GLUC_BOVIN
ID GLUC_BOVIN Reviewed; 180 AA.
AC P01272; Q3T0X0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 158.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6577439; DOI=10.1073/pnas.80.18.5485;
RA Lopez L.C., Frazier M.L., Su C.-J., Kumar A., Saunders G.F.;
RT "Mammalian pancreatic preproglucagon contains three glucagon-related
RT peptides.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:5485-5489(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 53-81.
RX PubMed=5102927; DOI=10.1016/s0021-9258(18)62256-2;
RA Bromer W.W., Boucher M.E., Koffenberger J.E. Jr.;
RT "Amino acid sequence of bovine glucagon.";
RL J. Biol. Chem. 246:2822-2827(1971).
RN [4]
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 [5]
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 [6]
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 [7]
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 [8]
RP STRUCTURE BY NMR OF 53-81.
RX PubMed=6631957; DOI=10.1016/s0022-2836(83)80143-0;
RA Braun W., Wider G., Lee K.H., Wuethrich K.;
RT "Conformation of glucagon in a lipid-water interphase by 1H nuclear
RT magnetic resonance.";
RL J. Mol. Biol. 169:921-948(1983).
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.
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 -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR EMBL; K00107; AAA30538.1; -; mRNA.
DR EMBL; BC102221; AAI02222.1; -; mRNA.
DR PIR; A93970; GCBO.
DR RefSeq; NP_776341.1; NM_173916.3.
DR PDB; 1KX6; NMR; -; A=53-81.
DR PDBsum; 1KX6; -.
DR AlphaFoldDB; P01272; -.
DR BMRB; P01272; -.
DR SMR; P01272; -.
DR PaxDb; P01272; -.
DR Ensembl; ENSBTAT00000000972; ENSBTAP00000000972; ENSBTAG00000000730.
DR GeneID; 280802; -.
DR KEGG; bta:280802; -.
DR CTD; 2641; -.
DR VEuPathDB; HostDB:ENSBTAG00000000730; -.
DR VGNC; VGNC:29284; GCG.
DR eggNOG; ENOG502RYPR; Eukaryota.
DR GeneTree; ENSGT00390000005372; -.
DR HOGENOM; CLU_090687_0_0_1; -.
DR InParanoid; P01272; -.
DR OMA; KRNGQQG; -.
DR OrthoDB; 1349644at2759; -.
DR Reactome; R-BTA-163359; Glucagon signaling in metabolic regulation.
DR Reactome; R-BTA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-BTA-416476; G alpha (q) signalling events.
DR Reactome; R-BTA-420092; Glucagon-type ligand receptors.
DR Reactome; R-BTA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR EvolutionaryTrace; P01272; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000000730; Expressed in ascending colon and 33 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; IMP:AgBase.
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:0019249; P:lactate biosynthetic process; IMP:AgBase.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:AgBase.
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; IMP:AgBase.
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 PEPTIDE 21..89
FT /note="Glicentin"
FT /evidence="ECO:0000250|UniProtKB:P01274"
FT /id="PRO_0000011223"
FT PEPTIDE 21..50
FT /note="Glicentin-related polypeptide"
FT /evidence="ECO:0000250|UniProtKB:P09686"
FT /id="PRO_0000011224"
FT PEPTIDE 53..89
FT /note="Oxyntomodulin"
FT /evidence="ECO:0000250|UniProtKB:P06883"
FT /id="PRO_0000011225"
FT PEPTIDE 53..81
FT /note="Glucagon"
FT /evidence="ECO:0000269|PubMed:5102927"
FT /id="PRO_0000011226"
FT PROPEP 84..89
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011227"
FT PEPTIDE 92..128
FT /note="Glucagon-like peptide 1"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011228"
FT PEPTIDE 98..128
FT /note="Glucagon-like peptide 1(7-37)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011229"
FT PEPTIDE 98..127
FT /note="Glucagon-like peptide 1(7-36)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011230"
FT PROPEP 131..145
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011231"
FT PEPTIDE 146..178
FT /note="Glucagon-like peptide 2"
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011232"
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 TURN 60..64
FT /evidence="ECO:0007829|PDB:1KX6"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:1KX6"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:1KX6"
SQ SEQUENCE 180 AA; 20944 MW; 8D9B4FF05B9F15FF CRC64;
MKSLYFVAGL FVMLVQGSWQ RSLQNTEEKS SSFPAPQTDP LGDPDQINED KRHSQGTFTS
DYSKYLDSRR AQDFVQWLMN TKRNKNNIAK RHDEFERHAE GTFTSDVSSY LEGQAAKEFI
AWLVKGRGRR DFPEEVNIVE ELRRRHADGS FSDEMNTVLD SLATRDFINW LLQTKITDRK
