Glucagon receptor

Details

Name
Glucagon receptor
Synonyms
  • GL-R
Gene Name
GCGR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016117|Glucagon receptor
MPPCQPQRPLLLLLLLLACQPQVPSAQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNR
TFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQ
CQMDGEEIEVQKEVAKMYSSFQVMYTVGYSLSLGALLLALAILGGLSKLHCTRNAIHANL
FASFVLKASSVLVIDGLLRTRYSQKIGDDLSVSTWLSDGAVAGCRVAAVFMQYGIVANYC
WLLVEGLYLHNLLGLATLPERSFFSLYLGIGWGAPMLFVVPWAVVKCLFENVQCWTSNDN
MGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMHHTDYKFRLAKSTLTLIPLLGV
HEVVFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHRWRL
GKVLWEERNTSNHRASSSPGHGPPSKELQFGRGGGSQDSSAETPLAGGLPRLAESPF
Number of residues
477
Molecular Weight
54008.44
Theoretical pI
8.83
GO Classification
Functions
glucagon receptor activity / guanyl-nucleotide exchange factor activity / peptide hormone binding
Processes
adenylate cyclase-activating G-protein coupled receptor signaling pathway / adenylate cyclase-modulating G-protein coupled receptor signaling pathway / cell surface receptor signaling pathway / cellular response to glucagon stimulus / energy reserve metabolic process / exocytosis / generation of precursor metabolites and energy / glucose homeostasis / hormone-mediated signaling pathway / positive regulation of GTPase activity / regulation of blood pressure / regulation of glycogen metabolic process / response to nutrient / response to starvation / small molecule metabolic process
Components
endosome / integral component of membrane / integral component of plasma membrane / plasma membrane
General Function
Peptide hormone binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
137-161 174-198 226-249 264-285 304-326 351-369 382-402
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0016118|Glucagon receptor (GCGR)
ATGCCCCCCTGCCAGCCACAGCGACCCCTGCTGCTGTTGCTGCTGCTGCTGGCCTGCCAG
CCACAGGTCCCCTCCGCTCAGGTGATGGACTTCCTGTTTGAGAAGTGGAAGCTCTACGGT
GACCAGTGTCACCACAACCTGAGCCTGCTGCCCCCTCCCACGGAGCTGGTGTGCAACAGA
ACCTTCGACAAGTATTCCTGCTGGCCGGACACCCCCGCCAATACCACGGCCAACATCTCC
TGCCCCTGGTACCTGCCTTGGCACCACAAAGTGCAACACCGCTTCGTGTTCAAGAGATGC
GGGCCCGACGGTCAGTGGGTGCGTGGACCCCGGGGGCAGCCTTGGCGTGATGCCTCCCAG
TGCCAGATGGATGGCGAGGAGATTGAGGTCCAGAAGGAGGTGGCCAAGATGTACAGCAGC
TTCCAGGTGATGTACACAGTGGGCTACAGCCTGTCCCTGGGGGCCCTGCTCCTCGCCTTG
GCCATCCTGGGGGGCCTCAGCAAGCTGCACTGCACCCGCAATGCCATCCACGCGAATCTG
TTTGCGTCCTTCGTGCTGAAAGCCAGCTCCGTGCTGGTCATTGATGGGCTGCTCAGGACC
CGCTACAGCCAGAAAATTGGCGACGACCTCAGTGTCAGCACCTGGCTCAGTGATGGAGCG
GTGGCTGGCTGCCGTGTGGCCGCGGTGTTCATGCAATATGGCATCGTGGCCAACTACTGC
TGGCTGCTGGTGGAGGGCCTGTACCTGCACAACCTGCTGGGCCTGGCCACCCTCCCCGAG
AGGAGCTTCTTCAGCCTCTACCTGGGCATCGGCTGGGGTGCCCCCATGCTGTTCGTCGTC
CCCTGGGCAGTGGTCAAGTGTCTGTTCGAGAACGTCCAGTGCTGGACCAGCAATGACAAC
ATGGGCTTCTGGTGGATCCTGCGGTTCCCCGTCTTCCTGGCCATCCTGATCAACTTCTTC
ATCTTCGTCCGCATCGTTCAGCTGCTCGTGGCCAAGCTGCGGGCACGGCAGATGCACCAC
ACAGACTACAAGTTCCGGCTGGCCAAGTCCACGCTGACCCTCATCCCTCTGCTGGGCGTC
