General Information of Drug Off-Target (DOT) (ID: OTXU08VF)

DOT Name Pro-glucagon (GCG)
Gene Name GCG
UniProt ID
GLUC_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1BH0 ; 1D0R ; 1NAU ; 2G49 ; 2L63 ; 2L64 ; 2M5P ; 2M5Q ; 3IOL ; 4APD ; 4ZGM ; 5OTU ; 5OTV ; 5OTW ; 5OTX ; 5VAI ; 5YQZ ; 6EDS ; 6LMK ; 6LML ; 6NZN ; 6PHI ; 6PHJ ; 6PHK ; 6PHL ; 6PHO ; 6PHP ; 6VCB ; 6X18 ; 7D68 ; 7DUQ ; 7KI0 ; 7KI1 ; 7XM8 ; 8ANJ ; 8ANK ; 8JRV
Pfam ID
PF00123
Sequence
MKSIYFVAGLFVMLVQGSWQRSLQDTEEKSRSFSASQADPLSDPDQMNEDKRHSQGTFTS
DYSKYLDSRRAQDFVQWLMNTKRNRNNIAKRHDEFERHAEGTFTSDVSSYLEGQAAKEFI
AWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLAARDFINWLIQTKITDRK
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 (Probable); [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.
Tissue Specificity
.Secreted in the A cells of the islets of Langerhans.; [Glucagon-like peptide 1]: Secreted in the A cells of the islets of Langerhans . Secreted from enteroendocrine L cells throughout the gastrointestinal tract . Also secreted in selected neurons in the brain.; [Glucagon-like peptide 2]: Secreted from enteroendocrine cells throughout the gastrointestinal tract. Also secreted in selected neurons in the brain.; [Glicentin]: Secreted from enteroendocrine cells throughout the gastrointestinal tract.; [Oxyntomodulin]: Secreted from enteroendocrine cells throughout the gastrointestinal tract.
KEGG Pathway
cAMP sig.ling pathway (hsa04024 )
Neuroactive ligand-receptor interaction (hsa04080 )
Thermogenesis (hsa04714 )
Insulin secretion (hsa04911 )
Glucagon sig.ling pathway (hsa04922 )
Reactome Pathway
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676 )
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771 )
G alpha (q) signalling events (R-HSA-416476 )
G alpha (s) signalling events (R-HSA-418555 )
Glucagon-type ligand receptors (R-HSA-420092 )
Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085 )
Glucagon signaling in metabolic regulation (R-HSA-163359 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Pro-glucagon (GCG). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Pro-glucagon (GCG). [8]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Pro-glucagon (GCG). [2]
Bicalutamide DMZMSPF Approved Bicalutamide decreases the expression of Pro-glucagon (GCG). [3]
Orlistat DMRJSP8 Approved Orlistat decreases the expression of Pro-glucagon (GCG). [4]
Gatifloxacin DMSL679 Approved Gatifloxacin increases the expression of Pro-glucagon (GCG). [7]
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3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Clofibrate DMPC1J7 Approved Clofibrate affects the secretion of Pro-glucagon (GCG). [5]
Metoclopramide DMFA5MY Approved Metoclopramide increases the secretion of Pro-glucagon (GCG). [6]
geraniol DMS3CBD Investigative geraniol increases the secretion of Pro-glucagon (GCG). [9]
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References

1 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2 Retinoic acid can induce markers of endocrine transdifferentiation in pancreatic ductal adenocarcinoma: preliminary observations from an in vitro cell line model. J Clin Pathol. 2006 Jun;59(6):603-10. doi: 10.1136/jcp.2005.032003. Epub 2006 Feb 10.
3 Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
4 Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003 Aug;88(8):3829-34. doi: 10.1210/jc.2003-030199.
5 Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment. Metabolism. 1975 Aug;24(8):901-14. doi: 10.1016/0026-0495(75)90081-5.
6 Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion. Am J Physiol Gastrointest Liver Physiol. 2010 Dec;299(6):G1326-33. doi: 10.1152/ajpgi.00476.2009. Epub 2010 Sep 9.
7 Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats. Toxicol Appl Pharmacol. 2013 Feb 1;266(3):375-84. doi: 10.1016/j.taap.2012.11.015. Epub 2012 Nov 28.
8 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
9 Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1 secretion in enteroendocrine cells and attenuates hyperglycemia in type 2 diabetic mice. Sci Rep. 2017 Oct 25;7(1):13978. doi: 10.1038/s41598-017-14086-5.