1CM8,3COI,3GP0,1LEW,1LEZ,2FST,3HVC,2NPQ,1BL7,1ZZ2,3PY3,3NEW


Conserved Protein Domain Family
STKc_p38

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cd07851: STKc_p38 
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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.
Statistics
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PSSM-Id: 143356
View PSSM: cd07851
Aligned: 26 rows
Threshold Bit Score: 539.573
Threshold Setting Gi: 30315977
Created: 18-Jul-2006
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:1CM8_B; Human p38gamma binds MgAMP-PNP; defined at 4A contacts.
    View structure with Cn3D
  • Structure:3GP0_A; Human p38beta binds Nilotinib inhibitor; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1ZZ2_A; Human p38alpha binds inhibitor; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1BL7_A; Human p38alpha binds inhibitor SB220025; defined at 4A contacts.
    View structure with Cn3D
  • Citation:PMID 9753691

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                              ##   # ##                   # #                     #     
1CM8_B        11 FYRQEVtkTAWEVRAVYRDLQpVGSGAYGAVCSAVDGr-------tGAKVAIKKLYRPFQseLFAKRAYRELRLLKHMRH 83
gi 172087829   9 FVPVEInqLRWDLPDRYTPVNvAGQGSFGTVSSAFDKy-------lQREVAIKKLDRPFEnaEFAKRTYRELAILAQMDH 81
gi 162287320   9 FHRLDIqkTTWDVPDRYTSLKpVGSGAYGTVCFAVDQk-------tKEKVAIKKLYRPFQslIHAKRAYRELRLLRHIQH 81
gi 30315988   19 YYVVELnrSVWVVPNYYINLTpIGTGAYGTVCAAECTr-------sGTRVAIKKFNRPFQsiIHARRTYRELRLLRCMCH 91
gi 71051188    9 FYRQDInkTKWEAPVRYRELAaVGSGAYGTVCSAQDRl-------tGERVAIKKLLRPFQslVHAKRAYRELRLLKHMKH 81
3COI_A        10 FYKQDVnkTAWELPKTYVSPThVGSGAYGSVCSAIDKr-------sGEKVAIKKLSRPFQseIFAKRAYRELLLLKHMQH 82
gi 196004108  11 YYRCELnkTVWEIPIHYQNLSpIGSGAYGQVCSAIDTr-------tNIEIAIKKLSRPFEsnTFGKRTFREMKLLMHMNQ 83
gi 156400728   8 FYRTELvnTVYEVPRKYQELSpIGTGAYGQVCSSTITepdptnpdgPNTVAIKKLSRPFQstMHAKRTYRELKLLRHMRH 87
gi 17368358    4 FVRVAIneSLWEFPDIYEFVRfLGGGSFGQVAKVRLRg-------tENYFAMKRLMRPFEreEDAKGTYREIRLLKHMNH 76
gi 198452518   4 FTKFVMdeKAWEVPDVYEIERlLGAGSFGQVSKAKLRg-------gDVNVAIKKLLQPFEtaEHAKRVYREIRLLKHMDH 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           # #                    # ####  #                                     # # ##  
1CM8_B        84 ENVIGLLDVFTPdetl---ddfTDFYLVMPFMGTDLGKLMKheKLGEDRIQFLVYQMLKGLRYIHAAGIIHRDLKPGNLA 160
gi 172087829  82 ENVICLIDAFTPqtsl---etfEDVYLVTPLMDADLGAIVAqqVLTDDQICFLAYQMLRALKYMHGAHIIHRDLKPSNIG 158
gi 162287320  82 DNVICLLNVFTPdssl---ekfDTFYMVMPFVAQDLGHIMKrkQLTSNVITYLFYQILRGLKYIHSAGIIHRDLKPNNLA 158
gi 30315988   92 ENIIDLLDVFTPnenv---ndiEDVYFVSMLMGADLSNILKiqRLNDDHIQFLVYQILRGLKYIHSADIIHRDLKPSNIA 168
gi 71051188   82 ENVISLLNVFTPdesv---etfQTFYLVMPFIAVDLSRVMRmqRLNQSTIVYLLYQILRGLQYIHSAGIVHRDLKPSNLG 158
3COI_A        83 ENVIGLLDVFTPassl---rnfYDFYLVMPFMQTDLQKIMGl-KFSEEKIQYLVYQMLKGLKYIHSAGVVHRDLKPGNLA 158
gi 196004108  84 EQVISLLDTFTPtsgr---snfSDVYLVTPLMGADLNTVIKcqPLSDDHVKFLVYQLMRGLKYIHSCRIIHRDLKPSNIA 160
gi 156400728  88 ENVISLLDVFTTasaf---ehfQDVYMVTELMGSDLNGILRfqKLSDEHVQFLVYQILRGLKYIHSAGVIHRDLKPSNIA 164
gi 17368358   77 RNVISLLNVFHPpahn--mmefQQVYLVTHLMDADLHRYSRskRMSDQEIRIILYQILRGLKYIHSAGVVHRDLKPCNIA 154
