384
Cdd:cd07831  85 NLYELIKGRKRPL--PEKRVkNYMYQLLKSLDHMHRNGIFHRDIKPENILI-KDDILKLADFGSCRGIY------SKPPy 155
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 385 -----VKW-TAPEALRENKFSN-KTDVWSFGVLLWEIYS 416
Cdd:cd07831 156 teyisTRWyRAPECLLTDGYYGpKMDIWAVGCVFFEILS 194
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
267-466 2.41e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 73.37  E-value: 2.41e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 267 QFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLiDYLRSRGRAVITKqnqidFARDVVKGMVYLESQNFVH 346
Cdd:cd06619  45 QIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGGSL-DVYRKIPEHVLGR-----IAVAVVKGLTYLWSLKILH 118
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 347 RDLAARNVLIAEDNVAKVSDFGLaksSSNVKQEGAKLPV---KWTAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYP 423
Cdd:cd06619 119 RDVKPSNMLVNTRGQVKLCDFGV---STQLVNSIAKTYVgtnAYMAPERISGEQYGIHSDVWSLGISFMEL-ALGRFPYP 194
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824 424 R--------VPVEDVANHVEngyrmESPDGCPDQIYK-----IMMDCWEKDPSQRP 466
Cdd:cd06619 195 QiqknqgslMPLQLLQCIVD-----EDPPVLPVGQFSekfvhFITQCMRKQPKERP 245
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
247-410 2.41e-14

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: 73.03  E-value: 2.41e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 247 GKKVAMKSMKDHLKDekaKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRgrAVITKQNQI 326
Cdd:cd14110  28 GQMLAAKIIPYKPED---KQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSGPELLYNLAER--NSYSEAEVT 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 327 DFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVK---QEGAKLPVKWTAPEALRENKFSNKTD 403
Cdd:cd14110 103 DYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKvlmTDKKGDYVETMAPELLEGQGAGPQTD 182

                ....*..
gi 18150824 404 VWSFGVL 410
Cdd:cd14110 183 IWAIGVT 189
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
109-184 2.67e-14

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 68.65  E-value: 2.67e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVR--RNEKGLVTVDD--DEYFDNLIKLVEHY 184
Cdd:cd09926   9 WYFGPMSRQEAQELLQGQRHGVFLVRDSSTIPGDYVLSVSENSRVSHYIINslGQPAPNQSRYRigDQEFDDLPALLEFY 88
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
231-466 2.71e-14

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 73.17  E-value: 2.71e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSMKdHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14046  13 VLGKGAFGQVVKvrNKLDGRYYAIKKIK-LRSESKNNSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCEKSTL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRgravitKQNQIDFA----RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvKQEGAKLP 384
Cdd:cd14046  92 RDLIDSG------LFQDTDRLwrlfRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLATSNKL-NVELATQD 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VK---------------------WTAPEAL--RENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVPVEDVANHVENgyrmE 441
Cdd:cd14046 165 INkstsaalgssgdltgnvgtalYVAPEVQsgTKSTYNEKVDMYSLGIIFFEMCYPFSTGMERVQILTALRSVSI----E 240
                       250       260
                ....*....|....*....|....*....
gi 18150824 442 SPDGCPDQIY----KIMMDCWEKDPSQRP 466
Cdd:cd14046 241 FPPDFDDNKHskqaKLIRWLLNHDPAKRP 269
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
271-473 2.75e-14

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: 72.68  E-value: 2.75e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNP--IYLITEFmAKGSLIDYLRSRGRAVI-TKQNQIDFARdVVKGMVYLESQNFVHR 347
Cdd:cd14119  44 EIQILRRLNHRNVIKLVDVLYNEEKqkLYMVMEY-CVGGLQEMLDSAPDKRLpIWQAHGYFVQ-LIDGLEYLHSQGIIHK 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 348 DLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGA-----KLPvKWTAPEALRENK-FSN-KTDVWSFGVLLWEIYSyGRV 420
Cdd:cd14119 122 DIKPGNLLLTTDGTLKISDFGVAEALDLFAEDDTcttsqGSP-AFQPPEIANGQDsFSGfKVDIWSAGVTLYNMTT-GKY 199
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 18150824 421 PYPRVPVEDVANHVENG-YRMesPDGCPDQIYKIMMDCWEKDPSQRPNFTRIEK 473
Cdd:cd14119 200 PFEGDNIYKLFENIGKGeYTI--PDDVDPDLQDLLRGMLEKDPEKRFTIEQIRQ 251
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
109-191 2.78e-14

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 68.22  E-value: 2.78e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLL--TPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQK 186
Cdd:cd10348   2 WLHGALDRNEAVEILkqKADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDDGPYFESLEHLIEHYTQ 81

                ....*
gi 18150824 187 EADGL 191
Cdd:cd10348  82 FADGL 86
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
232-415 3.24e-14

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 73.14  E-value: 3.24e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVM---TTLRHPNLV-----CLIGISLDDNPIYLIT 300
Cdd:cd07862   9 IGEGAYGKVFKArDLKngGRFVALKRVRVQTGEEGMPLSTIREVAVLrhlETFEHPNVVrlfdvCTVSRTDRETKLTLVF 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKgSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEG 380
Cdd:cd07862  89 EHVDQ-DLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALT 167
                       170       180       190
                ....*....|....*....|....*....|....*.
gi 18150824 381 AKLPVKW-TAPEALRENKFSNKTDVWSFGVLLWEIY 415
Cdd:cd07862 168 SVVVTLWyRAPEVLLQSSYATPVDLWSVGCIFAEMF 203
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
231-408 3.31e-14

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 72.92  E-value: 3.31e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLG-DYE-GKKVAMKSMkdhLKDEKAKTQflaEASVMTTLRHPNLVCLIG--ISLDDNP--IYL--ITEF 302
Cdd:cd14137  11 VIGSGSFGVVYQAkLLEtGEVVAIKKV---LQDKRYKNR---ELQIMRRLKHPNIVKLKYffYSSGEKKdeVYLnlVMEY 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKgSLIDYLRSRGRAvitkQNQID------FARDVVKGMVYLESQNFVHRDLAARNVLI-AEDNVAKVSDFGLAK---- 371
Cdd:cd14137  85 MPE-TLYRVIRHYSKN----KQTIPiiyvklYSYQLFRGLAYLHSLGICHRDIKPQNLLVdPETGVLKLCDFGSAKrlvp 159
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 372 SSSNVkqegaklpvkwT--------APEALRENK-FSNKTDVWSFG 408
Cdd:cd14137 160 GEPNV-----------SyicsryyrAPELIFGATdYTTAIDIWSAG 194
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
229-422 3.36e-14

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: 73.50  E-value: 3.36e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWL------GDYegkkVAMKSMKDH-LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd05601   6 KNVIGRGHFGEVQVvkekatGDI----YAMKVLKKSeTLAQEEVSFFEEERDIMAKANSPWITKLQYAFQDSENLYLVME 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLrSRGRAVITKqnqiDFARDVVKGMVY----LESQNFVHRDLAARNVLIAEDNVAKVSDFG-LAKSSSNv 376
Cdd:cd05601  82 YHPGGDLLSLL-SRYDDIFEE----SMARFYLAELVLaihsLHSMGYVHRDIKPENILIDRTGHIKLADFGsAAKLSSD- 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 377 KQEGAKLPV---KWTAPEAL-RENKFSNKT-----DVWSFGVLLWEIYsYGRVPY 422
Cdd:cd05601 156 KTVTSKMPVgtpDYIAPEVLtSMNGGSKGTygvecDWWSLGIVAYEML-YGKTPF 209
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
231-412 3.70e-14

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: 72.37  E-value: 3.70e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEV--WLGDYEGKKVAMKSM-------KDHLKDEkaktqflaEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd14184   8 VIGDGNFAVVkeCVERSTGKEFALKIIdkakccgKEHLIEN--------EVSILRRVKHPNIIMLIEEMDTPAELYLVME 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE----DNVAKVSDFGLAKSSSNVK 377
Cdd:cd14184  80 LVKGGDLFDAITSSTK--YTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCEypdgTKSLKLGDFGLATVVEGPL 157
                       170       180       190
                ....*....|....*....|....*....|....*
gi 18150824 378 QEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14184 158 YTVCGTPT-YVAPEIIAETGYGLKVDIWAAGVITY 191
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
226-410 4.07e-14

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: 72.26  E-value: 4.07e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKKSLIGKGEFGEV--WLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVM-TTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd14198  10 ILTSKELGRGKFAVVrqCISKSTGQEYAAKFLKKRRRGQDCRAEILHEIAVLeLAKSNPRVVNLHEVYETTSEIILILEY 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV---AKVSDFGLAK--SSSNVK 377
Cdd:cd14198  90 AAGGEIFNLCVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFGMSRkiGHACEL 169
                       170       180       190
                ....*....|....*....|....*....|...
gi 18150824 378 QEGAKLPvKWTAPEALRENKFSNKTDVWSFGVL 410
Cdd:cd14198 170 REIMGTP-EYLAPEILNYDPITTATDMWNIGVI 201
PHA02988 PHA02988
hypothetical protein; Provisional
243-471 4.31e-14

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 72.47  E-value: 4.31e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  243 GDYEGKKVAMKSMKDHLKDEKAKT-QFLAEASVMTTLRHPNLVCLIGISL---DDNP-IYLITEFMAKGSLIDYLRSRGR 317
Cdd:PHA02988  39 GIFNNKEVIIRTFKKFHKGHKVLIdITENEIKNLRRIDSNNILKIYGFIIdivDDLPrLSLILEYCTRGYLREVLDKEKD 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  318 avITKQNQIDFARDVVKGMVYL-ESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVKWtaPEALREN 396
Cdd:PHA02988 119 --LSFKTKLDMAIDCCKGLYNLyKYTNKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNFMVYF--SYKMLND 194
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824  397 KFSNKT---DVWSFGVLLWEIYSyGRVPYPRVPVEDVANH-VENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:PHA02988 195 IFSEYTikdDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLiINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEI 272
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
279-412 5.10e-14

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: 72.00  E-value: 5.10e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 279 RHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSrgraVIT---KQNQIdFARDVVKGMVYLESQNFVHRDLAARNVL 355
Cdd:cd14093  67 GHPNIIELHDVFESPTFIFLVFELCRKGELFDYLTE----VVTlseKKTRR-IMRQLFEAVEFLHSLNIVHRDLKPENIL 141
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 356 IAEDNVAKVSDFGLAKsssnVKQEGAKL------PvKWTAPEALRENKFSN------KTDVWSFGVLLW 412
Cdd:cd14093 142 LDDNLNVKISDFGFAT----RLDEGEKLrelcgtP-GYLAPEVLKCSMYDNapgygkEVDMWACGVIMY 205
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
230-422 5.47e-14

