2FYS,3UIB,1GOL,2Z7L,2ERK,1CM8,2B9H,1LEZ,1JNK,1UKI,2GMX,3PY3,1BL7,3OZ6,4B99


Conserved Protein Domain Family
STKc_MAPK

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cd07834: STKc_MAPK 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 270828
View PSSM: cd07834
Aligned: 52 rows
Threshold Bit Score: 378.406
Threshold Setting Gi: 71747040
Created: 31-Jul-2009
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 22 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               #### ## #            # #                                 #               
2FYS_A        28 RYTNLSyIGEGAYGMVCSAYDNlnkVRVAIKKISPFeh-qTYCQRTLREIKILLRFr---HENIIGINDIIRapti-eqm 102
1GOL_A        28 RYTNLSyIGEGAYGMVCSAYDNlnkVRVAIRKISPFeh-qTYCQRTLREIKILLRFr---HENIIGINDIIRapti-eqm 102
3OZ6_A        10 KYELVKkLGKGAYGIVWKSIDRrtgEVVAVKKIFDAfqnsTDAQRTFREIMILTELs--gHENIVNLLNVLRad----nd 83
gi 68127696   31 RYNVQHfVGRGAYGFVCSAVDAvtnEPVAIKKVMHLfddaVDAKRVLREVKLLAYLk---HPNILSLKDLFKspdpvdty 107
gi 1015929    29 SHKLVKfIGSGSYGSVCSAVDEdsgERVAIKRIQRVfsdlKEGKRILREMDILTSLh---HTNLVRLRQFIRpvrk-ddf 104
gi 124423437  25 DYEIIKqIGSGSYGQVVEAMQKstnKKVAIKRLTAIfddeIDCKRILREICILRELk---HQNLIQIIEILEpqdp-ksf 100
gi 206598146  44 HYSVTTvVGHGAYGVVCAALDErtgREVAIKRIGRIfddlVDGRRILREITILRLLreskCRNVLQLHRVLRpfepvdtf 123
gi 62358516   32 KYTLLKiLGMGAYGIACSCLNEetqEKVSIKKCREVfrdlDDGRRVLREVAMMRFFr---HENLLHVMDILPpmkgynef 108
gi 62359256   29 RYEVNNvVGRGAYGIVCSAIDTetgDKVAIKKIGNVfadvVDGKRTLREVKLLRFLk---HPNIISMRDVFRpvs--edf 103
gi 62358835   37 RYTLTSvVGYGAYGVVCSAFDNtnfRDVAIKRVGHVfedlIDGRRIWREIVIHRLLrehrCRNILNLTRILPprqrissf 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              ####  #  #                                      # ## #            ##      
2FYS_A       103 KDVYIVQDLMETDLYKLLKtq--hlSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTT---CDLKICDFGLARV 177
1GOL_A       103 KDVYIVQDLMETDLYKLLKtq--hlSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTT---CDLKICDFGLARV 177
3OZ6_A        84 RDVYLVFDYMETDLHAVIRan--ilEPVHKQYVVYQLIKVIKYLHSGGLLHRDMKPSNILLNAE---CHVKVADFGLSRS 158
gi 68127696  108 SELYVVTDLMESDMDAILRsprirlAAGHGQYFTLQLLCALQYIHSAHVLHRDLKPGNLLTDSE---CNLKLGDFGLARG 184
gi 1015929   105 SDIYIVMDLYDTDLHRIIRsrq-slTNEHYQYLMIQAFRGLFYLHTAKVIHRDLKPSNLLVNAD---CTLAICDFGLARD 180
gi 124423437 101 DTIYVVMEYAQSDLKKLFKspi-hlQFLHIQTIVYNICVGLKYLHSAKVLHRDLKPANVLLNED---CTVKICDFGLARS 176
gi 206598146 124 RDLYVVTELLDHDLYSWIRqkr-dtSTQQIRHVIAQVLRCLADMHAMGIIHRDIKPSNVLLNDS---EDVFVCDFGLARA 199
gi 62358516  109 RDVYIVTPLKDVDMNVVLRsrq-vlEETHVRYFIYQILRGLKYLHSAGVAHRDLKPANLVTDIS---CELKIIDFGLSRS 184
gi 62359256  104 SDVYVVTELMSSDLQTVVKspnvqlMSIHCQYLTYQLLCALQYMHSADIIHRDLKPANILTDSD---CVVKVCDFGLARG 180
gi 62358835  117 RDLYIVTDLYDTDLHSAIHatk-tvDIKALQRIMVRVLRCIADMHFMGIIHRDLKPSNILLNDDaenENAVVCDFGLARA 195
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
2FYS_A       178 ADPdhdh--------------------------------------tgfLTEYVATRWYRAPEIMLNsk-gYTKSIDIWSV 218
1GOL_A       178 ADPdhdh--------------------------------------tgfLTEYVATRWYRAPEIMLNsk-gYTKSIDIWSV 218
3OZ6_A       159 FVNirrvtnniplsin--------------------entenfdddqpiLTDYVATRWYRAPEILLGst-kYTKGIDMWSL 217
gi 68127696  185 IGHdd------------------------------------------tMTQYVFTRWYRPPELLLVck-hCNYSADMWAV 221
gi 1015929   181 DQCtqt----------------------------------------saLTEYVVTRWYRPPEVLGMgshrYTNAVDVWSL 220
gi 124423437 177 VQGidatdqaleeelarqqeepkkkdekkgprmlqkqnklnakavkreLTGHVVTRWYRAPEVILLek-dYTAAIDVWSV 255
