3LB7,3II5,3C4C,3OMV


Conserved Protein Domain Family
STKc_Raf

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cd14062: STKc_Raf 
Click on image for an interactive view with Cn3D
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf 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: 270964
Aligned: 14 rows
Threshold Bit Score: 469.567
Created: 17-Jul-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 20 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3II5; Human B-Raf binds a pyrazolo pyrimidine inhibitor; contacts at 4A.
  • Structure:3OMV; Human C-Raf binds pyrazole based inhibitor; contacts at 4A.
  • Structure:3C4C; Human B-Raf binds to selective inhibitor Plx4720; contacts at 4A.
  • Comment:also based on structures of other members of the superfamily bound with ATP or ATP analogs or inhibitors

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1        #####   #         # #                              #              ####   #      
3LB7_A        44 IGSGSFGTVYKGKWHGDVAVKILKVvdptpeqfqAFRNEVAVLRKTRHVNILLFMGYMtkdnLAIVTQWCEgsSLYKHLH 123 human
3II5_A        43 IGSGSFGTVYKGKWHGDVAVKMLNVtaptpqqlqAFKNEVGVLRKTRHVNILLFMGYStkpqLAIVTQWCEgsSLYHHLH 122 human
3C4C_A        20 IGSGSFGTVYKGKWHGDVAVKMLNVtaptpqqlqAFKNEVGVLRKTRHVNILLFMGYStkpqLAIVTQWCEgsSLYHHLH 99  human
Q07292       487 VGSGSFGTVYRGEFFGTVAIKKLNVvdptpsqmaAFKNEVAVLKKTRHLNVLLFMGWVrepeIAIITQWCEgsSLYRHIH 566 nematode
BAE06664     437 IGSGSYGIVYRCRWHGIVAVKVLNVsnptpsqlqEFKNEVAVLRKTRHVNILLFMGYTiknqLCIVTQWCDgsSLYRHLH 516 Ciona intestinalis
CAD56892     580 IGNGSFGTVYKADYFGTVAVKKLNItspgpelslAFKNEVTVLRKARHGNVLNFLGVIkepeLAIVTQWCSgsSLYRHLH 659 Meloidogyne art...
XP_001639152 441 IGSGSYGTVYKGNWHGAVAIKTLNVtdptptqlqAFKNEVAVLRKTRHVNVLLFMGCMskpkLAIVTQWCEgsSLYRHLH 520 starlet sea ane...
XP_002112616  18 IGSGSYGTVFKGHWHGPVAIKKLNVtdptpsqlqAFKNEVTVLRKTRHVNVLLFMGVMskpfLAIVTQWCEgsSLYRHLH 97  Trichoplax adha...
AAN17562     371 IGSGSFGTVYRAHWHGPVAVKTLNVktpsptqlqAFKNEVAMLKKTRHCNILLFMGCVskpsLAIVTQWCEgsSLYKHVH 450 fruit fly
EFX83242     495 IGSGSFGTVYRGHWHGPVAVKTLNVkdptpaqlqAFKNEVAVLRKTRHVNILLFMGCVskpqLAIVTQWCEgsSLYKHLH 574 common water flea
Feature 1                                           # # ## #           #                         
3LB7_A       124 vqe--tkfQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEg-LTVKIGDFGLATVKSRWSGsqq---veQPTGS 197 human
3II5_A       123 iie--tkfEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEd-LTVKIGDFGLATVKSRWSGshq---feQLSGS 196 human
3C4C_A       100 ase--tkfEMKKLIDIARQTARGMDYLHAKSIIHRDLKSNNIFLHEd-NTVKIGDFGLATVKSRWSGshq---feQLSGS 173 human
Q07292       567 vqeprvefEMGAIIDILKQVSLGMNYLHSKNIIHRDLKTNNIFLMDdmSTVKIGDFGLATVKTKWTVnggq-qqqQPTGS 645 nematode
