Human Gene GCG (ENST00000418842.7) from GENCODE V44
Description: Homo sapiens glucagon (GCG), mRNA. (from RefSeq NM_002054) RefSeq Summary (NM_002054): The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signalling pathway controls cell proliferation. Two of the other peptides are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms. Finally, the fourth peptide is similar to glicentin, an active enteroglucagon. [provided by RefSeq, Jul 2008]. Sequence Note: A downstream translational start codon is selected for this RefSeq based on transcript support and on the presence of a predicted signal peptide in the protein N-terminus. Several upstream in-frame start codons are also present with sparse transcript support, and would result in proteins that are up to 83 aa longer at the N-terminus and lack predicted signal peptides. Leaky scanning by ribosomes may allow translation initiation at the downstream start codon. Gencode Transcript: ENST00000418842.7 Gencode Gene: ENSG00000115263.15 Transcript (Including UTRs) Position: hg38 chr2:162,142,882-162,152,247 Size: 9,366 Total Exon Count: 6 Strand: - Coding Region Position: hg38 chr2:162,143,364-162,149,178 Size: 5,815 Coding Exon Count: 5
ID:GLUC_HUMAN DESCRIPTION: RecName: Full=Glucagon; Contains: RecName: Full=Glicentin; Contains: RecName: Full=Glicentin-related polypeptide; Short=GRPP; Contains: RecName: Full=Oxyntomodulin; Short=OXM; Short=OXY; Contains: RecName: Full=Glucagon; Contains: RecName: Full=Glucagon-like peptide 1; Short=GLP-1; AltName: Full=Incretin hormone; Contains: RecName: Full=Glucagon-like peptide 1(7-37); Short=GLP-1(7-37); Contains: RecName: Full=Glucagon-like peptide 1(7-36); Short=GLP-1(7-36); Contains: RecName: Full=Glucagon-like peptide 2; Short=GLP-2; Flags: Precursor; 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. FUNCTION: 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. FUNCTION: 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. FUNCTION: 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. FUNCTION: 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. SUBCELLULAR LOCATION: Secreted. 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. PTM: 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. PHARMACEUTICAL: Available under the names Glucagon (Eli Lilly) and GlucaGen or Glucagon Novo Nordisk (Novo Nordisk). Used to treat severe hypoglycemia in insulin-dependent diabetics. MISCELLANEOUS: In the glucagon antagonist, His-53 and Phe-58 are missing. This antagonist has been successfully utilized to reduce glucose concentration in vivo. SIMILARITY: Belongs to the glucagon family. WEB RESOURCE: Name=Glucagon at Eli Lilly; Note=Clinical information on Eli Lilly glucagon products; URL="http://www.lillyDiabetes.com/Products/PatientInfo.cfm";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01275
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0007165 signal transduction GO:0007186 G-protein coupled receptor signaling pathway GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway GO:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007631 feeding behavior GO:0008283 cell proliferation GO:0010469 regulation of receptor activity GO:0010737 protein kinase A signaling GO:0010800 positive regulation of peptidyl-threonine phosphorylation GO:0032092 positive regulation of protein binding GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus GO:0035948 positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter GO:0042594 response to starvation GO:0043066 negative regulation of apoptotic process GO:0045860 positive regulation of protein kinase activity GO:0050796 regulation of insulin secretion GO:0051571 positive regulation of histone H3-K4 methylation GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071377 cellular response to glucagon stimulus GO:0090280 positive regulation of calcium ion import GO:1900118 negative regulation of execution phase of apoptosis
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