ID GLUC_HUMAN Reviewed; 180 AA. AC P01275; A6NN65; Q53TP6; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 3. DT 10-JUN-2026, entry version 240. DE RecName: Full=Pro-glucagon; DE Contains: DE RecName: Full=Glicentin; DE Contains: DE RecName: Full=Glicentin-related polypeptide; DE Short=GRPP; DE Contains: DE RecName: Full=Oxyntomodulin; DE Short=OXM; DE Short=OXY; DE Contains: DE RecName: Full=Glucagon; DE Contains: DE RecName: Full=Glucagon-like peptide 1 {ECO:0000305}; DE Short=GLP-1; DE AltName: Full=Incretin hormone; DE Contains: DE RecName: Full=Glucagon-like peptide 1(7-37); DE Short=GLP-1(7-37); DE Contains: DE RecName: Full=Glucagon-like peptide 1(7-36); DE Short=GLP-1(7-36); DE Contains: DE RecName: Full=Glucagon-like peptide 2; DE Short=GLP-2; DE Flags: Precursor; GN Name=GCG {ECO:0000312|HGNC:HGNC:4191}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2901414; DOI=10.1016/s0021-9258(18)68261-4; RA Drucker D.J., Asa S.; RT "Glucagon gene expression in vertebrate brain."; RL J. Biol. Chem. 263:13475-13478(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3725587; DOI=10.1093/nar/14.12.4719; RA White J.W., Saunders G.F.; RT "Structure of the human glucagon gene."; RL Nucleic Acids Res. 14:4719-4730(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Liver; RX PubMed=6877358; DOI=10.1038/304368a0; RA Bell G.I., Sanchez-Pescador R., Laybourn P.J., Najarian R.C.; RT "Exon duplication and divergence in the human preproglucagon gene."; RL Nature 304:368-371(1983). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 53-81. RX PubMed=11946536; DOI=10.1016/0014-5793(72)80192-3; RA Thomsen J., Kristiansen K., Brunfeldt K., Sundby F.; RT "The amino acid sequence of human glucagon."; RL FEBS Lett. 21:315-319(1972). RN [8] RP PROTEIN SEQUENCE OF 98-127, AND AMIDATION AT ARG-127. RX PubMed=2753890; DOI=10.1016/s0021-9258(18)51561-1; RA Orskov C., Bersani M., Johnsen A.H., Hoejrup P., Holst J.J.; RT "Complete sequences of glucagon-like peptide-1 from human and pig small RT intestine."; RL J. Biol. Chem. 264:12826-12829(1989). RN [9] RP FUNCTION OF GLP1 BIOACTIVE FORMS. RX PubMed=8482423; DOI=10.2337/diab.42.5.658; RA Orskov C., Wettergren A., Holst J.J.; RT "Biological effects and metabolic rates of glucagonlike peptide-1 7-36 RT amide and glucagonlike peptide-1 7-37 in healthy subjects are RT indistinguishable."; RL Diabetes 42:658-661(1993). RN [10] RP FUNCTION OF OXYNTOMODULIN. RX PubMed=14557443; DOI=10.1210/jc.2003-030421; RA Cohen M.A., Ellis S.M., Le Roux C.W., Batterham R.L., Park A., RA Patterson M., Frost G.S., Ghatei M.A., Bloom S.R.; RT "Oxyntomodulin suppresses appetite and reduces food intake in humans."; RL J. Clin. Endocrinol. Metab. 88:4696-4701(2003). RN [11] RP FUNCTION OF GLICENTIN. RX PubMed=14632334; DOI=10.1080/08035250310000514; RA Tadokoro R., Shimizu T., Hosaka A., Kaneko N., Satoh Y., Yamashiro Y.; RT "Postnatal and postprandial changes in plasma concentrations of glicentin RT in term and preterm infants."; RL Acta Paediatr. 