4B99,4IC7


Conserved Protein Domain Family
STKc_ERK5

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cd07855: STKc_ERK5 
Click on image for an interactive view with Cn3D
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 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: 270842
Aligned: 11 rows
Threshold Bit Score: 558.906
Created: 27-Jul-2006
Updated: 2-Oct-2020
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:
  • Structure:4IC7: Human ERK5 binds ANP; contacts at 4A.
  • Structure:4B99: Human ERK5 binds inhibitor; contacts at 4A.
  • Comment:also based on the structures of other MAPKs bound to ATP or ATP analogs
  • Citation:PMID 8107865
  • Citation:PMID 9739089

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                        #### ## #            # #                               #         
4B99_A         50 FDVG---DEYEIIETIGNGAYGVVSSARRRltgQQVAIKKIPNAFDvvTNAKRTLRELKILKHFK-HDNIIAIKDILRpt 125  human
4IC7_A         51 FDVG---DEYEIIETIGNGAYGVVSSARRRltgQQVAIKKIPNAFDvvTNAKRTLRELKILKHFK-HDNIIAIKDILRpt 126  human
BAE06414       32 FDVG---PQYKILETIGTGAYGIVCSAIDNktgKHVAIKKVVQAFEvvTTAKRTLRELKLLLHFK-HDNIVGIKSIIQsk 107  Ciona intesti...
XP_001632636   17 FVVD---ARYKLIETIGNGAYGVVCSAMDTrtgAKVAVKKISRAFDvlTTARRTHRELKILRHFK-HDNIICIRDILKpp 92   starlet sea a...
XP_002108552   13 FDVH---LRYKPIECIGAGAYGVVCSAIDNrtgCRVAIKKIAKVFDnlILAKRTYRELKILRHFK-HDNIIAIREILLan 88   Trichoplax ad...
XP_001742318   25 FRLD---PRFSPDRVIGSGAYGMVCSALDSvsrKKVAIKKISSAFTmiQVAKRTLREIKLLKHFHaHPNIVSILTIQRpp 101  Monosiga brev...
Q13164         49 FDVG---DEYEIIETIGNGAYGVVSSARRRltgQQVAIKKIPNAFDvvTNAKRTLRELKILKHFK-HDNIIAIKDILRpt 124  human
XP_001892881   24 FQFGaagSSYEAIRNIGSGAFGIVCEAVETnsgKKVAIKKIGHASAtpTSARRTLREIRVLRYIA-HDNIVSLRDIFRtp 102  agent of lymp...
NP_741908      73 FKLEraaETYEPTQNIGSGAFGIVCEAVETssnQKVAIKKVAHASAtpTLARRTLREIRVLRYIN-HPNIVPLRDIFRtk 151  nematode
BAE48519       44 FEVG---DEYEIIETIGVGAYGVVSSARRKgsgQRVAIKKIPNAFDvvTNAKRTLRELKILKHFK-HDNVIAIKDILKps 119  African clawe...
XP_780133      21 FDIAn--SNYKPLEKIGTGAYGVVCSAINKkngEKVAIKKIPNSFDelTTAKRTFRELKILRHFR-HENVIAIREILMpk 97   purple sea ur...
Feature 1                     ####  #  #                                      # ## #         ##   
4B99_A        126 vpygefKSVYVVLDLMESDLHQIIHSSQP-LTLEHVRYFLYQLLRGLKYMHSAQVIHRDLKPSNLLVNENCELKIGDFGM 204  human
4IC7_A        127 vpygefKSVYVVLDLMESDLHQIIHSSQP-LTLEHVRYFLYQLLRGLKYMHSAQVIHRDLKPSNLLVNENCELKIGDFGM 205  human
BAE06414      108 k--edfKHVYFVMDLMESDLHHIIRSDQP-LTTEHICYFMYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELRIGDFGM 184  Ciona intesti...
XP_001632636   93 vnldefDDVYVVLDLMESDLHRIIHTDQP-LTTEHVRYFLYQILRGLKYIHSAKVLHRDLKPSNLLVNENAELKIGDFGM 171  starlet sea a...