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: 72.82  E-value: 5.47e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWL-----GDYEGKKVAMKSMKDH--LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd05584   2 KVLGKGGYGKVFQvrkttGSDKGKIFAMKVLKKAsiVRNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILEY 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGravITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkQEGA 381
Cdd:cd05584  82 LSGGELFMHLEREG---IFMEDTACFyLAEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKESI---HDGT 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 382 KL-----PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05584 156 VThtfcgTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLT-GAPPF 200
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
232-413 5.56e-14

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 72.30  E-value: 5.56e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMKSMKDHLKdEKAKTQFLAEASVMTTLRHPNLVC-------LIGISLDDNPIyLITEF 302
Cdd:cd14038   2 LGTGGFGNVlrWINQETGEQVAIKQCRQELS-PKNRERWCLEIQIMKRLNHPNVVAardvpegLQKLAPNDLPL-LAMEY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRS-------RGRAVITkqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDN---VAKVSDFGLAK- 371
Cdd:cd14038  80 CQGGDLRKYLNQfenccglREGAILT------LLSDISSALRYLHENRIIHRDLKPENIVLQQGEqrlIHKIIDLGYAKe 153
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 372 ---SSSNVKQEGAklpVKWTAPEALRENKFSNKTDVWSFGVLLWE 413
Cdd:cd14038 154 ldqGSLCTSFVGT---LQYLAPELLEQQKYTVTVDYWSFGTLAFE 195
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
227-412 5.90e-14

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: 71.94  E-value: 5.90e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLIGKGEFGEVwLGDYE---GKKVAMKSMKDHLKDEKaKTQFLAEASvmttlRHPNLVCLIGISLD----DNPIYLI 299
Cdd:cd14172   7 LSKQVLGLGVNGKV-LECFHrrtGQKCALKLLYDSPKARR-EVEHHWRAS-----GGPHIVHILDVYENmhhgKRCLLII 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA---EDNVAKVSDFGLAKSSS-- 374
Cdd:cd14172  80 MECMEGGELFSRIQERGDQAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTskeKDAVLKLTDFGFAKETTvq 159
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 375 NVKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14172 160 NALQTPCYTPY-YVAPEVLGPEKYDKSCDMWSLGVIMY 196
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
231-423 6.09e-14

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 72.34  E-value: 6.09e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK--VAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSL 308
Cdd:cd07848   8 VVGEGAYGVVLKCRHKETKeiVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEK-NM 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQiDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLPVK 386
Cdd:cd07848  87 LELLEEMPNGVPPEKVR-SYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARnlSEGSNANYTEYVATR 165
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 387 W-TAPEALRENKFSNKTDVWSFGVLLWEIySYGRVPYP 423
Cdd:cd07848 166 WyRSPELLLGAPYGKAVDMWSVGCILGEL-SDGQPLFP 202
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
231-414 6.44e-14

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 72.44  E-value: 6.44e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDY--EGKKVAMKSMK---DHLKDEKAKTQFLAEASvmttlRHPNLVCLIGISLDDNP------IYLI 299
Cdd:cd06637  13 LVGNGTYGQVYKGRHvkTGQLAAIKVMDvtgDEEEEIKQEINMLKKYS-----HHRNIATYYGAFIKKNPpgmddqLWLV 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNVKQ 378
Cdd:cd06637  88 MEFCGAGSVTDLIKNTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVsAQLDRTVGR 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 18150824 379 EGAKLPVK-WTAPE--ALREN---KFSNKTDVWSFGVLLWEI 414
Cdd:cd06637 168 RNTFIGTPyWMAPEviACDENpdaTYDFKSDLWSLGITAIEM 209
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
231-414 6.55e-14

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 71.96  E-value: 6.55e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDY--EGKKVAMKSM---KDHLKDEKAKTQFLAEASvmttlRHPNLVCLIGISLDDNP------IYLI 299
Cdd:cd06636  23 VVGNGTYGQVYKGRHvkTGQLAAIKVMdvtEDEEEEIKLEINMLKKYS-----HHRNIATYYGAFIKKSPpghddqLWLV 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKGSLIDYLR-SRGRAVitKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGL-AKSSSNV 376
Cdd:cd06636  98 MEFCGAGSVTDLVKnTKGNAL--KEDWIAYiCREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVsAQLDRTV 175
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18150824 377 KQEGAKLPVK-WTAPE--ALREN---KFSNKTDVWSFGVLLWEI 414
Cdd:cd06636 176 GRRNTFIGTPyWMAPEviACDENpdaTYDYRSDIWSLGITAIEM 219
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
105-196 7.79e-14

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 67.65  E-value: 7.79e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTP--PKNGRFLVRESQNYPGDYTLCVSYDGRVENYR---VRRNEKGLVTVDDDEY-FDNLI 178
Cdd:cd10414   3 RSQPWFHHKISRDEAQRLIIQqgLVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQiipVEDDGELFHTLDDGHTrFTDLI 82
                        90
                ....*....|....*...
gi 18150824 179 KLVEHYQKEADGLCTRLK 196
Cdd:cd10414  83 QLVEFYQLNKGVLPCKLK 100
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
231-465 7.81e-14

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: 71.95  E-value: 7.81e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05631   7 VLGKGGFGEVCACQVRatGKMYACKKLeKKRIKKRKGEAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGD 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA-KSSSNVKQEGAKLPVK 386
Cdd:cd05631  87 LKFHIYNMGNPGFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAvQIPEGETVRGRVGTVG 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 387 WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY----PRVPVEDVANHVENGyRMESPDGCPDQIYKIMMDCWEKDP 462
Cdd:cd05631 167 YMAPEVINNEKYTFSPDWWGLGCLIYEMIQ-GQSPFrkrkERVKREEVDRRVKED-QEEYSEKFSEDAKSICRMLLTKNP 244

                ...
gi 18150824 463 SQR 465
Cdd:cd05631 245 KER 247
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
104-199 9.14e-14

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 67.28  E-value: 9.14e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 104 LKTMPWFHGRISREDAEKLL-TPPKNGRFLVRESQNYpGDYTLCV------SYDGRVENYRVRRNEKGLVTVDDDEYFDN 176
Cdd:cd10398   3 LEIYEWYHKNITRNQAERLLrQESKEGAFIVRDSRHL-GSYTISVftrarrSTEASIKHYQIKKNDSGQWYVAERHLFQS 81
                        90       100
                ....*....|....*....|...
gi 18150824 177 LIKLVEHYQKEADGLCTRLKAPV 199
Cdd:cd10398  82 IPELIQYHQHNAAGLMSRLRYPV 104
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
104-199 9.37e-14

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 67.04  E-value: 9.37e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 104 LKTMPWFHGRISREDAEKLLTPP-KNGRFLVRESQNyPGDYTLCV----SYDGRVENYRVRRNEKGLVTVDDDEYFDNLI 178
Cdd:cd09934   3 LEKYEWYVGDMSRQRAESLLKQEdKEGCFVVRNSST-KGLYTVSLftkvPGSPHVKHYHIKQNARSEFYLAEKHCFETIP 81
                        90       100
                ....*....|....*....|.
gi 18150824 179 KLVEHYQKEADGLCTRLKAPV 199
Cdd:cd09934  82 ELINYHQHNSGGLATRLKYPV 102
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
232-412 1.06e-13

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: 71.12  E-value: 1.06e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLR-HPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14197  17 LGRGKFAVVrkCVEKDSGKEFAAKFMRKRRKGQDCRMEIIHEIAVLELAQaNPWVINLHEVYETASEMILVLEYAAGGEI 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNV---AKVSDFGLAK--SSSNVKQEGAKL 383
Cdd:cd14197  97 FNQCVADREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPlgdIKIVDFGLSRilKNSEELREIMGT 176
                       170       180
                ....*....|....*....|....*....
gi 18150824 384 PvKWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14197 177 P-EYVAPEILSYEPISTATDMWSIGVLAY 204
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
231-467 1.13e-13

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: 71.16  E-value: 1.13e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSMkdHLKDEKAKTQFLAEASVMTTLR-HPNLVCLIG-----ISLDDNPIYLITEF 302
Cdd:cd14037  10 YLAEGGFAHVYLvkTSNGGNRAALKRV--YVNDEHDLNVCKREIEIMKRLSgHKNIVGYIDssanrSGNGVYEVLLLMEY 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQN--FVHRDLAARNVLIAEDNVAKVSDFGLAKSS------- 373
Cdd:cd14037  88 CKGGGVIDLMNQRLQTGLTESEILKIFCDVCEAVAAMHYLKppLIHRDLKVENVLISDSGNYKLCDFGSATTKilppqtk 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 374 ---SNVKQEGAK-LPVKWTAPEAL---RENKFSNKTDVWSFGVLLWEIYSYgrvpypRVPVEDVAN-HVENGyRMESPDG 445
Cdd:cd14037 168 qgvTYVEEDIKKyTTLQYRAPEMIdlyRGKPITEKSDIWALGCLLYKLCFY------TTPFEESGQlAILNG-NFTFPDN 240
                       250       260
                ....*....|....*....|....
gi 18150824 446 CP--DQIYKIMMDCWEKDPSQRPN 467
Cdd:cd14037 241 SRysKRLHKLIRYMLEEDPEKRPN 264
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
232-421 1.21e-13

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 71.67  E-value: 1.21e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV----WLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLR-HPNLVCLIGISLDD----NPIYLITEF 302
Cdd:cd07857   8 LGQGAYGIVcsarNAETSEEETVAIKKITNVFSKKILAKRALRELKLLRHFRgHKNITCLYDMDIVFpgnfNELYLYEEL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MaKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAK 382
Cdd:cd07857  88 M-EADLHQIIRSGQP--LTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSENPGENAG 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 383 -----LPVKW-TAPEALRENK-FSNKTDVWSFGVLLWEIysYGRVP 421
Cdd:cd07857 165 fmteyVATRWyRAPEIMLSFQsYTKAIDVWSVGCILAEL--LGRKP 208
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
230-410 1.36e-13

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: 71.39  E-value: 1.36e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVWLGDYEG--KKVAMKSMKDHLkDEKAktqFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd14085   9 SELGRGATSVVYRCRQKGtqKPYAVKKLKKTV-DKKI---VRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGE 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIA---EDNVAKVSDFGLAKSssnVKQEGAKLP 384
Cdd:cd14085  85 LFDRIVEKG--YYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYAtpaPDAPLKIADFGLSKI---VDQQVTMKT 159
                       170       180       190
                ....*....|....*....|....*....|
gi 18150824 385 VKWT----APEALRENKFSNKTDVWSFGVL 410
Cdd:cd14085 160 VCGTpgycAPEILRGCAYGPEVDMWSVGVI 189
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
109-198 1.71e-13

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 66.21  E-value: 1.71e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYDG----RVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10368   5 WYFGKLGRKDAERQLLSFGNprGTFLIRESETTKGAYSLSIrDWDDmkgdHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....*..
gi 18150824 182 EHYQKEADGLCTRLKAP 198
Cdd:cd10368  85 QHYSETANGLCKVLIVT 101
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
271-422 1.88e-13

