4L6R,4K5Y,5UZ7


Conserved Protein Domain Family
7tm_classB

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cd13952: 7tm_classB 
Click on image for an interactive view with Cn3D
class B family of seven-transmembrane G protein-coupled receptors
The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. 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. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.
Statistics
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PSSM-Id: 341314
View PSSM: cd13952
Aligned: 177 rows
Threshold Bit Score: 96.9035
Threshold Setting Gi: 24654652
Created: 21-Dec-2011
Updated: 26-Jul-2017
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 16 residues -Click on image for an interactive view with Cn3D
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:
Feature 1             #   #                                         #  ##  #                   
4L6R_A     122 YSSFQVMYTVGYSLSLGALLLALAILGGLSKlhctrNAIHANLFASFVLKASSVLVIDGLLrtrysqkigddlsvstwls 201 
EEN51361   543 DPYQGWLTLGLVIASAVAVLGYVVFRFRSGQlkkvpEQLKVQMMLCMVLAEGMFVARVWVPlg----------------- 605  Florida lancelet
EEN48758   783 DPGQAWLTLGLVVASAVAVFSFVVHTFRSGQlkklpEKLKVQMMVSVAFAEFLFVSRVWIPsg----------------- 845  Florida lancelet
EEN68015   369 EDDQGWLTLGLVIVSVVAVLGFVGYTVGSGNwkkapEKLKVQMLTCMAVAESLFVARLLPRpg----------------- 431  Florida lancelet
EEN57318   574 YSVQGLLTTSLLSLSIASGVGFTAHSVYYKKfsstpDRLKLQLVVMLTLAECLFLSRALLTlq----------------- 636  Florida lancelet
EEN64891   143 YTPQEILTLALSSLSFVSMLVFIAAAVVKKMyrkipDILKLNLTCSLLVAQTIFVFSDEIPlg----------------- 205  Florida lancelet
EEN65988   692 DNVTGILNIALTALSAVGGIVYLALCVVTREyhsipGRLKMQLVITLTAAQSVFLGRVVAQvst---------------- 755  Florida lancelet
EFX79407   532 LIVESYLTLCLMSVSILAMMATIVTYLIFPElrnlaGLAVMNLCLMTSGFQLCIMIGMSLSvhqk--------------- 596  common water flea
ELU08226   615 AKIERLLTLVCQMLSIVSLVVTLTVYSLIPSlrtvpGRCVMCLCSALLLAQILLQFGSFAHnvr---------------- 678  Capitella sp. I ...
EDO36509   751 SEVLRMVTFVCLLISVIALGFVLVTYSLFSElrttpGKNLMNLSTAILLSQIFWLSGSGQVhdr---------------- 814  starlet sea anemone
Feature 1             #      #                                                                 
4L6R_A     202 dgavagCRVAAVFMQYGIVANYCWLLVEGLYLHNLLGlatl--------perSFFSLYLGIGWGAPMLFVVPWAVVKclf 273 
EEN51361   606 ----qaCVVFAIFLHYFMLTAFTSMNALAMDLCLTFRddl----------erIELYKYVLYTWLMPVPVVVVTVIVDfsn 671  Florida lancelet
EEN48758   846 ----sgCAAFAVILHYFLLAAFTSMNALAIDLFFTFRdal----------erAELRQYLMYTWLMPVPIVVVTVIVEfgs 911  Florida lancelet
EEN68015   432 ----vgCVVYGIILHYFLLTAFTSMNALSLDLFLTFRqas----------erAKLRTYMLYTWLIPLLVVAVTAFVEfcp 497  Florida lancelet
EEN57318   637 ----rlCTAVAVLLHFCFLVTFLSMSSLAFDLFRKLCcaqf-------ssygVPYRRYAVFSFGLPLILVSVCVFLDfsp 705  Florida lancelet
EEN64891   206 ----kfCVFLAILTHYMFLVAFLTMNVLAFDLFRTLGrvsg-------amvfRSVKGYMCYIWLAPCLIVTISTIVEfsl 274  Florida lancelet