92:1175-1179(2003). RN [12] RP PROTEOLYTIC PROCESSING BY PCSK2. RX PubMed=9287128; DOI=10.1016/s0014-5793(97)00892-2; RA Rouille Y., Bianchi M., Irminger J.C., Halban P.A.; RT "Role of the prohormone convertase PC2 in the processing of proglucagon to RT glucagon."; RL FEBS Lett. 413:119-123(1997). RN [13] RP PROTEOLYTIC PROCESSING BY PCSK1. RX PubMed=12651102; DOI=10.1016/s1046-5928(02)00653-8; RA Bonic A., Mackin R.B.; RT "Expression, purification, and PC1-mediated processing of human RT proglucagon, glicentin, and major proglucagon fragment."; RL Protein Expr. Purif. 28:15-24(2003). RN [14] RP REVIEW. RX PubMed=10605628; DOI=10.1210/edrv.20.6.0385; RA Kieffer T.J., Habener J.F.; RT "The glucagon-like peptides."; RL Endocr. Rev. 20:876-913(1999). RN [15] RP REVIEW. RX PubMed=10322410; DOI=10.1016/s1043-2760(98)00136-2; RA Drucker D.J.; RT "Glucagon-like peptide 2."; RL Trends Endocrinol. Metab. 10:153-156(1999). RN [16] RP REVIEW. RX PubMed=12626323; DOI=10.1152/ajpendo.00492.2002; RA Jiang G., Zhang B.B.; RT "Glucagon and regulation of glucose metabolism."; RL Am. J. Physiol. 284:E671-E678(2003). RN [17] RP REVIEW. RX PubMed=14719035; DOI=10.1139/y03-107; RA Brubaker P.L., Anini Y.; RT "Direct and indirect mechanisms regulating secretion of glucagon-like RT peptide-1 and glucagon-like peptide-2."; RL Can. J. Physiol. Pharmacol. 81:1005-1012(2003). RN [18] RP REVIEW. RX PubMed=12554744; DOI=10.1210/me.2002-0306; RA Drucker D.J.; RT "Glucagon-like peptides: regulators of cell proliferation, differentiation, RT and apoptosis."; RL Mol. Endocrinol. 17:161-171(2003). RN [19] RP INDUCTION BY IL6 (GLUCAGON-LIKE PEPTIDE 1), FUNCTION (GLUCAGON-LIKE PEPTIDE RP 1), AND TISSUE SPECIFICITY (GLUCAGON-LIKE PEPTIDE 1). RX PubMed=22037645; DOI=10.1038/nm.2513; RA Ellingsgaard H., Hauselmann I., Schuler B., Habib A.M., Baggio L.L., RA Meier D.T., Eppler E., Bouzakri K., Wueest S., Muller Y.D., Hansen A.M., RA Reinecke M., Konrad D., Gassmann M., Reimann F., Halban P.A., Gromada J., RA Drucker D.J., Gribble F.M., Ehses J.A., Donath M.Y.; RT "Interleukin-6 enhances insulin secretion by increasing glucagon-like RT peptide-1 secretion from L cells and alpha cells."; RL Nat. Med. 17:1481-1489(2011). RN [20] RP FUNCTION (GLUCAGON-LIKE PEPTIDE 1), AND SUBCELLULAR LOCATION (GLUCAGON-LIKE RP PEPTIDE 1). RX PubMed=40446798; DOI=10.1016/j.cell.2025.05.010; RA Lin J., Nie Q., Cheng J., Zhong Y.N., Zhang T., Zhang X., Ge X., Ding Y., RA Niu C., Gao Y., Wang K., Gao M., Wang X., Chen W., Yun C., Ye C., Xu J., RA Shaoyong W., Zhang L., Shang P., Luo X., Zhang Z., Zheng X., Sha X., RA Zhang J., Nie S., Zhang X., Ren F., Liu H., Dong E., Yu X., Ji L., Pang Y., RA Sun J.P., Jiang C.; RT "A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, RT improves glucose homeostasis via the orphan receptor MRGPRE."; RL Cell 0:0-0(2025). RN [21] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 53-81. RX PubMed=9667960; DOI=10.1021/jm980084a; RA Sturm N.S., Lin Y., Burley S.K., Krstenansky J.L., Ahn J.-M., Azizeh B.Y., RA Trivedi D., Hruby V.J.; RT "Structure-function studies on positions 17, 18, and 21 replacement RT analogues of glucagon: the importance of charged residues and salt bridges RT in glucagon biological activity."; RL J. Med. Chem. 41:2693-2700(1998). RN [22] RP STRUCTURE BY NMR OF 98-127. RX PubMed=11943215; DOI=10.1016/s0014-5793(02)02466-3; RA Chang X., Keller D., O'Donoghue S.I., Led J.J.; RT "NMR studies of the aggregation of glucagon-like peptide-1: formation of a RT symmetric helical dimer."; RL FEBS Lett. 515:165-170(2002). RN [23] RP STRUCTURE BY NMR OF GLUCAGON ANTAGONIST. RX PubMed=12627948; DOI=10.1021/bi026629r; RA Ying J., Ahn J.