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: 70.59  E-value: 1.88e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSrgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd14105  58 EVSILRQVLHPNIITLHDVFENKTDVVLILELVAGGELFDFLAE--KESLSEEEATEFLKQILDGVNYLHTKNIAHFDLK 135
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 351 ARNVLIAEDNVA----KVSDFGLAK--SSSNVKQEGAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14105 136 PENIMLLDKNVPipriKLIDFGLAHkiEDGNEFKNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
232-415 1.93e-13

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: 70.81  E-value: 1.93e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNP--------IYLITE 301
Cdd:cd07866  16 LGEGTFGEVYKARQikTGRVVALKKILMHNEKDGFPITALREIKILKKLKHPNVVPLIDMAVERPDkskrkrgsVYMVTP 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAK--GSLIDYLRsrgraVITKQNQID-FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK----SSS 374
Cdd:cd07866  96 YMDHdlSGLLENPS-----VKLTESQIKcYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARpydgPPP 170
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 375 NVKQEGAKLPVKWT---------APE-ALRENKFSNKTDVWSFGVLLWEIY 415
Cdd:cd07866 171 NPKGGGGGGTRKYTnlvvtrwyrPPElLLGERRYTTAVDIWGIGCVFAEMF 221
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
103-145 2.14e-13

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 66.22  E-value: 2.14e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 18150824 103 QLKTMPWFHGRISREDAEKLLTppKNGRFLVRESQNYPGDYTL 145
Cdd:cd09925   3 QLRGEPWYHGKMSRRDAESLLQ--TDGDFLVRESTTTPGQYVL 43
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
231-422 2.17e-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: 69.99  E-value: 2.17e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEV--WLGDYEGKKVAMKSMKdhLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14192  11 VLGGGRFGQVhkCTELSTGLTLAAKIIK--VKGAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGEL 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAED--NVAKVSDFGLAKSSsnvkQEGAKLPV- 385
Cdd:cd14192  89 FDRITDESYQ-LTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCVNStgNQIKIIDFGLARRY----KPREKLKVn 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 18150824 386 ----KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14192 164 fgtpEFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPF 203
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
232-414 2.48e-13

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 70.07  E-value: 2.48e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd06645  19 IGSGTYGDVYKARnvNTGELAAIKVIKLEPGEDFAVVQ--QEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEFCGGGSLQ 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLPVK 386
Cdd:cd06645  97 DIYHVTGP---LSESQIAYvSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAqiTATIAKRKSFIGTPY 173
                       170       180       190
                ....*....|....*....|....*....|.
gi 18150824 387 WTAPEAL---RENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06645 174 WMAPEVAaveRKGGYNQLCDIWAVGITAIEL 204
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
232-414 2.70e-13

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 70.25  E-value: 2.70e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLR--HPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd14157   1 ISEGTFADIYKGYRHGKQYVIKRLKETECESPKSTERFFQTEVQICFRccHPNILPLLGFCVESDCHCLIYPYMPNGSLQ 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLR-SRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVKWT 388
Cdd:cd14157  81 DRLQqQGGSHPLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNLLPKLGHSGLRLCPVDKKSVYTMMKTKVL 160
                       170       180       190
                ....*....|....*....|....*....|...
gi 18150824 389 A------PEA-LRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd14157 161 QislaylPEDfVRHGQLTEKVDIFSCGVVLAEI 193
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
232-414 2.72e-13

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 70.68  E-value: 2.72e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCL--IGIS-LDDnpIYLITEFMAKg 306
Cdd:cd07856  18 VGMGAFGLVCSArdQLTGQNVAVKKIMKPFSTPVLAKRTYRELKLLKHLRHENIISLsdIFISpLED--IYFVTELLGT- 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGravITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKsSSNVKQEGAKLPVK 386
Cdd:cd07856  95 DLHRLLTSRP---LEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLAR-IQDPQMTGYVSTRY 170
                       170       180
                ....*....|....*....|....*....
gi 18150824 387 WTAPE-ALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd07856 171 YRAPEiMLTWQKYDVEVDIWSAGCIFAEM 199
STKc_GRK3 cd05633
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs ...
231-465 2.74e-13

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270781 [Multi-domain]  Cd Length: 346  Bit Score: 70.86  E-value: 2.74e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVW---LGDyEGKKVAMKSM-KDHLKDEKAKTQFLAEA---SVMTTLRHPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd05633  12 IIGRGGFGEVYgcrKAD-TGKMYAMKCLdKKRIKMKQGETLALNERimlSLVSTGDCPFIVCMTYAFHTPDKLCFILDLM 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKL 383
Cdd:cd05633  91 NGGDLHYHLSQHG--VFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVG 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 PVKWTAPEALRE-NKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDV--ANHVENGYRMESPDGCPDQIYKIMMDCWEK 460
Cdd:cd05633 169 THGYMAPEVLQKgTAYDSSADWFSLGCMLFKLLR-GHSPFRQHKTKDKheIDRMTLTVNVELPDSFSPELKSLLEGLLQR 247

                ....*
gi 18150824 461 DPSQR 465
Cdd:cd05633 248 DVSKR 252
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
233-422 2.76e-13

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: 69.85  E-value: 2.76e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 233 GKGEFGEVWL--GDYEGKkvaMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd14111  12 ARGRFGVIRRcrENATGK---NFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFCSGKELLH 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSS--NVKQEGAKL-PVKW 387
Cdd:cd14111  89 SLIDRFR--YSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNplSLRQLGRRTgTLEY 166
                       170       180       190
                ....*....|....*....|....*....|....*
gi 18150824 388 TAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14111 167 MAPEMVKGEPVGPPADIWSIGVLTYIMLS-GRSPF 200
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
259-471 2.85e-13

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 71.59  E-value: 2.85e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  259 LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQN--------QIDFAR 330
Cdd:PTZ00267 103 LNDERQAAYARSELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSGGDLNKQIKQRLKEHLPFQEyevgllfyQIVLAL 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  331 DVVkgmvylESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-----SSNVKQEGAKLPVkWTAPEALRENKFSNKTDVW 405
Cdd:PTZ00267 183 DEV------HSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQysdsvSLDVASSFCGTPY-YLAPELWERKRYSKKADMW 255
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824  406 SFGVLLWEIYSYGRvPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:PTZ00267 256 SLGVILYELLTLHR-PFKGPSQREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRPTTQQL 320
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
222-465 2.89e-13

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 70.13  E-value: 2.89e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 222 PKASLLKKSL-IGKGEFGEVWLG-DYEG-KKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLI----GISLDDN 294
Cdd:cd14031   7 PGGRFLKFDIeLGRGAFKTVYKGlDTETwVEVAWCELQDRKLTKAEQQRFKEEAEMLKGLQHPNIVRFYdsweSVLKGKK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 295 PIYLITEFMAKGSLIDYLRsrgRAVITKQNQI-DFARDVVKGMVYLESQN--FVHRDLAARNVLI-AEDNVAKVSDFGLA 370
Cdd:cd14031  87 CIVLVTELMTSGTLKTYLK---RFKVMKPKVLrSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLA 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 371 KSSSNVKQEGAKLPVKWTAPEaLRENKFSNKTDVWSFGVLLWEIYSygrVPYPRVPVEDVAN---HVENGYRMESPDGCP 447
Cdd:cd14031 164 TLMRTSFAKSVIGTPEFMAPE-MYEEHYDESVDVYAFGMCMLEMAT---SEYPYSECQNAAQiyrKVTSGIKPASFNKVT 239
                       250
                ....*....|....*....
gi 18150824 448 D-QIYKIMMDCWEKDPSQR 465
Cdd:cd14031 240 DpEVKEIIEGCIRQNKSER 258
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
12-64 3.11e-13

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: 63.92  E-value: 3.11e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 18150824  12 IGKYNFPGSSPHDLPFKKGDRLVIVapSKD-PNWYKARREDGLEGMIPFNYVQE 64
Cdd:cd11758   4 RALFDFPGNDDEDLPFKKGEILTVI--RKPeEQWWNARNSEGKTGMIPVPYVEK 55
SH2_SAP1 cd10342
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked ...
107-199 3.13e-13

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198205  Cd Length: 103  Bit Score: 65.82  E-value: 3.13e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 107 MPWFHGRISREDAEKLLTPPK-NGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEY-----FDNLIKL 180
Cdd:cd10342   3 VAVYHGKISRETGEKLLLATGlDGSYLLRDSESVPGVYCLCVLYHGYIYTYRVSQTETGSWSAETAPGvhkryFRKIKNL 82
                        90
                ....*....|....*....
gi 18150824 181 VEHYQKEADGLCTRLKAPV 199
Cdd:cd10342  83 ISAFQKPDQGIVIPLQYPV 101
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
219-422 3.25e-13

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 70.04  E-value: 3.25e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASllKKSligKGEFGEVWLGDyegKKV---AMKSMKDHLKdEKAKtqflAEASVMTTLRHPNLVCLI-GISLDDN 294
Cdd:cd14011  10 WKIYNGS--KKS---TKQEVSVFVFE---KKQleeYSKRDREQIL-ELLK----RGVKQLTRLRHPRILTVQhPLEESRE 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 295 PIYLITEFmAKGSLIDYLRSRGRAVITKQNQIDFAR----------DVVKGMVYL-ESQNFVHRDLAARNVLIAEDNVAK 363
Cdd:cd14011  77 SLAFATEP-VFASLANVLGERDNMPSPPPELQDYKLydveikygllQISEALSFLhNDVKLVHGNICPESVVINSNGEWK 155
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18150824 364 VSDFGLAKSSSN-------VKQEGAKLPV------KWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPY 422
Cdd:cd14011 156 LAGFDFCISSEQatdqfpyFREYDPNLPPlaqpnlNYLAPEYILSKTCDPASDMFSLGVLIYAIYNKGKPLF 227
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
232-465 3.37e-13

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: 70.08  E-value: 3.37e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd05605   8 LGKGGFGEVCACQVRatGKMYACKKLeKKRIKKRKGEAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA---KSSSNVKqeGAKLPV 385
Cdd:cd05605  88 KFHIYNMGNPGFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAveiPEGETIR--GRVGTV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 386 KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY----PRVPVEDVANHVENGyRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:cd05605 166 GYMAPEVVKNERYTFSPDWWGLGCLIYEMIE-GQAPFrarkEKVKREEVDRRVKED-QEEYSEKFSEEAKSICSQLLQKD 243

                ....
gi 18150824 462 PSQR 465
Cdd:cd05605 244 PKTR 247
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
271-412 3.41e-13

