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Protein

Glucagon

Gene

GCG

Organism
Homo sapiens (Human)
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. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
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.
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.
Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.
Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.

GO - Molecular functioni

  • glucagon receptor binding Source: GO_Central
  • hormone activity Source: GO_Central
  • identical protein binding Source: IntAct
  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115263-MONOMER.
ReactomeiR-HSA-163359. Glucagon signaling in metabolic regulation.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-HSA-416476. G alpha (q) signalling events.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-420092. Glucagon-type ligand receptors.
R-HSA-422085. Synthesis, secretion, and deacylation of Ghrelin.
SIGNORiP01275.

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
Alternative name(s):
Incretin hormone
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:4191. GCG.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Available under the names Glucagon (Eli Lilly) and GlucaGen or Glucagon Novo Nordisk (Novo Nordisk). Used to treat severe hypoglycemia in insulin-dependent diabetics.

Organism-specific databases

DisGeNETi2641.
OpenTargetsiENSG00000115263.
PharmGKBiPA28606.

Chemistry databases

ChEMBLiCHEMBL5736.

Polymorphism and mutation databases

BioMutaiGCG.
DMDMi125987831.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Add BLAST20
PeptideiPRO_000001125321 – 89GlicentinBy similarityAdd BLAST69
PeptideiPRO_000001125421 – 50Glicentin-related polypeptideBy similarityAdd BLAST30
PeptideiPRO_000001125553 – 89OxyntomodulinBy similarityAdd BLAST37
PeptideiPRO_000001125653 – 81GlucagonAdd BLAST29
PropeptideiPRO_000001125784 – 896
PeptideiPRO_000001125892 – 128Glucagon-like peptide 1Add BLAST37
PeptideiPRO_000001125998 – 128Glucagon-like peptide 1(7-37)Add BLAST31
PeptideiPRO_000001126098 – 127Glucagon-like peptide 1(7-36)Add BLAST30
PropeptideiPRO_0000011261131 – 145By similarityAdd BLAST15
PeptideiPRO_0000011262146 – 178Glucagon-like peptide 2By similarityAdd BLAST33

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei54PhosphoserineBy similarity1
Modified residuei105PhosphoserineBy similarity1
Modified residuei108PhosphoserineBy similarity1
Modified residuei127Arginine amide1 Publication1
Modified residuei150PhosphoserineBy similarity1
Modified residuei152PhosphoserineBy similarity1

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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei52 – 53Cleavage; by PCSK22
Sitei83 – 84Cleavage; by PCSK1 and PCSK22
Sitei91 – 92Cleavage; by PCSK12
Sitei97 – 98Cleavage; by PCSK12
Sitei130 – 131Cleavage; by PCSK12
Sitei145 – 146Cleavage; by PCSK12

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Phosphoprotein

Proteomic databases

PaxDbiP01275.
PeptideAtlasiP01275.
PRIDEiP01275.

PTM databases

iPTMnetiP01275.
PhosphoSitePlusiP01275.

Miscellaneous databases

PMAP-CutDBP01275.

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.

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.

Gene expression databases

BgeeiENSG00000115263.
CleanExiHS_GCG.
GenevisibleiP01275. HS.

Organism-specific databases

HPAiCAB000040.
HPA036760.
HPA036761.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-7629173,EBI-7629173
DPP4P274874EBI-7629173,EBI-2871277
FAPQ128844EBI-7629173,EBI-4319803

GO - Molecular functioni

  • glucagon receptor binding Source: GO_Central
  • hormone activity Source: GO_Central
  • identical protein binding Source: IntAct
  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi108911. 2 interactors.
DIPiDIP-46470N.
IntActiP01275. 4 interactors.
MINTiMINT-8090511.
STRINGi9606.ENSP00000387662.

Chemistry databases

BindingDBiP01275.

Structurei

Secondary structure

1180
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni55 – 57Combined sources3
Turni59 – 62Combined sources4
Beta strandi63 – 65Combined sources3
Helixi68 – 70Combined sources3
Turni71 – 73Combined sources3
Beta strandi76 – 78Combined sources3
Helixi104 – 124Combined sources21
Helixi150 – 153Combined sources4
Helixi154 – 156Combined sources3
Helixi157 – 172Combined sources16
Turni173 – 177Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BH0X-ray3.00A53-81[»]
1D0RNMR-A98-127[»]
1NAUNMR-A59-81[»]
2G49X-ray2.50C/D53-81[»]
2L63NMR-A146-178[»]
2L64NMR-A146-178[»]
2M5PNMR-X53-81[»]
2M5QNMR-X53-81[»]
3IOLX-ray2.10B98-128[»]
4APDNMR-A98-128[»]
4ZGMX-ray1.80B98-128[»]
ProteinModelPortaliP01275.
SMRiP01275.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01275.

Family & Domainsi

Sequence similaritiesi

Belongs to the glucagon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IKZ8. Eukaryota.
ENOG4111VKC. LUCA.
GeneTreeiENSGT00390000005372.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP01275.
KOiK05259.
OMAiKMKSIYF.
OrthoDBiEOG091G0PJK.
PhylomeDBiP01275.
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.

