Hmdb loader
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP13585
Secondary Accession Numbers None
Name Pro-glucagon
Synonyms Not Available
Gene Name GCG
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.Potent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6 (PubMed:22037645). Plays important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Has growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis (Probable).Stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.Significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.May modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.
Pathways
  • cAMP signaling pathway
  • Glucagon signaling pathway
  • Insulin secretion
  • Neuroactive ligand-receptor interaction
  • Thermogenesis
Reactions Not Available
GO Classification
Biological Process
negative regulation of inflammatory response to antigenic stimulus
positive regulation of protein kinase activity
negative regulation of apoptotic process
positive regulation of insulin secretion involved in cellular response to glucose stimulus
G-protein coupled receptor signaling pathway
positive regulation of histone H3-K4 methylation
positive regulation of calcium ion import
positive regulation of protein binding
positive regulation of ERK1 and ERK2 cascade
positive regulation of peptidyl-threonine phosphorylation
positive regulation of gluconeogenesis
feeding behavior
glucose homeostasis
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
negative regulation of execution phase of apoptosis
protein kinase A signaling
response to activity
regulation of insulin secretion
positive regulation of peptidyl-serine phosphorylation
adenylate cyclase-activating G-protein coupled receptor signaling pathway
cellular response to glucagon stimulus
Cellular Component
endoplasmic reticulum lumen
extracellular region
extracellular space
secretory granule lumen
Molecular Function
receptor binding
hormone activity
glucagon receptor binding
identical protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 180
Molecular Weight 20909.025
Theoretical pI 6.232
Pfam Domain Function
Signals
  • 1-20;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P01275
UniProtKB/Swiss-Prot Entry Name GLUC_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621 ]
  2. 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 ]
  3. Drucker DJ, Asa S: Glucagon gene expression in vertebrate brain. J Biol Chem. 1988 Sep 25;263(27):13475-8. [PubMed:2901414 ]
  4. White JW, Saunders GF: Structure of the human glucagon gene. Nucleic Acids Res. 1986 Jun 25;14(12):4719-30. [PubMed:3725587 ]
  5. Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC: Exon duplication and divergence in the human preproglucagon gene. Nature. 1983 Jul 28-Aug 3;304(5924):368-71. [PubMed:6877358 ]
  6. Orskov C, Bersani M, Johnsen AH, Hojrup P, Holst JJ: Complete sequences of glucagon-like peptide-1 from human and pig small intestine. J Biol Chem. 1989 Aug 5;264(22):12826-9. [PubMed:2753890 ]
  7. Orskov C, Wettergren A, Holst JJ: Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. [PubMed:8482423 ]
  8. Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR: Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. [PubMed:14557443 ]
  9. Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y: Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. [PubMed:14632334 ]
  10. Rouille Y, Bianchi M, Irminger JC, Halban PA: Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon. FEBS Lett. 1997 Aug 11;413(1):119-23. [PubMed:9287128 ]
  11. Bonic A, Mackin RB: Expression, purification, and PC1-mediated processing of human proglucagon, glicentin, and major proglucagon fragment. Protein Expr Purif. 2003 Mar;28(1):15-24. [PubMed:12651102 ]
  12. Drucker DJ: Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol. 2003 Feb;17(2):161-71. [PubMed:12554744 ]
  13. Jiang G, Zhang BB: Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E671-8. [PubMed:12626323 ]
  14. Kieffer TJ, Habener JF: The glucagon-like peptides. Endocr Rev. 1999 Dec;20(6):876-913. [PubMed:10605628 ]
  15. Sturm NS, Lin Y, Burley SK, Krstenansky JL, Ahn JM, Azizeh BY, Trivedi D, Hruby VJ: Structure-function studies on positions 17, 18, and 21 replacement analogues of glucagon: the importance of charged residues and salt bridges in glucagon biological activity. J Med Chem. 1998 Jul 16;41(15):2693-700. [PubMed:9667960 ]
  16. Chang X, Keller D, O'Donoghue SI, Led JJ: NMR studies of the aggregation of glucagon-like peptide-1: formation of a symmetric helical dimer. FEBS Lett. 2002 Mar 27;515(1-3):165-70. [PubMed:11943215 ]
  17. Ying J, Ahn JM, Jacobsen NE, Brown MF, Hruby VJ: NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles. Biochemistry. 2003 Mar 18;42(10):2825-35. [PubMed:12627948 ]
  18. Drucker DJ: Glucagon-like Peptide 2. Trends Endocrinol Metab. 1999 May;10(4):153-156. doi: 10.1016/s1043-2760(98)00136-2. [PubMed:10322410 ]
  19. Thomsen J, Kristiansen K, Brunfeldt K, Sundby F: The amino acid sequence of human glucagon. FEBS Lett. 1972 Apr 1;21(3):315-319. doi: 10.1016/0014-5793(72)80192-3. [PubMed:11946536 ]
  20. Brubaker PL, Anini Y: Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol. 2003 Nov;81(11):1005-12. doi: 10.1139/y03-107. [PubMed:14719035 ]
  21. Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL, Meier DT, Eppler E, Bouzakri K, Wueest S, Muller YD, Hansen AM, Reinecke M, Konrad D, Gassmann M, Reimann F, Halban PA, Gromada J, Drucker DJ, Gribble FM, Ehses JA, Donath MY: Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011 Oct 30;17(11):1481-9. doi: 10.1038/nm.2513. [PubMed:22037645 ]