Glucagon receptor

UniProt P47871 Organism Homo sapiens Gene GCGR

Also known as: GCGR

Function

G protein-coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system.

Classification

Family (Pfam): PF00002 7tm_2, PF02793 HRM
InterPro: GPCR_2, GPCR_2-like_7TM, GPCR_2_extracell_dom_sf, GPCR_2_extracellular_dom, GPCR_2_GLP1/glucagon_rcpt, GPCR_2_glucagon_rcpt, GPCR_2_secretin-like, GPCR_2_secretin-like_CS
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 22

2A83 X-ray 1.40A
3CZF X-ray 1.20A
4ERS X-ray 2.64A
4L6R X-ray 3.30A
4LF3 X-ray 2.74A
5EE7 X-ray 2.50A
5XEZ X-ray 3.00A
5XF1 X-ray 3.19A
5YQZ X-ray 3.00A
6LMK EM 3.70A
6LML EM 3.90A
6WHC EM 3.40A
… and 10 more

A predicted model is available from AlphaFold.

Gene Ontology · 16

Disease associations

GCGR-related hyperglucagonemia MONDO:0018582

Drugs targeting this protein · 5

MK-0893 antagonist
MK-3577 antagonist
PF-06291874 antagonist
ADOMEGLIVANT antagonist
COTADUTIDE agonist

Related proteins · sequence + function similarity

Glucagon receptor 0.98
Glucagon receptor 0.97
Gastric inhibitory polypeptide receptor 0.96
Gastric inhibitory polypeptide receptor 0.96
Glucagon receptor 0.96
Gastric inhibitory polypeptide receptor 0.96
Glucagon-like peptide 1 receptor 0.95
Gastric inhibitory polypeptide receptor 0.95
Glucagon-like peptide 2 receptor 0.94
Secretin receptor 0.94
Glucagon-like peptide 2 receptor 0.93
Growth hormone-releasing hormone receptor 0.93

Co-cited proteins · studied together in the literature

Glucagon receptor 1 shared papers
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 2 shared papers
Pro-glucagon 1 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-1 1 shared papers

Literature · 19 cited papers

Molecular features of the ligand-free GLP-1R, GCGR and GIPR in complex with Gs proteins. Cell Discov. · 2024
Characterization of a naturally occurring mutation V368M in the human glucagon receptor and its association with metabolic disorders. Biochem. J. · 2020
Structural basis of Gs and Gi recognition by the human glucagon receptor. Science · 2020
The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine. Mol. Genet. Metab. Rep. · 2018
Hypercalcemia in glucagon cell hyperplasia and neoplasia (Mahvash syndrome): a new association. J. Clin. Endocrinol. Metab. · 2018
Structure of the full-length glucagon class B G-protein-coupled receptor. Nature · 2017
Extra-helical binding site of a glucagon receptor antagonist. Nature · 2016
Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations. J. Clin. Endocrinol. Metab. · 2015
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Structure of the human glucagon class B G-protein-coupled receptor. Nature · 2013
Molecular basis for negative regulation of the glucagon receptor. Proc. Natl. Acad. Sci. U.S.A. · 2012
Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas · 2009
… and 7 more in the literature graph

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