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: 69.64  E-value: 3.41e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd14183  54 EVSILRRVKHPNIVLLIEEMDMPTELYLVMELVKGGDLFDAITSTNK--YTERDASGMLYNLASAIKYLHSLNIVHRDIK 131
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18150824 351 ARNVLIAE----DNVAKVSDFGLAKSSSNVKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14183 132 PENLLVYEhqdgSKSLKLGDFGLATVVDGPLYTVCGTPT-YVAPEIIAETGYGLKVDIWAAGVITY 196
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
232-416 3.81e-13

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 70.37  E-value: 3.81e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGI-----SLDD-NPIYLITEFM 303
Cdd:cd07880  23 VGSGAYGTVCsaLDRRTGAKVAIKKLYRPFQSELFAKRAYRELRLLKHMKHENVIGLLDVftpdlSLDRfHDFYLVMPFM 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AK--GSLIDYLRsrgraviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNvKQEG 380
Cdd:cd07880 103 GTdlGKLMKHEK-------LSEDRIQFlVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQTDS-EMTG 174
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 18150824 381 AKLPVKWTAPEA-LRENKFSNKTDVWSFGVLLWEIYS 416
Cdd:cd07880 175 YVVTRWYRAPEViLNWMHYTQTVDIWSVGCIMAEMLT 211
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
232-453 4.03e-13

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 69.26  E-value: 4.03e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYEGK-KVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLI----GISLDDNPIYLITEFMAK 305
Cdd:cd14033   9 IGRGSFKTVYRGlDTETTvEVAWCELQTRKLSKGERQRFSEEVEMLKGLQHPNIVRFYdswkSTVRGHKCIILVTELMTS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRsRGRAVITKQNQiDFARDVVKGMVYLESQN--FVHRDLAARNVLI-AEDNVAKVSDFGLA--KSSSNVKQEg 380
Cdd:cd14033  89 GTLKTYLK-RFREMKLKLLQ-RWSRQILKGLHFLHSRCppILHRDLKCDNIFItGPTGSVKIGDLGLAtlKRASFAKSV- 165
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18150824 381 AKLPvKWTAPEaLRENKFSNKTDVWSFGVLLWEIYSygrVPYPRVPVEDVANHvengYRMESPDGCPDQIYKI 453
Cdd:cd14033 166 IGTP-EFMAPE-MYEEKYDEAVDVYAFGMCILEMAT---SEYPYSECQNAAQI----YRKVTSGIKPDSFYKV 229
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
231-431 4.50e-13

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: 69.55  E-value: 4.50e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05607   9 VLGKGGFGEVCAVQVKntGQMYACKKLdKKRLKKKSGEKMALLEKEILEKVNSPFIVSLAYAFETKTHLCLVMSLMNGGD 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVK- 386
Cdd:cd05607  89 LKYHIYNVGERGIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGKPITQRAGTNg 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 387 WTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYpRVPVEDVA 431
Cdd:cd05607 169 YMAPEILKEESYSYPVDWFAMGCSIYEMVA-GRTPF-RDHKEKVS 211
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
227-425 5.02e-13

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 69.60  E-value: 5.02e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKslIGKGEFGEVWLG--DYEGKKVAMKSMkdHLKDEKAkTQFLA--EASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd07870   5 LEK--LGEGSYATVYKGisRINGQLVALKVI--SMKTEEG-VPFTAirEASLLKGLKHANIVLLHDIIHTKETLTFVFEY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MaKGSLIDYLrSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE-GA 381
Cdd:cd07870  80 M-HTDLAQYM-IQHPGGLHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARAKSIPSQTySS 157
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 382 KLPVKWTAPE--ALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRV 425
Cdd:cd07870 158 EVVTLWYRPPdvLLGATDYSSALDIWGAGCIFIEMLQ-GQPAFPGV 202
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
258-423 5.26e-13

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 69.77  E-value: 5.26e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 258 HLKDEKA-KTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQIDFArdVVKGM 336
Cdd:cd06615  35 HLEIKPAiRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPENILGKISIA--VLRGL 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 337 VYL-ESQNFVHRDLAARNVLIAEDNVAKVSDFG----LAKSSSN--VkqeGAKlpvKWTAPEALRENKFSNKTDVWSFGV 409
Cdd:cd06615 113 TYLrEKHKIMHRDVKPSNILVNSRGEIKLCDFGvsgqLIDSMANsfV---GTR---SYMSPERLQGTHYTVQSDIWSLGL 186
                       170
                ....*....|....
gi 18150824 410 LLWEIySYGRVPYP 423
Cdd:cd06615 187 SLVEM-AIGRYPIP 199
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
108-184 8.25e-13

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 63.60  E-value: 8.25e-13
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 108 PWFHGRISREDAEKLL-TPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVdDDEYFDNLIKLVEHY 184
Cdd:cd10354   1 IWFHGKISREEAYNMLvKVGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIIPTGNNQFMM-GGRYFSSLDDVIDRY 77
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
232-422 8.63e-13

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 68.35  E-value: 8.63e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG---DYEGKkVAMKSMKDHLKDEKAKTQFLA-EASVMTTLRHPNLVCLIG-ISLDDNPIYLITEFMAKg 306
Cdd:cd14164   8 IGEGSFSKVKLAtsqKYCCK-VAIKIVDRRRASPDFVQKFLPrELSILRRVNHPNIVQMFEcIEVANGRLYIVMEAAAT- 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLI-AEDNVAKVSDFGLAKSSSNVKQEGAKL-- 383
Cdd:cd14164  86 DLLQKIQEVHH--IPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLsADDRKIKIADFGFARFVEDYPELSTTFcg 163
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18150824 384 PVKWTAPEALRENKF-SNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14164 164 SRAYTPPEVILGTPYdPKKYDVWSLGVVLYVMVT-GTMPF 202
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
232-465 9.15e-13

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: 9.15e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL-----GDYEGKKVAMKSMKDHLKDEKAKTQ--FLAEASVMTTLRH-PNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd05583   2 LGTGAYGKVFLvrkvgGHDAGKLYAMKVLKKATIVQKAKTAehTMTERQVLEAVRQsPFLVTLHYAFQTDAKLHLILDYV 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAK 382
Cdd:cd05583  82 NGGELFTHLYQREH---FTESEVRIyIGEIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLPGENDRAY 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 383 L---PVKWTAPEALR--ENKFSNKTDVWSFGVLLWEIYSyGRVPYprvPVEDVAN-HVENGYRME----------SPDgC 446
Cdd:cd05583 159 SfcgTIEYMAPEVVRggSDGHDKAVDWWSLGVLTYELLT-GASPF---TVDGERNsQSEISKRILkshppipktfSAE-A 233
                       250
                ....*....|....*....
gi 18150824 447 PDQIYKIMMdcweKDPSQR 465
Cdd:cd05583 234 KDFILKLLE----KDPKKR 248
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
271-476 9.26e-13

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: 68.72  E-value: 9.26e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSRGRA--VITKQNQIDFARDVVKGMVYLESQNFVHRD 348
Cdd:cd14094  55 EASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGADLCFEIVKRADAgfVYSEAVASHYMRQILEALRYCHDNNIIHRD 134
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 349 LAARNVLIA-EDNVA--KVSDFGLAKSSSNVKQE-GAKLPV-KWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd14094 135 VKPHCVLLAsKENSApvKLGGFGVAIQLGESGLVaGGRVGTpHFMAPEVVKREPYGKPVDVWGCGVILFILLS-GCLPFY 213
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 424 RVPVEDVANHVENGYRMESP--DGCPDQIYKIMMDCWEKDPSQRpnfTRIEKALE 476
Cdd:cd14094 214 GTKERLFEGIIKGKYKMNPRqwSHISESAKDLVRRMLMLDPAER---ITVYEALN 265
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
219-423 9.69e-13

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 69.30  E-value: 9.69e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKaSLLKKSLIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGI-----SL 291
Cdd:cd07877  13 WEVPE-RYQNLSPVGSGAYGSVCaaFDTKTGLRVAVKKLSRPFQSIIHAKRTYRELRLLKHMKHENVIGLLDVftparSL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 292 DD-NPIYLITEFMAkGSLIDYLRSRGravITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA 370
Cdd:cd07877  92 EEfNDVYLVTHLMG-ADLNNIVKCQK---LTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLA 167
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18150824 371 KSSSNvkQEGAKLPVKW-TAPEALRENKFSNKT-DVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07877 168 RHTDD--EMTGYVATRWyRAPEIMLNWMHYNQTvDIWSVGCIMAELLT-GRTLFP 219
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
232-473 1.00e-12

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 68.11  E-value: 1.00e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYEGKK-VAMKSMK-DHLKDekaktqflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd13995  12 IPRGAFGKVYLAqDTKTKKrMACKLIPvEQFKP--------SDVEIQACFRHENIAELYGALLWEETVHLFMEAGEGGSV 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVsDFGLA-KSSSNV----KQEGAKL 383
Cdd:cd13995  84 LEKLESCGP--MREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAVLV-DFGLSvQMTEDVyvpkDLRGTEI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 pvkWTAPEALRENKFSNKTDVWSFGVLLWEIYS--------YGRVPYPRV---------PVEDVanhvengyrmesPDGC 446
Cdd:cd13995 161 ---YMSPEVILCRGHNTKADIYSLGATIIHMQTgsppwvrrYPRSAYPSYlyiihkqapPLEDI------------AQDC 225
                       250       260
                ....*....|....*....|....*..
gi 18150824 447 PDQIYKIMMDCWEKDPSQRPNFTRIEK 473
Cdd:cd13995 226 SPAMRELLEAALERNPNHRSSAAELLK 252
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
232-412 1.05e-12

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: 67.87  E-value: 1.05e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL--GDYEGKKVAMKSMKDHLK-DEKAKTQFLAEASvmttLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14662   8 IGSGNFGVARLmrNKETKELVAVKYIERGLKiDENVQREIINHRS----LRHPNIIRFKEVVLTPTHLAIVMEYAAGGEL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIaEDNVA---KVSDFGLAKSSsnVKQEGAKLPV 385
Cdd:cd14662  84 FERICNAGR--FSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLL-DGSPAprlKICDFGYSKSS--VLHSQPKSTV 158
                       170       180       190
                ....*....|....*....|....*....|.
gi 18150824 386 ---KWTAPEALRENKFSNK-TDVWSFGVLLW 412
Cdd:cd14662 159 gtpAYIAPEVLSRKEYDGKvADVWSCGVTLY 189
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
219-465 1.14e-12

