Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLRHQ5F)

• DOT Name: Alpha/beta hydrolase domain-containing protein 17A (ABHD17A)
• Synonyms: Abhydrolase domain-containing protein 17A; EC 3.1.2.22
• Gene Name: ABHD17A
• UniProt ID: AB17A_HUMAN
• EC Number: 3.1.2.22
• Pfam ID: PF12146
• Sequence:
  MNGLSLSELCCLFCCPPCPGRIAAKLAFLPPEATYSLVPEPEPGPGGAGAAPLGTLRASS
  GAPGRWKLHLTERADFQYSQRELDTIEVFPTKSARGNRVSCMYVRCVPGARYTVLFSHGN
  AVDLGQMSSFYIGLGSRLHCNIFSYDYSGYGASSGRPSERNLYADIDAAWQALRTRYGIS
  PDSIILYGQSIGTVPTVDLASRYECAAVVLHSPLTSGMRVAFPDTKKTYCFDAFPNIEKV
  SKITSPVLIIHGTEDEVIDFSHGLALYERCPKAVEPLWVEGAGHNDIELYSQYLERLRRF
  ISQELPSQRA
• Function: Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards NRAS. Has depalmitoylating activity towards DLG4/PSD95. May have depalmitoylating activity towards MAP6.
• Reactome Pathway: RAS processing (R-HSA-9648002)

Molecular Interaction Atlas (MIA) of This DOT

4 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 Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Alpha/beta hydrolase domain-containing protein 17A (ABHD17A).	[8]

References

• [1] 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.
• [2] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [3] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [4] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [5] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [7] 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.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.