BAE06664     517 mid--tkfDMLQTINIARQTAQGMEYLHAKNIIHRDMKSNNIFLLEd-YTVKIGDFGLATVKSRWSGseq---lmQPTGS 590 Ciona intestinalis
CAD56892     660 vlepkvdfELQTILDICKQISQGMNYLHSRGVIHRDLKTNNIFLSEg-TTVKIGDFGLATVKTRSNAlpngapnpNPTGS 738 Meloidogyne art...
XP_001639152 521 vle--nrfEVLNLIDIARQTAQGMDYLHAKKIIHRDLKSNNIFLQEd-LTVKIGDFGLATIKTRWSGsqy---seQPSGS 594 starlet sea ane...
XP_002112616  98 vme--tkfEMLQITEIARQTAQGMDYLHAKFIIHRDLKSNNIFLHDd-LTVKIGDFGLATVKSRWSTcqd---seQPSGS 171 Trichoplax adha...
AAN17562     451 vse--tkfKLNTLIDIGRQVAQGMDYLHAKNIIHRDLKSNNIFLHEd-LSVKIGDFGLATAKTRWSGekq---anQPTGS 524 fruit fly
EFX83242     575 vle--tkfELLTLIETARQTAQGMDYLHAKNIIHRDLKSNNIFLHDd-LTVKIGDFGLATVKTRWSGshq---fqQPSGS 648 common water flea
Feature 1                                                                                        
3LB7_A       198 VLWMAPEVIRMqdnnPFSFQSDVYSYGIVLYELmtgeLPYSHINnrdQIIFMVGRGYASPDLSKLykncPKAMKRLVADC 277 human
3II5_A       197 ILWMAPEVIRMqdknPYSFQSDVYAFGIVLYELmtgqLPYSNINnrdQIIFMVGRGYLSPDLSKVrsncPKAMKRLMAEC 276 human
3C4C_A       174 ILWMAPEVIRMqdsnPYSFQSDVYAFGIVLYELmtgqLPYSNINnrdQIIEMVGRGSLSPDLSKVrsncPKRMKRLMAEC 253 human
Q07292       646 ILWMAPEVIRMqddnPYTPQSDVYSFGICMYEIlsshLPYSNINnrdQILFMVGRGYLRPDRSKIrhdtPKSMLKLYDNC 725 nematode
BAE06664     591 ILWMAPEVIRMidgnPYTFQSDVYAFGVVLYEMtsntLPYSHIGnrdMILFQVGRGYLSPDLDLIrsdtPRSCRKLIVDC 670 Ciona intestinalis
CAD56892     739 ILWMAPEVIRMqcenPYSTQSDVYAFGICLYELltskLPYEDIKgrdQILFMVGSGLLRPNIKNLrsdtPRPLRSVFEQC 818 Meloidogyne art...
XP_001639152 595 ILWMAAEVIRMldpnPYSFHSDVYAFGIVLYELlsssLPYAHVGnkdQILYMVGRGYLRPDMSKArndiPKAFNRLCLEC 674 starlet sea ane...
XP_002112616 172 ILWMAPEVMRMqdvtPYTVRSDIYSFGMVLLELttgeLPYSQKSr-dQIIFMVGCGLLKPNLNQCrpetPKHLKAIISDC 250 Trichoplax adha...
AAN17562     525 ILWMAPEVIRMqelnPYSFQSDVYAFGIVMYELlaecLPYGHISnkdQILFMVGRGLLRPDMSQVrsdaPQALKRLAEDC 604 fruit fly
EFX83242     649 ILWMAPEVIRMkdenPYSFQSDVYAFGVVLYELfsgqLPYSHISnkdQILFMVGRGFLRPDLSHVrsdtPKALRRLLESS 728 common water flea
Feature 1                           
3LB7_A       278 vkkvKEERPLFpQILSSIE 296 human
3II5_A       277 lkkkRDERPLFpQILASIE 295 human
3C4C_A       254 lkkkRDERPSFpRILAEIE 272 human
Q07292       726 imfdRNERPVFgEVLERLR 744 nematode
BAE06664     671 ikknREDRPLFpQIWGDLD 689 Ciona intestinalis
CAD56892     819 irfeRSERPEFrMIYAILD 837 Meloidogyne artiellia
XP_001639152 675 ikfnRDERPLFpQILASLE 693 starlet sea anemone
XP_002112616 251 ckysRDERPDFaQVLGVLE 269 Trichoplax adhaerens
AAN17562     605 ikytPKDRPLFrPLLNMLE 623 fruit fly
EFX83242     729 ikftREERPLFrQILVSLE 747 common water flea

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