EEN65988   756 ----afCYFVAVLGHYLFLAAFLTMSALAFDLHNTFSrgis-------esrfNSYRLYILYTWLLPAVVVGVTAFVDfcp 824  Florida lancelet
EFX79407   597 ---selCVASAILVHYEGLASIFWTNVMAIDLFLTLGrwsaa-----prkpsKILPRYSLYAYGLPLAIVSVAVAINfcd 668  common water flea
ELU08226   679 ----slCIALAALDHWAWLASFCWMVALAYDISSAMSketltd----gqvhaRQFRCYLVLGWGCPTLIVGSCLAVSivr 750  Capitella sp. I ...
EDO36509   815 ----taCTVVAILLHYFFLASFIWTAIIAWDTWRAFShrshrsaktmkrenlIGTLRCMAVGWLPALLFVAITTAIDlsg 890  starlet sea anemone
Feature 1                            ## # #                                                    
4L6R_A     274 e---------nvqCWTsndNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKlrarqm--hhtdyKFRLAKSTLTLIPLL 342 
EEN51361   672 svr----vgygenCWIg-nPTSSLVSFGVPVICALLVNAVLVTFVLLAIRRSfeiana--alarsNSSKAWVYIRISCLM 744  Florida lancelet
EEN48758   912 svr----vgygenCWIg-nPVASLLAFGVPVLCAIILNAVLVTFVLLAIRKSfkiadv--aksrsNSTKAWVYLRISFLM 984  Florida lancelet
EEN68015   498 cssv--rvgygdhCWIg-nPTGRLVAFGVPVFCTLLINAVLITQTLLAIRKAfniada--alsrsWSSKAWVYVRISFLM 572  Florida lancelet
EEN57318   706 wteaarigyggggCWIg-nPWASLLAFGVVVGLVVLSNAFFLVWIILSLYRSaretsa--artgsEFALMRVCLRITTLM 782  Florida lancelet
EEN64891   275 eskf--lgygtdvCWIk-nPVALVVTFVAPIGLVLASNMYFFIHTVLNITVSsirtar--arhgaTYSQLQAFLKISTLM 349  Florida lancelet
EEN65988   825 cittvsvgyggqaCWIg-ePYALLAVFGGPVALVLITNAIFMVLTVVALQKAtkavsk--irrdkSRSLLWVYVRITVLL 901  Florida lancelet
EFX79407   669 ctgefeveygklfCWIs-nPTANMVFFGLPLALALVANIVLFVRTVAIIYSSsacqgkqcsrrqrALCQLKLYARMSTVM 747  common water flea
ELU08226   751 phlm--aytdgsvCWIssgMTSLLFTFALPLSIALVFNAAFFLRTVLAIRRAmeiteh-vknasqTQSQLVLYVRLASLM 827  Capitella sp. I ...
EDO36509   891 avai--gygsdvaCWIt-nGTPLLVVFGLPVVVILVFNSIFYALTIIAIRATakqarf-assdsrQKAHFWIYLRIAAIM 966  starlet sea anemone
Feature 1         #  #                #   #                         
4L6R_A     343 GVHEVVFAFVTDehaqgtlrSAKLFFDLFLSSFQGLLVAVLYCFLNkEVQSEL 395 
EEN51361   745 GFTWILGFIYPFan-----sRAVEYIFIVLNASQGLLLTLILAITS-EVVQNW 791  Florida lancelet
EEN48758   985 GFTWLLGFIYPFvn-----sSAVEYIFIVLNASQGLLLTLIVTLTG-KVVEKG 1031 Florida lancelet
EEN68015   573 GFTWILGFIVPYvd-----sRVLEYIFIVLNGSQGFLQALLLTMTS-KVMQKC 619  Florida lancelet
EEN57318   783 GLTWALGLVAPFvd-----nSVLWFVFTALNGAQGLLIVLALTVKN-CNACGP 829  Florida lancelet
EEN64891   350 GLGWIVGFIAAGtq-----qDALWYIFIILNSSQGFLISISFMTSPrDKAADN 397  Florida lancelet
EEN65988   902 GFTWGLGFAVSFvr-----sLVLDYIFTVLSAAQAFLVALAFVLNR-SMLRRC 948  Florida lancelet
EFX79407   748 GFAWIFAFIAACfdpsstagMIFTFVYVILNSMGGLFIFVAFTCNR-RVYLLY 799  common water flea
ELU08226   828 GFTWLLGLLQNAlp-----yAGMRYAFIVCNALQGVGIMACFVCKR-RVLRMI 874  Capitella sp. I Grassle & Grassle, 1976
EDO36509   967 GFTWVFGFIAAVg------iTALWYVFVILNCLQGVYIALAFALTE-RARNLY 1012 starlet sea anemone

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