CACGAAGTGGTCTTCGCCTTCGTGACGGACGAGCACGCCCAGGGCACCCTGCGCTCCGCC
AAGCTCTTCTTCGACCTCTTCCTCAGCTCCTTCCAGGGCCTGCTGGTGGCTGTCCTCTAC
TGCTTCCTCAACAAGGAGGTGCAGTCGGAGCTGCGGCGGCGTTGGCACCGCTGGCGCCTG
GGCAAAGTGCTATGGGAGGAGCGGAACACCAGCAACCACAGGGCCTCATCTTCGCCCGGC
CACGGCCCTCCCAGCAAGGAGCTGCAGTTTGGGAGGGGTGGTGGCAGCCAGGATTCATCT
GCGGAGACCCCCTTGGCTGGTGGCCTCCCTAGATTGGCTGAGAGCCCCTTCTGA
Chromosome Location
17
Locus
17q25
External Identifiers
ResourceLink
UniProtKB IDP47871
UniProtKB Entry NameGLR_HUMAN
GenBank Protein ID439690
GenBank Gene IDU03469
GenAtlas IDGCGR
HGNC IDHGNC:4192
General References
  1. MacNeil DJ, Occi JL, Hey PJ, Strader CD, Graziano MP: Cloning and expression of a human glucagon receptor. Biochem Biophys Res Commun. 1994 Jan 14;198(1):328-34. [PubMed:7507321]
  2. Lok S, Kuijper JL, Jelinek LJ, Kramer JM, Whitmore TE, Sprecher CA, Mathewes S, Grant FJ, Biggs SH, Rosenberg GB, et al.: The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization. Gene. 1994 Mar 25;140(2):203-9. [PubMed:8144028]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Menzel S, Stoffel M, Espinosa R 3rd, Fernald AA, Le Beau MM, Bell GI: Localization of the glucagon receptor gene to human chromosome band 17q25. Genomics. 1994 Mar 15;20(2):327-8. [PubMed:8020989]
  5. Buggy JJ, Heurich RO, MacDougall M, Kelley KA, Livingston JN, Yoo-Warren H, Rossomando AJ: Role of the glucagon receptor COOH-terminal domain in glucagon-mediated signaling and receptor internalization. Diabetes. 1997 Sep;46(9):1400-5. [PubMed:9287038]
  6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  7. Ruckert C, Fiorillo MT, Loll B, Moretti R, Biesiadka J, Saenger W, Ziegler A, Sorrentino R, Uchanska-Ziegler B: Conformational dimorphism of self-peptides and molecular mimicry in a disease-associated HLA-B27 subtype. J Biol Chem. 2006 Jan 27;281(4):2306-16. Epub 2005 Oct 12. [PubMed:16221670]
  8. Koth CM, Murray JM, Mukund S, Madjidi A, Minn A, Clarke HJ, Wong T, Chiang V, Luis E, Estevez A, Rondon J, Zhang Y, Hotzel I, Allan BB: Molecular basis for negative regulation of the glucagon receptor. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14393-8. doi: 10.1073/pnas.1206734109. Epub 2012 Aug 20. [PubMed:22908259]
  9. 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 MW, Stevens RC: Structure of the human glucagon class B G-protein-coupled receptor. Nature. 2013 Jul 25;499(7459):444-9. doi: 10.1038/nature12393. Epub 2013 Jul 17. [PubMed:23863937]
  10. Fujisawa T, Ikegami H, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Ueda H, Fukuda M, Ogihara T: A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus. Diabetologia. 1995 Aug;38(8):983-5. [PubMed:7589886]
  11. Zhou C, Dhall D, Nissen NN, Chen CR, Yu R: Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas. 2009 Nov;38(8):941-6. doi: 10.1097/MPA.0b013e3181b2bb03. [PubMed:19657311]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00040GlucagonapprovedyesagonistDetails