GenomeNet

Database: UniProt
Entry: P01275
LinkDB: P01275
Original site: P01275 
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   02-JUN-2021, entry version 218.
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;
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;
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   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   SMR; P01275; -.
DR   BioGRID; 108911; 265.
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; P01275; -.
DR   PeptideAtlas; P01275; -.
DR   PRIDE; P01275; -.
DR   ProteomicsDB; 51367; -.
DR   ABCD; P01275; 12 sequenced antibodies.
DR   Antibodypedia; 3506; 1885 antibodies.
DR   DNASU; 2641; -.
DR   Ensembl; ENST00000375497; ENSP00000364647; ENSG00000115263.
DR   Ensembl; ENST00000418842; ENSP00000387662; ENSG00000115263.
DR   GeneID; 2641; -.
DR   KEGG; hsa:2641; -.
DR   UCSC; uc002ucc.5; human.
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   neXtProt; NX_P01275; -.
DR   OpenTargets; ENSG00000115263; -.
DR   PharmGKB; PA28606; -.
DR   VEuPathDB; HostDB:ENSG00000115263.14; -.
DR   eggNOG; ENOG502RYPR; Eukaryota.
DR   GeneTree; ENSGT00390000005372; -.
DR   HOGENOM; CLU_090687_0_0_1; -.
DR   InParanoid; P01275; -.
DR   OMA; WQRSLQN; -.
DR   OrthoDB; 1349644at2759; -.
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   Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR   SIGNOR; P01275; -.
DR   BioGRID-ORCS; 2641; 6 hits in 985 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 islet of Langerhans and 94 other 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: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; TAS:Reactome.
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:1900118; P:negative regulation of execution phase of apoptosis; IEA:Ensembl.
DR   GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
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:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR   GO; GO:0045860; P:positive regulation of protein kinase activity; 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   InterPro; IPR015550; Glucagon.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   PANTHER; PTHR11418; PTHR11418; 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
//
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