Conserved Protein Domain Family
7tmF_FZD8

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cd15250: 7tmF_FZD8 
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors
This group includes subfamily 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.
Statistics
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PSSM-Id: 320378
View PSSM: cd15250
Aligned: 5 rows
Threshold Bit Score: 593.829
Threshold Setting Gi: 637309450
Created: 22-Jan-2014
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:TM helix 1 [structural motif]
Evidence:
  • Comment:All members of this receptor family contain a seven-transmembrane helix domain.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                 ##########################                                             
gi 4164471   228 PYFTQDERTFTAFWIGLWSVLCFISTFATVATFLIDMERFKYPERPIIFLSACYMFVSIGYIVRLIAgHEKVACNre--- 304
gi 17432990  226 PFFSPEERTFTEFWIGLWSVLCFASTFATVSTFLIDMERFKYPERPIIFLSACYLLVSTGYLIRLIAgHEKVACSrge-- 303
gi 3983449   221 PYLSQEERTFATFWIGIWSVLCFLSTFATVATFLIDIERFKYPERPIIFLSACYMFVSLGYIIRLIAgHERVACNqn--- 297
gi 119606315 267 PFFSQDERAFTVFWIGLWSVLCFVSTFATVSTFLIDMERFKYPERPIIFLSACYLFVSVGYLVRLVAgHEKVACSggapg 346
gi 637309450 245 PTSPQXERAFTAFWIGLWTIICFLSTFATVSTFLIDMERFKYPERPIVFLAACYLFVSLGYLVRLVAgHEKVACSggaaa 324
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 4164471   305 ----------------------------------ydVEHIHYETtGPALCTVVFLLIYFFGMASSIWWVILSLTWFLAAG 350
gi 17432990  304 ---------------------------------ldlEHIIHYETtGPALCTLVFLLIYFFGMASSIWWVILSLTWFLAAG 350
gi 3983449   298 ----------------------------------heVDHIHYETtGPALCTLVFLLIYFFGMASAIWWVILSFTWFLAAG 343
gi 119606315 347 aggaggaggaaagagaagagaggpggrgeyeelgavEQHVRYETtGPALCTVVFLLVYFFGMASSIWWVILSLTWFLAAG 426
gi 637309450 325 agpsgasgasagaaavavggrgaaggaaelqpelagAEHVRYEStGPALCTVVFLLVYFFGMASSIWWVILSLTWFLAAG 404
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 4164471   351 MKWGnEAIAGYSQYFHLAAWLIPSMKSIAVLALSSVDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVS 430
gi 17432990  351 MKWGnEAIAGYSQYFHLAAWLVPSIKSIAVLALSSVDGDPVAGICFVGNQNLDNLRGFVLAPLVIYLFIGSMFLLAGFVS 430
gi 3983449   344 LKWGnEAIARYSQYFHMAAWLIPSVKSITVLALSSVDGDSIAGICYVGNQNLDNLRGFVLAPLVIYLFIGTIFLFAGFVS 423
gi 119606315 427 MKWGnEAIAGYSQYFHLAAWLVPSVKSIAVLALSSVDGDPVAGICYVGNQSLDNLRGFVLAPLVIYLFIGTMFLLAGFVS 506
gi 637309450 405 MKWGnEAIASYAQYFHLAAWLLPSVKSIAVLALSSVDGDPVAGICYVGNQSLENLRGFVLAPLLIYLAIGSMFLLAGFVS 484
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 4164471   431 LFRIRSVIKQg--gTKTDKLEKLMIRIGIFTVLYTVPATIIVACYFYEQHNRQsWEITHNCSclle---qeiKRPDYAVF 505
gi 17432990  431 LFRIRSVIKQg--gTKTDKLEKLMIRIGIFSVLYTVPATIVVACFFYEQHNRQgWEVAHNCNscqpe-maqpHRPDYAVF 507
gi 3983449   424 MFRIRSVIKQg--gTKTDKLERLMVRIGVFTVLYTVVAIMIVACYVYEHHNREaWEIAHACNcssd---kkaPKPDYAVF 498
gi 119606315 507 LFRIRSVIKQqdgpTKTHKLEKLMIRLGLFTVLYTVPAAVVVACLFYEQHNRPrWEATHNCPclrdlqpdqaRRPDYAVF 586
gi 637309450 485 LFRIRSVIKQqggpTKTHKLEKLMIRLGLFTVLYTVPAASVVACLFYEQHNRPrWEATHNCPclrdqqpdqaRRPDYAVF 564
                        330       340       350
                 ....*....|....*....|....*....|..
Feature 1                                        
gi 4164471   506 MLKYFMCLLVGITSGVWTWSGKTLESWRSFCT 537
gi 17432990  508 MLKYFMCLVVGITSGVWIWSGKTLESWRAFCT 539
gi 3983449   499 MLKYLMCLLIGITSGAWTWSSKTLDSWRALCT 530
gi 119606315 587 MLKYFMCLVVGITSGVWVWSGKTLESWRSLCT 618
gi 637309450 565 MLKYFMCLVVGITSGVWVWSGKTLESWKALCT 596

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