-M., Jacobsen N.E., Brown M.F., Hruby V.J.; RT "NMR solution structure of the glucagon antagonist [desHis1, desPhe6, RT Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine RT micelles."; RL Biochemistry 42:2825-2835(2003). RN [24] {ECO:0007744|PDB:6LMK, ECO:0007744|PDB:6LML} RP STRUCTURE BY ELECTRON MICROSCOPY (3.70 ANGSTROMS) OF 53-81, FUNCTION RP (GLUCAGON), AND INTERACTION WITH GCGR (GLUCAGON). RX PubMed=32193322; DOI=10.1126/science.aaz5346; RA Qiao A., Han S., Li X., Li Z., Zhao P., Dai A., Chang R., Tai L., Tan Q., RA Chu X., Ma L., Thorsen T.S., Reedtz-Runge S., Yang D., Wang M.W., RA Sexton P.M., Wootten D., Sun F., Zhao Q., Wu B.; RT "Structural basis of Gs and Gi recognition by the human glucagon RT receptor."; RL Science 367:1346-1352(2020). CC -!- FUNCTION: [Glucagon]: Plays a key role in glucose metabolism and CC homeostasis. Regulates blood glucose by increasing gluconeogenesis and CC decreasing glycolysis. A counterregulatory hormone of insulin, raises CC plasma glucose levels in response to insulin-induced hypoglycemia. CC Plays an important role in initiating and maintaining hyperglycemic CC conditions in diabetes. Binds to and activates the glucagon receptor CC GCGR, which couples to the G(s) G protein and elevates intracellular CC cAMP, triggering downstream metabolic responses (PubMed:32193322). CC {ECO:0000269|PubMed:32193322, ECO:0000303|PubMed:10605628, CC ECO:0000303|PubMed:12626323}. CC -!- FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose- CC dependent insulin release (PubMed:22037645, PubMed:40446798). Also CC stimulates insulin release in response to IL6 (PubMed:22037645). Plays CC important roles on gastric motility and the suppression of plasma CC glucagon levels (PubMed:10605628, PubMed:14719035, PubMed:12554744). CC May be involved in the suppression of satiety and stimulation of CC glucose disposal in peripheral tissues, independent of the actions of CC insulin (PubMed:10605628, PubMed:14719035, PubMed:12554744). Has CC growth-promoting activities on intestinal epithelium (PubMed:10605628, CC PubMed:14719035, PubMed:12554744). May also regulate the hypothalamic CC pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and CC vasopressin secretion (PubMed:10605628, PubMed:14719035, CC PubMed:12554744). Increases islet mass through stimulation of islet CC neogenesis and pancreatic beta cell proliferation (PubMed:10605628, CC PubMed:14719035, PubMed:12554744). Inhibits beta cell apoptosis CC (PubMed:10605628, PubMed:14719035, PubMed:12554744). CC {ECO:0000269|PubMed:22037645, ECO:0000269|PubMed:40446798, CC ECO:0000303|PubMed:10605628, ECO:0000303|PubMed:12554744, CC ECO:0000303|PubMed:14719035}. CC -!- FUNCTION: [Glucagon-like peptide 2]: Stimulates intestinal growth and CC up-regulates villus height in the small intestine, concomitant with CC increased crypt cell proliferation and decreased enterocyte apoptosis. CC The gastrointestinal tract, from the stomach to the colon is the CC principal target for GLP-2 action. Plays a key role in nutrient CC homeostasis, enhancing nutrient assimilation through enhanced CC gastrointestinal function, as well as increasing nutrient disposal. CC Stimulates intestinal glucose transport and decreases mucosal CC permeability. {ECO:0000303|PubMed:10322410, CC ECO:0000303|PubMed:10605628, ECO:0000303|PubMed:12554744, CC ECO:0000303|PubMed:14719035}. CC -!