Conserved Protein Domain Family
STKc_MAP4K3_like

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cd06613: STKc_MAP4K3_like (this model, PSSM-Id:173727 is obsolete and has been replaced by 270788)
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase-like Protein Serine/Threonine Kinases
Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3-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. 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, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). 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. 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).
Statistics
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PSSM-Id: 173727
View PSSM: cd06613
Aligned: 19 rows
Threshold Bit Score: 464.075
Threshold Setting Gi: 154334775
Created: 21-Aug-2006
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:
  • Comment:The active site is composed of the ATP binding site and the substrate binding site. The substrate binding site is based on the binding of human PAK4 to a consensus peptide.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                  #####   #            # #                              #               
gi 29427817   12 PQEDFELIQRIGSGTYGDVYKARNVNtGELAAIKVIKLEPge--dfAVVQQEIIMMKDCKHPNIVAYFGSYLRrDKLWIC 89
gi 66820650   25 PQTIYHIQERLGKGSFGQVFKAVHFAnGKVVAIKIISLDDqe--aiKDVRKEISILAECNYPNIVQYFGSYFKdHQLWIV 102
gi 2352084   245 PTTKYEFLNELGKGSYGSVYKARDLKtSEIVAVKVISLTEgee-gyEEIRGEIEMLQQCNHPNVVRYLGSYQGeDYLWIV 323
gi 76157479   10 PKEEYKILSPIGSGTYGDVFKAVHRErRTLVAVKVMKIDLkd--diRSICQEIHTLRECRHPNIVQFYGSYLRnNKLWIC 87
gi 62175728   16 PEELYEELGPIGVGNYGSVIKARNRHtQEITAIKLVLLVDkd--erDFVQREISILKHCRHPNIVHYYGAHKSlSKLWIV 93
gi 156406554  14 PDKVFDLIEKVGGGTYGDVFKARVIAtGDLAAVKVVKVEPgd--dfELIQQEIAMMQQCRHNNIINYIGAYMRrDKLWIG 91
gi 168010893 135 PSLKYELLNELGKGSYGAVYKARDLLtSELVAVKVISLTEgee-gyEEIRGEIGMLQQCNHPNVVRYLGSFQGeDYLWIV 213
gi 195997539   8 LQEQFDIKKKIGSGSYGDVFKVRVRQtDQIAALKVIKIQEdd--dlAIIEQEIQILRGCVHPNIVQYFHSEFRrQQLWIT 85
gi 167517449  11 PESVFELIKQIGSGSYGSVHKARIIKsGKSAAVKMINMEDgd--elEDVQNEIRMLESCKHDNIVAYFGAFQRgHTMWIA 88
gi 159485932   6 ARSRFQLQSVLGKGAYGTVYAAIDTAsGERVAIKVIPVTEqdreefKQIQREVAFLADCNHPNVVRYLGSYRLsGELWIV 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ####  ##  #                                    # #### #          #  #           
gi 29427817   90 MEFCGGGSLQDIYHVt-gPLSELQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTdnGHVKLADFGVSAQITATIaKR 168
gi 66820650  103 MEYCGGGSVSDLLQVi-dTISEDEIALICREALKGLNYLHEFKKIHRDIKGGNILLNdrGEVKLADFGVSAQLFNTFsKR 181
