P01274 · GLUC_PIG
- ProteinPro-glucagon
- GeneGCG
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids180 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
Glucagon-like peptide 1
Potent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6. 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.
Glucagon-like peptide 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
GLP-2 does not have cleavage on a pair of basic residues at C-terminus as in other mammals.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 52-53 | Cleavage; by PCSK2 | ||||
Sequence: RH | ||||||
Site | 83-84 | Cleavage; by PCSK1 and PCSK2 | ||||
Sequence: RN | ||||||
Site | 91-92 | Cleavage; by PCSK1 | ||||
Sequence: RH | ||||||
Site | 97-98 | Cleavage; by PCSK1 | ||||
Sequence: RH | ||||||
Site | 130-131 | Cleavage; by PCSK1 | ||||
Sequence: RD | ||||||
Site | 145-146 | Cleavage; by PCSK1 | ||||
Sequence: RH |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular space | |
Molecular Function | glucagon receptor binding | |
Molecular Function | hormone activity | |
Biological Process | adenylate cyclase-modulating G protein-coupled receptor signaling pathway | |
Biological Process | glucose homeostasis | |
Biological Process | negative regulation of apoptotic process | |
Biological Process | positive regulation of insulin secretion involved in cellular response to glucose stimulus | |
Biological Process | protein kinase A signaling | |
Biological Process | regulation of insulin secretion | |
Biological Process | response to activity |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePro-glucagon
- Cleaved into 8 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus
Accessions
- Primary accessionP01274
- Secondary accessions
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for signal, peptide, modified residue, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MKTIYFVAGLFVMLVQGSWQ | ||||||
Peptide | PRO_0000011294 | 21-50 | Glicentin-related polypeptide | |||
Sequence: RSLQNTEEKSRSFPAPQTDPLDDPDQMTED | ||||||
Peptide | PRO_0000011293 | 21-89 | Glicentin | |||
Sequence: RSLQNTEEKSRSFPAPQTDPLDDPDQMTEDKRHSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNKNNIA | ||||||
Peptide | PRO_0000011296 | 53-81 | Glucagon | |||
Sequence: HSQGTFTSDYSKYLDSRRAQDFVQWLMNT | ||||||
Peptide | PRO_0000011295 | 53-89 | Oxyntomodulin | |||
Sequence: HSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNKNNIA | ||||||
Modified residue | 54 | Phosphoserine | ||||
Sequence: S | ||||||
Propeptide | PRO_0000011297 | 84-89 | ||||
Sequence: NKNNIA | ||||||
Peptide | PRO_0000011298 | 92-128 | Glucagon-like peptide 1 | |||
Sequence: HDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG | ||||||
Peptide | PRO_0000011300 | 98-127 | Glucagon-like peptide 1(7-36) | |||
Sequence: HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR | ||||||
Peptide | PRO_0000011299 | 98-128 | Glucagon-like peptide 1(7-37) | |||
Sequence: HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG | ||||||
Modified residue | 105 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 108 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 127 | Arginine amide | ||||
Sequence: R | ||||||
Propeptide | PRO_0000011301 | 131-145 | ||||
Sequence: DFPEEVTIVEELRRR | ||||||
Peptide | PRO_0000011302 | 146-180 | Glucagon-like peptide 2 | |||
Sequence: HADGSFSDEMNTVLDNLATRDFINWLLHTKITDSL | ||||||
Modified residue | 150 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 152 | Phosphoserine | ||||
Sequence: S |
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 (By similarity).
Keywords
- PTM
Proteomic databases
Expression
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. GLP-1 and GLP-2 are also secreted in selected neurons in the brain.
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 (By similarity).
Gene expression databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 25-59 | Disordered | ||||
Sequence: NTEEKSRSFPAPQTDPLDDPDQMTEDKRHSQGTFT |
Sequence similarities
Belongs to the glucagon family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length180
- Mass (Da)21,029
- Last updated2004-03-29 v4
- Checksum362997AB72197EE6
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 143 | in Ref. 6; AA sequence | ||||
Sequence: R → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY242124 EMBL· GenBank· DDBJ | AAO88211.1 EMBL· GenBank· DDBJ | mRNA |