Conserved Protein Domain Family
7tmB2_Latrophilin

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cd15436: 7tmB2_Latrophilin 
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors
Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, 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
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PSSM-Id: 320552
View PSSM: cd15436
Aligned: 4 rows
Threshold Bit Score: 443.465
Threshold Setting Gi: 47223915
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 47116772  861 DLLLDVITWVGILLSLVCLLICIFTFCFFRGL-QSDRNTIHKNLCISLFVAELLFLIGINRTdqpIACAVFAALLHFFFL 939
gi 47223915  821 ELLVFVVCWVGISVALVCLLTCLTTLCCQGALwHTDHSTIHCNLWANLVITELLFILGANRTqytVVCSITAGLLHFSLL 900
gi 46576868  844 ELLLTVITWVGIVISLVCLAICIFTFCFFRGL-QSDRNTIHKNLCINLFIAEFIFLIGIDKTkyaIACPIFAGLLHFFFL 922
gi 46576871  856 ELLLSVITWVGIVISLVCLAICISTFCFLRGL-QTDRNTIHKNLCINLFLAELLFLVGIDKTqyeIACPIFAGLLHYFFL 934
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                           ## # #       
gi 47116772  940 AAFTWMFLEGVQLYIMLVEVFESehSRRKYFYLVGYGMPALIVAVSAAVDYRSYGTDKVCWLRLDTYFIWSFIGPATLII 1019
gi 47223915  901 SVFCWLCLEGVELCLLQREVFEGhnSRRKYFYLCGYSIPGLVVAVSAAIDFRGYGSKTACWLRSDNYFIWSFLGPVGAVI 980
gi 46576868  923 AAFAWMCLEGVQLYLMLVEVFESeySRKKYYYVAGYLFPATVVGVSAAIDYKSYGTEKACWLHVDNYFIWSFIGPVTFII 1002
gi 46576871  935 AAFSWLCLEGVHLYLLLVEVFESeySRTKYYYLGGYCFPALVVGIAAAIDYRSYGTEKACWLRVDNYFIWSFIGPVSFVI 1014
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                        #  #           #   #            
gi 47116772 1020 MLNVIFLGIALYKMFHHTAILKPEsgcldNIKSWVIGAIALLCLLGLTWAFGLMYINEsTVIMAYLFTIFNSLQGMFIFI 1099
gi 47223915  981 TLNLVVLVMTLHRMHSTADLKPDSgr-hdNLRAWAVGSLTLLFLQSVTWSSGLMFLSApSLLLAYLFSSLNTAQALLITI 1059
gi 46576868 1003 LLNIIFLVITLCKMVKHSNTLKPDssrleNIKSWVLGAFALLCLLGLTWSFGLLFINEeTIVMAYLFTIFNAFQGVFIFI 1082
gi 46576871 1015 VVNLVFLMVTLHKMVRSSSVLKPDssrldNIKSWALGAIALLFLLGLTWAFGLLFINKeSVVMAYLFTTFNAFQGVFIFV 1094
                        250
                 ....*....|....*....
Feature 1                           
gi 47116772 1100 FHCVLQKKVRKEYGKCLRT 1118
gi 47223915 1060 LHCTLARKGQKDYSRCLRL 1078
gi 46576868 1083 FHCALQKKVRKEYGKCFRH 1101
gi 46576871 1095 FHCALQKKVHKEYSKCLRH 1113

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