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Protein

Glucagon

Gene

GCG

Organism
Cavia porcellus (Guinea pig)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia (By similarity).By similarity
GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation (By similarity).By similarity
GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability (By similarity).By similarity
Oxyntomodulin significantly reduces food intake.By similarity
Glicentin may modulate gastric acid secretion and gastro-pyloro-duodenal activity.By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hormone

Names & Taxonomyi

Protein namesi
Recommended name:
Glucagon
Cleaved into the following 8 chains:
Oxyntomodulin
Short name:
OXM
Short name:
OXY
Glucagon-like peptide 1
Short name:
GLP-1
Glucagon-like peptide 1(7-37)
Short name:
GLP-1(7-37)
Glucagon-like peptide 1(7-36)
Short name:
GLP-1(7-36)
Glucagon-like peptide 2
Short name:
GLP-2
Gene namesi
Name:GCG
OrganismiCavia porcellus (Guinea pig)
Taxonomic identifieri10141 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricognathiCaviidaeCavia
Proteomesi
  • UP000005447 Componenti: Unassembled WGS sequence

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Add
BLAST
Peptidei21 – 8969GlicentinBy similarityPRO_0000011243Add
BLAST
Peptidei21 – 5030Glicentin-related polypeptideBy similarityPRO_0000011244Add
BLAST
Peptidei53 – 8937OxyntomodulinPRO_0000011245Add
BLAST
Peptidei53 – 8129GlucagonPRO_0000011246Add
BLAST
Propeptidei84 – 896By similarityPRO_0000011247
Peptidei92 – 12837Glucagon-like peptide 1By similarityPRO_0000011248Add
BLAST
Peptidei98 – 12831Glucagon-like peptide 1(7-37)By similarityPRO_0000011249Add
BLAST
Peptidei98 – 12730Glucagon-like peptide 1(7-36)By similarityPRO_0000011250Add
BLAST
Propeptidei131 – 14515By similarityPRO_0000011251Add
BLAST
Peptidei146 – 17833Glucagon-like peptide 2By similarityPRO_0000011252Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei54 – 541PhosphoserineBy similarity
Modified residuei105 – 1051PhosphoserineBy similarity
Modified residuei108 – 1081PhosphoserineBy similarity
Modified residuei127 – 1271Arginine amideBy similarity
Modified residuei150 – 1501PhosphoserineBy similarity
Modified residuei152 – 1521PhosphoserineBy similarity

Post-translational modificationi

Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei52 – 532Cleavage; by PCSK2By similarity
Sitei83 – 842Cleavage; by PCSK1 and PCSK2By similarity
Sitei91 – 922Cleavage; by PCSK1By similarity
Sitei97 – 982Cleavage; by PCSK1By similarity
Sitei130 – 1312Cleavage; by PCSK1By similarity
Sitei145 – 1462Cleavage; by PCSK1By similarity

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Phosphoprotein

Expressioni

Inductioni

Glucagon release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. GLP-1 and GLP-2 are induced in response to nutrient ingestion (By similarity).By similarity

Interactioni

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000014570.

Structurei

3D structure databases

ProteinModelPortaliP05110.
SMRiP05110. Positions 53-80, 98-127.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glucagon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IKZ8. Eukaryota.
ENOG4111VKC. LUCA.
GeneTreeiENSGT00390000005372.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP05110.
OMAiKMKSIYF.
OrthoDBiEOG7WMCM1.
TreeFamiTF332333.

Family and domain databases

InterProiIPR015550. Glucagon.
IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PANTHERiPTHR11418:SF0. PTHR11418:SF0. 1 hit.
PfamiPF00123. Hormone_2. 3 hits.
[Graphical view]
PRINTSiPR00275. GLUCAGON.
SMARTiSM00070. GLUCA. 3 hits.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P05110-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSVYFVAGL FIMLAQGSWQ RSLQDTEEKP RSVSASQTDM LDDPDQMNED
60 70 80 90 100
KRHSQGTFTS DYSKYLDSRR AQQFLKWLLN VKRNRNNIAK RHDEFERHAE
110 120 130 140 150
GTFTSDVSSY LEGQAAKEFI AWLVKGRGRR DFPEEVAIVE ELGRRHADGS
160 170 180
FSDEMNTILD NLATRDFINW LIQTKITDRK
Length:180
Mass (Da):20,972
Last modified:August 13, 1987 - v1
Checksum:i702FB181161D2776
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00014 mRNA. Translation: BAA00010.1.
PIRiA24856. GCGP.
RefSeqiNP_001166423.1. NM_001172952.1.

Genome annotation databases

EnsembliENSCPOT00000028211; ENSCPOP00000014570; ENSCPOG00000024193.
GeneIDi100135526.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00014 mRNA. Translation: BAA00010.1.
PIRiA24856. GCGP.
RefSeqiNP_001166423.1. NM_001172952.1.

3D structure databases

ProteinModelPortaliP05110.
SMRiP05110. Positions 53-80, 98-127.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000014570.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCPOT00000028211; ENSCPOP00000014570; ENSCPOG00000024193.
GeneIDi100135526.

Organism-specific databases

CTDi2641.

Phylogenomic databases

eggNOGiENOG410IKZ8. Eukaryota.
ENOG4111VKC. LUCA.
GeneTreeiENSGT00390000005372.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP05110.
OMAiKMKSIYF.
OrthoDBiEOG7WMCM1.
TreeFamiTF332333.

Family and domain databases

InterProiIPR015550. Glucagon.
IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PANTHERiPTHR11418:SF0. PTHR11418:SF0. 1 hit.
PfamiPF00123. Hormone_2. 3 hits.
[Graphical view]
PRINTSiPR00275. GLUCAGON.
SMARTiSM00070. GLUCA. 3 hits.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Mutations in the guinea pig preproglucagon gene are restricted to a specific portion of the prohormone sequence."
    Seino S., Welsh M., Bell G.I., Chan S.J., Steiner D.F.
    FEBS Lett. 203:25-30(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Guinea pig glucagon differs from other mammalian glucagons."
    Huang C.G., Eng J., Pan Y.-C.E., Hulmes J.D., Yalow R.S.
    Diabetes 35:508-512(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 53-81.
  3. "Primary structure of glucagon and a partial sequence of oxyntomodulin (glucagon-37) from the guinea pig."
    Conlon J.M., Hansen H.F., Schwartz T.W.
    Regul. Pept. 11:309-320(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 53-89.
  4. "Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis."
    Drucker D.J.
    Mol. Endocrinol. 17:161-171(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  5. "Glucagon and regulation of glucose metabolism."
    Jiang G., Zhang B.B.
    Am. J. Physiol. 284:E671-E678(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. Cited for: REVIEW.
  7. Cited for: REVIEW.

Entry informationi

Entry nameiGLUC_CAVPO
AccessioniPrimary (citable) accession number: P05110
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: March 16, 2016
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.