5VEX,5VAI


Conserved Protein Domain Family
7tmB1_GLP1R

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cd15268: 7tmB1_GLP1R 
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glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors
Glucagon-like peptide-1 receptor (GLP1R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor and GLP2R. GLP1R is activated by glucagon-like peptide 1 (GLP1), which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, 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 B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.
Statistics
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PSSM-Id: 341342
View PSSM: cd15268
Aligned: 5 rows
Threshold Bit Score: 450.943
Threshold Setting Gi: 1193829560
Created: 11-Nov-2013
Updated: 26-Jul-2017
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:polypeptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Structure:5VAI: Oryctolagus cuniculus Glucagon-like Peptide-1 Receptor (GLP1R) binds Glucagon-like Peptide 1; contacts at 4A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1      #                                               #   #  #   #  #                
5VEX_A     15 LLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALCVFFKDAALKWMG-------SGDGLLSY 87 
5VAI_R    180 LLSLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYstaaqqhQWDGLLSY 259 rabbit
P32301    141 LLSLYIIYTVGYALSFSALVIASAILVSFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYstaaqqhQWDGLLSY 220 Norway rat
ACG63711  137 LLNLSIIYTIGYALSFSALVIATAILLGFRHLHCTRNYIHLNLFTSFILRAISVFIKDSVVKWMYstatqehQWEGLISF 216 chicken
P43220    141 LLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYstaaqqhQWDGLLSY 220 human
Feature 1                 ##  #   #                                                           
5VEX_A     88 QdslaCRLVFLLXQYCVAANYYWLLVEGVYLYTLLAfnifemlrideglrlkiykdtegyytigighlltkspslnaaks 167
5VAI_R    260 QdslgCRLVFLLMQYCVAANYYWLLVEGAYLYTLLAfa------------------------------------------ 297 rabbit
P32301    221 QdslgCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAfs------------------------------------------ 258 Norway rat
ACG63711  217 QeslsCRLVFVMMQYCVAANYYWLLVEGMYLYTLLVls------------------------------------------ 254 chicken
P43220    221 QdslsCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAfs------------------------------------------ 258 human
Feature 1                                                                                     
5VEX_A    168 eldkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalinmvfqmgetgvagftnslrmlqqk 247
5VAI_R        -------------------------------------------------------------------------------- rabbit
P32301        -------------------------------------------------------------------------------- Norway rat
ACG63711      -------------------------------------------------------------------------------- chicken
P43220        -------------------------------------------------------------------------------- human
Feature 1                                                                              ###    
5VEX_A    248 rwdeaavnlaksrwynqtpnrakrvittfrtgtwdaySEQWIFRLYVAIGWGVPLLFVVPWGIVKYlyEDEGCWTRnsNM 327
5VAI_R    298 -----------------------------------vfSEQRIFKLYLSIGWGVPLLFVIPWGIVKYlyEDEGCWTRnsNM 342 rabbit
P32301    259 -----------------------------------vfSEQRIFKLYLSIGWGVPLLFVIPWGIVKYlyEDEGCWTRnsNM 303 Norway rat
ACG63711  255 -----------------------------------vfSEQRIFRLYLCIGWGVPMLFVILWGTVKYlyEDEGCWSRnyNM 299 chicken
P43220    259 -----------------------------------vlSEQWIFRLYVSIGWGVPLLFVVPWGIVKYlyEDEGCWTRnsNM 303 human
Feature 1       #  ##                                                                         
5VEX_A    328 NYWLIIRLPILFACIVNFLIFVRVICIVVSKLKANLMCKTDIAFRLAKSTLTLIPLLCTHEVIFAFVMDEHARgtlRFIK 407
5VAI_R    343 NYWLIIRLPILFAIGVNFLIFIRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARgtlRFVK 422 rabbit
P32301    304 NYWLIIRLPILFAIGVNFLVFIRVICIVIAKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARgtlRFVK 383 Norway rat
ACG63711  300 NYWLIIRLPILIAIGVNFLIFIRVICIIISKLQANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFITDEHARgmlRFVK 379 chicken
P43220    304 NYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARgtlRFIK 383 human
Feature 1      #  #                               
5VEX_A    408 LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWER 443
5VAI_R    423 LFTELSFTSFQGLMVAILYCFVNNEVQMEFRKSWER 458 rabbit
P32301    384 LFTELSFTSFQGFMVAVLYCFVNNEVQMEFRKSWER 419 Norway rat
ACG63711  380 LFTELSFASFQGLMVAILYCFINNEVQMEFRKSWER 415 chicken
P43220    384 LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWER 419 human

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