Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS3UKDP)

• DOT Name: Acyl-coenzyme A thioesterase THEM5 (THEM5)
• Synonyms: Acyl-CoA thioesterase THEM5; EC 3.1.2.2; Acyl-coenzyme A thioesterase 15; Thioesterase superfamily member 5
• Gene Name: THEM5
• Related Disease:
  Catecholaminergic polymorphic ventricular tachycardia 1
  Fatty liver disease
• UniProt ID: THEM5_HUMAN
• PDB ID: 4AE7
• EC Number: 3.1.2.2
• Pfam ID: PF03061
• Sequence:
  MIRRCFQVAARLGHHRGLLEAPRILPRLNPASAFGSSTDSMFSRFLPEKTDLKDYALPNA
  SWCSDMLSLYQEFLEKTKSSGWIKLPSFKSNRDHIRGLKLPSGLAVSSDKGDCRIFTRCI
  QVEGQGFEYVIFFQPTQKKSVCLFQPGSYLEGPPGFAHGGSLAAMMDETFSKTAFLAGEG
  LFTLSLNIRFKNLIPVDSLVVMDVELDKIEDQKLYMSCIAHSRDQQTVYAKSSGVFLQLQ
  LEEESPQ
• Function: Has acyl-CoA thioesterase activity towards long-chain (C16 and C18) fatty acyl-CoA substrates, with a preference for linoleoyl-CoA and other unsaturated long-chain fatty acid-CoA esters. Plays an important role in mitochondrial fatty acid metabolism, and in remodeling of the mitochondrial lipid cardiolipin. Required for normal mitochondrial function.
• KEGG Pathway:
  Fatty acid elongation (hsa00062)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	Strong	Genetic Variation	[1]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acyl-coenzyme A thioesterase THEM5 (THEM5).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Acyl-coenzyme A thioesterase THEM5 (THEM5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Acyl-coenzyme A thioesterase THEM5 (THEM5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acyl-coenzyme A thioesterase THEM5 (THEM5).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Acyl-coenzyme A thioesterase THEM5 (THEM5).	[7]

References

• [1] The genetics underlying idiopathic ventricular fibrillation: A special role for catecholaminergic polymorphic ventricular tachycardia?.Int J Cardiol. 2018 Jan 1;250:139-145. doi: 10.1016/j.ijcard.2017.10.016. Epub 2017 Oct 5.
• [2] Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling and fatty liver development.Mol Cell Biol. 2012 Jul;32(14):2685-97. doi: 10.1128/MCB.00312-12. Epub 2012 May 14.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] 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.
• [5] 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.
• [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.