GLUC_RAT
ID GLUC_RAT Reviewed; 180 AA.
AC P06883;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 155.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6094539; DOI=10.1016/s0021-9258(18)89859-3;
RA Heinrich G., Gros P., Habener J.F.;
RT "Glucagon gene sequence. Four of six exons encode separate functional
RT domains of rat pre-proglucagon.";
RL J. Biol. Chem. 259:14082-14087(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6548696; DOI=10.1210/endo-115-6-2176;
RA Heinrich G., Gros P., Lund P.K., Bentley R.C., Habener J.F.;
RT "Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino
RT acid sequences of the rat pancreatic complementary deoxyribonucleic acid.";
RL Endocrinology 115:2176-2181(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3528148; DOI=10.1016/s0021-9258(18)67324-7;
RA Mojsov S., Heinrich G., Wilson I.B., Ravazzola M., Orci L., Habener J.F.;
RT "Preproglucagon gene expression in pancreas and intestine diversifies at
RT the level of post-translational processing.";
RL J. Biol. Chem. 261:11880-11889(1986).
RN [4]
RP PROTEIN SEQUENCE OF 53-89.
RX PubMed=7937770; DOI=10.1073/pnas.91.20.9362;
RA Collie N.L., Walsh J.H., Wong H.C., Shively J.E., Davis M.T., Lee T.D.,
RA Reeve J.R. Jr.;
RT "Purification and sequence of rat oxyntomodulin.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9362-9366(1994).
RN [5]
RP FUNCTION OF OXYNTOMODULIN.
RX PubMed=11564680; DOI=10.1210/endo.142.10.8430;
RA Dakin C.L., Gunn I., Small C.J., Edwards C.M., Hay D.L., Smith D.M.,
RA Ghatei M.A., Bloom S.R.;
RT "Oxyntomodulin inhibits food intake in the rat.";
RL Endocrinology 142:4244-4250(2001).
RN [6]
RP PROTEOLYTIC PROCESSING BY PCSK1 AND PCSK2.
RX PubMed=8721980; DOI=10.1210/mend.10.4.8721980;
RA Dhanvantari S., Seidah N.G., Brubaker P.L.;
RT "Role of prohormone convertases in the tissue-specific processing of
RT proglucagon.";
RL Mol. Endocrinol. 10:342-355(1996).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=1692320; DOI=10.1016/s0021-9258(19)39030-1;
RA Mojsov S., Kopczynski M.G., Habener J.F.;
RT "Both amidated and nonamidated forms of glucagon-like peptide I are
RT synthesized in the rat intestine and the pancreas.";
RL J. Biol. Chem. 265:8001-8008(1990).
RN [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (Probable). Also stimulates insulin release
CC in response to IL6 (By similarity). Plays important roles on gastric
CC motility and the suppression of plasma glucagon levels. May be involved
CC in the 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:0000250|UniProtKB:P01275,
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: [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 -!- FUNCTION: Oxyntomodulin significantly reduces food intake.
CC {ECO:0000269|PubMed:11564680}.
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.
CC {ECO:0000269|PubMed:1692320}.
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.
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:8721980}.
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; K02813; AAA41235.1; -; Genomic_DNA.
DR EMBL; K02809; AAA41235.1; JOINED; Genomic_DNA.
DR EMBL; K02810; AAA41235.1; JOINED; Genomic_DNA.
DR EMBL; K02811; AAA41235.1; JOINED; Genomic_DNA.
DR EMBL; K02812; AAA41235.1; JOINED; Genomic_DNA.
DR PIR; A22655; GCRT.
DR AlphaFoldDB; P06883; -.
DR BMRB; P06883; -.
DR STRING; 10116.ENSRNOP00000007356; -.
DR iPTMnet; P06883; -.
DR PhosphoSitePlus; P06883; -.
DR PaxDb; P06883; -.
DR PRIDE; P06883; -.
DR UCSC; RGD:2668; rat.
DR RGD; 2668; Gcg.
DR eggNOG; ENOG502RYPR; Eukaryota.
DR InParanoid; P06883; -.
DR PhylomeDB; P06883; -.
DR Reactome; R-RNO-163359; Glucagon signaling in metabolic regulation.
DR Reactome; R-RNO-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-RNO-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-420092; Glucagon-type ligand receptors.
DR Reactome; R-RNO-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR PRO; PR:P06883; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0031769; F:glucagon receptor binding; IDA:RGD.
DR GO; GO:0005179; F:hormone activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0032099; P:negative regulation of appetite; IMP:RGD.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; ISO:RGD.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0090280; P:positive regulation of calcium ion import; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:RGD.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; ISO:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0010737; P:protein kinase A signaling; ISO:RGD.
DR GO; GO:0019538; P:protein metabolic process; TAS:RGD.
DR GO; GO:0006109; P:regulation of carbohydrate metabolic process; TAS:RGD.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; TAS:RGD.
DR GO; GO:0014823; P:response to activity; ISS:UniProtKB.
DR GO; GO:1903576; P:response to L-arginine; IEP:RGD.
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 Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Hormone; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT PEPTIDE 21..89
FT /note="Glicentin"
FT /evidence="ECO:0000250|UniProtKB:P01274"
FT /id="PRO_0000011303"
FT PEPTIDE 21..50
FT /note="Glicentin-related polypeptide"
FT /evidence="ECO:0000250|UniProtKB:P09686"
FT /id="PRO_0000011304"
FT PEPTIDE 53..89
FT /note="Oxyntomodulin"
FT /evidence="ECO:0000269|PubMed:7937770"
FT /id="PRO_0000011305"
FT PEPTIDE 53..81
FT /note="Glucagon"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011306"
FT PROPEP 84..89
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011307"
FT PEPTIDE 92..128
FT /note="Glucagon-like peptide 1"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011308"
FT PEPTIDE 98..128
FT /note="Glucagon-like peptide 1(7-37)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011309"
FT PEPTIDE 98..127
FT /note="Glucagon-like peptide 1(7-36)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011310"
FT PROPEP 131..145
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011311"
FT PEPTIDE 146..178
FT /note="Glucagon-like peptide 2"
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011312"
FT REGION 23..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..42
FT /note="Polar residues"
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:0007744|PubMed:22673903"
SQ SEQUENCE 180 AA; 20846 MW; 76931409D03C7978 CRC64;
MKTVYIVAGL FVMLVQGSWQ HAPQDTEENA RSFPASQTEP LEDPDQINED KRHSQGTFTS
DYSKYLDSRR AQDFVQWLMN TKRNRNNIAK RHDEFERHAE GTFTSDVSSY LEGQAAKEFI
AWLVKGRGRR DFPEEVAIAE ELGRRHADGS FSDEMNTILD NLATRDFINW LIQTKITDKK
