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Protein

Glucagon

Gene

GCG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Miscellaneous

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

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionHormone

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000115263.14
HGNCiHGNC:4191 GCG
MIMi138030 gene
neXtProtiNX_P01275

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi51367

PTM databases

iPTMnetiP01275
PhosphoSitePlusiP01275

Miscellaneous databases

PMAP-CutDBiP01275

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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi108911, 19 interactors
DIPiDIP-46470N
IntActiP01275, 6 interactors
MINTiP01275
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

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
OMAiTRDFINW
OrthoDBiEOG091G0PJK
PhylomeDBiP01275
TreeFamiTF332333

Family and domain databases

InterProiView protein in InterPro
IPR015550 Glucagon
IPR000532 Glucagon_GIP_secretin_VIP
PANTHERiPTHR11418 PTHR11418, 1 hit
PfamiView protein in Pfam
PF00123 Hormone_2, 3 hits
PRINTSiPR00275 GLUCAGON
SMARTiView protein in SMART
SM00070 GLUCA, 3 hits
PROSITEiView protein in PROSITE
PS00260 GLUCAGON, 4 hits

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 dbSNP:rs5650Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiGLUC_HUMAN
AccessioniPrimary (citable) accession number: P01275
Secondary accession number(s): A6NN65, Q53TP6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 6, 2007
Last modified: June 20, 2018
This is version 197 of the entry and version 3 of the sequence. See 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

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

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