XP_002108552   89 q--adgQDIYVIFDLMETDLHHIIHSQQP-LTNDHMQFFMYQLLRGLKYIHSANVLHRDLKPSNLLINSNCELKIGDFGM 165  Trichoplax ad...
XP_001742318  102 attadfKDLYVVLELQECDLHRIIHSDQP-LSEAHVRYFLYQLLCGLKYIHSANVLHRDIKPGNLLINSDCSLRIGDFGM 180  Monosiga brev...
Q13164        125 vpygefKSVYVVLDLMESDLHQIIHSSQP-LTLEHVRYFLYQLLRGLKYMHSAQVIHRDLKPSNLLVNENCELKIGDFGM 203  human
XP_001892881  103 g--nlgINVYLVMDLMEGNLHHLIYCGGP-MEDDLISHFLYQILRGLRYIHAAGIAHRDLKPSNLLVNGDCHLRIADFGM 179  agent of lymp...
NP_741908     152 g--plgIDVFLVMDLMQNNLHHIIYGNEDpLEEHYINAFLGQLLRGLEYLHAACIAHRDLKPSNLLVNQDGTLRIADFGM 229  nematode
BAE48519      120 vpyndfRSVYVVLDLMESDLHQIIHSSQP-LTLEHARYFLYQLLRGLKYIHSANVLHRDLKPSNLLINENCELKIGDFGM 198  African clawe...
XP_780133      98 eplsemKDVYVVFDLMESDLHQIIHSNQP-FSLEHIRFFLYQILRGLKYIHSADVIHRDLKPSNLLVNENCELKVGDFGM 176  purple sea ur...
Feature 1                                                                                         
4B99_A        205 ARGLCTSPAE-----HQYFMTEYVATRWYRAPELMLSlheYTQAIDLWSVGCIFGEMLARRQLFPGKNYVHQLQLIMMVL 279  human
4IC7_A        206 ARGLCTSPAE-----HQYFMTEYVATRWYRAPELMLSlheYTQAIDLWSVGCIFGEMLARRQLFPGKNYVHQLQLIMMVL 280  human
BAE06414      185 ARAVSQEPED-----HKSFMTEYVATRWYRAPELMLSfgrYSQAIDMWSVGCIFAEMIGRRQIFPGKHYVHQLQLIISVL 259  Ciona intesti...
XP_001632636  172 ARGLCSSPLE-----QKRFMTEYVATRWYRAPELMLSlneYSEAIDMWSVGCILAEMIGRRPLFPGANYLNQLQMILSVT 246  starlet sea a...
XP_002108552  166 ARCISSSQID-----HTTYMTEYVATRWYRAPELMLSlqgYTRAIDMWSVGCIFAEMLGRKQLFPGKTYVHQLRLIIGVL 240  Trichoplax ad...
XP_001742318  181 AREMASKPEQ-----HQNFMTEYVATRWYRAPEVLLSfdrYTQAIDMWSVGCILAEMLGRRHLFPGKDYLHQLGLILSLL 255  Monosiga brev...
Q13164        204 ARGLCTSPAE-----HQYFMTEYVATRWYRAPELMLSlheYTQAIDLWSVGCIFGEMLARRQLFPGKNYVHQLQLIMMVL 278  human
XP_001892881  180 AKLAMKNQVEev-eeHSFYMTQHITTLPYRAPELLFVmpeHSTAVDLWAVACIFAEMIIRRELFPGRSVSGQIKIIVTML 258  agent of lymp...
NP_741908     230 AKCADNSSKKhddeeHCYYMTQHVATLPYRAPELLFVlpeHSTAVDMWAVGCIFGEMVIRNEILPGRSVQGQIKMLLTML 309  nematode
BAE48519      199 ARGLCTKPDE-----YKYFMTEYVATRWYRAPELMLSlheYTQAIDMWSVGCIFAEMLGRKPLFPGNNYLHQLHLIMTVL 273  African clawe...
XP_780133     177 ARGLSTFSTDk----KKMFMTSYVATRWYRAPELLFSsddYTLAVDVWSVGCILGEMIGRKQMFPGKNPIDQLSLIVDVL 252  purple sea ur...
