Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH8P977)

• DOT Name: Phospholipase ABHD3 (ABHD3)
• Synonyms: EC 3.1.1.32; EC 3.1.1.4; Abhydrolase domain-containing protein 3
• Gene Name: ABHD3
• UniProt ID: ABHD3_HUMAN
• EC Number: 3.1.1.32; 3.1.1.4
• Pfam ID: PF00561
• Sequence:
  MQRLAMDLRMLSRELSLYLEHQVRVGFFGSGVGLSLILGFSVAYAFYYLSSIAKKPQLVT
  GGESFSRFLQDHCPVVTETYYPTVWCWEGRGQTLLRPFITSKPPVQYRNELIKTADGGQI
  SLDWFDNDNSTCYMDASTRPTILLLPGLTGTSKESYILHMIHLSEELGYRCVVFNNRGVA
  GENLLTPRTYCCANTEDLETVIHHVHSLYPSAPFLAAGVSMGGMLLLNYLGKIGSKTPLM
  AAATFSVGWNTFACSESLEKPLNWLLFNYYLTTCLQSSVNKHRHMFVKQVDMDHVMKAKS
  IREFDKRFTSVMFGYQTIDDYYTDASPSPRLKSVGIPVLCLNSVDDVFSPSHAIPIETAK
  QNPNVALVLTSYGGHIGFLEGIWPRQSTYMDRVFKQFVQAMVEHGHELS
• Function: Phospholipase that may play a role in phospholipids remodeling. May selectively cleave myristate (C14)-containing phosphatidylcholines through its predominant phospholipase 1 activity, cleaving preferentially acyl groups in sn1 position. In parallel, may have a minor phospholipase 2 activity acting on acyl groups in position sn2. In addition to (C14)-containing phosphatidylcholines, may also act on other medium-chain-containing and oxidatively truncated phospholipids.
• Reactome Pathway: Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Phospholipase ABHD3 (ABHD3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phospholipase ABHD3 (ABHD3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phospholipase ABHD3 (ABHD3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Phospholipase ABHD3 (ABHD3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phospholipase ABHD3 (ABHD3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phospholipase ABHD3 (ABHD3).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Phospholipase ABHD3 (ABHD3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phospholipase ABHD3 (ABHD3).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phospholipase ABHD3 (ABHD3).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Phospholipase ABHD3 (ABHD3).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Phospholipase ABHD3 (ABHD3).	[10]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Phospholipase ABHD3 (ABHD3).	[11]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Phospholipase ABHD3 (ABHD3).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Phospholipase ABHD3 (ABHD3).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phospholipase ABHD3 (ABHD3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phospholipase ABHD3 (ABHD3).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phospholipase ABHD3 (ABHD3).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phospholipase ABHD3 (ABHD3).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Phospholipase ABHD3 (ABHD3).	[18]

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 affects the methylation of Phospholipase ABHD3 (ABHD3).	[14]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [10] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [11] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] 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.