1S9J,1S9I,1S9I


Conserved Protein Domain Family
PKc_MEK

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cd06615: PKc_MEK 
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Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase
PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK 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: 132946
View PSSM: cd06615
Aligned: 10 rows
Threshold Bit Score: 552.042
Threshold Setting Gi: 167522000
Created: 4-Apr-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 23 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:
Feature 1                ##### # #            # #                             #               ###
1S9J_A         6 DDFEKISELGAGNGGVVFKVSHKPsgLVMARKLIHLEIKPAIRNQIIRELQVLHECnSPYIVGFYGAFYSDGEISICMEH 85  human
1S9I_B        16 DDFERISELGAGNGGVVTKVQHRPsgLIMARKLIHLEIKPAIRNQIIRELQVLHECnSPYIVGFYGAFYSDGEISICMEH 95  human
Q24324        85 EDLEKLGELGSGNGGVVMKVRHTHthLIMARKLIHLEVKPAIKKQILRELKVLHECnFPHIVGFYGAFYSDGEISICMEY 164 fruit fly
Q10664        71 DMLQTEGELGHGNGGVVNKCVHRKtgVIMARKLVHLEIKPSVRQQIVKELAVLHKCnSPFIVGFYGAFVDNNDISICMEY 150 nematode
BAE06544      64 SDFTKKGELGAGNGGVVHLVVHNAtgFVMARKLIHLEVKQAILNQITRELQVLHDCrSPYIVGYYGTFYSDGEISICMES 143 Ciona intestinalis
XP_781505     85 DDFEVLKELGAGNGGVVTKVKHKMsgMVMARKLIKLEIKPAIRNQIIRELKVLHECnSPYIVGFFGAYYSDGEICICMEN 164 Strongylocentro...
XP_001637616  37 DDFEKITELGAGNGGVVTKVLHKPtgLIMARKLIHLEVKPAIRTQIIRELKVLHDCnSPYIVGFFGAFYSDGEISICMEH 116 starlet sea ane...
XP_002110508  70 EDFETLCELGAGNGGVVTKVRHTPsgLIMARKLIHLEIKAAVRNQIIRELKILHECnSPYIVGFYGAFYSDGEISICMEH 149 Trichoplax adha...
XP_001745338  78 TDLRELVVLGRGNGGSVCKVLHVKsnIIMARKSIHLEIRPEVRNQILRELRILHKCsSPHIIGFYGSFWHDGEINILMEY 157 Monosiga brevic...
1S9I_A        16 DDFERISELGAGNGGVVTKVQHRPsgLIMARKLIHLEIKPAIRNQIIRELQVLHECnSPYIVGFYGAFYSDGEISICMEH 95  human
Feature 1        #  ## ##                                        # ## #          #               
1S9J_A        86 MDgGSLDQVLKka--gRIPEQILGKVSIAVIKGLTYLREkHKIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 163 human
1S9I_B        96 MDgGSLDQVLKea--kRIPEEILGKVSIAVLRGLAYLREkHQIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 173 human
Q24324       165 MDgGSLDLILKra--gRIPESILGRITLAVLKGLSYLRDnHAIIHRDVKPSNILVNSsGEIKICDFGVSGQLIDSMANSF 242 fruit fly
Q10664       151 MDgLSLDIVLKkv--gRLPEKFVGRISVAVVRGLTYLKDeIKILHRDVKPSNMLVNSnGEIKLCDFGVSGMLIDSMANSF 228 nematode
BAE06544     144 MDaGSLDLVLKka--rKIPEIYLGKVSKAVILGLKYLREeRSIIHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 221 Ciona intestinalis
XP_781505    165 MDgGSLDQVMKsapkgRIPENILGKVTVAVLRGLIYLRDvHDIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 244 Strongylocentro...
XP_001637616 117 MDgGSLDLILKka--gRIPEDILGKISIAVLKGLCYLREiHQIIHRDVKPSNILVNSrGEIKMCDFGVSGQLIDSMANSF 194 starlet sea ane...
XP_002110508 150 MDaGSLDKVMKka--rRIPEPILGKIAIAVIKGLTYLREkHKIMHRDVKPSNILVNSrGEIKMCDFGVSGQLIDSMANSF 227 Trichoplax adha...
XP_001745338 158 MDgGSLDAVVRri--gRIPENVLAEITYCILDGLVYLRDkLSIMHRDIKPSNVLVSSdGDCKLCDFGVSGELHNSLANTF 235 Monosiga brevic...