Feature 1                                                                                         
4B99_A        280 GTPSPAVIQAVGAERVRAYIQ-SLPPRQPVPWETVYPGA----------DRQALSLLGRMLRFEPSARISaAAALRHPFL 348  human
4IC7_A        281 GTPSPAVIQAVGAERVRAYIQ-SLPPRQPVPWETVYPGA----------DRQALSLLGRMLRFEPSARISaAAALRHPFL 349  human
BAE06414      260 GSPPSGLVSTIRSDRVRNYVT-GLPSKSATPFKQLYTKA----------TQPMVDLLTSLLRFNPEERPTsVQALTHPFL 328  Ciona intesti...
XP_001632636  247 GTPSQNFIERMGAERVKTYLN-QLPHKDPVPFEKFFPKA----------HPEAINLLSQMLQLDPKERITvENALQHPFL 315  starlet sea a...
XP_002108552  241 GTPCHQFLLSSGAERVRKYID-SLPQRQRIAWTVLFPSI----------TEHALTLLDQLLQFDPSQRLNvEEALLHPYL 309  Trichoplax ad...
XP_001742318  256 GSPSEDVLDRIGSSLARRCLQ-NFQNIPALDLHTVFPDA----------RQDLLNLLSLMLTFDPEQRVTvDQALENPFF 324  Monosiga brev...
Q13164        279 GTPSPAVIQAVGAERVRAYIQ-SLPPRQPVPWETVYPGA----------DRQALSLLGRMLRFEPSARISaAAALRHPFL 347  human
XP_001892881  259 GAPSGKILNQIQCDRTRRLIE-NFGDHPVRPWNEIIRDKa--------dSIETLDLIAKMAKMDPEERIDvNEAIQHPYF 329  agent of lymp...
NP_741908     310 GQPPQEVINEVRCDRTRKLIQ-DFGRKADAEWDDIMFCKargddqivrgNCDTIDFVKQLFQYDAQKRINiQDALLHPYI 388  nematode
BAE48519      274 GTPSSQVIRAIGAERVRAYIQ-SLPSRQPVPWATLYPQA----------GKKALDLLSKMLRFDTRDRISvAEALRHPFL 342  African clawe...
XP_780133     253 GMPPTHMLKSTSSDHLYNFFQkNFANKTPKDLSKLYPKA----------DPQGLDLLAKMLIFEPSERITvNKALQHPFL 322  purple sea ur...
Feature 1                                                  
4B99_A        349 a-KYHDPDDEPDCaPPFDFAFDRea---lTRERIKEAIVAE 385  human
4IC7_A        350 a-KYHDPDDEPDCaPPFDFAFDRea---lTRERIKEAIVAE 386  human
BAE06414      329 s-GYHDKDDEPTChAPFDFQFEAtatregVHEEVTAVIKKY 368  Ciona intestinalis
XP_001632636  316 k-EYHSEEDEPTCySPLDFKFDTvl---mTKEALKEAIVNE 352  starlet sea anemone
XP_002108552  310 a-SLHDAEDEPVCtSSFDFDFEKnt---lSSNALKEVIVDE 346  Trichoplax adhaerens
XP_001742318  325 q-GHRRPDLERVC-EPFSFDFEVa----sLCQPLLDLIVYH 359  Monosiga brevicollis MX1
Q13164        348 a-KYHDPDDEPDCaPPFDFAFDRea---lTRERIKEAIVAE 384  human
XP_001892881  330 keYYPSVINEQACpFKVKMDMAAie--tlSHEGLVQALIND 368  agent of lymphatic filariasis
NP_741908     389 --QRVIPAEAPQKkCPFRVKKDMm----qVEDLNHQELISM 423  nematode
BAE48519      343 s-KYHDPDDEPECiPAFDFGFDKni---lTKDQIKEAITTE 379  African clawed frog
XP_780133     323 a-TYYSPDDEPDCfPKFDFSFEShv---mSREQIKQQIGKM 359  purple sea urchin

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