Glucagon receptor

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Glucagon receptor
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GCGR ; GGR; GL-R
External IDs OMIM138033 MGI99572 HomoloGene131 IUPHAR: glucagon receptor ChEMBL: 1985 GeneCards: GCGR Gene
Orthologs
Species Human Mouse
Entrez 2642 14527
Ensembl ENSG00000215644 ENSMUSG00000025127
UniProt P47871 Q61606
RefSeq (mRNA) NM_000160 NM_008101
RefSeq (protein) NP_000151 NP_032127
Location (UCSC) Chr 17:
79.76 – 79.77 Mb
Chr 11:
120.53 – 120.54 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, Gs and to a lesser extent G alpha q.[1] 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.[2][3]

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.

Structure[edit]

The 3D crystallographic structures of the seven transmembrane helical domain (7TM)[4] and the extracellular domain (ECD)[5] of the glucagon receptor have been determined.

Clinical significance[edit]

A missense mutation in the GCGR gene is associated with diabetes mellitus type 2.[6]

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.[7]

References[edit]

  1. ^ Brubaker PL, Drucker DJ (2002). "Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors". Recept. Channels 8 (3-4): 179–88. doi:10.1080/10606820213687. PMID 12529935. 
  2. ^ Lok S, Kuijper JL, Jelinek LJ, Kramer JM, Whitmore TE, Sprecher CA, Mathewes S, Grant FJ, Biggs SH, Rosenberg GB (March 1994). "The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization". Gene 140 (2): 203–9. doi:10.1016/0378-1119(94)90545-2. PMID 8144028. 
  3. ^ Menzel S, Stoffel M, Espinosa R, Fernald AA, Le Beau MM, Bell GI (March 1994). "Localization of the glucagon receptor gene to human chromosome band 17q25". Genomics 20 (2): 327–8. doi:10.1006/geno.1994.1179. PMID 8020989. 
  4. ^ PDB 4L6R; Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, Zhou C, Xu Q, Wacker D, Joseph JS, Liu W, Lau J, Cherezov V, Katritch V, Wang M-W, Stevens RC (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature 499 (7459): 444–449. doi:10.1038/nature12393. PMC 3820480. PMID 23863937. 
  5. ^ PDB 4ERS; Koth CM, Murray JM, Mukund S, Madjidi A, Minn A, Clarke HJ, Wong T, Chiang V, Luis E, Estevez A, Rondon J, Zhang Y, Hötzel I, Allan BB (September 2012). "Molecular basis for negative regulation of the glucagon receptor". Proc. Natl. Acad. Sci. U.S.A. 109 (36): 14393–8. doi:10.1073/pnas.1206734109. PMC 3437825. PMID 22908259. 
  6. ^ Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C (March 1995). "A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus". Nat. Genet. 9 (3): 299–304. doi:10.1038/ng0395-299. PMID 7773293. 
  7. ^ Zhou C, Dhall D, Nissen NN, Chen CR, Yu R (2009). "Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor.". Pancreas 38 (8): 941–6. doi:10.1097/MPA.0b013e3181b2bb03. PMC 2767399. PMID 19657311. 

Further reading[edit]