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: 68.07  E-value: 1.14e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKASLLK---KSLIGKGEFGEV--WLGDYEGKKVAMKSMK---DHLKDEKAKTQFLAEASVMTTLR----HPNLVCL 286
Cdd:cd14181   2 WAGAKEFYQKydpKEVIGRGVSSVVrrCVHRHTGQEFAVKIIEvtaERLSPEQLEEVRSSTLKEIHILRqvsgHPSIITL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 287 IGISLDDNPIYLITEFMAKGSLIDYLRSRgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSD 366
Cdd:cd14181  82 IDSYESSTFIFLVFDLMRRGELFDYLTEK--VTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSD 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 367 FGLakssSNVKQEGAKL-----PVKWTAPEALR------ENKFSNKTDVWSFGVLLWEIYSyGRVPY-PRVPVEDVANHV 434
Cdd:cd14181 160 FGF----SCHLEPGEKLrelcgTPGYLAPEILKcsmdetHPGYGKEVDLWACGVILFTLLA-GSPPFwHRRQMLMLRMIM 234
                       250       260       270
                ....*....|....*....|....*....|...
gi 18150824 435 ENGYRMESP--DGCPDQIYKIMMDCWEKDPSQR 465
Cdd:cd14181 235 EGRYQFSSPewDDRSSTVKDLISRLLVVDPEIR 267
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
232-412 1.16e-12

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: 67.70  E-value: 1.16e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL--GDYEGKKVAMKSMKDHLK-DEKAKTQFLAEASvmttLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14665   8 IGSGNFGVARLmrDKQTKELVAVKYIERGEKiDENVQREIINHRS----LRHPNIVRFKEVILTPTHLAIVMEYAAGGEL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA--KVSDFGLAKSSSNVKQEGAKLPV- 385
Cdd:cd14665  84 FERICNAGR--FSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPrlKICDFGYSKSSVLHSQPKSTVGTp 161
                       170       180
                ....*....|....*....|....*...
gi 18150824 386 KWTAPEALRENKFSNK-TDVWSFGVLLW 412
Cdd:cd14665 162 AYIAPEVLLKKEYDGKiADVWSCGVTLY 189
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
207-468 1.28e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 68.17  E-value: 1.28e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 207 FVVDVNDFKEKGwaipkasllkksLIGKGEFGEVWLGDYE--GKKVAMKSM-KDHLKDEKAKtqFLAEASVMTtLRH--P 281
Cdd:cd06618  10 YKADLNDLENLG------------EIGSGTCGQVYKMRHKktGHVMAVKQMrRSGNKEENKR--ILMDLDVVL-KSHdcP 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 282 NLVCLIGISLDDNPIYLITEFMAkgSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYL-ESQNFVHRDLAARNVLIAEDN 360
Cdd:cd06618  75 YIVKCYGYFITDSDVFICMELMS--TCLDKLLKRIQGPIPEDILGKMTVSIVKALHYLkEKHGVIHRDVKPSNILLDESG 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 361 VAKVSDFG----LAKSSSNVKQEGAKLpvkWTAPEALRENKFSN---KTDVWSFGVLLWEIYSyGRVPYPRVPVE-DVAN 432
Cdd:cd06618 153 NVKLCDFGisgrLVDSKAKTRSAGCAA---YMAPERIDPPDNPKydiRADVWSLGISLVELAT-GQFPYRNCKTEfEVLT 228
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 18150824 433 HVENgyrMESPDGCPDQIYKIMM-----DCWEKDPSQRPNF 468
Cdd:cd06618 229 KILN---EEPPSLPPNEGFSPDFcsfvdLCLTKDHRYRPKY 266
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
232-421 1.37e-12

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: 68.55  E-value: 1.37e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW--LGDYEGKKVAMKSMK---DHLKDEKaKTqfLAEASVMTTLRHPNLVCLIGI-------SLDDnpIYLI 299
Cdd:cd07858  13 IGRGAYGIVCsaKNSETNEKVAIKKIAnafDNRIDAK-RT--LREIKLLRHLDHENVIAIKDImppphreAFND--VYIV 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMaKGSLIDYLRSRgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:cd07858  88 YELM-DTDLHQIIRSS--QTLSDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTSEKGDF 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 380 GAKLPVK--WTAPEALRE-NKFSNKTDVWSFGVLLWEIysYGRVP 421
Cdd:cd07858 165 MTEYVVTrwYRAPELLLNcSEYTTAIDVWSVGCIFAEL--LGRKP 207
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
248-478 1.39e-12

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 68.19  E-value: 1.39e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 248 KKVAMKSMKDHLKDEKAKTQFlaEASVMTTLRHPNLVCLIG-ISLDDNPIYLITEFMAK--GSLIDYLRSRGRAVITKQN 324
Cdd:cd14001  34 KKINSKCDKGQRSLYQERLKE--EAKILKSLNHPNIVGFRAfTKSEDGSLCLAMEYGGKslNDLIEERYEAGLGPFPAAT 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 325 QIDFARDVVKGMVYLESQ-NFVHRDLAARNVLIAED-NVAKVSDFGLA---------KSSSNVKQEGAKlpvKWTAPEAL 393
Cdd:cd14001 112 ILKVALSIARALEYLHNEkKILHGDIKSGNVLIKGDfESVKLCDFGVSlpltenlevDSDPKAQYVGTE---PWKAKEAL 188
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 394 RENK-FSNKTDVWSFGVLLWEIYSYgRVPYPRVP---------------VEDVANHVENGYRMESPDGCPDQIYKIMMD- 456
Cdd:cd14001 189 EEGGvITDKADIFAYGLVLWEMMTL-SVPHLNLLdiedddedesfdedeEDEEAYYGTLGTRPALNLGELDDSYQKVIEl 267
                       250       260
                ....*....|....*....|....*
gi 18150824 457 ---CWEKDPSQRPNFTRIEKALESV 478
Cdd:cd14001 268 fyaCTQEDPKDRPSAAHIVEALEAH 292
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
271-422 1.40e-12

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: 67.72  E-value: 1.40e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSrgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd14195  58 EVNILREIQHPNIITLHDIFENKTDVVLILELVSGGELFDFLAE--KESLTEEEATQFLKQILDGVHYLHSKRIAHFDLK 135
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 351 ARNVLIAEDNVA----KVSDFGLAK--SSSNVKQEGAKLPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14195 136 PENIMLLDKNVPnpriKLIDFGIAHkiEAGNEFKNIFGTP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
232-412 1.51e-12

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: 67.76  E-value: 1.51e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMKSMKDHLKDEKAKTQFLAEASV-MTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSL 308
Cdd:cd14106  16 LGRGKFAVVrkCIHKETGKEYAAKFLRKRRRGQDCRNEILHEIAVlELCKDCPRVVNLHEVYETRSELILILELAAGGEL 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVA---KVSDFGLAKsssnVKQEGAKL-- 383
Cdd:cd14106  96 QTLLDEEEC--LTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPLgdiKLCDFGISR----VIGEGEEIre 169
                       170       180       190
                ....*....|....*....|....*....|..
gi 18150824 384 ---PVKWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14106 170 ilgTPDYVAPEILSYEPISLATDMWSIGVLTY 201
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
109-195 1.58e-12

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 63.54  E-value: 1.58e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKN--GRFLVRESQNYPGDYTLCV-SYDG----RVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10419   5 WYFGKLGRKDAERQLLSFGNprGTFLIRESETTKGAYSLSIrDWDDmkgdHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                        90
                ....*....|....
gi 18150824 182 EHYQKEADGLCTRL 195
Cdd:cd10419  85 QHYSEKADGLCFNL 98
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
232-415 1.94e-12

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 67.68  E-value: 1.94e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLR---HPNLVCLIGISLD-----DNPIYLITE 301
Cdd:cd07863   8 IGVGAYGTVYKARdpHSGHFVALKSVRVQTNEDGLPLSTVREVALLKRLEafdHPNIVRLMDVCATsrtdrETKVTLVFE 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKgSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkQEGA 381
Cdd:cd07863  88 HVDQ-DLRTYLDKVPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARIYS---CQMA 163
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 382 KLPVKWT----APEALRENKFSNKTDVWSFGVLLWEIY 415
Cdd:cd07863 164 LTPVVVTlwyrAPEVLLQSTYATPVDMWSVGCIFAEMF 201
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
232-471 1.96e-12

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: 67.32  E-value: 1.96e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMKSMKDHLKDEKAKTQFLA-EASVMTTLRHPNLVCLIGI-SLDDNPIYLITEFMAKGS 307
Cdd:cd14163   8 IGEGTYSKVkeAFSKKHQRKVAIKIIDKSGGPEEFIQRFLPrELQIVERLDHKNIIHVYEMlESADGKIYLVMELAEDGD 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYL-------RSRGRAVItkqnqidfaRDVVKGMVYLESQNFVHRDLAARNVLIAEDNVaKVSDFGLAKSSSNVKQEG 380
Cdd:cd14163  88 VFDCVlhggplpEHRAKALF---------RQLVEAIRYCHGCGVAHRDLKCENALLQGFTL-KLTDFGFAKQLPKGGREL 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 381 AKL---PVKWTAPEALRENKF-SNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVENGYRMESPDGCPDQIYKIMMD 456
Cdd:cd14163 158 SQTfcgSTAYAAPEVLQGVPHdSRKGDIWSMGVVLYVMLC-AQLPFDDTDIPKMLCQQQKGVSLPGHLGVSRTCQDLLKR 236
                       250
                ....*....|....*
gi 18150824 457 CWEKDPSQRPNFTRI 471
Cdd:cd14163 237 LLEPDMVLRPSIEEV 251
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
232-414 1.99e-12

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: 67.63  E-value: 1.99e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYE-GKKVAMKsmkdHLKDEKAKTQF----LAEASVMTTLRHPNLVCL----IGISLDDnpIYLITE 301
Cdd:cd07843  13 IEEGTYGVVYRArDKKtGEIVALK----KLKMEKEKEGFpitsLREINILLKLQHPNIVTVkevvVGSNLDK--IYMVME 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMA---KgSLIDYLRSRgravitkqnqidFARDVVK--------GMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA 370
Cdd:cd07843  87 YVEhdlK-SLMETMKQP------------FLQSEVKclmlqllsGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLA 153
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18150824 371 KSSSNVKQEGAKLPVK-W-TAPEAL-RENKFSNKTDVWSFGVLLWEI 414
Cdd:cd07843 154 REYGSPLKPYTQLVVTlWyRAPELLlGAKEYSTAIDMWSVGCIFAEL 200
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
232-473 2.10e-12

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 67.45  E-value: 2.10e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKtQFLAEASV-MTTLRHPNLVCLIGISLDDNPIYLITEFMaKGSL 308
Cdd:cd06617   9 LGRGAYGVVDKMRHVptGTIMAVKRIRATVNSQEQK-RLLMDLDIsMRSVDCPYTVTFYGALFREGDVWICMEVM-DTSL 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSrgraVITKQNQI------DFARDVVKGMVYLESQ-NFVHRDLAARNVLIAEDNVAKVSDFG----LAKSSSNVK 377
Cdd:cd06617  87 DKFYKK----VYDKGLTIpedilgKIAVSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGisgyLVDSVAKTI 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 378 QEGAKlpvKWTAPE----ALRENKFSNKTDVWSFGVLLWEIySYGRVPYP--RVPVEDVANHVENgyrmESP----DGCP 447
Cdd:cd06617 163 DAGCK---PYMAPErinpELNQKGYDVKSDVWSLGITMIEL-ATGRFPYDswKTPFQQLKQVVEE----PSPqlpaEKFS 234
                       250       260
                ....*....|....*....|....*.
gi 18150824 448 DQIYKIMMDCWEKDPSQRPNFTRIEK 473
Cdd:cd06617 235 PEFQDFVNKCLKKNYKERPNYPELLQ 260
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
265-417 2.43e-12

