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P06883 (GLUC_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glucagon

Cleaved into the following 8 chains:

  1. Glicentin
  2. Glicentin-related polypeptide
    Short name=GRPP
  3. Oxyntomodulin
    Short name=OXM
    Short name=OXY
  4. Glucagon
  5. Glucagon-like peptide 1
    Short name=GLP-1
  6. Glucagon-like peptide 1(7-37)
    Short name=GLP-1(7-37)
  7. Glucagon-like peptide 1(7-36)
    Short name=GLP-1(7-36)
  8. Glucagon-like peptide 2
    Short name=GLP-2
Gene names
Name:Gcg
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length180 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. Ref.5

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. Inhibits beta cell apoptosis. Ref.5

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. Ref.5

Oxyntomodulin significantly reduces food intake. Ref.5

Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. Ref.5

Subcellular location

Secreted.

Tissue specificity

Glucagon is secreted in the A cells of the islets of Langerhans. GLP-1, GLP-2, oxyntomodulin and glicentin are secreted from enteroendocrine cells throughout the gastrointestinal tract. Ref.7

Induction

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.

Post-translational modification

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. Ref.6

Sequence similarities

Belongs to the glucagon family.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Cleavage on pair of basic residues
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 12960094. Source: RGD

negative regulation of apoptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of appetite

Inferred from mutant phenotype PubMed 11557638. Source: RGD

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein kinase A signaling

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein metabolic process

Traceable author statement Ref.2. Source: RGD

regulation of carbohydrate metabolic process

Traceable author statement Ref.2. Source: RGD

regulation of lipid metabolic process

Traceable author statement Ref.2. Source: RGD

response to starvation

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 12876072. Source: RGD

   Molecular_functionglucagon receptor binding

Inferred from direct assay PubMed 12960094. Source: RGD

hormone activity

Inferred from direct assay PubMed 12960094. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Peptide21 – 8969Glicentin By similarity
PRO_0000011303
Peptide21 – 5030Glicentin-related polypeptide By similarity
PRO_0000011304
Peptide53 – 8937Oxyntomodulin Ref.4
PRO_0000011305
Peptide53 – 8129Glucagon By similarity
PRO_0000011306
Propeptide84 – 896 By similarity
PRO_0000011307
Peptide92 – 12837Glucagon-like peptide 1 By similarity
PRO_0000011308
Peptide98 – 12831Glucagon-like peptide 1(7-37) By similarity
PRO_0000011309
Peptide98 – 12730Glucagon-like peptide 1(7-36) By similarity
PRO_0000011310
Propeptide131 – 14515 By similarity
PRO_0000011311
Peptide146 – 17833Glucagon-like peptide 2 By similarity
PRO_0000011312

Sites

Site52 – 532Cleavage; by PCSK2 By similarity
Site83 – 842Cleavage; by PCSK1 and PCSK2 By similarity
Site91 – 922Cleavage; by PCSK1 By similarity
Site97 – 982Cleavage; by PCSK1 By similarity
Site130 – 1312Cleavage; by PCSK1 By similarity
Site145 – 1462Cleavage; by PCSK1 By similarity

Amino acid modifications

Modified residue1271Arginine amide By similarity

Sequences

Sequence LengthMass (Da)Tools
P06883 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 76931409D03C7978

FASTA18020,846
        10         20         30         40         50         60 
MKTVYIVAGL FVMLVQGSWQ HAPQDTEENA RSFPASQTEP LEDPDQINED KRHSQGTFTS 

        70         80         90        100        110        120 
DYSKYLDSRR AQDFVQWLMN TKRNRNNIAK RHDEFERHAE GTFTSDVSSY LEGQAAKEFI 

       130        140        150        160        170        180 
AWLVKGRGRR DFPEEVAIAE ELGRRHADGS FSDEMNTILD NLATRDFINW LIQTKITDKK 

« Hide

References

[1]"Glucagon gene sequence. Four of six exons encode separate functional domains of rat pre-proglucagon."
Heinrich G., Gros P., Habener J.F.
J. Biol. Chem. 259:14082-14087(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid."
Heinrich G., Gros P., Lund P.K., Bentley R.C., Habener J.F.
Endocrinology 115:2176-2181(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing."
Mojsov S., Heinrich G., Wilson I.B., Ravazzola M., Orci L., Habener J.F.
J. Biol. Chem. 261:11880-11889(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Purification and sequence of rat oxyntomodulin."
Collie N.L., Walsh J.H., Wong H.C., Shively J.E., Davis M.T., Lee T.D., Reeve J.R. Jr.
Proc. Natl. Acad. Sci. U.S.A. 91:9362-9366(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 53-89.
[5]"Oxyntomodulin inhibits food intake in the rat."
Dakin C.L., Gunn I., Small C.J., Edwards C.M., Hay D.L., Smith D.M., Ghatei M.A., Bloom S.R.
Endocrinology 142:4244-4250(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF OXYNTOMODULIN.
[6]"Role of prohormone convertases in the tissue-specific processing of proglucagon."
Dhanvantari S., Seidah N.G., Brubaker P.L.
Mol. Endocrinol. 10:342-355(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING BY PCSK1 AND PCSK2.
[7]"Both amidated and nonamidated forms of glucagon-like peptide I are synthesized in the rat intestine and the pancreas."
Mojsov S., Kopczynski M.G., Habener J.F.
J. Biol. Chem. 265:8001-8008(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2."
Brubaker P.L., Anini Y.
Can. J. Physiol. Pharmacol. 81:1005-1012(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"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.
[10]"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.
[11]"Glucagon-like peptide 2."
Drucker D.J.
Trends Endocrinol. Metab. 10:153-156(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[12]"The glucagon-like peptides."
Kieffer T.J., Habener J.F.
Endocr. Rev. 20:876-913(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K02813 expand/collapse EMBL AC list , K02809, K02810, K02811, K02812 Genomic DNA. Translation: AAA41235.1.
PIRGCRT. A22655.
UniGeneRn.54383.

3D structure databases

ProteinModelPortalP06883.
SMRP06883. Positions 53-81, 98-127.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000007356.

PTM databases

PhosphoSiteP06883.

Proteomic databases

PRIDEP06883.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:2668. rat.

Organism-specific databases

RGD2668. Gcg.

Phylogenomic databases

eggNOGNOG42743.
HOGENOMHOG000231876.
HOVERGENHBG003010.
InParanoidP06883.
PhylomeDBP06883.

Enzyme and pathway databases

ReactomeREACT_205051. Metabolism.

Gene expression databases

GenevestigatorP06883.

Family and domain databases

InterProIPR015550. Glucagon-like.
IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PANTHERPTHR11418. PTHR11418. 1 hit.
PfamPF00123. Hormone_2. 3 hits.
[Graphical view]
PRINTSPR00275. GLUCAGON.
SMARTSM00070. GLUCA. 3 hits.
[Graphical view]
PROSITEPS00260. GLUCAGON. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio13948569.
PROP06883.

Entry information

Entry nameGLUC_RAT
AccessionPrimary (citable) accession number: P06883
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families