Glucagon receptor

Glucagon receptor
Identifiers
Symbols	GCGR; FLJ97182; GGR; MGC138246
External IDs	OMIM: 138033 MGI: 99572 HomoloGene: 131 IUPHAR: glucagon receptor GeneCards: GCGR Gene
Gene Ontology Molecular function • glucagon receptor activity • peptide hormone binding Cellular component • endosome • plasma membrane • plasma membrane • integral to membrane Biological process • generation of precursor metabolites and energy • energy reserve metabolic process • exocytosis • G-protein signaling, coupled to cAMP nucleotide second messenger • activation of adenylate cyclase activity by G-protein signaling pathway • response to nutrient • regulation of blood pressure • hormone-mediated signaling pathway • cellular response to glucagon stimulus Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2642	14527
Ensembl	ENSG00000215644	ENSMUSG00000025127
UniProt	P47871	Q3UN81
RefSeq (mRNA)	NM_000160.3	NM_008101.2
RefSeq (protein)	NP_000151.1	NP_032127.2
Location (UCSC)	Chr 17: 79.76 – 79.77 Mb	Chr 11: 120.39 – 120.4 Mb
PubMed search	[1]	[2]

The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, G_s and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of intracellular cAMP. In humans, the glucagon receptor is encoded by the GCGR gene.

Glucagon receptors are mainly expressed in liver and in kidney with lesser amounts found in heart, adipose tissue, spleen, thymus, adrenal glands, pancreas, cerebral cortex, and gastrointestinal tract.

Clinical significance

A missense mutation in the GCGR gene is associated with diabetes mellitus type 2.

Inactivating mutation of glucagon receptor in humans causes resistance to glucagon and is associated with pancreatic alpha cell hyperplasia, nesidioblastosis, hyperglucagonemia, and pancreatic neuroendocrine tumors.

Further reading

• Levey GS, Weiss SR, Ruiz E (1975). "Characterization of the glucagon receptor in a pheochromocytoma.". J. Clin. Endocrinol. Metab. 40 (4): 720–3. doi:10.1210/jcem-40-4-720. PMID 165216. 
• Nakamura S, Rodbell M (1991). "Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes.". Proc. Natl. Acad. Sci. U.S.A. 88 (16): 7150–4. doi:10.1073/pnas.88.16.7150. PMC 52251. PMID 1908089. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=52251. 
• Horuk R, Wright DE (1983). "Partial purification and characterization of the glucagon receptor.". FEBS Lett. 155 (2): 213–7. doi:10.1016/0014-5793(82)80605-4. PMID 6303843. 
• MacNeil DJ, Occi JL, Hey PJ, et al. (1994). "Cloning and expression of a human glucagon receptor.". Biochem. Biophys. Res. Commun. 198 (1): 328–34. doi:10.1006/bbrc.1994.1046. PMID 7507321. 
• Fujisawa T, Ikegami H, Yamato E, et al. (1995). "A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus.". Diabetologia 38 (8): 983–5. doi:10.1007/BF00400589. PMID 7589886. 
• Unson CG, Macdonald D, Merrifield RB (1993). "The role of histidine-1 in glucagon action.". Arch. Biochem. Biophys. 300 (2): 747–50. doi:10.1006/abbi.1993.1103. PMID 8382034. 
• Chambers SM, Morris BJ (1996). "Glucagon receptor gene mutation in essential hypertension.". Nat. Genet. 12 (2): 122. doi:10.1038/ng0296-122. PMID 8563746. 
• Yamato E, Ikegami H, Takekawa K, et al. (1997). "Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1).". Horm. Metab. Res. 29 (2): 56–9. doi:10.1055/s-2007-978985. PMID 9105899. 
• Strazzullo P, Iacone R, Siani A, et al. (2001). "Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.". J. Mol. Med. 79 (10): 574–80. doi:10.1007/s001090100257. PMID 11692154. 
• Shiota D, Kasamatsu T, Dib SA, et al. (2002). "Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients with type 2 diabetes mellitus.". Pancreas 24 (4): 386–90. doi:10.1097/00006676-200205000-00010. PMID 11961492. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Runge S, Gram C, Brauner-Osborne H, et al. (2003). "Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus.". J. Biol. Chem. 278 (30): 28005–10. doi:10.1074/jbc.M301085200. PMID 12724331. 
• Hassel S, Eichner A, Yakymovych M, et al. (2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry.". Proteomics 4 (5): 1346–58. doi:10.1002/pmic.200300770. PMID 15188402. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Mortensen OH, Dichmann DS, Abrahamsen N, et al. (2007). "Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.". Gene 393 (1-2): 127–36. doi:10.1016/j.gene.2007.01.023. PMID 17374560.