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 67.98  E-value: 2.43e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  265 KTQFLAEASVMTTLRHPNLVCLIGiSLDDNPIYLITEFMAKGSLIDYLRSRGRAVITKQNQIdFARDVVKGMVYLESQNF 344
Cdd:PHA03209 101 KGTTLIEAMLLQNVNHPSVIRMKD-TLVSGAITCMVLPHYSSDLYTYLTKRSRPLPIDQALI-IEKQILEGLRYLHAQRI 178
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18150824  345 VHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE-GAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSY 417
Cdd:PHA03209 179 IHRDVKTENIFINDVDQVCIGDLGAAQFPVVAPAFlGLAGTVETNAPEVLARDKYNSKADIWSAGIVLFEMLAY 252
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
271-422 2.46e-12

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: 67.29  E-value: 2.46e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 271 EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLIDYLRSrgRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLA 350
Cdd:cd14196  58 EVSILRQVLHPNIITLHDVYENRTDVVLILELVSGGELFDFLAQ--KESLSEEEATSFIKQILDGVNYLHTKKIAHFDLK 135
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 351 ARNVLIAEDNVA----KVSDFGLA-KSSSNVKQEGAKLPVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd14196 136 PENIMLLDKNIPiphiKLIDFGLAhEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPF 211
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
15-64 2.59e-12

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 61.56  E-value: 2.59e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824  15 YNFPGSSPHDLPFKKGDRLVIVA-PSKDPNWYKARREDGLEGMIPFNYVQE 64
Cdd:cd11767   6 YPFTGENDEELSFEKGERLEIIEkPEDDPDWWKARNALGTTGLVPRNYVEV 56
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
7-63 3.10e-12

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: 61.40  E-value: 3.10e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824      7 VGTECIGKYNFPGSSPHDLPFKKGDRLVIVAPSkDPNWYKARREDGLEGMIPFNYVQ 63
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKS-DDGWWKGRLGRGKEGLFPSNYVE 56
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
231-422 3.19e-12

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: 67.62  E-value: 3.19e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDH--LKDEKAKTQfLAEASVMTTLR-HPNLVCLIGISLDDNPIYLITEFMAK 305
Cdd:cd05590   2 VLGKGSFGKVMLARLKesGRLYAVKVLKKDviLQDDDVECT-MTEKRILSLARnHPFLTQLYCCFQTPDRLFFVMEFVNG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYlrsrgravITKQNQIDFAR------DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQE 379
Cdd:cd05590  81 GDLMFH--------IQKSRRFDEARarfyaaEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNGKT 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18150824 380 GAKL--PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05590 153 TSTFcgTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPF 196
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
227-412 3.20e-12

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: 67.05  E-value: 3.20e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEKAKTqfLAEASVMTTLR-HPNLVCLIGISLDDNPIYLITEFM 303
Cdd:cd14090   5 LTGELLGEGAYASVQtcINLYTGKEYAVKIIEKHPGHSRSRV--FREVETLHQCQgHPNILQLIEYFEDDERFYLVFEKM 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE-DNVA--KVSDFGLAKS--SSNVKQ 378
Cdd:cd14090  83 RGGPLLSHIEKRVH--FTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCESmDKVSpvKICDFDLGSGikLSSTSM 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18150824 379 EGAKLP--------VKWTAPEAL-----RENKFSNKTDVWSFGVLLW 412
Cdd:cd14090 161 TPVTTPelltpvgsAEYMAPEVVdafvgEALSYDKRCDLWSLGVILY 207
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
225-471 3.39e-12

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: 66.49  E-value: 3.39e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 225 SLLKKSLIGKGEFGEVW-LGDYE-GKKVAMKSM-KDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITE 301
Cdd:cd14189   2 SYCKGRLLGKGGFARCYeMTDLAtNKTYAVKVIpHSRVAKPHQREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRSRgrAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGA 381
Cdd:cd14189  82 LCSRKSLAHIWKAR--HTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KL--PVKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDVANHVEN-GYRMESPDGCPDQiyKIMMDCW 458
Cdd:cd14189 160 TIcgTPNYLAPEVLLRQGHGPESDVWSLGCVMYTLLC-GNPPFETLDLKETYRCIKQvKYTLPASLSLPAR--HLLAGIL 236
                       250
                ....*....|...
gi 18150824 459 EKDPSQRPNFTRI 471
Cdd:cd14189 237 KRNPGDRLTLDQI 249
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
219-423 3.77e-12

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 67.38  E-value: 3.77e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 219 WAIPKaSLLKKSLIGKGEFGEVwLGDYEGK---KVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGI-----S 290
Cdd:cd07878  11 WEVPE-RYQNLTPVGSGAYGSV-CSAYDTRlrqKVAVKKLSRPFQSLIHARRTYRELRLLKHMKHENVIGLLDVftpatS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 291 LDD-NPIYLITEFMAKGslidyLRSRGRAVITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFG 368
Cdd:cd07878  89 IENfNEVYLVTNLMGAD-----LNNIVKCQKLSDEHVQFlIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFG 163
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18150824 369 LAKSSSNvkQEGAKLPVKW-TAPEALRENKFSNKT-DVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07878 164 LARQADD--EMTGYVATRWyRAPEIMLNWMHYNQTvDIWSVGCIMAELLK-GKALFP 217
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
108-184 3.98e-12

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 62.45  E-value: 3.98e-12
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18150824 108 PWFHGRISREDAEKLLTPPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTV-DDDEYFDNLIKLVEHY 184
Cdd:cd09945   2 GWYHGAITRIEAESLLRPCKEGSYLVRNSESTKQDYSLSLKSAKGFMHMRIQRNETGQYILgQFSRPFETIPEMIRHY 79
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
232-424 4.28e-12

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: 67.21  E-value: 4.28e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL--GDYEGKKVAMKSMKDHL---KDEKAKTqfLAEASVMTTLRHPNLVCLIGISLD---DNPIYLITEFM 303
Cdd:cd05586   1 IGKGTFGQVYQvrKKDTRRIYAMKVLSKKVivaKKEVAHT--IGERNILVRTALDESPFIVGLKFSfqtPTDLYLVTDYM 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS--SSNVKQEGA 381
Cdd:cd05586  79 SGGELFWHLQKEGR--FSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILLDANGHIALCDFGLSKAdlTDNKTTNTF 156
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18150824 382 KLPVKWTAPEALRENK-FSNKTDVWSFGVLLWEI------------------YSYGRVPYPR 424
Cdd:cd05586 157 CGTTEYLAPEVLLDEKgYTKMVDFWSLGVLVFEMccgwspfyaedtqqmyrnIAFGKVRFPK 218
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
279-471 4.53e-12

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 67.97  E-value: 4.53e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  279 RHPNLVCLIGISLDdnpiyliteFMAKGSLIDYLRSR---GRAVITKQNQIDFARdVVKGMVYLESQNFVHRDLAARNVL 355
Cdd:PTZ00283 106 RNPENVLMIALVLD---------YANAGDLRQEIKSRaktNRTFREHEAGLLFIQ-VLLAVHHVHSKHMIHRDIKSANIL 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824  356 IAEDNVAKVSDFGLAKSSSN-----VKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRvPYPRVPVEDV 430
Cdd:PTZ00283 176 LCSNGLVKLGDFGFSKMYAAtvsddVGRTFCGTPY-YVAPEIWRRKPYSKKADMFSLGVLLYELLTLKR-PFDGENMEEV 253
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 18150824  431 ANHVENGYRMESPDGCPDQIYKIMMDCWEKDPSQRPNFTRI 471
Cdd:PTZ00283 254 MHKTLAGRYDPLPPSISPEMQEIVTALLSSDPKRRPSSSKL 294
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
227-412 4.90e-12

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: 66.16  E-value: 4.90e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 227 LKKSLIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEK-AKTQFLAEAsvmttlrHPNLVCLIGI---SLDDNPIYLIT 300
Cdd:cd14089   4 ISKQVLGLGINGKVLecFHKKTGEKFALKVLRDNPKARReVELHWRASG-------CPHIVRIIDVyenTYQGRKCLLVV 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 -EFMAKGSLIDYLRSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAE---DNVAKVSDFGLAK--SSS 374
Cdd:cd14089  77 mECMEGGELFSRIQERADSAFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSkgpNAILKLTDFGFAKetTTK 156
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18150824 375 NVKQEGAKLPVkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14089 157 KSLQTPCYTPY-YVAPEVLGPEKYDKSCDMWSLGVIMY 193
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
12-64 5.17e-12

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. 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: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 60.75  E-value: 5.17e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 18150824  12 IGKYNFPGSSPHDLPFKKGDRLVIVaPSKDPNWYKARREDGLEGMIPFNYVQE 64
Cdd:cd11768   3 VALYDFQPIEPGDLPLEKGEEYVVL-DDSNEHWWRARDKNGNEGYIPSNYVTE 54
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
231-414 5.41e-12

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 66.29  E-value: 5.41e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYE--GKKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSL 308
Cdd:cd07846   8 LVGEGSYGMVMKCRHKetGQIVAIKKFLESEDDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVDH-TV 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSrgravitKQNQIDFAR------DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS-SSNVKQEGA 381
Cdd:cd07846  87 LDDLEK-------YPNGLDESRvrkylfQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTlAAPGEVYTD 159
                       170       180       190
                ....*....|....*....|....*....|....*
gi 18150824 382 KLPVKW-TAPEAL-RENKFSNKTDVWSFGVLLWEI 414
Cdd:cd07846 160 YVATRWyRAPELLvGDTKYGKAVDVWAVGCLVTEM 194
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
232-465 6.12e-12

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 65.87  E-value: 6.12e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG-DYEG-KKVAMKSMKDHLKDEKAKTQFLAEASVMTTLRHPNLVCLIGI----SLDDNPIYLITEFMAK 305
Cdd:cd14032   9 LGRGSFKTVYKGlDTETwVEVAWCELQDRKLTKVERQRFKEEAEMLKGLQHPNIVRFYDFwescAKGKRCIVLVTELMTS 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 306 GSLIDYLRsrgRAVITKQNQI-DFARDVVKGMVYLESQN--FVHRDLAARNVLI-AEDNVAKVSDFGLAKSSSNVKQEGA 381
Cdd:cd14032  89 GTLKTYLK---RFKVMKPKVLrSWCRQILKGLLFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLKRASFAKSV 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 382 KLPVKWTAPEaLRENKFSNKTDVWSFGVLLWEIYSygrVPYPRVPVEDVAN---HVENGYRMESPDGCPD-QIYKIMMDC 457
Cdd:cd14032 166 IGTPEFMAPE-MYEEHYDESVDVYAFGMCMLEMAT---SEYPYSECQNAAQiyrKVTCGIKPASFEKVTDpEIKEIIGEC 241