gi 198452518  77 PNVISLLDVFHPsspsptlenfQQVYLVTHLMDADLHKTIRsqKLSDNQIRVILYQILRALKYIHSAGVLHRDLKPGNIA 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                 ## #                                                                   
1CM8_B       161 VNEDCELKILDFGLARQADSEMXGXVVTRWYRAPEVILNWMRYTQTVDIWSVGCIMAEMITGKTLFKGSdHLDQLKEIMK 240
gi 172087829 159 VNSDVELRIIDFGLARQKNHLMTGYVATRWYRAPEVMLNWMHYNDSVDVWSVACILVELKTRQPLFRGLnHIDQVKQIMS 238
gi 162287320 159 VDENCELKILDFGLARHTETEMTGYVVTRWYRAPEVIFNWMHYTQTVDVWTAGCILAEMITGEVLFPGSdSIDQLKKILN 238
gi 30315988  169 VNEDCELKILDFGLARQTDSEMTGYVATRWYRAPEIMLNWMHYTQTVDVWSVGCILAELITGKTLFPGSdHIDQLTRIMS 248
gi 71051188  159 VNEDYELKILDFGLARQTEFEMTGYVVTRWYRAPEVILNWMHYNQTVDIWSVGCILAEMITGKVLFPGGdYFDELNRIIE 238
3COI_A       159 VNEDCELKILDFGLARHADAEMTGYVVTRWYRAPEVILSWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKdYLDQLTQILK 238
gi 196004108 161 VNENCELKILDFGLARKASEELTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAEMLTSRPLFPGNdHIDQLTRILE 240
gi 156400728 165 VNEDCELKILDFGLARMTDAEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTSKTLFPGNdHIDQLTKIMQ 244
gi 17368358  155 VNGNSEVRILDFGLSRMCADKMTDHVGTMWYLAPEIIFLRGQYTKAIDVWSVGCILAELITDRVLFRGEnYVSQIRCLIN 234
gi 198452518 157 VNKDCELRILDFGMARLNSKDMTTYVTTRWYRAPEILFCWRNYSKAIDMWSVGCIFAEMITGRPLFPGRdYTNQLDCIID 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1CM8_B       241 VTGTPPAEFVQRLqsDEAKNYMKGLPELEKKDFASILTNaSPLAVNLLEKMLVLDAEQRVTAGEALAHPYFe----SLHD 316
gi 172087829 239 IVGAPDEELMQKItsSSAREFIEKLNYTSKKDLKDAFPWaSPVLLDLLSKMLVLDPDRRLTAAQALAHPYFa----EYHN 314
gi 162287320 239 LTGTPNSTLVLKMqsKDAQSYVRSLPVQKKKAFKEVFSGmDPNAIDLLEGMLVLDPEVRLSAKNGLSHPYLs----EFHD 314
gi 30315988  249 VTGTPDEEFLKKIssEEARNYIRNLPKMTRRDFKRLFAQaTPQAIDLLEKMLHLDPDRRPTAKEAMEHEYLa----AYHD 324
gi 71051188  239 VTGSPQPSLINKMesSHAQDYVRMLPKKQKKNFKELFPTmSSIETELLEKMLDLDPEKRINATEALAHPYLe----EYND 314
3COI_A       239 VTGVPGTEFVQKLndKAAKSYIQSLPQTPRKDFTQLFPRaSPQAADLLEKMLELDVDKRLTAAQALTHPFFe----PFRD 314
gi 196004108 241 LVGCPSDEFIRKIqsEAARNYVAGMPKFPRKDFSTVFLGaNPEAIDLLEKMLTLDSSQRIDAIEALAHPYLa----EYAD 316
gi 156400728 245 LVGKPSDDFLQKIdsESARNYIAQMPDYRKTPFDEYFVGaNPLAVDLLEKMLNLDTDHRITAVEALSHPYLa----SYAD 320
gi 17368358  235 IMGTPTREFITGIsmERSRNYLEGYPLRQRCDFHHLFMGyDVQAIDLMEKMLEMVPEKRITAAEAMLHPYLrdliePHHH 314
gi 198452518 237 IMGTPSDEFKSKIdlESARTYVESLPRRTKSDFMELFGMgNYQAVDLIEKMLVMDPDNRITADEALRHPFLknlvqPQHN 316
                        330       340       350
                 ....*....|....*....|....*....|....*....
Feature 1                                               
1CM8_B       317 TEDEPq-vQKYDDSFDDv-dRTLDEWKRVTYKEVLSFKP 353
gi 172087829 315 ESDEPvgePLEDDLIDSd-nLTMEEWKEATWNLLQNFKP 352
gi 162287320 315 PENEPv-sPPYDDSFESm-dLAVSEWKSLIHMEIMTFDP 351
gi 30315988  325 ETDEPi-aEEMDLNDDVr-aDTIDEWKKIIWEEISDFQK 361
gi 71051188  315 SDPDPp-aEKYDDSFESl-dLDVHEWKSLSHMEIMTFEP 351
3COI_A       315 PEEETeaqQPFDDSLEHe-kLTVDEWKQHIYKEIVNFSP 352
gi 196004108 317 PDDEPs-gEPFDEGFEDl-eISVEQWKDMVYKQIEEFKR 353
gi 156400728 321 PNDEPt-cSTFDDSFDEk-eLSIEGWRALVYQEILDFQQ 357
gi 17368358  315 AEDTA---PVYDQNFENm-vLPVKCWKELVSHEIRNFRP 349
gi 198452518 317 DEDTA---PLYDQNFENmdwLSVKCWKELVLNEIMNFRP 352

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