Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4BKEJ9)

• DOT Name: G-protein coupled bile acid receptor 1 (GPBAR1)
• Synonyms: G-protein coupled receptor GPCR19; hGPCR19; Membrane-type receptor for bile acids; M-BAR; hBG37; BG37
• Gene Name: GPBAR1
• UniProt ID: GPBAR_HUMAN
• PDB ID: 7BW0; 7CFM; 7CFN; 7XTQ
• Pfam ID: PF00001
• Sequence:
  MTPNSTGEVPSPIPKGALGLSLALASLIITANLLLALGIAWDRRLRSPPAGCFFLSLLLA
  GLLTGLALPTLPGLWNQSRRGYWSCLLVYLAPNFSFLSLLANLLLVHGERYMAVLRPLQP
  PGSIRLALLLTWAGPLLFASLPALGWNHWTPGANCSSQAIFPAPYLYLEVYGLLLPAVGA
  AAFLSVRVLATAHRQLQDICRLERAVCRDEPSALARALTWRQARAQAGAMLLFGLCWGPY
  VATLLLSVLAYEQRPPLGPGTLLSLLSLGSASAAAVPVAMGLGDQRYTAPWRAAAQRCLQ
  GLWGRASRDSPGPSIAYHPSSQSSVDLDLN
• Function: Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids.
• Tissue Specificity: Ubiquitously expressed. Expressed at higher level in spleen and placenta. Expressed at lower level in other tissues. In digestive tissues, it is expressed in stomach, duodenum, ileocecum, ileum, jejunum, ascending colon, transverse colon, descending colon, cecum and liver, but not in esophagus and rectum.
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

Molecular Interaction Atlas (MIA) 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 increases the methylation of G-protein coupled bile acid receptor 1 (GPBAR1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of G-protein coupled bile acid receptor 1 (GPBAR1).	[5]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[2]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid decreases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[3]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[4]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[4]
Cholic acid	DM7OKQV	Approved	Cholic acid increases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[6]
	DM9CEI5		increases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[4]
Tauroursodeoxycholic acid	DMFKRQE	Investigative	Tauroursodeoxycholic acid decreases the expression of G-protein coupled bile acid receptor 1 (GPBAR1).	[3]

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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [3] Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes. PLoS One. 2013 Dec 3;8(12):e82086. doi: 10.1371/journal.pone.0082086. eCollection 2013.
• [4] Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.
• [5] 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.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.