Details of Drug Off-Target (DOT)

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

• DOT Name: 2-acylglycerol O-acyltransferase 2 (MOGAT2)
• Synonyms: EC 2.3.1.20; EC 2.3.1.22; Acyl-CoA:monoacylglycerol acyltransferase 2; MGAT2; hMGAT2; Diacylglycerol O-acyltransferase candidate 5; hDC5; Diacylglycerol acyltransferase 2-like protein 5; Monoacylglycerol O-acyltransferase 2
• Gene Name: MOGAT2
• UniProt ID: MOGT2_HUMAN
• EC Number: 2.3.1.20; 2.3.1.22
• Pfam ID: PF03982
• Sequence:
  MVEFAPLFMPWERRLQTLAVLQFVFSFLALAEICTVGFIALLFTRFWLLTVLYAAWWYLD
  RDKPRQGGRHIQAIRCWTIWKYMKDYFPISLVKTAELDPSRNYIAGFHPHGVLAVGAFAN
  LCTESTGFSSIFPGIRPHLMMLTLWFRAPFFRDYIMSAGLVTSEKESAAHILNRKGGGNL
  LGIIVGGAQEALDARPGSFTLLLRNRKGFVRLALTHGAPLVPIFSFGENDLFDQIPNSSG
  SWLRYIQNRLQKIMGISLPLFHGRGVFQYSFGLIPYRRPITTVVGKPIEVQKTLHPSEEE
  VNQLHQRYIKELCNLFEAHKLKFNIPADQHLEFC
• Function: Involved in glycerolipid synthesis and lipid metabolism. Catalyzes the formation of diacylglycerol, the precursor of triacylglycerol, by transferring the acyl chain of a fatty acyl-CoA to a monoacylglycerol. Plays a central role in absorption of dietary fat in the small intestine by catalyzing the resynthesis of triacylglycerol in enterocytes. Has a preference toward monoacylglycerols containing unsaturated fatty acids in an order of C18:3 > C18:2 > C18:1 > C18:0 at sn-2. Able to use 1-monoalkylglycerol (1-MAkG, 1-O-alkylglycerol) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG, 1-O-alkyl-3-acylglycerol or 1-O-alkyl-2-acylglycerol) and subsequently, with lower efficiency, may add another acyl chain producing monoalkyl-diacylglycerol (MADAG, 1-O-alkyl-2,3-diacylglycerol). Possesses weak but significant activity with diacylglycerol as substrate, producing triacylglycerol (triacyl-sn-glycerol).
• Tissue Specificity: Highly expressed in liver, small intestine, colon, stomach and kidney.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway: Triglyceride biosynthesis (R-HSA-75109)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 2-acylglycerol O-acyltransferase 2 (MOGAT2).	[6]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.