GLUC_PIG
ID GLUC_PIG Reviewed; 180 AA.
AC P01274; Q864V8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2004, sequence version 4.
DT 03-AUG-2022, entry version 148.
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;
DE Short=GLP-1;
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas, and Small intestine;
RA Siggers R.H., Goldade B.G., Laarveld B., Van Kessel A.G.;
RT "Cloning of porcine proglucagon.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 21-89.
RX PubMed=6894800; DOI=10.1016/0167-0115(81)90007-0;
RA Thim L., Moody A.J.;
RT "The primary structure of porcine glicentin (proglucagon).";
RL Regul. Pept. 2:139-150(1981).
RN [3]
RP PROTEIN SEQUENCE OF 21-89.
RX PubMed=7045833; DOI=10.1016/0196-9781(81)90007-3;
RA Thim L., Moody A.J.;
RT "The amino acid sequence of porcine glicentin.";
RL Peptides 2 Suppl. 2:37-39(1981).
RN [4]
RP PROTEIN SEQUENCE OF 53-81.
RA Bromer W.W., Sinn L.G., Behrens O.K.;
RT "The amino acid sequence of glucagon. V. Location of amide groups, acid
RT degradation studies and summary of sequential evidence.";
RL J. Am. Chem. Soc. 79:2807-2810(1957).
RN [5]
RP PROTEIN SEQUENCE OF 98-127.
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 [6]
RP PROTEIN SEQUENCE OF 131-178.
RX PubMed=3379036; DOI=10.1016/s0021-9258(18)68350-4;
RA Buhl T., Thim L., Kofod H., Orskov C., Harling H., Holst J.J.;
RT "Naturally occurring products of proglucagon 111-160 in the porcine and
RT human small intestine.";
RL J. Biol. Chem. 263:8621-8624(1988).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=3530719; DOI=10.1210/endo-119-4-1467;
RA Orskov C., Holst J.J., Knuhtsen S., Baldissera F.G., Poulsen S.S.,
RA Nielsen O.V.;
RT "Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon
RT gene, are secreted separately from pig small intestine but not pancreas.";
RL Endocrinology 119:1467-1475(1986).
RN [8]
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 [9]
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 [10]
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 [11]
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 [12]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 53-81.
RX PubMed=171582; DOI=10.1038/257751a0;
RA Sasaki K., Dockerill S., Adamiak D.A., Tickle I.J., Blundell T.L.;
RT "X-ray analysis of glucagon and its relationship to receptor binding.";
RL Nature 257:751-757(1975).
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:0000250|UniProtKB:P55095}.
CC -!- FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose-
CC dependent insulin release. Also stimulates insulin release in response
CC to IL6. Plays important roles on gastric motility and the suppression
CC of plasma glucagon levels. May be involved in the suppression of
CC satiety and stimulation of glucose disposal in peripheral tissues,
CC independent of the actions of insulin. Has growth-promoting activities
CC on intestinal epithelium. May also regulate the hypothalamic pituitary
CC axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin
CC secretion. Increases islet mass through stimulation of islet neogenesis
CC and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.
CC {ECO:0000250|UniProtKB:P55095}.
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:0000250|UniProtKB:P55095}.
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:0000250|UniProtKB:P55095}.
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:0000250|UniProtKB:P55095}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01275}.
CC -!- SUBCELLULAR LOCATION: [Glucagon-like peptide 1]: Secreted
CC {ECO:0000250|UniProtKB:P01275}.
CC -!- TISSUE SPECIFICITY: Glucagon is secreted in the A cells of the islets
CC of Langerhans. GLP-1, GLP-2, oxyntomodulin and glicentin are secreted
CC from enteroendocrine cells throughout the gastrointestinal tract. GLP-1
CC and GLP-2 are also secreted in selected neurons in the brain.
CC {ECO:0000269|PubMed:3530719}.
CC -!- INDUCTION: Glucagon release is stimulated by hypoglycemia and inhibited
CC by hyperglycemia, insulin, and somatostatin. GLP-1 and GLP-2 are
CC induced in response to nutrient ingestion (By similarity).
CC {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: GLP-2 does not have cleavage on a pair of basic residues
CC at C-terminus as in other mammals.
CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR EMBL; AY242124; AAO88211.1; -; mRNA.
DR RefSeq; NP_999489.1; NM_214324.1.
DR RefSeq; XP_005671939.1; XM_005671882.2.
DR PDB; 1GCN; X-ray; 3.00 A; A=53-81.
DR PDB; 7LLY; EM; 3.30 A; P=53-89.
DR PDBsum; 1GCN; -.
DR PDBsum; 7LLY; -.
DR AlphaFoldDB; P01274; -.
DR BMRB; P01274; -.
DR SMR; P01274; -.
DR STRING; 9823.ENSSSCP00000016844; -.
DR PaxDb; P01274; -.
DR PeptideAtlas; P01274; -.
DR PRIDE; P01274; -.