1S9I_A        96 MDgGSLDQVLKea--kRIPEEILGKVSIAVLRGLAYLREkHQIMHRDVKPSNILVNSrGEIKLCDFGVSGQLIDSMANSF 173 human
Feature 1                                                                                        
1S9J_A       164 VGTRSYMSPERLQGtHYSVQSDIWSMGLSLVEMAVGRYPIPPPD--AKELELMFgcqvegdaaetpprpr----tpgrpl 237 human
1S9I_B       174 VGTRSYMAPERLQGtHYSVQSDIWSMGLSLVELAVGRYPIPPPD--AKELEAIFgrpvvdgeegephsisprprppgrpv 251 human
Q24324       243 VGTRSYMSPERLQGtHYSVQSDIWSLGLSLVEMAIGMYPIPPPN--TATLESIFadnaeesg------------------ 302 fruit fly
Q10664       229 VGTRSYMAPERLTGsHYTISSDIWSFGLSLVELLIGRYPVPAPS--QAEYATMFnvaeneieladsl----------eep 296 nematode
BAE06544     222 VGTRSYMAPERLQGsKYTILSDIWSLGLSLIEMAIGRFPIPPPT--ASQIAAIFntevsggsgk---------------- 283 Ciona intestinalis
XP_781505    245 VGTRSYMSPERLQGtHYTVQSDIWSLGLSLVEMAIGRYPIPAPD--ETALANLFgyelqagetknirk---------trv 313 Strongylocentro...
XP_001637616 195 VGTRSYMSPERLQGnQYTIQSDIWSFGLSLVEMAIGRYPIPPPD--PQEIEKVLsrepssmaspmsvgrl----ppgvrp 268 starlet sea ane...
XP_002110508 228 VGTRSYMSPERLTGsQYTVHSDIWSFGMSLVEMAIGRYPIPPPDneSLNQEIANdefspasvappg-------------r 294 Trichoplax adha...
XP_001745338 236 VGTRSYMSPERLQGqRYAVESDLWSLGLSLLEMATGVFPIPAENl-KKGLAPMHpppdkplea----------------- 297 Monosiga brevic...
1S9I_A       174 VGTRSYMAPERLQGtHYSVQSDIWSMGLSLVELAVGRYPIPPPD--AKELEAIFgrpvvdgeegephsisprprppgrpv 251 human
Feature 1                                                                                        
1S9J_A       238 ssygmdsrppMAIFELLDYIVNEPPPKLPSGv-FSLEFQDFVNKCLIKnPAERADLKQLMVHAFI--KRSDAee-vDFAG 313 human
1S9I_B       252 sghgmdsrpaMAIFELLDYIVNEPPPKLPNGv-FTPDFQEFVNKCLIKnPAERADLKMLTNHTFI--KRSEVee-vDFAG 327 human
Q24324       303 --qptdepraMAIFELLDYIVNEPPPKLEHKi-FSTEFKDFVDICLKKqPDERADLKTLLSHPWI--RKAELee-vDISG 376 fruit fly
Q10664       297 nyhppsnpasMAIFEMLDYIVNGPPPTLPKRf-FTDEVIGFVSKCLRKlPSERATLKSLTADVFFt-QYADHddqgEFAV 374 nematode
BAE06544     284 apnphdvarpMAIFELLDYIVNEPAPKLPQGi-FEKDFCDFVASCLKKePKERSDLGELMKAPFI--KNVSLtq-yEFAK 359 Ciona intestinalis
XP_781505    314 ggvfsdsprpMAIFELLNYIVEEHPPRLPSRa-FSEEFVDFVDVCLIKnPNERADLKKLKVHTFA--IMSEEar-vDFAG 389 Strongylocentro...
XP_001637616 269 psgvnnetrpMAIFELLDYIVNEPPPILPGAh-FSPEFCEFVQKCLVKnPKQRADLTYLMTHKFI--AKADKsn-vDFAK 344 starlet sea ane...
XP_002110508 295 avsgddapkpMAIFELLDYIVNQPPPRLPSGgvFSKEFQEFVDCCLQKdPKERPDLYELSKKPFI--QKWEAev-vDIAG 371 Trichoplax adha...
XP_001745338 298 --hapdatqsMAIFELLANIVESEPPRLPDDagFSDSFINFIDACLKRePSERMPLAELIQHPWLedMRASQp--vNMAE 373 Monosiga brevic...
1S9I_A       252 sghgmdsrpaMAIFELLDYIVNEPPPKLPNGv-FTPDFQEFVNKCLIKnPAERADLKMLTNHTFI--KRSEVee-vDFAG 327 human
Feature 1              
1S9J_A       314 WLCSTI 319 human
1S9I_B       328 WLCKTL 333 human
Q24324       377 WVCKTM 382 fruit fly
Q10664       375 FVKGTI 380 nematode
BAE06544     360 WVCSTM 365 Ciona intestinalis
XP_781505    390 WICATM 395 Strongylocentrotus purpuratus
XP_001637616 345 WISQFL 350 starlet sea anemone
XP_002110508 372 WICKVM 377 Trichoplax adhaerens
XP_001745338 374 WVRSTM 379 Monosiga brevicollis MX1
1S9I_A       328 WLCKTL 333 human

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