2DYL


Conserved Protein Domain Family
PKc_MKK7

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cd06618: PKc_MKK7 (this model, PSSM-Id:132949 is obsolete and has been replaced by 270791)
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Catalytic domain of the dual-specificity Protein Kinase, MAP kinase kinase 7
Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK7 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. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). 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 (not included in this subfamily) 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.
Statistics
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PSSM-Id: 132949
View PSSM: cd06618
Aligned: 10 rows
Threshold Bit Score: 482.258
Threshold Setting Gi: 16950399
Created: 4-Apr-2007
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 33 residues -Click on image for an interactive view with Cn3D
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:
Feature 1                               ##### # #            # #                              #   
2DYL_A         11 GYLTIGGQRYQaeiNDLENLGEMGSGTCGQVWKMRFrktgHVIAVKQMRRSgnkEENKRILMDLDVVLKShdCPYIVQCF 90   human
Q23977        181 GKLNINGRQYPtdiNDLKHLGDLGNGTSGNVVKMMHlssnTIIAVKQMRRTgnaEENKRILMDLDVVLKShdCKYIVKCL 260  fruit fly
XP_689405     105 GYLKIDGQRYPaevTDLISEGEIGSGTCGQVFKVRFkktgHVIAVKQMRRTgnkDENKRILMDLDVVLKShdCPYIIQCY 184  zebrafish
AAH68887      101 GYLGIDGQKYPadiNDLENLGEIGSGTCGQVWKMRFkktgHVIAVKQMRRSgnkEENKRILMDLDVVLKShdCPYIVQCY 180  African clawe...
BAE06548      114 GKLRIDSMIYEakvEQFENLGQIGSGTCGQVYKMRYit-gHVMAVKQMHRSgnrEENKRILMDLDIVQKShdCPNIVKCY 192  Ciona intesti...
AAA79746       56 GYLTLQGNRRKadlKELQFVEDIGHGSCGTVTKCRYk--sVIMAVKTMPRTsnsYEMSRILMDLDVICLSfdCPYIVRCF 133  nematode
AAA81711      106 GTLEIDGEKQVvdpNEIHIISLLGSGSCGVVESATVr--sKLMAVKTMYKNdnkENLKRILRDVRIMSMCn-SPFIVTSY 182  nematode
XP_001635447   27 GILKLGDKKYDfslDDLEMSGEIGYGTCGQVCKMKHkksgQVLAVKRMARShnkEEQKRILMDLEVVMKShdCPYIVTCM 106  starlet sea a...
EDP34102      126 GRITIMKTMYEttkESLKRIGELGSGTCGVVYKARFeqtgTIMAVKQMVMTsvaEENKRVLMDLEVVLXShdCPHIVRCY 205  agent of lymp...
XP_002109884   13 GLLTIDGKKYKiglDDLQVMGQIGSGTCGTVYAMEHaatrSVIAVKKIPRIqneEEKKRVLMDLQVVMKShdCPYIVKCF 92   Trichoplax ad...
Feature 1                     #### ## ##                                         # #### #         
2DYL_A         91 GTFITntDVFIAMELMgTCAEKLKKRmqg----piPERILGKMTVAIVKALYYLKEkHGVIHRDVKPSNILLDerGQIKL 166  human
Q23977        261 GCFVRdpDVWICMELMsMCFDKLLKLskk----pvPEQILGKVTVATVNALSYLKDkHGVIHRDVKPSNILIDerGNIKL 336  fruit fly
XP_689405     185 GAIVTntDVFIAMELMgTCAEKLKKRiqg----piPEAILGKMTVAIVNALLYLKEkHGVIHRDVKPSNILLDakGQIKL 260  zebrafish
AAH68887      181 GTFITntDVFIAMELMgTCAEKLKKRiqg----piPEAILGKMTVAIVNALYYLKEkHGVIHRDVKPSNILLDasGQIKL 256  African clawe...
BAE06548      193 GTFVTevNVWICMELMeTCFDKLKKKing----pmPENILGKLTVSVVKALHYLKEkHGVIHRDVKPSNILVNklGDVKL 268  Ciona intesti...
AAA79746      134 GYFITnfDVRVCMECMaTCLDRLLIRikq----piPERIIGKLSVSIIKALHYLKTkHQIMHRDVKPSNILLDwsGVIKL 209  nematode
