Conserved Protein Domain Family
7tmB2_Latrophilin-1

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cd16007: 7tmB2_Latrophilin-1 
Latrophilin-1, 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: 320673
View PSSM: cd16007
Aligned: 4 rows
Threshold Bit Score: 552.22
Threshold Setting Gi: 512875503
Created: 25-Jun-2014
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:
Feature 1                #   #                                         #  ##  #      #      #     
O97831        856 ELLLSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLVGIDKTqyeIACPIFAGLLHYFFLA 935  cattle
XP_008102812  854 ELLLSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFITELLFLIGIDKTqyeIACPIFAGLLHYFFLA 933  green anole
XP_004918934  854 ELLLSVISWVGIVISLVCLGICISTFCFLRGLQTDRNTIHKNLCISLFLAELLFLTGIDKTqyqVVCPILAGLLHFFSLS 933  western clawe...
XP_003964789  829 ELILFVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFVAELLFLIGIDKTdnqIACPIFAGLLHFFFLA 908  torafugu
Feature 1                                                                           ## # #        
O97831        936 AFSWLCLEGVHLYLLLVEVFESeySRTKYYYLGGYCFPALVVGIAAAIDYRSYGTEKACWLRVDNYFIWSFIGPVSFVIV 1015 cattle
XP_008102812  934 AFSWMCLEAIHLYLMLVEVFESeySRKKYYYLGGYCFPALVVGIAAAIDYRSYGTEKACWLRVDNYFIWSFIGPVSFVIV 1013 green anole
XP_004918934  934 AFSWLCLEGVQLYLMLVEVFETehSRRKYYYLCGYIFPALVVGISAAVDYRSYGTDKACWLRVDNYFIWSFIGPVSLVIV 1013 western clawe...
XP_003964789  909 AFSWMCLEGVQLYLMLVEVFESeySRKKYYYLCGYCFPALVVGISAAIDYRSYGTKKACWLRVDNYFIWSFIGPVSFVIM 988  torafugu
Feature 1                                                        #  #           #   #             
O97831       1016 VNLVFLMVTLHKMVRSSSVLKPDssrldNIKSWALGAIALLFLLGLTWAFGLLFINKeSVVMAYLFTTFNAFQGVFIFVF 1095 cattle
XP_008102812 1014 INLVFLMITLHKMIRNTSVLKPDssrldNIKSWALGAITLLFLLGLTWAFGLLFINKeSIVMAYLFTTFNAFQGMFIFVF 1093 green anole
XP_004918934 1014 VNLLILLVTLHKMLRSSSVLKPDssrleNIKSWALGAVTLLFLLGLTWAFGFLFINKeSLVLAYLFTTFNALQGLFIFIF 1093 western clawe...
XP_003964789  989 LNLIFLMVTLHKMICNSSALKPDssrldNIKSWSLGAITLLFLLGLTWAFGLLFINEnTVIMAYLFTIFNAFQGMFIFIF 1068 torafugu
Feature 1                           
O97831       1096 HCALQKKVHKEYSKCLRH 1113 cattle
XP_008102812 1094 HCALQKKVHREFSKCLRH 1111 green anole
XP_004918934 1094 HCALQKKVHKEYSKCLRH 1111 western clawed frog
XP_003964789 1069 HCALQKKVHKEYSKCLRH 1086 torafugu

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