P01275-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSIYFVAGL FVMLVQGSWQ RSLQDTEEKS RSFSASQADP LSDPDQMNED
60 70 80 90 100
KRHSQGTFTS DYSKYLDSRR AQDFVQWLMN TKRNRNNIAK RHDEFERHAE
110 120 130 140 150
GTFTSDVSSY LEGQAAKEFI AWLVKGRGRR DFPEEVAIVE ELGRRHADGS
160 170 180
FSDEMNTILD NLAARDFINW LIQTKITDRK
Length:180
Mass (Da):20,909
Last modified:February 6, 2007 - v3
Checksum:i7A99EEC629B2862C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti82K → N in CAA27627 (PubMed:3725587).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014596115A → V.Corresponds to variant rs5650dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04040 mRNA. Translation: AAA52567.1.
X03991 Genomic DNA. Translation: CAA27627.1.
V01515 Genomic DNA. Translation: CAA24759.1.
BT006813 mRNA. Translation: AAP35459.1.
AC007750 Genomic DNA. Translation: AAY24204.1.
BC005278 mRNA. Translation: AAH05278.1.
CCDSiCCDS46439.1.
PIRiA24377. GCHU.
RefSeqiNP_002045.1. NM_002054.4.
UniGeneiHs.516494.
Hs.741174.

Genome annotation databases

EnsembliENST00000375497; ENSP00000364647; ENSG00000115263.
ENST00000418842; ENSP00000387662; ENSG00000115263.
GeneIDi2641.
KEGGihsa:2641.
UCSCiuc002ucc.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Glucagon at Eli Lilly

Clinical information on Eli Lilly glucagon products

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04040 mRNA. Translation: AAA52567.1.
X03991 Genomic DNA. Translation: CAA27627.1.
V01515 Genomic DNA. Translation: CAA24759.1.
BT006813 mRNA. Translation: AAP35459.1.
AC007750 Genomic DNA. Translation: AAY24204.1.
BC005278 mRNA. Translation: AAH05278.1.
CCDSiCCDS46439.1.
PIRiA24377. GCHU.
RefSeqiNP_002045.1. NM_002054.4.
UniGeneiHs.516494.
Hs.741174.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BH0X-ray3.00A53-81[»]
1D0RNMR-A98-127[»]
1NAUNMR-A59-81[»]
2G49X-ray2.50C/D53-81[»]
2L63NMR-A146-178[»]
2L64NMR-A146-178[»]
2M5PNMR-X53-81[»]
2M5QNMR-X53-81[»]
3IOLX-ray2.10B98-128[»]
4APDNMR-A98-128[»]
4ZGMX-ray1.80B98-128[»]
ProteinModelPortaliP01275.
SMRiP01275.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108911. 2 interactors.
DIPiDIP-46470N.
IntActiP01275. 4 interactors.
MINTiMINT-8090511.
STRINGi9606.ENSP00000387662.

Chemistry databases

BindingDBiP01275.
ChEMBLiCHEMBL5736.

PTM databases

iPTMnetiP01275.
PhosphoSitePlusiP01275.

Polymorphism and mutation databases

BioMutaiGCG.
DMDMi125987831.

Proteomic databases

PaxDbiP01275.
PeptideAtlasiP01275.
PRIDEiP01275.

Protocols and materials databases

DNASUi2641.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375497; ENSP00000364647; ENSG00000115263.
ENST00000418842; ENSP00000387662; ENSG00000115263.
GeneIDi2641.
KEGGihsa:2641.
UCSCiuc002ucc.5. human.

Organism-specific databases

CTDi2641.
DisGeNETi2641.
GeneCardsiGCG.
HGNCiHGNC:4191. GCG.
HPAiCAB000040.
HPA036760.
HPA036761.
MIMi138030. gene.
neXtProtiNX_P01275.
OpenTargetsiENSG00000115263.
PharmGKBiPA28606.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKZ8. Eukaryota.
ENOG4111VKC. LUCA.
GeneTreeiENSGT00390000005372.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP01275.
KOiK05259.
OMAiKMKSIYF.
OrthoDBiEOG091G0PJK.
PhylomeDBiP01275.
TreeFamiTF332333.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115263-MONOMER.
ReactomeiR-HSA-163359. Glucagon signaling in metabolic regulation.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-381771. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
R-HSA-416476. G alpha (q) signalling events.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-420092. Glucagon-type ligand receptors.
R-HSA-422085. Synthesis, secretion, and deacylation of Ghrelin.
SIGNORiP01275.

Miscellaneous databases

ChiTaRSiGCG. human.
EvolutionaryTraceiP01275.
GeneWikiiGlucagon.
GenomeRNAii2641.
PMAP-CutDBP01275.
PROiP01275.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115263.
CleanExiHS_GCG.
GenevisibleiP01275. HS.

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...

Entry informationi

Entry nameiGLUC_HUMAN
AccessioniPrimary (citable) accession number: P01275
Secondary accession number(s): A6NN65, Q53TP6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 6, 2007
Last modified: November 30, 2016
This is version 184 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

In the glucagon antagonist, His-53 and Phe-58 are missing. This antagonist has been successfully utilized to reduce glucose concentration in vivo.

Keywords - Technical termi

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

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.