Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDE5QKC)

• DOT Name: Acyl-coenzyme A thioesterase 6 (ACOT6)
• Synonyms: Acyl-CoA thioesterase 6; EC 3.1.2.-
• Gene Name: ACOT6
• Related Disease: Schizophrenia
• UniProt ID: ACOT6_HUMAN
• EC Number: 3.1.2.-
• Pfam ID: PF08840 ; PF04775
• Sequence:
  MAATLILEPAGRCCWDEPLRIAVRGLAPEQPVTLRTSLRDEEGALFRAHARYRADARDEL
  DLERAPALGGSFAGLQPMGLLWALEPEKALVRLVKRDVRTPFAVELEVLDGHDTEPGRLL
  CLAQNKRDFLRPGVRREPVRAGPVRAALFLPPDEGPFPGIIDLFGSSRGLCEYRASLLAG
  HGFAVLALAYFRFEDLPEDLNDVHLEYFEEAVDFMLQHPKVKGPSIALLGFSKGGDLCLS
  MASFLKGITATVLINACVANTVAPLHYKDMIIPKLVDDLGKVKITKSGFLTFMDTWSNPL
  EEHNHQSLVPLEKAQVPFLFIVGMDDQSWKSEFYAQIASERLQAHGKERPQIICYPETGH
  CIDPPYFPPSRASVHAVLGEAIFYGGEPKAHSKAQVDAWQQIQTFFHKHLNGKKSVKHSK
  I
• Function: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Catalyzes the hydrolysis of phytanoyl-CoA and pristanoyl-CoA, two methyl-branched fatty acids derived from phytol, that enter the body via the diet.
• Reactome Pathway: Beta-oxidation of very long chain fatty acids (R-HSA-390247)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Acyl-coenzyme A thioesterase 6 (ACOT6).	[2]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Acyl-coenzyme A thioesterase 6 (ACOT6).	[4]
CITCO	DM0N634	Investigative	CITCO increases the expression of Acyl-coenzyme A thioesterase 6 (ACOT6).	[7]

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 6 (ACOT6).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acyl-coenzyme A thioesterase 6 (ACOT6).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Acyl-coenzyme A thioesterase 6 (ACOT6).	[6]

References

• [1] Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet. 2011 Aug 7;43(9):864-8. doi: 10.1038/ng.902.
• [2] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [3] 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.
• [4] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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] 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.
• [7] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.