UniProtKB - P01275 (GLUC_HUMAN)
Pro-glucagon
GCG
Functioni
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.
2 PublicationsPotent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6 (PubMed:22037645).
Plays 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. Has 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 (Probable).
3 Publications1 PublicationStimulates 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.
4 PublicationsSignificantly 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.
2 PublicationsMay 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.
2 PublicationsMiscellaneous
GO - Molecular functioni
- gastric inhibitory polypeptide receptor binding Source: BHF-UCL
- glucagon receptor binding Source: GO_Central
- hormone activity Source: GO_Central
- identical protein binding Source: IntAct
- signaling receptor binding Source: ProtInc
GO - Biological processi
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: Ensembl
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway Source: GO_Central
- feeding behavior Source: ProtInc
- glucose homeostasis Source: UniProtKB
- G protein-coupled receptor signaling pathway Source: GO_Central
- negative regulation of apoptotic process Source: GO_Central
- negative regulation of execution phase of apoptosis Source: Ensembl
- positive regulation of calcium ion import Source: Ensembl
- positive regulation of ERK1 and ERK2 cascade Source: Ensembl
- positive regulation of gluconeogenesis Source: Ensembl
- positive regulation of histone H3-K4 methylation Source: Ensembl
- positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: GO_Central
- positive regulation of peptidyl-serine phosphorylation Source: Ensembl
- positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
- positive regulation of protein binding Source: Ensembl
- positive regulation of protein kinase activity Source: Ensembl
- protein kinase A signaling Source: GO_Central
- regulation of insulin secretion Source: UniProtKB
- response to activity Source: UniProtKB
Keywordsi
Molecular function | Hormone |
Enzyme and pathway databases
PathwayCommonsi | P01275 |
Reactomei | R-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 R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | P01275 |
SIGNORi | P01275 |
Names & Taxonomyi
Protein namesi | Recommended name: Pro-glucagonCleaved into the following 8 chains: Alternative name(s): Incretin hormone |
Gene namesi | Name:GCGImported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4191, GCG |
MIMi | 138030, gene |
neXtProti | NX_P01275 |
VEuPathDBi | HostDB:ENSG00000115263 |
Subcellular locationi
Extracellular region or secreted
- Secreted Curated
Extracellular region or secreted
- Secreted 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Other locations
- secretory granule lumen Source: Reactome
Keywords - Cellular componenti
SecretedPathology & Biotechi
Pharmaceutical usei
Organism-specific databases
DisGeNETi | 2641 |
OpenTargetsi | ENSG00000115263 |
PharmGKBi | PA28606 |
Miscellaneous databases
Pharosi | P01275, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5736 |
Genetic variation databases
BioMutai | GCG |
DMDMi | 125987831 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Add BLAST | 20 | |
PeptideiPRO_0000011253 | 21 – 89 | GlicentinBy similarityAdd BLAST | 69 | |
PeptideiPRO_0000011254 | 21 – 50 | Glicentin-related polypeptideBy similarityAdd BLAST | 30 | |
PeptideiPRO_0000011255 | 53 – 89 | OxyntomodulinBy similarityAdd BLAST | 37 | |
PeptideiPRO_0000011256 | 53 – 81 | Glucagon1 PublicationAdd BLAST | 29 | |
PropeptideiPRO_0000011257 | 84 – 89 | 1 Publication | 6 | |
PeptideiPRO_0000011258 | 92 – 128 | Glucagon-like peptide 11 PublicationAdd BLAST | 37 | |
PeptideiPRO_0000011259 | 98 – 128 | Glucagon-like peptide 1(7-37)1 PublicationAdd BLAST | 31 | |
PeptideiPRO_0000011260 | 98 – 127 | Glucagon-like peptide 1(7-36)1 PublicationAdd BLAST | 30 | |