AAA81711      183 GYFMFdsSVKICMQIMsACCEKLLRRiyhskldffPEFVAGHIVYSAISALDYLKEkHSIIHRDIKPSNILFDdsGNVKL 262  nematode
XP_001635447  107 GALISksDVFICMELMaTCLDKLLKRlqn----piPEHILGKMAVAIVKALHYLKEeHGVMHRDVKPSNMLLDsaGCVKL 182  starlet sea a...
EDP34102      206 GCFITdfEVLICMELMaTCLDKLSKRvqg----gfPEDILGKMAVSIIKALDYLKVtQNIIHRDVKPSNILLDlnGTVKL 281  agent of lymp...
XP_002109884   93 GLLIAesDILICMEKMsTCLCKLLTRtgq----piPEDILGKITVAVVKALHYLKQnHGVIHRDVKPSNILLDadGNVKL 168  Trichoplax ad...
Feature 1          #  #            #### #                               #        #                
2DYL_A        167 CDFGISGRLVDDKAKDRSAGCAAYMAPERIDPpdptkpDYDIRADVWSLGISLVELAtGQFPYKncktDFEVLTKVLQEE 246  human
Q23977        337 CDFGISGRLVDSKANTRSAGCAAYMAPERIDPkk---pKYDIRADVWSLGITLVELAtARSPYEgcntDFEVLTKVLDSE 413  fruit fly
XP_689405     261 CDFGISGRLVDSKAKTRSAGCAAYMAPERIDPpdpskpDYDIRADVWSLGISLVELAtGQFPYKncktDFEVLTKVLQED 340  zebrafish
AAH68887      257 CDFGISGRLVDSKAKTRSAGCAAYMAPERIDPpdptkpDYDIRADVWSLGISLVELAtGQFPYKncktDFEVLTKVLQEE 336  African clawe...
BAE06548      269 CDFGISGRLVDSQAKTRAAGCTAYMAPERISPdps-hpNYDIRADVWSLGISLVELAtGVFPYHncktDFEMLTKILEEA 347  Ciona intesti...
AAA79746      210 CDFGIAGRLIESRAHSKQAGCPLYMGPERLDPnn--fdSYDIRSDVWSFGVTLVELAtGQYPYAg--tEFDMMSKILNDE 285  nematode
AAA81711      263 CDFGISGFMTDSMAHSKSAGCPPYMAPERLTIet--nsKYDVRSDVWSLGITVYQLVtGLYPFPlndmEFTTLTIIANLN 340  nematode
XP_001635447  183 CDFSISGRLVDSKAKTKSAGCAAYMAPERIDPpdpmnpNYDVRADVWSLGISLVELAtGEFPYRncttEFEVLTRVMGED 262  starlet sea a...
EDP34102      282 CDFGIAGRLVDSMARTRTAGCSAYMSPERLEAq----dEYDVRADVWSIGISLVELAkGEYPYRgcnsEFEVLSRIVSDP 357  agent of lymp...
XP_002109884  169 CDFGISGRLVDSKARTRGKGCAAYMSPERIDPsnp-tgTYDIRADVWSLGISLVELAtGKFPYDecegEFQVLTRILQDD 247  Trichoplax ad...
Feature 1                                                                                       
2DYL_A        247 PPLLPGHm----gFSGDFQSFVKDCLTKDHRKRPKYNKLLEHSFIKRYETle-------------vDVASWFKDVMAK 307  human
Q23977        414 PPCLPYGeg--ynFSQQFRDFVIKCLTKNHQDRPKYPELLAQPFIRIYESak-------------vDVPNWFQSIKDN 476  fruit fly
XP_689405     341 PPVLPLSm----gFSPDFQSFVKDCLTKDHRKRPKYHKLLEHSFIRRYEVse-------------vDVAGWFQAVMER 401  zebrafish
AAH68887      337 PPVLPHNm----gFTLLFQSFVKDCLTKDHRKRPKYNKLMEHPFLRRYETse-------------vEVASWFQDIMAR 397  African clawed ...
BAE06548      348 PPELPNDq----nFSIGFKRFVSFCCTKDYRYRPKYRDLLEHEFVRRHEHsm-------------vDIPAWLRKVLIT 408  Ciona intestinalis
AAA79746      286 PPRLDPAk-----FSPDFCQLVESCLQRDPTMRPNYDMLLQHPFVVHHEKie-------------tDVEEWFADVMGE 345  nematode
AAA81711      341 LPSPSLReetkrsFSPLFIEFLDLCLRKDVRERPEYRQLMKHDFYLDYDPasgsaykfkaingkcnQVADWFVDVIRL 418  nematode
XP_001635447  263 PPSLPGSk----gFSHDFSSFVDECLTKDFHYRPKYNKLLVHPFITSYDSke-------------vDVAGWLKESLAS 323  starlet sea ane...
EDP34102      358 APVLNPEe----gFSPMFCDFLRLCLTKNYQFRPKYKELLQHEWVIHYETar-------------vDVAGWYQRIVQS 418  agent of lympha...
XP_002109884  248 PPKLPSNg----qFSQEFCSFVEKCLIKDHDRRPKYAELLQHKFIQIYETkd-------------vDVASWFNQLIEE 308  Trichoplax adha...

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