                ....*...
gi 18150824 458 WEKDPSQR 465
Cdd:cd14032 242 ICKNKEER 249
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
226-422 6.24e-12

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: 66.48  E-value: 6.24e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKksLIGKGEFGEVWL-----GDYEGKKVAMKSMKDHLKDEKAKTQ--FLAEASVMTTLRH-PNLVCLIGISLDDNPIY 297
Cdd:cd05614   4 LLK--VLGTGAYGKVFLvrkvsGHDANKLYAMKVLRKAALVQKAKTVehTRTERNVLEHVRQsPFLVTLHYAFQTDAKLH 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 298 LITEFMAKGSLIDYLRSRGRaviTKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNV 376
Cdd:cd05614  82 LILDYVSGGELFTHLYQRDH---FSEDEVRFySGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTE 158
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 18150824 377 KQEGAKL---PVKWTAPEALRENKFSNKT-DVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05614 159 EKERTYSfcgTIEYMAPEIIRGKSGHGKAvDWWSLGILMFELLT-GASPF 207
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
104-185 6.53e-12

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198209  Cd Length: 97  Bit Score: 61.67  E-value: 6.53e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 104 LKTMPWFHGRISREDAEKLLT---PPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVdDDEYFDNLIKL 180
Cdd:cd10346   5 LSEYPWFHGTLSRSDAAQLVLhsgADGHGVFLVRQSETRRGEFVLTFNFQGRAKHLRLTLNEKGQCRV-QHLWFPSIFDM 83

                ....*
gi 18150824 181 VEHYQ 185
Cdd:cd10346  84 LEHFR 88
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
232-466 6.90e-12

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 65.99  E-value: 6.90e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD-------YEGKKVAMK--SMKDHLKdekaktqFLAEASVMTTLRHPNLVCLIGISLDDNPIYL-ITE 301
Cdd:cd14049  14 LGKGGYGKVYKVRnkldgqyYAIKKILIKkvTKRDCMK-------VLREVKVLAGLQHPNIVGYHTAWMEHVQLMLyIQM 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 302 FMAKGSLIDYLRSRGRAVITKQNQ------------IDFARDVVKGMVYLESQNFVHRDLAARNVLI-AEDNVAKVSDFG 368
Cdd:cd14049  87 QLCELSLWDWIVERNKRPCEEEFKsapytpvdvdvtTKILQQLLEGVTYIHSMGIVHRDLKPRNIFLhGSDIHVRIGDFG 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 369 LA------KSSSNVKQEGAKLP--------VKWTAPEALRENKFSNKTDVWSFGVLLWEIYSYGRVPYPRVpveDVANHV 434
Cdd:cd14049 167 LAcpdilqDGNDSTTMSRLNGLthtsgvgtCLYAAPEQLEGSHYDFKSDMYSIGVILLELFQPFGTEMERA---EVLTQL 243
                       250       260       270
                ....*....|....*....|....*....|...
gi 18150824 435 ENGYRMESPDG-CPDQIyKIMMDCWEKDPSQRP 466
Cdd:cd14049 244 RNGQIPKSLCKrWPVQA-KYIKLLTSTEPSERP 275
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
231-468 6.95e-12

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: 65.78  E-value: 6.95e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWL--GDYEGKKVAMKSMKDHLKDEKAKTQFLAEASVMttLRHPNLV-----CLIGISLDDNPIYLITEFM 303
Cdd:cd13986   7 LLGEGGFSFVYLveDLSTGRLYALKKILCHSKEDVKEAMREIENYRL--FNHPNILrlldsQIVKEAGGKKEVYLLLPYY 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 304 AKGSLIDYLRSRGRavitKQNQIDFAR---------DVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFG---LAK 371
Cdd:cd13986  85 KRGSLQDEIERRLV----KGTFFPEDRilhiflgicRGLKAMHEPELVPYAHRDIKPGNVLLSEDDEPILMDLGsmnPAR 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 372 SSSNVKQEGAKLPVK--------WTAPE--ALRENK-FSNKTDVWSFGVLLWEIYsYGRVPYPRVPVE--DVANHVENG- 437
Cdd:cd13986 161 IEIEGRREALALQDWaaehctmpYRAPElfDVKSHCtIDEKTDIWSLGCTLYALM-YGESPFERIFQKgdSLALAVLSGn 239
                       250       260       270
                ....*....|....*....|....*....|.
gi 18150824 438 YRMESPDGCPDQIYKIMMDCWEKDPSQRPNF 468
Cdd:cd13986 240 YSFPDNSRYSEELHQLVKSMLVVNPAERPSI 270
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
104-185 7.02e-12

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 62.74  E-value: 7.02e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 104 LKTMPWFHGRISREDAEKLLtpPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVD-------DDEYFDN 176
Cdd:cd10337   3 LRSHAWYHGRIPRQVAESLV--QREGDFLVRDSLSSPGDYVLTCRWKGQPLHFKINRVVLRPSEAYtrvqyqfEDEQFDS 80

                ....*....
gi 18150824 177 LIKLVEHYQ 185
Cdd:cd10337  81 IPALVHFYV 89
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
109-199 7.20e-12

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 61.66  E-value: 7.20e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPPKNGRFLVRESQNyPGDYTLCVSYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLVEHYQKEA 188
Cdd:cd09930   8 WLVGDINRTQAEELLRGKPDGTFLIRESST-QGCYACSVVCNGEVKHCVIYKTETGYGFAEPYNLYESLKELVLHYAHNS 86
                        90
                ....*....|....*.
gi 18150824 189 -----DGLCTRLKAPV 199
Cdd:cd09930  87 leqhnDSLTVTLAYPV 102
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
232-414 7.47e-12

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 65.80  E-value: 7.47e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVW--LGDYEGKKVAMKSMKD-HLKDEKAKtqflAEASVMTTLR-HPNLVCLIGI-----SLDDNPIYLITEF 302
Cdd:cd06638  26 IGKGTYGKVFkvLNKKNGSKAAVKILDPiHDIDEEIE----AEYNILKALSdHPNVVKFYGMyykkdVKNGDQLWLVLEL 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLIDYLR---SRGRavitKQNQIDFA---RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNV 376
Cdd:cd06638 102 CNGGSVTDLVKgflKRGE----RMEEPIIAyilHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQLTST 177
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 377 ---KQEGAKLPVkWTAPEALR-----ENKFSNKTDVWSFGVLLWEI 414
Cdd:cd06638 178 rlrRNTSVGTPF-WMAPEVIAceqqlDSTYDARCDVWSLGITAIEL 222
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
232-436 7.76e-12

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


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 66.19  E-value: 7.76e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDY--EGKKVAMKSM-KDHLKDEKAKTQFLAEASV-MTTLRHPNLVCLIGISLDDNPIYLITEFMAKGS 307
Cdd:cd05575   3 IGKGSFGKVLLARHkaEGKLYAVKVLqKKAILKRNEVKHIMAERNVlLKNVKHPFLVGLHYSFQTKDKLYFVLDYVNGGE 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLR-------SRGRAvitkqnqidFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKssSNVKQEG 380
Cdd:cd05575  83 LFFHLQrerhfpePRARF---------YAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCK--EGIEPSD 151
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18150824 381 AK-----LPvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVP-YPRvpveDVANHVEN 436
Cdd:cd05575 152 TTstfcgTP-EYLAPEVLRKQPYDRTVDWWCLGAVLYEML-YGLPPfYSR----DTAEMYDN 207
STKc_GRK2 cd14223
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs ...
231-465 8.21e-12

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271125 [Multi-domain]  Cd Length: 321  Bit Score: 66.22  E-value: 8.21e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVW--LGDYEGKKVAMKSM-KDHLKDEKAKTQFLAEA---SVMTTLRHPNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd14223   7 IIGRGGFGEVYgcRKADTGKMYAMKCLdKKRIKMKQGETLALNERimlSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMN 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLP 384
Cdd:cd14223  87 GGDLHYHLSQHG--VFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFGHVRISDLGLACDFSKKKPHASVGT 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 385 VKWTAPEALREN-KFSNKTDVWSFGVLLWEIYSyGRVPYPRVPVEDV--ANHVENGYRMESPDGCPDQIYKIMMDCWEKD 461
Cdd:cd14223 165 HGYMAPEVLQKGvAYDSSADWFSLGCMLFKLLR-GHSPFRQHKTKDKheIDRMTLTMAVELPDSFSPELRSLLEGLLQRD 243

                ....
gi 18150824 462 PSQR 465
Cdd:cd14223 244 VNRR 247
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
232-423 8.67e-12

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 65.87  E-value: 8.67e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLG--DYEGKKVAMKSMK-DHlkDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgSL 308
Cdd:cd07844   8 LGEGSYATVYKGrsKLTGQLVALKEIRlEH--EEGAPFTAIREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYLDT-DL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 309 IDYLRSRGRAvITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvkqegakLPVK-- 386
Cdd:cd07844  85 KQYMDDCGGG-LSMHNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLARAKS--------VPSKty 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 387 -------WTAPE--ALRENKFSNKTDVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07844 156 snevvtlWYRPPdvLLGSTEYSTSLDMWGVGCIFYEMAT-GRPLFP 200
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
10-62 9.31e-12

N-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 N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. 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: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 59.68  E-value: 9.31e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 18150824  10 ECIGKYNFPGSSPHDLPFKKGDRLVIVAPSKDPNWYKArREDGLEGMIPFNYV 62
Cdd:cd11804   1 EAVAKHDFKATAEDELSFKKGSILKVLNMEDDPNWYKA-ELDGKEGLIPKNYI 52
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
232-414 9.83e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 65.44  E-value: 9.83e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGD--YEGKKVAMKSMKDHLKDEKAKTQflAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLI 309
Cdd:cd06646  17 VGSGTYGDVYKARnlHTGELAAVKIIKLEPGDDFSLIQ--QEIFMVKECKHCNIVAYFGSYLSREKLWICMEYCGGGSLQ 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 310 DYLRSRGRaviTKQNQIDFA-RDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAK--SSSNVKQEGAKLPVK 386
Cdd:cd06646  95 DIYHVTGP---LSELQIAYVcRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAkiTATIAKRKSFIGTPY 171
                       170       180       190
                ....*....|....*....|....*....|.
gi 18150824 387 WTAPE--ALRENKFSNK-TDVWSFGVLLWEI 414
Cdd:cd06646 172 WMAPEvaAVEKNGGYNQlCDIWAVGITAIEL 202
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
232-465 1.01e-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: 65.19  E-value: 1.01e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWL------GDYEGKKVAMKSMKDHLKDekaKTQFLAEASVMTTLRH-PNLVCLIGISLDDNPIYLITEFMA 304
Cdd:cd05611   4 ISKGAFGSVYLakkrstGDYFAIKVLKKSDMIAKNQ---VTNVKAERAIMMIQGEsPYVAKLYYSFQSKDYLYLVMEYLN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 305 KGSLIDYLRSRGraVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnVKQEGAKL- 383
Cdd:cd05611  81 GGDCASLIKTLG--GLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGL-EKRHNKKFv 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 384 --PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYsYGRVPYPRVPVEDVANHVENGyRMESPDGCPDQIYKIMMDCWEK- 460
Cdd:cd05611 158 gtP-DYLAPETILGVGDDKMSDWWSLGCVIFEFL-FGYPPFHAETPDAVFDNILSR-RINWPEEVKEFCSPEAVDLINRl 234

