Glucagon-like peptide 1 receptor

Function

G protein-coupled receptor for glucagon-like peptide 1 (GLP-1). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels. Plays a role in regulating insulin secretion in response to GLP-1 (By similarity).

Classification

Family (Pfam)

PF00002 7tm_2, PF02793 HRM

InterPro

GLP1R_7TM, GPCR_2, GPCR_2-like_7TM, GPCR_2_extracell_dom_sf, GPCR_2_extracellular_dom, GPCR_2_GLP1/glucagon_rcpt, GPCR_2_GLP1_rcpt, GPCR_2_secretin-like, GPCR_2_secretin-like_CS

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 62

• 3C59 X-ray 2.30A
• 3C5T X-ray 2.10A
• 3IOL X-ray 2.10A
• 4ZGM X-ray 1.80A
• 5E94 X-ray 2.00A
• 5NX2 X-ray 3.70A
• 5OTT X-ray 1.92A
• 5OTU X-ray 1.80A
• 5OTV X-ray 2.00A
• 5OTW X-ray 2.10A
• 5OTX X-ray 2.00A
• 5VEW X-ray 2.70A
• … and 50 more

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0004967 glucagon receptor activity
• GO:0044508 glucagon-like peptide 1 receptor activity
• GO:0017046 peptide hormone binding
• GO:0004888 transmembrane signaling receptor activity
• GO:0007190 activation of adenylate cyclase activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0007166 cell surface receptor signaling pathway
• GO:0007611 learning or memory
• GO:0045777 positive regulation of blood pressure
• GO:0007204 positive regulation of cytosolic calcium ion concentration
• GO:0008016 regulation of heart contraction
• GO:1990911 response to psychosocial stress

Drugs targeting this protein · 4

• LIRAGLUTIDE agonist
• EXENATIDE agonist
• COTADUTIDE agonist
• DANUGLIPRON agonist

Related proteins · sequence + function similarity

• Glucagon-like peptide 1 receptor 0.99
• Glucagon-like peptide 1 receptor 0.99
• Glucagon receptor 0.95
• Gastric inhibitory polypeptide receptor 0.95
• Secretin receptor 0.95
• Glucagon receptor 0.95
• Glucagon receptor 0.94
• Gastric inhibitory polypeptide receptor 0.94
• Gastric inhibitory polypeptide receptor 0.94
• Glucagon receptor 0.94
• Secretin receptor 0.94
• Vasoactive intestinal polypeptide receptor 1 0.94

Co-cited proteins · studied together in the literature

• Gastric inhibitory polypeptide receptor 1 shared papers
• GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 1 shared papers
• Exendin-4 1 shared papers
• Exendin-4 1 shared papers

Literature · 16 cited papers

• Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature · 2017
• Structural insight into antibody-mediated antagonism of the Glucagon-like peptide-1 Receptor. Sci. Rep. · 2016
• Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J. Med. Chem. · 2015
• Regulation of GIP and GLP1 receptor cell surface expression by N-glycosylation and receptor heteromerization. PLoS ONE · 2012
• Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP-ribosyltransferase. Mol. Biol. Rep. · 2012
• Functional coupling of Cys-226 and Cys-296 in the glucagon-like peptide-1 (GLP-1) receptor indicates a disulfide bond that is close to the activation pocket. Peptides · 2010
• Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor. J. Biol. Chem. · 2010
• Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain. J. Biol. Chem. · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The DNA sequence and analysis of human chromosome 6. Nature · 2003
• Cloning and characterization of the 5' flanking sequences (promoter region) of the human GLP-1 receptor gene. Peptides · 1997
• Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor. Diabetes · 1993
• … and 4 more in the literature graph