Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI5RMWB)

• DOT Name: Phospholipase A and acyltransferase 2 (PLAAT2)
• Synonyms: EC 2.3.1.-; EC 3.1.1.32; EC 3.1.1.4; HRAS-like suppressor 2
• Gene Name: PLAAT2
• Related Disease: Obesity
• UniProt ID: PLAT2_HUMAN
• PDB ID: 4DPZ
• EC Number: 2.3.1.-; 3.1.1.32; 3.1.1.4
• Pfam ID: PF04970
• Sequence:
  MALARPRPRLGDLIEISRFGYAHWAIYVGDGYVVHLAPASEIAGAGAASVLSALTNKAIV
  KKELLSVVAGGDNYRVNNKHDDRYTPLPSNKIVKRAEELVGQELPYSLTSDNCEHFVNHL
  RYGVSRSDQVTGAVTTVGVAAGLLAAASLVGILLARSKRERQ
• Function: Exhibits both phospholipase A1/2 and acyltransferase activities. Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids. For most substrates, PLA1 activity is much higher than PLA2 activity. Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid. Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs). Catalyzes N-acylation of PE using both sn-1 and sn-2 palmitoyl groups of PC as acyl donor. Exhibits high phospholipase A1/2 activity and low N-acyltransferase activity.
• Tissue Specificity: Expressed in liver, kidney, small intestine testis and colon . Undetectable in testis, placenta, salivary gland and fetal brain .
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Arachidonic acid metabolism (hsa00590)
  Linoleic acid metabolism (hsa00591)
  alpha-Linolenic acid metabolism (hsa00592)
  Metabolic pathways (hsa01100)
  Ras sig.ling pathway (hsa04014)
  Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway: Acyl chain remodelling of PE (R-HSA-1482839)
• BioCyc Pathway: MetaCyc:ENSG00000133328-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[3]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[4]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[5]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Phospholipase A and acyltransferase 2 (PLAAT2).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Phospholipase A and acyltransferase 2 (PLAAT2).	[8]

References

• [1] Two-week administration of engineered Escherichia coli establishes persistent resistance to diet-induced obesity even without antibiotic pre-treatment.Appl Microbiol Biotechnol. 2019 Aug;103(16):6711-6723. doi: 10.1007/s00253-019-09958-x. Epub 2019 Jun 15.
• [2] 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.
• [3] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [5] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [6] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [7] Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
• [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] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.