Details of Drug Off-Target (DOT)

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

• DOT Name: Acyl-coenzyme A synthetase ACSM2B, mitochondrial (ACSM2B)
• Synonyms: EC 6.2.1.2; Acyl-CoA synthetase medium-chain family member 2B; Benzoate--CoA ligase; EC 6.2.1.25; Butyrate--CoA ligase 2B; Butyryl-coenzyme A synthetase 2B; Middle-chain acyl-CoA synthetase 2B; Xenobiotic/medium-chain fatty acid-CoA ligase HXM-A
• Gene Name: ACSM2B
• UniProt ID: ACS2B_HUMAN
• EC Number: 6.2.1.2; 6.2.1.25
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MHWLRKVQGLCTLWGTQMSSRTLYINSRQLVSLQWGHQEVPAKFNFASDVLDHWADMEKA
  GKRLPSPALWWVNGKGKELMWNFRELSENSQQAANILSGACGLQRGDRVAVMLPRVPEWW
  LVILGCIRAGLIFMPGTIQMKSTDILYRLQMSKAKAIVAGDEVIQEVDTVASECPSLRIK
  LLVSEKSCDGWLNFKKLLNEASTTHHCVETGSQEASAIYFTSGTSGLPKMAEHSYSSLGL
  KAKMDAGWTGLQASDIMWTISDTGWILNILGSLLESWTLGACTFVHLLPKFDPLVILKTL
  SSYPIKSMMGAPIVYRMLLQQDLSSYKFPHLQNCLAGGESLLPETLENWRAQTGLDIREF
  YGQTETGLTCMVSKTMKIKPGYMGTAASCYDVQVIDDKGNVLPPGTEGDIGIRVKPIRPI
  GIFSGYVENPDKTAANIRGDFWLLGDRGIKDEDGYFQFMGRADDIINSSGYRIGPSEVEN
  ALMKHPAVVETAVISSPDPVRGEVVKAFVILASQFLSHDPEQLTKELQQHVKSVTAPYKY
  PRKIEFVLNLPKTVTGKIQRTKLRDKEWKMSGKARAQ
• 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.
• Tissue Specificity: Detected in liver.
• KEGG Pathway:
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Conjugation of benzoate with glycine (R-HSA-177135)
  Conjugation of phenylacetate with glutamine (R-HSA-177162)
  Aspirin ADME (R-HSA-9749641)
  Conjugation of salicylate with glycine (R-HSA-177128)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Acyl-coenzyme A synthetase ACSM2B, mitochondrial (ACSM2B).	[1]

5 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 ACSM2B, mitochondrial (ACSM2B).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acyl-coenzyme A synthetase ACSM2B, mitochondrial (ACSM2B).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-coenzyme A synthetase ACSM2B, mitochondrial (ACSM2B).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-coenzyme A synthetase ACSM2B, mitochondrial (ACSM2B).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Acyl-coenzyme A synthetase ACSM2B, mitochondrial (ACSM2B).	[6]

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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [6] 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.