gi 2352084   324 MEYCGGGSVADLMNVteeALEEYQIAYICREALKGLAYLHSIYKVHRDIKGGNILLTeqGEVKLGDFGVAAQLTRTMsKR 403
gi 76157479   88 MEYCGGQSMQDIYLYtrrPLEEDCIAFVSRETLQGLNFMHNRGRIHRDIKGANILLTddGHVKVADFGVAAQLSTSIaKR 167
gi 62175728   94 MEYCEGGSIDMVYKVlrhPLPEPLIAYVCRQVLLGLQYLHANRKIHRDIKGGNILLTrdGGVKLADFGVSTELSHSLsRR 173
gi 156406554  92 MEYCGGGSIQDVYCVt-gPCSETQISFVTVETLKGLAYLHEKSLMHRDIKGANILLTtnGEVKLADFGISARITETMkKR 170
gi 168010893 214 MEYCGGGSVADLMNItdeALEEQQIAYICREALKGLTYLHSIFKVHRDIKGGNILLTeqGEVKLGDFGVAAQLTRTMsKR 293
gi 195997539  86 MEYCGGGSLQDIYKRt-gALTEQQIAFVCRESLRGLDYLHQQQKLHRDIKGANILLTedGDIKLADFGVAAQITNTFqKR 164
gi 167517449  89 MEYCGGGSVSDIYNKnctPLEEDVIAHITFYSLLGLEYLHQSHLVHRDIKGGNILLTedGCVKLADLGVSAQLTSTLaKR 168
gi 159485932  86 MEYCGGGSVSDLLSAgraPLPEELIAHICCESLKGLAYLHGLGKVHRDIKCGNILLTssGDVKIADFGVSAQLTNTMsKR 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #### #                                #        #                              
gi 29427817  169 KSFIGTPYWMAPEVAAVerk---ggYNQLCDLWAVGITAIELAELQPPMFDLHPMRALFLMTKsnfQPPKLKDKMKWSNS 245
gi 66820650  182 NTFVGTPYWMAPEVIQEn------kYDGKADVWSLGITAIEMAEGLPPNSNVHPMRVIFMIPRe--ESPALTDKSIWSDK 253
gi 2352084   404 NTFIGTPHWMAPEVIQEn------rYDGKVDVWALGVSAIEMAEGLPPRSSVHPMRVLFMISIe--PAPMLEDKEKWSLV 475
gi 76157479  168 TTLIGTPYWMAPEVASIecr--gsgYDGKCDIWGVGITAIEYAELQPPMFDLDPRKALQILGSrnyKPPSLQDRHKWSPL 245
gi 62175728  174 NTFVGTLLWMAPEAILEl------dYDEKADLWSLGITLIEMAEGAPPYIDTHPARALFMIPKm--DPPSLQDKERWSPQ 245
gi 156406554 171 KSFIGTPYWMAPEMAAVert---ggYDLKCDIWAVGITAIEMAELQPPMFDLHPMRALYIIGKksfIPPTLKEKDKWSNE 247
gi 168010893 294 NTFIGTPHWMAPEVIQEn------rYDGKVDVWALGVSAIEMAEGLPPRSNVHPMRVLFMISRe--PAPMLEDKERWSLV 365
gi 195997539 165 QTFIGTPYWMAPEVANVere---ggYDQACDIWAVGITAIELAQLKPPLYEIHPMKALLIIGKsdyKPPKLKEKNLWTVK 241
gi 167517449 169 KSFIGTPYWIAPEIIAVemkmgpdgYTSRCDVWSMGITCIEMAEMQPPMFDLHPMRALYLIPKn--PPPKLTDKSRWSKD 246
gi 159485932 166 QTFIGTPHWMAPEVIQEs------rYDGKVDVWALGISAIEMAEMTPPRWNVHPLRVIFMISRd--PPPRLSQPEKWSPV 237
                        250       260
                 ....*....|....*....|....*..
Feature 1                                   
gi 29427817  246 FHHFVKMALTKnPKKRPTAEKLLQHPF 272
gi 66820650  254 FQDFISKCLTKdPAERPTAKELLNHEF 280
gi 2352084   476 FHDFVAKCLTKePRLRPTAAEMLKHKF 502
gi 76157479  246 FHSFVKCCLIKaERRRPDAATMLTHNF 272
gi 62175728  246 MTLFLKRLLTKdHNARPTATTMLNDPF 272
gi 156406554 248 MHHFIKVALIKnPKKRPSADKMLTHPF 274
gi 168010893 366 FHDYVAKCLTKePRLRPTASALLSHKF 392
gi 195997539 242 FHDFIKETLTKdYTRRPSAGKLLQHHF 268
gi 167517449 247 FREFIKATLVKnPQKRPSAGALTKVRD 273
gi 159485932 238 FIDTMTQALIKdPKQRPAARYLLQHRF 264

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