- FUNCTION: [Oxyntomodulin]: Significantly reduces food intake. Inhibits CC gastric emptying in humans. Suppression of gastric emptying may lead to CC increased gastric distension, which may contribute to satiety by CC causing a sensation of fullness. {ECO:0000303|PubMed:10605628, CC ECO:0000303|PubMed:12554744}. CC -!- FUNCTION: [Glicentin]: May modulate gastric acid secretion and the CC gastro-pyloro-duodenal activity. May play an important role in CC intestinal mucosal growth in the early period of life. CC {ECO:0000303|PubMed:10605628, ECO:0000303|PubMed:12554744}. CC -!- SUBUNIT: [Glucagon]: Interacts with GCGR. CC {ECO:0000269|PubMed:32193322}. CC -!- INTERACTION: CC P01275; P27487: DPP4; NbExp=4; IntAct=EBI-7629173, EBI-2871277; CC P01275; Q12884: FAP; NbExp=4; IntAct=EBI-7629173, EBI-4319803; CC P01275; P01275: GCG; NbExp=3; IntAct=EBI-7629173, EBI-7629173; CC P01275; P48546: GIPR; NbExp=2; IntAct=EBI-7629173, EBI-15653881; CC P01275; P14735-1: IDE; NbExp=3; IntAct=EBI-7629173, EBI-15607031; CC PRO_0000011256; P47871: GCGR; NbExp=2; IntAct=EBI-21915354, EBI-3929902; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Glucagon-like peptide 1]: Secreted CC {ECO:0000269|PubMed:22037645, ECO:0000269|PubMed:40446798}. CC -!- TISSUE SPECIFICITY: [Glucagon]: Secreted in the A cells of the islets CC of Langerhans. {ECO:0000269|PubMed:22037645}. CC -!- TISSUE SPECIFICITY: [Glucagon-like peptide 1]: Secreted in the A cells CC of the islets of Langerhans (PubMed:22037645). Secreted from CC enteroendocrine L cells throughout the gastrointestinal tract CC (PubMed:22037645). Also secreted in selected neurons in the brain. CC {ECO:0000269|PubMed:22037645}. CC -!- TISSUE SPECIFICITY: [Glucagon-like peptide 2]: Secreted from CC enteroendocrine cells throughout the gastrointestinal tract. Also CC secreted in selected neurons in the brain. CC -!- TISSUE SPECIFICITY: [Glicentin]: Secreted from enteroendocrine cells CC throughout the gastrointestinal tract. CC -!- TISSUE SPECIFICITY: [Oxyntomodulin]: Secreted from enteroendocrine CC cells throughout the gastrointestinal tract. CC -!- INDUCTION: [Glucagon]: Release is stimulated by hypoglycemia and CC inhibited by hyperglycemia, insulin, and somatostatin. CC {ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12626323}. CC -!- INDUCTION: [Glucagon-like peptide 1]: Production by islet alpha cell is CC increased by IL6. {ECO:0000269|PubMed:22037645}. CC -!- INDUCTION: [Glucagon-like peptide 2]: Induced in response to nutrient CC ingestion. {ECO:0000305|PubMed:10322410, ECO:0000305|PubMed:10605628, CC ECO:0000305|PubMed:12554744, ECO:0000305|PubMed:14719035}. CC -!- PTM: Proglucagon is post-translationally processed in a tissue-specific CC manner in pancreatic A cells and intestinal L cells. In pancreatic A CC cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In CC the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and CC oxyntomodulin. GLP-1 is further N-terminally truncated by post- CC translational processing in the intestinal L cells resulting in GLP- CC 1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither CC important for the metabolism of GLP-1 nor for its effects on the CC endocrine pancreas. {ECO:0000269|PubMed:12651102, CC ECO:0000269|PubMed:2753890, ECO:0000269|PubMed:9287128}. CC -!