Conserved Protein Domain Family
7tmB2_CELSR3

?
cd15993: 7tmB2_CELSR3 
Cadherin EGF LAG seven-pass G-type receptor 3, 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. 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 neuronal migration and axon guidance in the CNS. 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.
Statistics
?
PSSM-Id: 320659
View PSSM: cd15993
Aligned: 4 rows
Threshold Bit Score: 455.841
Threshold Setting Gi: 22095544
Created: 26-Jun-2014
Updated: 26-Jul-2017
Structure
?
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
?
Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #   #                                         #  ##  #                   
gi 22095544  2534 LELLAVFTHVVVAASVTALVLTAAVLLSLRSLKsNVRGIHANVAAALGVAELLFLLGIHRTh------------------ 2595
gi 465980528 2418 LETLAIVTYSLVSLSLVALLLTFSFLTCLKGLKsNTRGIHSNISVTLFFSELLFLLGINRTe------------------ 2479
gi 512840304 2858 LETLAIVSYTSLSISLAALVATFSILTFLKGLKsNTRGIHSNIAVALFLSELVFVLGINRTesevsardisecndliffi 2937
gi 528487904 2906 LETLAIVTYSSLSVSMAALLLTVLVLSCLRGLKsNTRSIHSNMAAATLLSHLTYLLGINQTe------------------ 2967
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                             #      #                                                    
gi 22095544  2596 ---------------nQLLCTVVAILLHYFFLSTFAWLLVQGLHLYRMQVEprnvdrGAMRFYHALGWGVPAVLLGLAVG 2660
gi 465980528 2480 ---------------nQFLCTVIAILLHYFFLSTFAWLFVQGLHIYRMQTEarninfGAMRFYYAIGWGVPAIITGLAVG 2544
gi 512840304 2938 ikylvqpttcsfscswQFLCTVIAILLHYFFLSTFAWLFVEGLHIYRMQTEvrnvnfGPMRFYFAIGWGVPAIITGLAVG 3017
gi 528487904 2968 ---------------qQFLCTVVAILLHYFFMSAFAWLFVEALHIYRMQTEarninyGAMRFYYAIGWGVPAIITGLAVG 3032
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                            ## # #                                                   #  #
gi 22095544  2661 LDPEgyGNPDFCWIsiHEPLIWSFAGPIVLVIVMNGIMFLLAARTSCSTGQREakktSVLRTLRSSFLLLLLVSASWLFG 2740
gi 465980528 2545 LDPEgyGNPDFCWIsiHDKLVWSFAGPITVVIVMNGVMFLLVAKMSCSPGQKEtkkkSVLMTLRSSFVLLLVISTTWLFG 2624
gi 512840304 3018 LDPEgfGNPDFCWIssHDKLVWSFAGPIAIVIVLNGVMFLLVAKMLCSPGQKEtkknSVLMTIRSSFILLLFISITWLFG 3097
gi 528487904 3033 LDPEgyGNPDFCWIsmYDKLMWSFAGPVSVVILMNGGMFLMVLRMTCNPTQKEikklPVISTIRSAFFLLLLSTCVWLFG 3112
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
Feature 1                    #   #                               
gi 22095544  2741 LLAVNHsVLAFHYLHAGLCGLQGLAVLLLFCVLNADARAAWTPACLG 2787
gi 465980528 2625 LLAVNNsVLAFHYLHTVLCSLQGLAVLVLFCVLNEEVQEAWKLACLG 2671
gi 512840304 3098 LLAVNNsVLAFHYLYVILCCLQGLAVLVLFCMLNEEVQEAWKVVCLG 3144
gi 528487904 3113 LMAVNNsVLAFHYLFIILCCIQGLAVLLVFTVLNSEVQEAWKLACLG 3159

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap