Conserved Protein Domain Family
7tmB2_CELSR_Adhesion_IV

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cd15441: 7tmB2_CELSR_Adhesion_IV 
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors
The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuron migration and axon guidance in the CNS.
Statistics
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PSSM-Id: 320557
View PSSM: cd15441
Aligned: 16 rows
Threshold Bit Score: 292.232
Threshold Setting Gi: 190579184
Created: 11-Nov-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative polypeptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Comment:based on mutagenesis of human glucagon receptor (GCGR), and modeling studies of GCGR and other related class B GPCRs
  • Comment:Residues in the globular N-terminal extracellular domain and the extracellular loops of the 7TM domain may also be involved in ligand binding.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #   #                                          #  ##  #          #      #
gi 40287630   373 VLPLKIVTYTTVSISLVALLITFILLVLIRTLr-sNLHSIHKNLVAALFFSELVFLIGINQTenp----fvCTVIAILLH 447
gi 556107184 2288 SVTVEVLTYILVFISLMLLVVAYLILLCFKRLq-cNWNSIHINLIVVVFVAELAFIIGINRTkse----ltCRLIAITLQ 2362
gi 443694652 2200 TADVQIITYIGLAIGLVCLFVAMVMFCCIRHVa-sNLNSIHLNLIFCLFVSLLIFLLGIDQTepk----ivCKLVAMFLH 2274
gi 386118337 2399 VYQPAFLVYIALAVAMLLFLIVFLVFLCLSQLk-sNANSIHKNLAFVLLLGWIVFTFAINRPdvg---kanCRIIAILIH 2474
gi 442623252 2809 SLLVQITSYSAFLVSLPLLLGVLLALALLRGQq-tNSNTIHQNIVLCVFCAELLFFVGMQSRrqllesefpCKLTAICLH 2887
gi 405952436 1300 VISLVIFSFVGIGISLVCLFVSFVIFCSFKRLq-cNANSILVNLVFTMFVAELAFITGVYRVssk----lmCRLVAICLH 1374
gi 307210796 2501 SLLEDVTSYSAFMLALPLLLAALLILALIRGGg-tNSNSIHKNLVLCVLLAETLYLIALKARnplisnefpCKLTAIGLH 2579
gi 212506116 2576 TFLEDLMTYVGFSVSIFLLIIALLILSCIRGRp-tNSNSIHKNIVFCILCGEIIYFAALKFRslllqqefpCKMIAMFLH 2654
gi 313226181 1992 VNPLKTICIVLLSITIAILTGCAGVFSCLSEVr-sAQAHLHNALSICLIFLHVIFLLGIDKTene----ysCMIVSIGLH 2066
gi 321476878 2530 TLIEDVVTYIGLVASVVFLAVAFICLSLISGQqqtNSNSIHRNFVVCLLLAQLLFLLALKLRgtvqhhefvCKLLAMGLH 2609
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                      ## 
gi 40287630   448 YFYMSTFAWMFVEQLHIYRMLTevrn-----infGHMRFYYVVGWGIPAIITGLAVGLDpqgygNPDFCWLs-vHDTLIW 521
gi 556107184 2363 YFYMAAFSWLFVEILHIYRMLTeirn-----inyGSMKFYYLIGYAIPGIIVGLAVGLYtdgygNSQFCWLy-tSNGIIW 2436
gi 443694652 2275 FFHLCVFAWIFVESLHLYRMLTeirn-----intGNMKFYYLLGYVIPGIVVGLAVGLRiedydNKEFCWIs-tNDLLVW 2348
gi 386118337 2475 YCLTCAFSWLMVEALHMYRMILeprd-----inyGQMMFYYFIGWGAPVIVVGVTAGLKpdgygTPEFCWIsakVNDSVW 2549