- PHARMACEUTICAL: Available under the names Glucagon (Eli Lilly) and CC GlucaGen or Glucagon Novo Nordisk (Novo Nordisk). Used to treat severe CC hypoglycemia in insulin-dependent diabetics. CC -!- MISCELLANEOUS: In the glucagon antagonist, His-53 and Phe-58 are CC missing. This antagonist has been successfully utilized to reduce CC glucose concentration in vivo. CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J04040; AAA52567.1; -; mRNA. DR EMBL; X03991; CAA27627.1; -; Genomic_DNA. DR EMBL; V01515; CAA24759.1; -; Genomic_DNA. DR EMBL; BT006813; AAP35459.1; -; mRNA. DR EMBL; AC007750; AAY24204.1; -; Genomic_DNA. DR EMBL; BC005278; AAH05278.1; -; mRNA. DR CCDS; CCDS46439.1; -. DR PIR; A24377; GCHU. DR RefSeq; NP_002045.1; NM_002054.5. DR PDB; 1BH0; X-ray; 3.00 A; A=53-81. DR PDB; 1D0R; NMR; -; A=98-127. DR PDB; 1NAU; NMR; -; A=59-81. DR PDB; 2G49; X-ray; 2.50 A; C/D=53-81. DR PDB; 2L63; NMR; -; A=146-178. DR PDB; 2L64; NMR; -; A=146-178. DR PDB; 2M5P; NMR; -; X=53-81. DR PDB; 2M5Q; NMR; -; X=53-81. DR PDB; 3IOL; X-ray; 2.10 A; B=98-128. DR PDB; 4APD; NMR; -; A=98-128. DR PDB; 4ZGM; X-ray; 1.80 A; B=98-128. DR PDB; 5OTU; X-ray; 1.80 A; B/D=98-128. DR PDB; 5OTV; X-ray; 2.00 A; B/D=98-128. DR PDB; 5OTW; X-ray; 2.10 A; B/D=98-128. DR PDB; 5OTX; X-ray; 2.00 A; B/D=98-128. DR PDB; 5VAI; EM; 4.10 A; P=98-128. DR PDB; 5YQZ; X-ray; 3.00 A; P=54-81. DR PDB; 6EDS; X-ray; 3.18 A; C/D=53-81. DR PDB; 6LMK; EM; 3.70 A; E=53-81. DR PDB; 6LML; EM; 3.90 A; E=53-81. DR PDB; 6NZN; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=53-81. DR PDB; 6PHI; X-ray; 1.10 A; A=53-81. DR PDB; 6PHJ; X-ray; 1.99 A; A=53-81. DR PDB; 6PHK; X-ray; 1.18 A; A=53-81. DR PDB; 6PHL; X-ray; 1.44 A; A=53-81. DR PDB; 6PHO; X-ray; 1.42 A; A=54-81. DR PDB; 6PHP; X-ray; 1.65 A; A=53-81. DR PDB; 6VCB; EM; 3.30 A; P=98-128. DR PDB; 6X18; EM; 2.10 A; P=98-127. DR PDB; 7D68; EM; 3.00 A; P=146-178. DR PDB; 7DUQ; EM; 2.50 A; P=98-127. DR PDB; 7KI0; EM; 2.50 A; P=98-128. DR PDB; 7KI1; EM; 2.50 A; P=98-127. DR PDB; 7XM8; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=53-81. DR PDB; 8ANJ; X-ray; 1.55 A; A=166-171. DR PDB; 8ANK; X-ray; 1.30 A; A=118-123. DR PDB; 8JRV; EM; 3.30 A; G=53-81. DR PDB; 9E2A; EM; 3.30 A; P=98-127. DR PDB; 9IVG; EM; 3.00 A; P=100-127. DR PDBsum; 1BH0; -. DR PDBsum; 1D0R; -. DR PDBsum; 1NAU; -. DR PDBsum; 2G49; -. DR PDBsum; 2L63; -. DR PDBsum; 2L64; -. DR PDBsum; 2M5P; -. DR PDBsum; 2M5Q; -. DR PDBsum; 3IOL; -. DR PDBsum; 4APD; -. DR PDBsum; 4ZGM; -. DR PDBsum; 5OTU; -. DR PDBsum; 5OTV; -. DR PDBsum; 5OTW; -. DR PDBsum; 5OTX; -. DR PDBsum; 5VAI; -. DR PDBsum; 5YQZ; -. DR PDBsum; 6EDS; -. DR PDBsum; 6LMK; -. DR PDBsum; 6LML; -. DR PDBsum; 6NZN; -. DR PDBsum; 6PHI; -. DR PDBsum; 6PHJ; -. DR PDBsum; 6PHK; -. DR PDBsum; 6PHL; -. DR PDBsum; 6PHO; -. DR PDBsum; 6PHP; -. DR PDBsum; 6VCB; -. DR PDBsum; 6X18; -. DR PDBsum; 7D68; -. DR PDBsum; 7DUQ; -. DR PDBsum; 7KI0; -. DR PDBsum; 7KI1; -. DR PDBsum; 7XM8; -. DR PDBsum; 8ANJ; -. DR PDBsum; 8ANK; -. DR