DR Ensembl; ENSSSCT00000017307; ENSSSCP00000016844; ENSSSCG00000015895.
DR Ensembl; ENSSSCT00005070154; ENSSSCP00005043696; ENSSSCG00005043651.
DR Ensembl; ENSSSCT00015017002; ENSSSCP00015006642; ENSSSCG00015012899.
DR Ensembl; ENSSSCT00025079210; ENSSSCP00025034389; ENSSSCG00025057867.
DR Ensembl; ENSSSCT00030026681; ENSSSCP00030011918; ENSSSCG00030019310.
DR Ensembl; ENSSSCT00035026829; ENSSSCP00035010233; ENSSSCG00035020634.
DR Ensembl; ENSSSCT00040101992; ENSSSCP00040046023; ENSSSCG00040073844.
DR Ensembl; ENSSSCT00045005515; ENSSSCP00045003690; ENSSSCG00045003381.
DR Ensembl; ENSSSCT00050030944; ENSSSCP00050012912; ENSSSCG00050022916.
DR Ensembl; ENSSSCT00055041841; ENSSSCP00055033310; ENSSSCG00055021297.
DR Ensembl; ENSSSCT00060013577; ENSSSCP00060005199; ENSSSCG00060010447.
DR Ensembl; ENSSSCT00065107745; ENSSSCP00065048044; ENSSSCG00065077860.
DR Ensembl; ENSSSCT00070050959; ENSSSCP00070043082; ENSSSCG00070025495.
DR GeneID; 397595; -.
DR KEGG; ssc:397595; -.
DR CTD; 2641; -.
DR VGNC; VGNC:96317; GCG.
DR eggNOG; ENOG502RYPR; Eukaryota.
DR GeneTree; ENSGT00390000005372; -.
DR InParanoid; P01274; -.
DR OMA; KRNGQQG; -.
DR OrthoDB; 1349644at2759; -.
DR EvolutionaryTrace; P01274; -.
DR Proteomes; UP000008227; Chromosome 15.
DR Proteomes; UP000314985; Chromosome 15.
DR Bgee; ENSSSCG00000015895; Expressed in ileum and 8 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
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; IEA:Ensembl.
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: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:1903348; P:positive regulation of bicellular tight junction assembly; IDA:AgBase.
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; IDA:AgBase.
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; Phosphoprotein; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:6894800,
FT ECO:0000269|PubMed:7045833"
FT PEPTIDE 21..89
FT /note="Glicentin"
FT /evidence="ECO:0000269|PubMed:6894800,
FT ECO:0000269|PubMed:7045833"
FT /id="PRO_0000011293"
FT PEPTIDE 21..50
FT /note="Glicentin-related polypeptide"
FT /evidence="ECO:0000250|UniProtKB:P09686"
FT /id="PRO_0000011294"
FT PEPTIDE 53..89
FT /note="Oxyntomodulin"
FT /evidence="ECO:0000250|UniProtKB:P06883"
FT /id="PRO_0000011295"
FT PEPTIDE 53..81
FT /note="Glucagon"
FT /evidence="ECO:0000269|Ref.4"
FT /id="PRO_0000011296"
FT PROPEP 84..89
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011297"
FT PEPTIDE 92..128
FT /note="Glucagon-like peptide 1"
FT /evidence="ECO:0000269|PubMed:2753890"
FT /id="PRO_0000011298"
FT PEPTIDE 98..128
FT /note="Glucagon-like peptide 1(7-37)"
FT /evidence="ECO:0000269|PubMed:2753890"
FT /id="PRO_0000011299"
FT PEPTIDE 98..127
FT /note="Glucagon-like peptide 1(7-36)"
FT /evidence="ECO:0000269|PubMed:2753890"
FT /id="PRO_0000011300"
FT PROPEP 131..145
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011301"
FT PEPTIDE 146..180
FT /note="Glucagon-like peptide 2"
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011302"
FT REGION 25..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 52..53
FT /note="Cleavage; by PCSK2"
FT /evidence="ECO:0000250"
FT SITE 83..84
FT /note="Cleavage; by PCSK1 and PCSK2"
FT /evidence="ECO:0000250"
FT SITE 91..92
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 97..98
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 130..131
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 145..146
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
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:0000250"
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 CONFLICT 143
FT /note="R -> G (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:1GCN"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:1GCN"
FT HELIX 66..75
FT /evidence="ECO:0007829|PDB:1GCN"
SQ SEQUENCE 180 AA; 21029 MW; 362997AB72197EE6 CRC64;
MKTIYFVAGL FVMLVQGSWQ RSLQNTEEKS RSFPAPQTDP LDDPDQMTED KRHSQGTFTS
DYSKYLDSRR AQDFVQWLMN TKRNKNNIAK RHDEFERHAE GTFTSDVSSY LEGQAAKEFI
AWLVKGRGRR DFPEEVTIVE ELRRRHADGS FSDEMNTVLD NLATRDFINW LLHTKITDSL