PropeptideiPRO_0000011261 | 131 – 145 | By similarityAdd BLAST | 15 | |
PeptideiPRO_0000011262 | 146 – 178 | Glucagon-like peptide 2By similarityAdd BLAST | 33 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 54 | PhosphoserineBy similarity | 1 | |
Modified residuei | 105 | PhosphoserineBy similarity | 1 | |
Modified residuei | 108 | PhosphoserineBy similarity | 1 | |
Modified residuei | 127 | Arginine amide1 Publication | 1 | |
Modified residuei | 150 | PhosphoserineBy similarity | 1 | |
Modified residuei | 152 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 52 – 53 | Cleavage; by PCSK2 | 2 | |
Sitei | 83 – 84 | Cleavage; by PCSK1 and PCSK2 | 2 | |
Sitei | 91 – 92 | Cleavage; by PCSK1 | 2 | |
Sitei | 97 – 98 | Cleavage; by PCSK1 | 2 | |
Sitei | 130 – 131 | Cleavage; by PCSK1 | 2 | |
Sitei | 145 – 146 | Cleavage; by PCSK1 | 2 |
Keywords - PTMi
Amidation, Cleavage on pair of basic residues, PhosphoproteinProteomic databases
jPOSTi | P01275 |
MassIVEi | P01275 |
PaxDbi | P01275 |
PeptideAtlasi | P01275 |
PRIDEi | P01275 |
ProteomicsDBi | 51367 |
PTM databases
iPTMneti | P01275 |
PhosphoSitePlusi | P01275 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000115263, Expressed in islet of Langerhans and 94 other tissues |
Genevisiblei | P01275, HS |
Organism-specific databases
HPAi | ENSG00000115263, Tissue enriched (pancreas) |
Interactioni
Binary interactionsi
P01275
GO - Molecular functioni
- gastric inhibitory polypeptide receptor binding Source: BHF-UCL
- 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
BioGRIDi | 108911, 269 interactors |
DIPi | DIP-46470N |
IntActi | P01275, 7 interactors |
MINTi | P01275 |
STRINGi | 9606.ENSP00000387662 |
Chemistry databases
BindingDBi | P01275 |
Miscellaneous databases
RNActi | P01275, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P01275 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P01275 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 26 – 59 | DisorderedSequence analysisAdd BLAST | 34 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 26 – 43 | Polar residuesSequence analysisAdd BLAST | 18 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502RYPR, Eukaryota |
GeneTreei | ENSGT00390000005372 |
HOGENOMi | CLU_090687_0_0_1 |
InParanoidi | P01275 |
OMAi | KRNGQQG |
OrthoDBi | 1349644at2759 |
PhylomeDBi | P01275 |
TreeFami | TF332333 |
Family and domain databases
InterProi | View protein in InterPro IPR015550, Glucagon IPR000532, Glucagon_GIP_secretin_VIP |
PANTHERi | PTHR11418, PTHR11418, 1 hit |
Pfami | View protein in Pfam PF00123, Hormone_2, 3 hits |
PRINTSi | PR00275, GLUCAGON |
SMARTi | View protein in SMART SM00070, GLUCA, 3 hits |
PROSITEi | View protein in PROSITE PS00260, GLUCAGON, 4 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 82 | K → N in CAA27627 (PubMed:3725587).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014596 | 115 | A → 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 |
CCDSi | CCDS46439.1 |
PIRi | A24377, GCHU |
RefSeqi | NP_002045.1, NM_002054.4 |
Genome annotation databases
Ensembli | ENST00000375497; ENSP00000364647; ENSG00000115263 ENST00000418842; ENSP00000387662; ENSG00000115263 |
GeneIDi | 2641 |
KEGGi | hsa:2641 |
MANE-Selecti | ENST00000418842.7; ENSP00000387662.2; NM_002054.5; NP_002045.1 |
UCSCi | uc002ucc.5, human |
Similar proteinsi
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 |
CCDSi | CCDS46439.1 |
PIRi | A24377, GCHU |
RefSeqi | NP_002045.1, NM_002054.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BH0 | X-ray | 3.00 | A | 53-81 | [»] | |
1D0R | NMR | - | A | 98-127 | [»] | |
1NAU | NMR | - | A | 59-81 | [»] | |
2G49 | X-ray | 2.50 | C/D | 53-81 | [»] | |
2L63 | NMR | - | A | 146-178 | [»] | |
2L64 | NMR | - | A | 146-178 | [»] | |
2M5P | NMR | - | X | 53-81 | [»] | |
2M5Q | NMR | - | X | 53-81 | [»] | |
3IOL | X-ray | 2.10 | B | 98-128 | [»] | |