PDBsum; 8JRV; -. DR PDBsum; 9E2A; -. DR PDBsum; 9IVG; -. DR AlphaFoldDB; P01275; -. DR EMDB; EMD-0917; -. DR EMDB; EMD-0918; -. DR EMDB; EMD-21147; -. DR EMDB; EMD-21992; -. DR EMDB; EMD-30590; -. DR EMDB; EMD-30866; -. DR EMDB; EMD-33290; -. DR EMDB; EMD-36607; -. DR EMDB; EMD-47447; -. DR EMDB; EMD-60927; -. DR EMDB; EMD-8653; -. DR SMR; P01275; -. DR BioGRID; 108911; 271. DR DIP; DIP-46470N; -. DR FunCoup; P01275; 643. DR IntAct; P01275; 32. DR MINT; P01275; -. DR NDEx; IQUERY-CP-GCG; 11 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000387662; -. DR BindingDB; P01275; -. DR ChEMBL; CHEMBL5736; -. DR DrugBank; DB15194; Cotadutide. DR iPTMnet; P01275; -. DR PhosphoSitePlus; P01275; -. DR BioMuta; GCG; -. DR DMDM; 125987831; -. DR jPOST; P01275; -. DR MassIVE; P01275; -. DR PaxDb; 9606-ENSP00000387662; -. DR PeptideAtlas; P01275; -. DR ProteomicsDB; 51367; -. DR ABCD; P01275; 12 sequenced antibodies. DR Antibodypedia; 3506; 1906 antibodies from 48 providers. DR DNASU; 2641; -. DR Ensembl; ENST00000375497.3; ENSP00000364647.3; ENSG00000115263.15. DR Ensembl; ENST00000418842.7; ENSP00000387662.2; ENSG00000115263.15. DR GeneID; 2641; -. DR KEGG; hsa:2641; -. DR MANE-Select; ENST00000418842.7; ENSP00000387662.2; NM_002054.5; NP_002045.1. DR UCSC; uc002ucc.5; human. DR AGR; HGNC:4191; -. DR ClinPGx; PA28606; -. DR CTD; 2641; -. DR DisGeNET; 2641; -. DR GeneCards; GCG; -. DR HGNC; HGNC:4191; GCG. DR HPA; ENSG00000115263; Tissue enriched (pancreas). DR MIM; 138030; gene. DR OpenTargets; ENSG00000115263; -. DR VEuPathDB; HostDB:ENSG00000115263; -. DR eggNOG; ENOG502RYPR; Eukaryota. DR GeneTree; ENSGT00390000005372; -. DR HOGENOM; CLU_090687_0_0_1; -. DR InParanoid; P01275; -. DR OMA; MNTKRNX; -. DR OrthoDB; 9904258at2759; -. DR PAN-GO; P01275; 6 GO annotations based on evolutionary models. DR PhylomeDB; P01275; -. DR PathwayCommons; P01275; -. DR Reactome; R-HSA-163359; Glucagon signaling in metabolic regulation. DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1). DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-420092; Glucagon-type ligand receptors. DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin. DR SignaLink; P01275; -. DR SIGNOR; P01275; -. DR Agora; ENSG00000115263; -. DR BioGRID-ORCS; 2641; 7 hits in 1144 CRISPR screens. DR ChiTaRS; GCG; human. DR EvolutionaryTrace; P01275; -. DR GeneWiki; Glucagon; -. DR GenomeRNAi; 2641; -. DR Pharos; P01275; Tchem. DR PRO; PR:P01275; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P01275; protein. DR Bgee; ENSG00000115263; Expressed in type B pancreatic cell and 115 other cell types or tissues. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0031769; F:glucagon receptor binding; IBA:GO_Central. DR GO; GO:0005179; F:hormone activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0048018; F:receptor ligand activity; TAS:Reactome. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEA:Ensembl. DR GO; GO:0007631; P:feeding behavior; TAS:ProtInc. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:GO_Central. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0090280; P:positive regulation of calcium ion import; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0032024; P:positive regulation of insulin secretion; TAS:Reactome. DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IBA:GO_Central. DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB. DR GO; GO:0014823; P:response to activity; ISS:UniProtKB. DR Gene3D; 6.10.250.590; -; 3. DR InterPro; IPR015550; Glucagon. DR InterPro; IPR000532; Glucagon_GIP_secretin_VIP. DR PANTHER; PTHR11418; GLUCAGON; 1. DR PANTHER; PTHR11418:SF0; PRO-GLUCAGON; 1. DR Pfam; PF00123; Hormone_2; 3. DR PRINTS; PR00275; GLUCAGON. DR SMART; SM00070; GLUCA; 3. DR PROSITE; PS00260; GLUCAGON; 4. PE 1: Evidence at protein level; KW 3D-structure; Amidation; Cleavage on pair of basic residues; KW Direct protein sequencing; Hormone; Pharmaceutical; Phosphoprotein; KW Proteomics identification; Reference proteome; Secreted; Signal. FT SIGNAL 1..20 FT PEPTIDE 21..89 FT /note="Glicentin" FT /evidence="ECO:0000250|UniProtKB:P01274" FT /id="PRO_0000011253" FT PEPTIDE 21..50 FT /note="Glicentin-related polypeptide" FT /evidence="ECO:0000250|UniProtKB:P09686" FT /id="PRO_0000011254" FT PEPTIDE 53..89 FT /note="Oxyntomodulin" FT /evidence="ECO:0000250|UniProtKB:P06883" FT /id="PRO_0000011255" FT PEPTIDE 53..81 FT /note="Glucagon" FT /evidence="ECO:0000269|PubMed:11946536" FT /id="PRO_0000011256" FT PROPEP 84..89 FT /evidence="ECO:0000269|PubMed:2753890" FT /id="PRO_0000011257" FT PEPTIDE 92..128 FT /note="Glucagon-like peptide 1" FT /evidence="ECO:0000269|PubMed:2753890" FT /id="PRO_0000011258" FT PEPTIDE 98..128 FT /note="Glucagon-like peptide 1(7-37)" FT /evidence="ECO:0000269|PubMed:2753890" FT /id="PRO_0000011259" FT PEPTIDE 98..127 FT /note="Glucagon-like peptide 1(7-36)" FT /evidence="ECO:0000269|PubMed:2753890" FT /id="PRO_0000011260" FT PROPEP 131..145 FT /evidence="ECO:0000250|UniProtKB:P15438" FT /id="PRO_0000011261" FT PEPTIDE 146..178 FT /note="Glucagon-like peptide 2" FT /evidence="ECO:0000250|UniProtKB:P15438" FT /id="PRO_0000011262" FT REGION 26..59 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 52..53 FT /note="Cleavage; by PCSK2" FT SITE 83..84 FT /note="Cleavage; by PCSK1 and PCSK2" FT SITE 91..92 FT /note="Cleavage; by PCSK1" FT SITE 97..98 FT /note="Cleavage; by PCSK1" FT SITE 130..131 FT /note="Cleavage; by PCSK1" FT SITE 145..146 FT /note="Cleavage; by PCSK1" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P55095" FT MOD_RES 105 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P55095" FT MOD_RES 108 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P55095" FT MOD_RES 127 FT /note="Arginine amide" FT /evidence="ECO:0000269|PubMed:2753890" FT MOD_RES 150 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P55095" FT MOD_RES 152 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P55095" FT VARIANT 115 FT /note="A -> V (in dbSNP:rs5650)" FT /id="VAR_014596" FT CONFLICT 82 FT /note="K -> N (in Ref. 2; CAA27627)" FT /evidence="ECO:0000305" FT HELIX 57..79 FT /evidence="ECO:0007829|PDB:6PHI" FT HELIX 104..124 FT /evidence="ECO:0007829|PDB:4ZGM" FT HELIX 148..173 FT /evidence="ECO:0007829|PDB:7D68" FT HELIX 174..177 FT /evidence="ECO:0007829|PDB:2L64" SQ SEQUENCE 180 AA; 20909 MW; 7A99EEC629B2862C CRC64; MKSIYFVAGL FVMLVQGSWQ RSLQDTEEKS RSFSASQADP LSDPDQMNED KRHSQGTFTS DYSKYLDSRR AQDFVQWLMN TKRNRNNIAK RHDEFERHAE GTFTSDVSSY LEGQAAKEFI AWLVKGRGRR DFPEEVAIVE ELGRRHADGS FSDEMNTILD NLAARDFINW LIQTKITDRK //