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Protein

Glucagon

Gene

GCG

Organism
Sus scrofa (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 (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.

GO - Molecular functioni

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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20202 PublicationsAdd
BLAST
Peptidei21 – 8969GlicentinPRO_0000011293Add
BLAST
Peptidei21 – 5030Glicentin-related polypeptideBy similarityPRO_0000011294Add
BLAST
Peptidei53 – 8937OxyntomodulinBy similarityPRO_0000011295Add
BLAST
Peptidei53 – 8129GlucagonPRO_0000011296Add
BLAST
Propeptidei84 – 896By similarityPRO_0000011297
Peptidei92 – 12837Glucagon-like peptide 1By similarityPRO_0000011298Add
BLAST
Peptidei98 – 12831Glucagon-like peptide 1(7-37)PRO_0000011299Add
BLAST
Peptidei98 – 12730Glucagon-like peptide 1(7-36)PRO_0000011300Add
BLAST
Propeptidei131 – 14515By similarityPRO_0000011301Add
BLAST
Peptidei146 – 18035Glucagon-like peptide 2By similarityPRO_0000011302Add
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

Proteomic databases

PaxDbiP01274.
PeptideAtlasiP01274.

Expressioni

Tissue specificityi

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. GLP-1 and GLP-2 are also secreted in selected neurons in the brain.1 Publication

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000016844.

Structurei

Secondary structure

1
180
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi59 – 624Combined sources
Turni63 – 653Combined sources
Helixi66 – 7510Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GCNX-ray3.00A53-81[»]
ProteinModelPortaliP01274.
SMRiP01274. Positions 53-81, 98-127.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01274.

Family & Domainsi

Sequence similaritiesi

Belongs to the glucagon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IKZ8. Eukaryota.
ENOG4111VKC. LUCA.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP01274.
KOiK05259.

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.

P01274-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTIYFVAGL FVMLVQGSWQ RSLQNTEEKS RSFPAPQTDP LDDPDQMTED
60 70 80 90 100
KRHSQGTFTS DYSKYLDSRR AQDFVQWLMN TKRNKNNIAK RHDEFERHAE
110 120 130 140 150
GTFTSDVSSY LEGQAAKEFI AWLVKGRGRR DFPEEVTIVE ELRRRHADGS
160 170 180
FSDEMNTVLD NLATRDFINW LLHTKITDSL
Length:180
Mass (Da):21,029
Last modified:March 29, 2004 - v4
Checksum:i362997AB72197EE6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti143 – 1431R → G AA sequence (PubMed:3379036).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY242124 mRNA. Translation: AAO88211.1.
RefSeqiNP_999489.1. NM_214324.1.
UniGeneiSsc.17225.

Genome annotation databases

GeneIDi397595.
KEGGissc:397595.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY242124 mRNA. Translation: AAO88211.1.
RefSeqiNP_999489.1. NM_214324.1.
UniGeneiSsc.17225.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GCNX-ray3.00A53-81[»]
ProteinModelPortaliP01274.
SMRiP01274. Positions 53-81, 98-127.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000016844.

Proteomic databases

PaxDbiP01274.
PeptideAtlasiP01274.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi397595.
KEGGissc:397595.

Organism-specific databases

CTDi2641.

Phylogenomic databases

eggNOGiENOG410IKZ8. Eukaryota.
ENOG4111VKC. LUCA.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP01274.
KOiK05259.

Miscellaneous databases

EvolutionaryTraceiP01274.

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. "Cloning of porcine proglucagon."
    Siggers R.H., Goldade B.G., Laarveld B., Van Kessel A.G.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pancreas and Small intestine.
  2. "The primary structure of porcine glicentin (proglucagon)."
    Thim L., Moody A.J.
    Regul. Pept. 2:139-150(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-89.
  3. "The amino acid sequence of porcine glicentin."
    Thim L., Moody A.J.
    Peptides 2 Suppl. 2:37-39(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 21-89.
  4. "The amino acid sequence of glucagon. V. Location of amide groups, acid degradation studies and summary of sequential evidence."
    Bromer W.W., Sinn L.G., Behrens O.K.
    J. Am. Chem. Soc. 79:2807-2810(1957)
    Cited for: PROTEIN SEQUENCE OF 53-81.
  5. "Complete sequences of glucagon-like peptide-1 from human and pig small intestine."
    Orskov C., Bersani M., Johnsen A.H., Hoejrup P., Holst J.J.
    J. Biol. Chem. 264:12826-12829(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 98-127.
  6. "Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine."
    Buhl T., Thim L., Kofod H., Orskov C., Harling H., Holst J.J.
    J. Biol. Chem. 263:8621-8624(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 131-178.
  7. "Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas."
    Orskov C., Holst J.J., Knuhtsen S., Baldissera F.G., Poulsen S.S., Nielsen O.V.
    Endocrinology 119:1467-1475(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "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.
  9. "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.
  10. Cited for: REVIEW.
  11. Cited for: REVIEW.
  12. "X-ray analysis of glucagon and its relationship to receptor binding."
    Sasaki K., Dockerill S., Adamiak D.A., Tickle I.J., Blundell T.L.
    Nature 257:751-757(1975) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 53-81.

Entry informationi

Entry nameiGLUC_PIG
AccessioniPrimary (citable) accession number: P01274
Secondary accession number(s): Q864V8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 29, 2004
Last modified: July 6, 2016
This is version 115 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

GLP-2 does not have cleavage on a pair of basic residues at C-terminus as in other mammals.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.