gi 442623252 2888 YFWLAAFAWTTVDCVHLYRMLTemrd-----inhGPMGFYFAMGYGAPAIVVGLSVGVRaheygNSLFCWLs-vYEPVVW 2961
gi 405952436 1375 YFYLAAFSWLFVEMLHLYRRLIeird-----inhGTMKFYYLLGYVIPGIIVGLSVGLYtdgygNSSFCWMd-iSETFIW 1448
gi 307210796 2580 YSWLSTFAWTLVDSVHLYRMLTemrd-----vnhGQMRFYYTMGYGLPAVIVGLTIGVRadqygNFYFCWLs-iYETVIW 2653
gi 212506116 2655 YFWLSSFSWTLVDSLHLYRMLTelrd-----inhGQMRFYYCLGYGLPAIIVGLSVGVRadqygNFYFCWLs-iYESVVW 2728
gi 313226181 2067 YFYLAVFTWVALETFHLYRRLAqphfqiaqradrQAVQFYYGLGFGVPAIIVATSVGLQpagygNARFCWLd-sSDPLVG 2145
gi 321476878 2610 YLWLCIFSWLMIESIHLYRMLTelrd-----vnhGHMSFYYSVGYGLPAIILGLSVGVRadqygNYYFCWLs-vFESVIW 2683
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         # #                                                      #  #           #   #   
gi 40287630   522 SFAGPIVIVVVINTVIFILAMKASCRRRQrsf---ektGVISVLRTAFLLLLLISATWLLGLMAVNSdVMTFHYLFAIFS 598
gi 556107184 2437 SFAGPIAMSTLISVLVFILAVQASLLEKThvr---diqTVRMGLMCSIIMLALLCLTWVTGLISVNYgIKALHYVFACFM 2513
gi 443694652 2349 SFAGPICVSIAVTMVMFLMALRASCHVTKkset--emaSIKYGLKAAILLTPLCSLAWVFGLLSVNEgVMAFNYLFAALS 2426
gi 386118337 2550 TYVAPIFAIIAGTFIIIILALASSCEKANikgkkaklaRIRYRLAISFFFLFIMMVTVFGGLLEVSFdMTLLTYIFAGTC 2629
gi 442623252 2962 WLVGPIAGMSVVNLLILFVSVKAAFTLKDhvl---gfgNLRTLLWLSVVSLPLMGVMWVLAVLAASEhSQLLSLLLSGVV 3038
gi 405952436 1449 SFAGPVAFVIPATIMMFVLALHSSCQEKVnvs---ditSFRARIFSGVILLLLLGITWILGLLSVNYdLQPLHYVYAGFA 1525
gi 307210796 2654 SLIGPVCAAVLVNFCILIMCIRAAFTLKEhvm---gfgNLRTLLWLSVASLPLLGSTWTLAVLNASEnSSTLSYLLSVAI 2730
gi 212506116 2729 SLVGPITFVVVITMIMLMLSIRAAFTLKNhil---gygNLRTLVWVSVIFLPLLGIVWIFLILNVSEpLALLPHALSLAV 2805
gi 313226181 2146 AMIVPICLTFIATCGGLIMSLREYLTVKRvdi---ikeEVRRDIRLLSFLAPVLLFAWASSLSAVNMnSSVLYIITCILH 2222
gi 321476878 2684 SLVGPCCFMIVCSLITFGMGLRAAFTLKDhie---gygNLRTLIWLGLALLPVTATVWVLAVMSASDtSEILFYAFSLCS 2760
                         250       260
                  ....*....|....*....|....*...
Feature 1                                     
gi 40287630   599 CLQGLFIFFFHCIFNKEVRKHLKNTLTG 626
gi 556107184 2514 FAIGAFFFVTQILLQRKVRLQLKKAWYR 2541
gi 443694652 2427 FLQGLFILLAYVAFNKEVSFHLRNKWKR 2454
gi 386118337 2630 ALEGVYMFLFYVCFNRKVRREAYNAYKR 2657
gi 442623252 3039 LLHALFCLIGYCIINKRVRENLQRTCLR 3066
gi 405952436 1526 FLQGLFIFLAYIVGDKKVRYNLKKQWYK 1553
gi 307210796 2731 VVHAAFSLIGYCFVNGRVRRNLYQSLLR 2758
gi 212506116 2806 IIQAVYTLAGFCFVNARVRRNLYVSLLK 2833
gi 313226181 2223 LSVALFILVAHVLRSAEVKRAWQLERTK 2250
gi 321476878 2761 VLESIFIMLGYCLLNRRVRLGLLHLAGR 2788

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