ID GLUC_CANLF Reviewed; 180 AA.
AC P29794; Q95LG0;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 27-MAR-2024, entry version 122.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas, and Stomach;
RX PubMed=11916259; DOI=10.3109/10425170109024999;
RA Irwin D.M.;
RT "cDNA cloning of proglucagon from the stomach and pancreas of the dog.";
RL DNA Seq. 12:253-260(2001).
RN [2]
RP PROTEIN SEQUENCE OF 21-89.
RC TISSUE=Ileum;
RX PubMed=3238052; DOI=10.1016/0167-0115(88)90230-3;
RA Shinomura Y., Eng J., Yalow R.S.;
RT "Immunoreactive glucagons purified from dog pancreas, stomach and ileum.";
RL Regul. Pept. 23:299-308(1988).
RN [3]
RP PROTEOLYTIC PROCESSING BY PCSK1 AND PCSK2.
RX PubMed=10499540; DOI=10.1210/endo.140.10.7068;
RA Damholt A.B., Buchan A.M., Holst J.J., Kofod H.;
RT "Proglucagon processing profile in canine L cells expressing endogenous
RT prohormone convertase 1/3 and prohormone convertase 2.";
RL Endocrinology 140:4800-4808(1999).
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).
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 -!- 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; AF308439; AAL09425.1; -; mRNA.
DR PIR; A60318; GCDG69.
DR RefSeq; NP_001003044.1; NM_001003044.1.
DR AlphaFoldDB; P29794; -.
DR SMR; P29794; -.
DR STRING; 9615.ENSCAFP00000015307; -.
DR PaxDb; 9612-ENSCAFP00000015307; -.
DR GeneID; 403571; -.
DR KEGG; cfa:403571; -.
DR CTD; 2641; -.
DR eggNOG; ENOG502RYPR; Eukaryota.
DR InParanoid; P29794; -.
DR OrthoDB; 5318261at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR Proteomes; UP000694429; Unplaced.
DR Proteomes; UP000694542; Unplaced.
DR Proteomes; UP000805418; Unplaced.
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:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA: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:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IBA:GO_Central.
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 Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Hormone; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:3238052"
FT PEPTIDE 21..89
FT /note="Glicentin"
FT /evidence="ECO:0000269|PubMed:3238052"
FT /id="PRO_0000011233"
FT PEPTIDE 21..50
FT /note="Glicentin-related polypeptide"
FT /evidence="ECO:0000250|UniProtKB:P09686"
FT /id="PRO_0000011234"
FT PEPTIDE 53..89
FT /note="Oxyntomodulin"
FT /evidence="ECO:0000250|UniProtKB:P06883"
FT /id="PRO_0000011235"
FT PEPTIDE 53..81
FT /note="Glucagon"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011236"
FT PROPEP 84..89
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011237"
FT PEPTIDE 92..128
FT /note="Glucagon-like peptide 1"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011238"
FT PEPTIDE 98..128
FT /note="Glucagon-like peptide 1(7-37)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011239"
FT PEPTIDE 98..127
FT /note="Glucagon-like peptide 1(7-36)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011240"
FT PROPEP 131..145
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011241"
FT PEPTIDE 146..178
FT /note="Glucagon-like peptide 2"
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011242"
FT REGION 26..56
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: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"
SQ SEQUENCE 180 AA; 21115 MW; 80F66941AFC324FD CRC64;
MKSIYFVAGL FVMLVQGSWQ RSLQDTEEKS RSFSAPQTEP LNDLDQMNED KRHSQGTFTS
DYSKYLDSRR AQDFVQWLMN TKRNKNNIAK RHDEFERHAE GTFTSDVSSY LEGQAAKEFI
AWLVKGRGRR DFPEEVAIVE EFRRRHADGS FSDEMNTVLD TLATRDFINW LLQTKITDRK
//
