Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTML8QW4)

• DOT Name: Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A)
• Synonyms: EC 6.2.1.2; Acyl-CoA synthetase medium-chain family member 2A; Benzoate--CoA ligase; EC 6.2.1.25; Butyrate--CoA ligase 2A; Butyryl-coenzyme A synthetase 2A; Middle-chain acyl-CoA synthetase 2A
• Gene Name: ACSM2A
• Related Disease: Cerebral palsy
• UniProt ID: ACS2A_HUMAN
• PDB ID: 2VZE; 2WD9; 3B7W; 3C5E; 3DAY; 3EQ6; 3GPC
• EC Number: 6.2.1.2; 6.2.1.25
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MHWLRKVQGLCTLWGTQMSSRTLYINSRQLVSLQWGHQEVPAKFNFASDVLDHWADMEKA
  GKRLPSPALWWVNGKGKELMWNFRELSENSQQAANVLSGACGLQRGDRVAVVLPRVPEWW
  LVILGCIRAGLIFMPGTIQMKSTDILYRLQMSKAKAIVAGDEVIQEVDTVASECPSLRIK
  LLVSEKSCDGWLNFKKLLNEASTTHHCVETGSQEASAIYFTSGTSGLPKMAEHSYSSLGL
  KAKMDAGWTGLQASDIMWTISDTGWILNILCSLMEPWALGACTFVHLLPKFDPLVILKTL
  SSYPIKSMMGAPIVYRMLLQQDLSSYKFPHLQNCVTVGESLLPETLENWRAQTGLDIRES
  YGQTETGLTCMVSKTMKIKPGYMGTAASCYDVQIIDDKGNVLPPGTEGDIGIRVKPIRPI
  GIFSGYVDNPDKTAANIRGDFWLLGDRGIKDEDGYFQFMGRANDIINSSGYRIGPSEVEN
  ALMEHPAVVETAVISSPDPVRGEVVKAFVVLASQFLSHDPEQLTKELQQHVKSVTAPYKY
  PRKIEFVLNLPKTVTGKIQRAKLRDKEWKMSGKARAQ
• Function: Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism. Capable of activating medium-chain fatty acids (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate.
• KEGG Pathway:
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Aspirin ADME (R-HSA-9749641)
  Conjugation of salicylate with glycine (R-HSA-177128)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral palsy	DIS82ODL	Strong	Genetic Variation	[1]

2 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 Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Acyl-coenzyme A synthetase ACSM2A, mitochondrial (ACSM2A).	[7]

References

• [1] Effect of the severity of manual impairment and hand dominance on anticipatory and compensatory postural adjustments during manual reaching in children with cerebral palsy.Res Dev Disabil. 2018 Dec;83:47-56. doi: 10.1016/j.ridd.2018.08.007. Epub 2018 Aug 21.
• [2] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.