Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZP43K4)

• DOT Name: 2-acylglycerol O-acyltransferase 1 (MOGAT1)
• Synonyms: EC 2.3.1.22; Acyl-CoA:monoacylglycerol acyltransferase 1; MGAT1; Diacylglycerol O-acyltransferase candidate 2; hDC2; Diacylglycerol acyltransferase 2-like protein 1; Monoacylglycerol O-acyltransferase 1
• Gene Name: MOGAT1
• Related Disease:
  Multiple sclerosis
  Fatty liver disease
  Overnutrition
• UniProt ID: MOGT1_HUMAN
• EC Number: 2.3.1.22
• Pfam ID: PF03982
• Sequence:
  MKVEFAPLNIQLARRLQTVAVLQWVLKYLLLGPMSIGITVMLIIHNYLFLYIPYLMWLYF
  DWHTPERGGRRSSWIKNWTLWKHFKDYFPIHLIKTQDLDPSHNYIFGFHPHGIMAVGAFG
  NFSVNYSDFKDLFPGFTSYLHVLPLWFWCPVFREYVMSVGLVSVSKKSVSYMVSKEGGGN
  ISVIVLGGAKESLDAHPGKFTLFIRQRKGFVKIALTHGASLVPVVSFGENELFKQTDNPE
  GSWIRTVQNKLQKIMGFALPLFHARGVFQYNFGLMTYRKAIHTVVGRPIPVRQTLNPTQE
  QIEELHQTYMEELRKLFEEHKGKYGIPEHETLVLK
• 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, mainly at the sn-1 or sn-3 positions. It uses both sn-2-monoacylglycerol (2-acylglycerol) and sn-1-monoacylglycerol (1-acyl-sn-glycerol) equally well as substrates, and uses sn-3-monoacylglycerol (3-acyl-sn-glycerol) with lower efficiency. Probably not involved in absorption of dietary fat in the small intestine.
• Tissue Specificity: Expressed in stomach and liver.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Triglyceride biosynthesis (R-HSA-75109)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[1]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[2]
Overnutrition	DISGAJIG	Strong	Genetic Variation	[2]

3 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 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[11]

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 1 (MOGAT1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-acylglycerol O-acyltransferase 1 (MOGAT1).	[9]

References

• [1] Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis.Nat Commun. 2011;2:334. doi: 10.1038/ncomms1333.
• [2] Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.FASEB J. 2018 May 29:fj201700717RR. doi: 10.1096/fj.201700717RR. Online ahead of print.
• [3] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.