Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSGT89T)

• DOT Name: Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3)
• Synonyms: 3-demethylubiquinol 3-O-methyltransferase; EC 2.1.1.64; Polyprenyldihydroxybenzoate methyltransferase; EC 2.1.1.114
• Gene Name: COQ3
• UniProt ID: COQ3_HUMAN
• EC Number: 2.1.1.114; 2.1.1.64
• Pfam ID: PF13489
• Sequence:
  MWSGRKLGSSGGWFLRVLGPGGCNTKAARPLISSAVYVKNQLSGTLQIKPGVFNEYRTIW
  FKSYRTIFSCLNRIKSFRYPWARLYSTSQTTVDSGEVKTFLALAHKWWDEQGVYAPLHSM
  NDLRVPFIRDNLLKTIPNHQPGKPLLGMKILDVGCGGGLLTEPLGRLGASVIGIDPVDEN
  IKTAQCHKSFDPVLDKRIEYRVCSLEEIVEETAETFDAVVASEVVEHVIDLETFLQCCCQ
  VLKPGGSLFITTINKTQLSYALGIVFSEQIASIVPKGTHTWEKFVSPETLESILESNGLS
  VQTVVGMLYNPFSGYWHWSENTSLNYAAYAVKSRVQEHPASAEFVLKGETEELQANACTN
  PAVHEKLKK
• Function: O-methyltransferase that catalyzes the 2 O-methylation steps in the ubiquinone biosynthetic pathway.
• KEGG Pathway:
  Ubiquinone and other terpenoid-quinone biosynthesis (hsa00130)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Ubiquinol biosynthesis (R-HSA-2142789)
• BioCyc Pathway: MetaCyc:HS05632-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

15 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 Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[15]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[16]

2 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 Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ubiquinone biosynthesis O-methyltransferase, mitochondrial (COQ3).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.