                ....*...
gi 18150824 461 ---DPSQR 465
Cdd:cd05611 235 lcmDPAKR 242
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
226-415 1.03e-11

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: 66.04  E-value: 1.03e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 226 LLKKslIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKDEK-AKTQFlAEASVMTTLR-HPNLVCLIGI--SLDDNPIYLI 299
Cdd:cd07852  11 ILKK--LGKGAYGIVWkaIDKKTGEVVALKKIFDAFRNATdAQRTF-REIMFLQELNdHPNIIKLLNVirAENDKDIYLV 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 300 TEFMAKgsliDyLRSRGRAVITKQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVkQ 378
Cdd:cd07852  88 FEYMET----D-LHAVIRANILEDIHKQYiMYQLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSLSQL-E 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 379 EGAKLPV-------KW-TAPEAL-RENKFSNKTDVWSFGVLLWEIY 415
Cdd:cd07852 162 EDDENPVltdyvatRWyRAPEILlGSTRYTKGVDMWSVGCILGEML 207
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
104-186 1.31e-11

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 61.06  E-value: 1.31e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 104 LKTMPWFHGRISREDAEKLLT---PPKNGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNEKGLVTVdDDEYFDNLIKL 180
Cdd:cd10412   5 LSCYPWFHGPISRVKAAQLVQlqgPDAHGVFLVRQSETRRGEYVLTFNFQGRAKHLRLSLTERGQCRV-QHLHFPSVVDM 83

                ....*.
gi 18150824 181 VEHYQK 186
Cdd:cd10412  84 LHHFQR 89
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
105-185 1.41e-11

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 61.08  E-value: 1.41e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 105 KTMPWFHGRISREDAEKLLTPPK--NGRFLVRESQNYPGDYTLCVSYDGRVENYRVRRNE---KGLVTVDDDEY-FDNLI 178
Cdd:cd10413   3 RTQPWFHGRISREESQRLIGQQGlvDGVFLVRESQRNPQGFVLSLCHLQKVKHYLILPSEeegRLYFSMDDGQTrFTDLL 82

                ....*..
gi 18150824 179 KLVEHYQ 185
Cdd:cd10413  83 QLVEFHQ 89
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
231-422 1.47e-11

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: 65.79  E-value: 1.47e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 231 LIGKGEFGEVWLGDYEGKK--VAMKSMKDH--LKDEKAKTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKG 306
Cdd:cd05615  17 VLGKGSFGKVMLAERKGSDelYAIKILKKDvvIQDDDVECTMVEKRVLALQDKPPFLTQLHSCFQTVDRLYFVMEYVNGG 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 307 SLIDYLRSRGRavITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKS---SSNVKQEGAKL 383
Cdd:cd05615  97 DLMYHIQQVGK--FKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEhmvEGVTTRTFCGT 174
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18150824 384 PvKWTAPEALRENKFSNKTDVWSFGVLLWEIYSyGRVPY 422
Cdd:cd05615 175 P-DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPF 211
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
229-423 1.57e-11

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: 65.40  E-value: 1.57e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 229 KSLIGKGEFGEVWLGDYE--GKKVAMKSMK--DHlkdekakTQF----LAEASVMTTLRHPNLVCLIGI----SLDD-NP 295
Cdd:cd07849  10 LSYIGEGAYGMVCSAVHKptGQKVAIKKISpfEH-------QTYclrtLREIKILLRFKHENIIGILDIqrppTFESfKD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 296 IYLITEFMAKgsliDYLRsrgraVITKQNQID-----FARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLA 370
Cdd:cd07849  83 VYIVQELMET----DLYK-----LIKTQHLSNdhiqyFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLA 153
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18150824 371 KSSSNVKQEGAKL----PVKW-TAPE-ALRENKFSNKTDVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07849 154 RIADPEHDHTGFLteyvATRWyRAPEiMLNSKGYTKAIDIWSVGCILAEMLS-NRPLFP 211
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
232-423 1.88e-11

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 65.07  E-value: 1.88e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYEGKKVAMKSMKDHLKDEKA-KTQFLAEASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKGSLID 310
Cdd:cd06649  13 LGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPAiRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQ 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 311 YLRSRGRAVITKQNQIDFArdVVKGMVYL-ESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVKWTA 389
Cdd:cd06649  93 VLKEAKRIPEEILGKVSIA--VLRGLAYLrEKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMS 170
                       170       180       190
                ....*....|....*....|....*....|....
gi 18150824 390 PEALRENKFSNKTDVWSFGVLLWEIySYGRVPYP 423
Cdd:cd06649 171 PERLQGTHYSVQSDIWSMGLSLVEL-AIGRYPIP 203
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
232-412 1.92e-11

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: 64.75  E-value: 1.92e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEV--WLGDYEGKKVAMK-------SMKDHLKDEKaktqflaEASVMTTLRHPNLVCLIGISLDDNPIYLITEF 302
Cdd:cd14086   9 LGKGAFSVVrrCVQKSTGQEFAAKiintkklSARDHQKLER-------EARICRLLKHPNIVRLHDSISEEGFHYLVFDL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 303 MAKGSLID-------YLRSRGRAVItkqNQIdfardvVKGMVYLESQNFVHRDLAARNVLIA---EDNVAKVSDFGLAKS 372
Cdd:cd14086  82 VTGGELFEdivarefYSEADASHCI---QQI------LESVNHCHQNGIVHRDLKPENLLLAsksKGAAVKLADFGLAIE 152
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 18150824 373 SSNVKQEG---AKLPVkWTAPEALRENKFSNKTDVWSFGVLLW 412
Cdd:cd14086 153 VQGDQQAWfgfAGTPG-YLSPEVLRKDPYGKPVDIWACGVILY 194
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
247-414 1.92e-11

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 65.19  E-value: 1.92e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 247 GKKVAMKsmKDHLKDEKAKTQFLAEASVMTTLRHPNLVCL---IGISLDDNPIYL--ITEFMAKGSLIDYLRSRGRAVIt 321
Cdd:cd07854  30 DKRVAVK--KIVLTDPQSVKHALREIKIIRRLDHDNIVKVyevLGPSGSDLTEDVgsLTELNSVYIVQEYMETDLANVL- 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 322 KQNQID------FARDVVKGMVYLESQNFVHRDLAARNVLI-AEDNVAKVSDFGLAK------SSSNVKQEGakLPVKW- 387
Cdd:cd07854 107 EQGPLSeeharlFMYQLLRGLKYIHSANVLHRDLKPANVFInTEDLVLKIGDFGLARivdphySHKGYLSEG--LVTKWy 184
                       170       180
                ....*....|....*....|....*...
gi 18150824 388 TAPE-ALRENKFSNKTDVWSFGVLLWEI 414
Cdd:cd07854 185 RSPRlLLSPNNYTKAIDMWAAGCIFAEM 212
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
232-435 2.02e-11

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 64.71  E-value: 2.02e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 232 IGKGEFGEVWLGDYE--GKKVAMKSMKdhLKDEKAkTQFLA--EASVMTTLRHPNLVCLIGISLDDNPIYLITEFMAKgS 307
Cdd:cd07869  13 LGEGSYATVYKGKSKvnGKLVALKVIR--LQEEEG-TPFTAirEASLLKGLKHANIVLLHDIIHTKETLTLVFEYVHT-D 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 308 LIDYLrSRGRAVITKQNQIDFARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSNVKQEGAKLPVK- 386
Cdd:cd07869  89 LCQYM-DKHPGGLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARAKSVPSHTYSNEVVTl 167
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 18150824 387 WTAPE--ALRENKFSNKTDVWSFGVLLWEIYSyGRVPYPrvPVEDVANHVE 435
Cdd:cd07869 168 WYRPPdvLLGSTEYSTCLDMWGVGCIFVEMIQ-GVAAFP--GMKDIQDQLE 215
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
108-186 2.18e-11

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 60.22  E-value: 2.18e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 108 PWFHGRISREDAEKLLTPP-KNGRFLVRESQNYPGDYTLCVSYDGRVENYRVrRNEKGLVTVDDDEyFDNLIKLVEHYQK 186
Cdd:cd09943   2 PWYYGRITRHQAETLLNEHgHEGDFLIRDSESNPGDYSVSLKAPGRNKHFKV-QVVDNVYCIGQRK-FHTMDELVEHYKK 79
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
230-423 2.29e-11

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: 65.01  E-value: 2.29e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 230 SLIGKGEFGEVW--LGDYEGKKVAMKSMKDHLKD-EKAKTQFlAEASVMTTLRHPNLVCLIGI-----SLDD-NPIYLIT 300
Cdd:cd07851  21 SPVGSGAYGQVCsaFDTKTGRKVAIKKLSRPFQSaIHAKRTY-RELRLLKHMKHENVIGLLDVftpasSLEDfQDVYLVT 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 301 EFMAKgSLIDYLRSRgraVITkQNQIDF-ARDVVKGMVYLESQNFVHRDLAARNVLIAEDNVAKVSDFGLAKSSSnvKQE 379
Cdd:cd07851 100 HLMGA-DLNNIVKCQ---KLS-DDHIQFlVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLARHTD--DEM 172
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18150824 380 GAKLPVKW-TAPEALRENKFSNKT-DVWSFGVLLWEIYSyGRVPYP 423
Cdd:cd07851 173 TGYVATRWyRAPEIMLNWMHYNQTvDIWSVGCIMAELLT-GKTLFP 217
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
109-199 2.33e-11

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 60.35  E-value: 2.33e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18150824 109 WFHGRISREDAEKLLTPP-KNGRFLVRESqNYPGDYTLCV------SYDGRVENYRVRRNEKGLVTVDDDEYFDNLIKLV 181
Cdd:cd10399   8 WFAGNISRSQSEQLLRQKgKEGAFMVRNS-SQVGMYTVSLfskavnDKKGTVKHYHVHTNAENKLYLAENYCFDSIPKLI 86
                        90
                ....*....|....*...
gi 18150824 182 EHYQKEADGLCTRLKAPV 199
Cdd:cd10399  87 HYHQHNSAGMITRLRHPV 104
 
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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