Details of Drug Off-Target (DOT)

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

• DOT Name: 2-acylglycerol O-acyltransferase 3 (MOGAT3)
• Synonyms: EC 2.3.1.20; EC 2.3.1.22; Acyl-CoA:monoacylglycerol acyltransferase 3; MGAT3; Diacylglycerol O-acyltransferase candidate 7; hDC7; Diacylglycerol acyltransferase 2-like protein 7; Monoacylglycerol O-acyltransferase 3
• Gene Name: MOGAT3
• Related Disease:
  Alzheimer disease
  Non-alcoholic fatty liver disease
• UniProt ID: MOGT3_HUMAN
• EC Number: 2.3.1.20; 2.3.1.22
• Pfam ID: PF03982
• Sequence:
  MGVATTLQPPTTSKTLQKQHLEAVGAYQYVLTFLFMGPFFSLLVFVLLFTSLWPFSVFYL
  VWLYVDWDTPNQGGRRSEWIRNRAIWRQLRDYYPVKLVKTAELPPDRNYVLGAHPHGIMC
  TGFLCNFSTESNGFSQLFPGLRPWLAVLAGLFYLPVYRDYIMSFGLCPVSRQSLDFILSQ
  PQLGQAVVIMVGGAHEALYSVPGEHCLTLQKRKGFVRLALRHGASLVPVYSFGENDIFRL
  KAFATGSWQHWCQLTFKKLMGFSPCIFWGRGLFSATSWGLLPFAVPITTVVGRPIPVPQR
  LHPTEEEVNHYHALYMTALEQLFEEHKESCGVPASTCLTFI
• Function: Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. Also able to catalyze the terminal step in triacylglycerol synthesis by using diacylglycerol and fatty acyl-CoA as substrates. Has a preference toward palmitoyl-CoA and oleoyl-CoA. May be involved in absorption of dietary fat in the small intestine by catalyzing the resynthesis of triacylglycerol in enterocytes. Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG).
• Tissue Specificity: Selectively expressed in the digestive system. Highly expressed in the ileum, and at lower level in jejunum, duodenum, colon, cecum and the rectum. Not expressed in the stomach and the esophagus and trachea. Expressed at very low level in liver.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[2]

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 2-acylglycerol O-acyltransferase 3 (MOGAT3).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 2-acylglycerol O-acyltransferase 3 (MOGAT3).	[8]

5 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 3 (MOGAT3).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of 2-acylglycerol O-acyltransferase 3 (MOGAT3).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-acylglycerol O-acyltransferase 3 (MOGAT3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 2-acylglycerol O-acyltransferase 3 (MOGAT3).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 2-acylglycerol O-acyltransferase 3 (MOGAT3).	[9]

References

• [1] Immune blood biomarkers of Alzheimer disease patients.J Neuroimmunol. 2009 May 29;210(1-2):67-72. doi: 10.1016/j.jneuroim.2009.02.015. Epub 2009 Mar 28.
• [2] Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver.J Lipid Res. 2012 May;53(5):990-999. doi: 10.1194/jlr.P025536. Epub 2012 Mar 6.
• [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] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] 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.
• [9] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.