Details of Drug Off-Target (DOT)

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

• DOT Name: Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5)
• Synonyms: EC 6.2.1.2; Acyl-CoA synthetase medium-chain family member 5
• Gene Name: ACSM5
• UniProt ID: ACSM5_HUMAN
• EC Number: 6.2.1.2
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MRPWLRHLVLQALRNSRAFCGSHGKPAPLPVPQKIVATWEAISLGRQLVPEYFNFAHDVL
  DVWSRLEEAGHRPPNPAFWWVNGTGAEIKWSFEELGKQSRKAANVLGGACGLQPGDRMML
  VLPRLPEWWLVSVACMRTGTVMIPGVTQLTEKDLKYRLQASRAKSIITSDSLAPRVDAIS
  AECPSLQTKLLVSDSSRPGWLNFRELLREASTEHNCMRTKSRDPLAIYFTSGTTGAPKMV
  EHSQSSYGLGFVASGRRWVALTESDIFWNTTDTGWVKAAWTLFSAWPNGSCIFVHELPRV
  DAKVILNTLSKFPITTLCCVPTIFRLLVQEDLTRYQFQSLRHCLTGGEALNPDVREKWKH
  QTGVELYEGYGQSETVVICANPKGMKIKSGSMGKASPPYDVQIVDDEGNVLPPGEEGNVA
  VRIRPTRPFCFFNCYLDNPEKTAASEQGDFYITGDRARMDKDGYFWFMGRNDDVINSSSY
  RIGPVEVESALAEHPAVLESAVVSSPDPIRGEVVKAFIVLTPAYSSHDPEALTRELQEHV
  KRVTAPYKYPRKVAFVSELPKTVSGKIQRSKLRSQEWGK
• Function: Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.
• Tissue Specificity: Detected in kidney and liver.
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acyl-coenzyme A synthetase ACSM5, mitochondrial (ACSM5).	[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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [8] 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.