4APD | NMR | - | A | 98-128 | [»] | |
4ZGM | X-ray | 1.80 | B | 98-128 | [»] | |
5OTU | X-ray | 1.80 | B/D | 98-128 | [»] | |
5OTV | X-ray | 2.00 | B/D | 98-128 | [»] | |
5OTW | X-ray | 2.10 | B/D | 98-128 | [»] | |
5OTX | X-ray | 2.00 | B/D | 98-128 | [»] | |
5VAI | electron microscopy | 4.10 | P | 98-128 | [»] | |
5YQZ | X-ray | 3.00 | P | 54-81 | [»] | |
6EDS | X-ray | 3.18 | C/D | 53-81 | [»] | |
6LMK | electron microscopy | 3.70 | E | 53-81 | [»] | |
6LML | electron microscopy | 3.90 | E | 53-81 | [»] | |
6NZN | NMR | - | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P | 53-81 | [»] | |
6PHI | X-ray | 1.10 | A | 53-81 | [»] | |
6PHJ | X-ray | 1.99 | A | 53-81 | [»] | |
6PHK | X-ray | 1.18 | A | 53-81 | [»] | |
6PHL | X-ray | 1.44 | A | 53-81 | [»] | |
6PHO | X-ray | 1.42 | A | 54-81 | [»] | |
6PHP | X-ray | 1.65 | A | 53-81 | [»] | |
6VCB | electron microscopy | 3.30 | P | 98-128 | [»] | |
6X18 | electron microscopy | 2.10 | P | 98-127 | [»] | |
7D68 | electron microscopy | 3.00 | P | 146-178 | [»] | |
7DUQ | electron microscopy | 2.50 | P | 98-127 | [»] | |
SMRi | P01275 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108911, 269 interactors |
DIPi | DIP-46470N |
IntActi | P01275, 7 interactors |
MINTi | P01275 |
STRINGi | 9606.ENSP00000387662 |
Chemistry databases
BindingDBi | P01275 |
ChEMBLi | CHEMBL5736 |
PTM databases
iPTMneti | P01275 |
PhosphoSitePlusi | P01275 |
Genetic variation databases
BioMutai | GCG |
DMDMi | 125987831 |
Proteomic databases
jPOSTi | P01275 |
MassIVEi | P01275 |
PaxDbi | P01275 |
PeptideAtlasi | P01275 |
PRIDEi | P01275 |
ProteomicsDBi | 51367 |
Protocols and materials databases
ABCDi | P01275, 12 sequenced antibodies |
Antibodypediai | 3506, 1921 antibodies from 45 providers |
DNASUi | 2641 |
Genome annotation databases
Ensembli | ENST00000375497; ENSP00000364647; ENSG00000115263 ENST00000418842; ENSP00000387662; ENSG00000115263 |
GeneIDi | 2641 |
KEGGi | hsa:2641 |
MANE-Selecti | ENST00000418842.7; ENSP00000387662.2; NM_002054.5; NP_002045.1 |
UCSCi | uc002ucc.5, human |
Organism-specific databases
CTDi | 2641 |
DisGeNETi | 2641 |
GeneCardsi | GCG |
HGNCi | HGNC:4191, GCG |
HPAi | ENSG00000115263, Tissue enriched (pancreas) |
MIMi | 138030, gene |
neXtProti | NX_P01275 |
OpenTargetsi | ENSG00000115263 |
PharmGKBi | PA28606 |
VEuPathDBi | HostDB:ENSG00000115263 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RYPR, Eukaryota |
GeneTreei | ENSGT00390000005372 |
HOGENOMi | CLU_090687_0_0_1 |
InParanoidi | P01275 |
OMAi | KRNGQQG |
OrthoDBi | 1349644at2759 |
PhylomeDBi | P01275 |
TreeFami | TF332333 |
Enzyme and pathway databases
PathwayCommonsi | P01275 |
Reactomei | R-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 R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | P01275 |
SIGNORi | P01275 |
Miscellaneous databases
BioGRID-ORCSi | 2641, 7 hits in 1036 CRISPR screens |
ChiTaRSi | GCG, human |
EvolutionaryTracei | P01275 |
GeneWikii | Glucagon |
GenomeRNAii | 2641 |
Pharosi | P01275, Tchem |
PROi | PR:P01275 |
RNActi | P01275, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000115263, Expressed in islet of Langerhans and 94 other tissues |
Genevisiblei | P01275, HS |
Family and domain databases
InterProi | View protein in InterPro IPR015550, Glucagon IPR000532, Glucagon_GIP_secretin_VIP |
PANTHERi | PTHR11418, PTHR11418, 1 hit |
Pfami | View protein in Pfam PF00123, Hormone_2, 3 hits |
PRINTSi | PR00275, GLUCAGON |
SMARTi | View protein in SMART SM00070, GLUCA, 3 hits |
PROSITEi | View protein in PROSITE PS00260, GLUCAGON, 4 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | GLUC_HUMAN | |
Accessioni | P01275Primary (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: | February 23, 2022 | |
This is version 220 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Pharmaceutical, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families