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 27-MAR-2024, entry version 231.
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 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 [21]
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 [22]
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).
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. {ECO:0000305|PubMed:10605628,
CC ECO:0000305|PubMed:12626323}.
CC -!- FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose-
CC dependent insulin release. Also stimulates insulin release in response
CC to IL6 (PubMed:22037645). Plays important roles on gastric motility and
CC the suppression of plasma glucagon levels. May be involved in the
CC suppression of satiety and stimulation of glucose disposal in
CC peripheral tissues, independent of the actions of insulin. Has growth-
CC promoting activities on intestinal epithelium. May also regulate the
CC hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH,
CC oxytocin, and vasopressin secretion. Increases islet mass through
CC stimulation of islet neogenesis and pancreatic beta cell proliferation.
CC Inhibits beta cell apoptosis (Probable). {ECO:0000269|PubMed:22037645,
CC ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744,
CC ECO:0000305|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:0000305|PubMed:10322410,
CC ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744,
CC ECO:0000305|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:0000305|PubMed:10605628,
CC ECO:0000305|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:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744}.
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Glucagon-like peptide 1]: Secreted
CC {ECO:0000269|PubMed:22037645}.
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 -!- WEB RESOURCE: Name=Glucagon at Eli Lilly; Note=Clinical information on
CC Eli Lilly glucagon products;
CC URL="https://www.lillydiabetes.com/assets/pdf/pp-ld-us-1198-types_of_treatments.pdf";
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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_002054.4.
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 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 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-36607; -.
DR EMDB; EMD-8653; -.
DR SMR; P01275; -.
DR BioGRID; 108911; 269.
DR DIP; DIP-46470N; -.
DR IntAct; P01275; 7.
DR MINT; P01275; -.
DR STRING; 9606.ENSP00000387662; -.
DR BindingDB; P01275; -.
DR ChEMBL; CHEMBL5736; -.
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; 2088 antibodies from 46 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 DisGeNET; 2641; -.
DR GeneCards; GCG; -.
DR HGNC; HGNC:4191; GCG.
DR HPA; ENSG00000115263; Tissue enriched (pancreas).
DR MIM; 138030; gene.
DR neXtProt; NX_P01275; -.
DR OpenTargets; ENSG00000115263; -.
DR PharmGKB; PA28606; -.
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; 5318261at2759; -.
DR PhylomeDB; P01275; -.
DR TreeFam; TF332333; -.
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 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 Genevisible; P01275; HS.
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: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:0006094; P:gluconeogenesis; IEA:Ensembl.
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:1900118; P:negative regulation of execution phase of apoptosis; IEA:Ensembl.
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:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IEA:Ensembl.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IBA:GO_Central.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0010737; P:protein kinase A signaling; 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 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 COMPBIAS 26..43
FT /note="Polar residues"
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
//
