Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7IWAOI)

• DOT Name: Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A)
• Gene Name: COQ10A
• UniProt ID: CQ10A_HUMAN
• Pfam ID: PF03364
• Sequence:
  MAWAGSRRVPAGTRAAAERCCRLSLSPGAQPAPPPGPLPPPRPMRFLTSCSLLLPRAAQI
  LAAEAGLPSSRSFMGFAAPFTNKRKAYSERRIMGYSMQEMYEVVSNVQEYREFVPWCKKS
  LVVSSRKGHLKAQLEVGFPPVMERYTSAVSMVKPHMVKAVCTDGKLFNHLETIWRFSPGI
  PAYPRTCTVDFSISFEFRSLLHSQLATMFFDEVVKQNVAAFERRAATKFGPETAIPRELM
  FHEVHQT
• Function: Required for the function of coenzyme Q in the respiratory chain. May serve as a chaperone or may be involved in the transport of Q6 from its site of synthesis to the catalytic sites of the respiratory complexes (Probable).
• Reactome Pathway: Respiratory electron transport (R-HSA-611105)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[9]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Coenzyme Q-binding protein COQ10 homolog A, mitochondrial (COQ10A).	[10]

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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10) in human cells. J Biochem Mol Toxicol. 2011 Sep-Oct;25(5):280-9. doi: 10.1002/jbt.20387. Epub 2011 Feb 9.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.