Conserved Protein Domain Family
PKc_MKK5

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cd06619: PKc_MKK5 
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5
PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 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: 132950
View PSSM: cd06619
Aligned: 5 rows
Threshold Bit Score: 540.236
Threshold Setting Gi: 156383362
Created: 4-Apr-2007
Updated: 2-Mar-2014
Structure
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Aligned Rows:
 
Feature 1:active site [active 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                #####   #                                 # #                           
gi 21729895  164 QDIRYRDTLGHGNGGTVYKAYHvp---------------------sgKILAVKVILLDITleLQKQIMSELEILYKCdSS 222
gi 82568556  164 LDIQCRDILGHGNGGTVYKAYHvp---------------------sgKILAVKVIPLDITveLQRQIMSELEILYKCdSL 222
gi 47230679  114 QDIYYQEQLGHGNGGAVYNLLVplfvptsdieknhhgsvrayhvltrRVFAVKVIPLDITveLQKQIMSELEILYKCdSP 193
gi 156383362 151 EQIQHLEILGYGNGGTVYKAIHlt---------------------trRIIAVKVIPLDVTpeVQRQIISEMEISFQCaSP 209
gi 148608640 163 HDLQYQEQLGHGNGGTVYKAYHll---------------------gkRIVAVKVIPLDITveLQKQIMSELEILYKCdSP 221
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #               ####  ##  #                               # #### #         ## 
gi 21729895  223 YIIGFYGAFFVenRISICTEFMdgGSLDVYRkmPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNtRGQVKLCDF 302
gi 82568556  223 YIIGFYGAFFVenRISICTEFMdgGSLDVYRkiPEQVLGRIAVAVLKGLTYLWSLKILHRDVKPSNMLVNtRGHVKLCDF 302
gi 47230679  194 YIITFFSAFFVenRISICTEFMdgGSLDVYKkiPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNtRGQVKLCDF 273
gi 156383362 210 YIIEFYGAFFVenRISMCTEYMdgGSLDMYGsiPEPVLGRIAVAVVKGLAYLWGLKIMHRDVKPSNILVNtRGQVKLCDF 289
gi 148608640 222 YIIKFYSAFFVenRISICTEFMdgGSLDVYWriPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNtRGQVKLCDF 301
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #           #### #                          #        #                         
gi 21729895  303 GVSTQLVNSIAKTYVGTNAYMAPERISGeQYGIHSDVWSLGISFMELAlGRFPYPq---------IQKNQGsLMPLQLLQ 373
gi 82568556  303 GVSTQLVNSIAKTYVGTNAYMAPERIAGeQYGIHSDVWSLGISFMELAlGRFPYPq---------IQKNHGsLMPLQILQ 373
gi 47230679  274 GVSTQLVNSIAKTYVGTNAYMAPERISGeQYGIHADVWSVGISFMELAlGMFPYPq---------IQKNQGsLMPLQLLQ 344
gi 156383362 290 GVSRQLVNSIATTYVGTNAYMAPERILGdEYSILSEVWSLGVSLLEMAsGRFPYLkvsiqlasyfFFGNHCfLVPIELLQ 369
gi 148608640 302 GVSTQLVNSIAKTYVGTNAYMAPERISGeQYGIHSDVWSVGISFMELAlGSFPYPq---------IQKNQGsLMPLQLLQ 372
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
Feature 1                                                                             
gi 21729895  374 CIVDEDSPVLPVGeFSEPFVHFITQCMRKqPKERPApEELMGHPFIVQFNDGNAAVVSMWVCRALEERR 442
gi 82568556  374 CIVDEECPVLPVGeFSESFVHFITQCMRKpPKERPApEMLMDHPFIVQFNDGNTEAVSMWVCRALEERR 442
gi 47230679  345 CIVDEDPPVLPVGqFSDKFIHFITQCMRRqPKERPApNNLMDHSFIVQYNDGNAEVVSMWVCRCLEERR 413
gi 156383362 370 CIVHEAPPRLPDHlFSPVFVDFVAQCMQKsPSTRLTpEAVLDHIFIRMSDDGNIDMISMWVCRRLEEKR 438
gi 148608640 373 CIVDEDPPVLPVGqFSEKFVHFITQCMRKlPKERPApNNLMDHPFIVQYNDGNTEVVSMWVCRSLEDRK 441

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