gi 206598146 200 GMHefre--------------------------------------ptdLTDYVVTRWYRPPELLMMc--kYHLPVDVWTA 239
gi 62358516  185 VTIph-----------------------------------------hdLTDYVITRWYRPPELLLEns-yYDTAVDIWSV 222
gi 62359256  181 VGVn--------------------------------------------VTSYVVTRWYRPPELLLVgd-dCDGAVDMWGV 215
gi 62358835  196 GVLdlqe--------------------------------------pvdLTDYVVTRWYRPPELLLMc--rYSLPIDLWAI 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
2FYS_A       219 GCILAEMLSn-----------RPIFPGKh--------------------YLDQLNHILGILGSPSQedlnc--iinlKAR 265
1GOL_A       219 GCILAEMLSn-----------RPIFPGKh--------------------YLDQLNHILGILGSPSQedlnc--iinlKAR 265
3OZ6_A       218 GCILGEILCg-----------KPIFPGSs--------------------TMNQLERIIGVIDFPSNedves--iqspFAK 264
gi 68127696  222 GCLAAEMFTg-----------KPLFPGKd--------------------YINQINLIVELLGIPDLardlp-pstskEAI 269
gi 1015929   221 GLIFAELMVg-----------KTLLPGSd--------------------YIHQLIMIVHLLGTPASedme---flseEAK 266
gi 124423437 256 GCIFAELLNmmkenaptfldrAPLFPGTscfplspersaiakkggfpysNTDQLTVIFSVLGTPGEkdmdf--vtdkKAI 333
gi 206598146 240 GCVMAEFAMq-----------RPLFSGRd--------------------YIHQLSLLVSTVQVRSIefvq---esgsAAA 285
gi 62358516  223 GCIMAEMYNr-----------KPVLPGRn--------------------TIDQLRLICTHIGKPPRdmv-----esaEAL 266
gi 62359256  216 ACLVAEIVLr-----------CPLFPGRd--------------------YIHQLNLLVDALGLPQVeqdlq-hirspEAL 263
gi 62358835  236 GCIICEFVLk-----------RPLFGGRd--------------------YIHQMQLVVSSVAVTNWdfargscpgttTFM 284
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
2FYS_A       266 NYLLslphknkvp----------------------------------------------wnrlfpnaDSKALDLLDKMLT 299
1GOL_A       266 NYLLslphknkvp----------------------------------------------wnrlfpnaDSKALDLLDKMLT 299
3OZ6_A       265 TMIEslkekveirqsnkrdif------------------------------tkwknlllkinpkadcNEEALDLLDKLLQ 314
gi 68127696  270 HYLSslppskgkkleeyapelrrrfdettfyd-------sfdteleeaiavegaiiarprphppeeyYAEFVDFIFGLLC 342
gi 1015929   267 NFLLaqpfqearp----------------------------------------------ftelfpaaTPEAADLLSKLLV 300
gi 124423437 334 EYLKsfpkkpkva----------------------------------------------fveifpgaPPEALDFLDKCLQ 367
gi 206598146 286 GFLSelvsksqplt-------------------------------------------rpltrvlsmlPPDGIDVVEKMLA 322
gi 62358516  267 EKLNqlpdgeldm----------------------------------------------gklvpgltSADGIDFLSQMWE 300
gi 62359256  264 AYLRslpkrkplglegvhptlkqayltafsygteddyemegttthgnakdggsaaseadiaaaaekeYALFKDFLLKLLL 343
gi 62358835  285 NEIVrkyqgrrp-----------------------------------------------issvmstmPREGIDLVTKLLA 317
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                    
2FYS_A       300 FNPHKRIEvEQALAHPYLe-QYYDPSDEpiaeapfkf----dmelddlpkEKLKELIFEE 354
1GOL_A       300 FNPHKRIEvEQALAHPYLe-QYYDPSDEpiaeapfkf----dmelddlpkEKLKELIFEE 354
3OZ6_A       315 FNPNKRISaNDALKHPFVs-IFHNPNEEpncdhiitip---indnvkhsiDDYRNLVYSE 370
gi 68127696  343 YNPAKRRTaKESIAHAWLs-DVRGPQETiggceaeriyr-wdadgtaftiPQLRQLFIDE 400
gi 1015929   301 FHPDKRLTaKEVIEHAYFa-KFRNPAAEtgakepyvw-----rhnegltlEGLREEMWRI 354
gi 124423437 368 FSPKIRITlDQAIEHPMLq-KVRDKKKEtaapgpiyld---feqegdlqiPRLRELFLRE 423
gi 206598146 323 FDPKERITaREALRHPFFa-SVGGESQAiypkpptenldmsfdlqcdiseAQLRRKVWDE 381
gi 62358516  301 LDPRKRPSaAELLRHPFMa-PLHDEVDEpvcptsfaw----pyemqemslDSLRRAFWDE 355
gi 62359256  344 YNPKERMTaAEAVTHPWLrdIRKKCEDEgleiqpsnrfh-wnfdsaeftePVLRAVMKAE 402
gi 62358835  318 FDPNTRITaAEALRHPFF--SDVGAEGEskctipekvdf-sfdlhaeiseAQLRRNIWKE 374

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