GLUC_CHICK
ID GLUC_CHICK Reviewed; 206 AA.
AC P68259; P01277; Q91410;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Pro-glucagon;
DE Contains:
DE RecName: Full=Glicentin-related polypeptide;
DE Short=GRPP;
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PANCREATIC).
RC TISSUE=Pancreas;
RX PubMed=2338135; DOI=10.1016/0014-5793(90)80779-i;
RA Hasegawa S., Terazono K., Nata K., Takada T., Yamamoto H., Okamoto H.;
RT "Nucleotide sequence determination of chicken glucagon precursor cDNA.
RT Chicken preproglucagon does not contain glucagon-like peptide II.";
RL FEBS Lett. 264:117-120(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM INTESTINAL).
RC TISSUE=Intestinal mucosa;
RX PubMed=7776976; DOI=10.1210/mend.9.3.7776976;
RA Irwin D.M., Wong J.;
RT "Trout and chicken proglucagon: alternative splicing generates mRNA
RT transcripts encoding glucagon-like peptide 2.";
RL Mol. Endocrinol. 9:267-277(1995).
RN [3]
RP PROTEIN SEQUENCE OF 55-83.
RX PubMed=1194290; DOI=10.1016/s0021-9258(19)40654-6;
RA Pollock H.G., Kimmel J.R.;
RT "Chicken glucagon. Isolation and amino acid sequence studies.";
RL J. Biol. Chem. 250:9377-9380(1975).
RN [4]
RP PROTEIN SEQUENCE OF 55-83.
RX PubMed=2828209; DOI=10.1055/s-2007-1011878;
RA Huang J., Eng J., Yalow R.S.;
RT "Chicken glucagon: sequence and potency in receptor assay.";
RL Horm. Metab. Res. 19:542-544(1987).
CC -!- FUNCTION: [Glucagon]: Plays a key role in glucose metabolism and
CC homeostasis. Regulates blood glucose by increasing gluconeogenesis and
CC decreasing glycolysis. {ECO:0000250|UniProtKB:P01275}.
CC -!- FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose-
CC dependent insulin release. Plays important roles on gastric motility
CC and 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 {ECO:0000250|UniProtKB:P01275}.
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:P01275}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Intestinal;
CC IsoId=P68259-1, P01277-1;
CC Sequence=Displayed;
CC Name=Pancreatic;
CC IsoId=P68259-2, P01277-2;
CC Sequence=VSP_001753, VSP_001754;
CC -!- INDUCTION: Produced in the A cells of the islets of Langerhans in
CC response to a drop in blood sugar concentration.
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 and GLP-2. GLP-1 is
CC further N-terminally truncated by post-translational processing in the
CC intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR EMBL; Y07539; CAA68827.1; -; mRNA.
DR EMBL; S78477; AAB34506.1; -; mRNA.
DR PIR; I51301; I51301.
DR PIR; S09992; GCCH.
DR RefSeq; NP_001177094.1; NM_001190165.3. [P68259-1]
DR RefSeq; NP_990591.1; NM_205260.4. [P68259-2]
DR RefSeq; XP_015145124.1; XM_015289638.1.
DR RefSeq; XP_015145125.1; XM_015289639.1. [P68259-1]
DR RefSeq; XP_015145126.1; XM_015289640.1.
DR AlphaFoldDB; P68259; -.
DR SMR; P68259; -.
DR STRING; 9031.ENSGALP00000018068; -.
DR PaxDb; P68259; -.
DR Ensembl; ENSGALT00000033134; ENSGALP00000032494; ENSGALG00000011104. [P68259-1]
DR GeneID; 396196; -.
DR KEGG; gga:396196; -.
DR CTD; 2641; -.
DR VEuPathDB; HostDB:geneid_396196; -.
DR eggNOG; ENOG502RYPR; Eukaryota.
DR GeneTree; ENSGT00390000005372; -.
DR HOGENOM; CLU_090687_0_0_1; -.
DR InParanoid; P68259; -.
DR OMA; KRNGQQG; -.
DR PhylomeDB; P68259; -.
DR TreeFam; TF332333; -.
DR Reactome; R-GGA-163359; Glucagon signaling in metabolic regulation.
DR Reactome; R-GGA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR Reactome; R-GGA-416476; G alpha (q) signalling events.
DR Reactome; R-GGA-418555; G alpha (s) signalling events.
DR Reactome; R-GGA-420092; Glucagon-type ligand receptors.
DR Reactome; R-GGA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR PRO; PR:P68259; -.
DR Proteomes; UP000000539; Chromosome 7.
DR Bgee; ENSGALG00000011104; Expressed in spermatocyte and 10 other tissues.
DR ExpressionAtlas; P68259; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0032099; P:negative regulation of appetite; IDA:AgBase.
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; 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:0014823; P:response to activity; IEA:Ensembl.
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 Alternative splicing; Amidation; Cleavage on pair of basic residues;
KW Direct protein sequencing; Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT PEPTIDE 23..52
FT /note="Glicentin-related polypeptide"
FT /evidence="ECO:0000250|UniProtKB:P09686"
FT /id="PRO_0000011325"
FT PEPTIDE 55..83
FT /note="Glucagon"
FT /evidence="ECO:0000269|PubMed:1194290,
FT ECO:0000269|PubMed:2828209"
FT /id="PRO_0000011326"
FT PROPEP 86..109
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011327"
FT PEPTIDE 112..148
FT /note="Glucagon-like peptide 1"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011328"
FT PEPTIDE 118..148
FT /note="Glucagon-like peptide 1(7-37)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011329"
FT PEPTIDE 118..147
FT /note="Glucagon-like peptide 1(7-36)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011330"
FT PROPEP 151..163
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011331"
FT PEPTIDE 166..198
FT /note="Glucagon-like peptide 2"
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011332"
FT PROPEP 199..206
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011333"
FT REGION 27..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..52
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 54..55
FT /note="Cleavage; by PCSK2"
FT /evidence="ECO:0000250"
FT SITE 85..86
FT /note="Cleavage; by PCSK1 and PCSK2"
FT /evidence="ECO:0000250"
FT SITE 111..112
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 117..118
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 150..151
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 165..166
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT MOD_RES 147
FT /note="Arginine amide"
FT /evidence="ECO:0000250"
FT VAR_SEQ 151
FT /note="D -> E (in isoform Pancreatic)"
FT /evidence="ECO:0000303|PubMed:2338135"
FT /id="VSP_001753"
FT VAR_SEQ 152..206
FT /note="Missing (in isoform Pancreatic)"
FT /evidence="ECO:0000303|PubMed:2338135"
FT /id="VSP_001754"
SQ SEQUENCE 206 AA; 23876 MW; AB299E1B02FC6AA4 CRC64;
MKMKSIYFIA GLLLMIVQGS WQNPLQDTEE KSRSFKASQS EPLDESRQLN EVKRHSQGTF
TSDYSKYLDS RRAQDFVQWL MSTKRNGQQG QEDKENDKFP DQLSSNAISK RHSEFERHAE
GTYTSDITSY LEGQAAKEFI AWLVNGRGRR DFPEKALMAE EMGRRHADGT FTSDINKILD
DMAAKEFLKW LINTKVTQRD LLGEYQ
