Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRLXGS6)

• DOT Name: 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5)
• Synonyms: EC 2.1.1.201; Ubiquinone biosynthesis methyltransferase COQ5
• Gene Name: COQ5
• Related Disease:
  Cerebellar ataxia
  Intellectual disability
  Myocardial infarction
  Coenzyme q10 deficiency, primary, 9
• UniProt ID: COQ5_HUMAN
• EC Number: 2.1.1.201
• Pfam ID: PF01209
• Sequence:
  MAAPGSCALWSYCGRGWSRAMRGCQLLGLRSSWPGDLLSARLLSQEKRAAETHFGFETVS
  EEEKGGKVYQVFESVAKKYDVMNDMMSLGIHRVWKDLLLWKMHPLPGTQLLDVAGGTGDI
  AFRFLNYVQSQHQRKQKRQLRAQQNLSWEEIAKEYQNEEDSLGGSRVVVCDINKEMLKVG
  KQKALAQGYRAGLAWVLGDAEELPFDDDKFDIYTIAFGIRNVTHIDQALQEAHRVLKPGG
  RFLCLEFSQVNNPLISRLYDLYSFQVIPVLGEVIAGDWKSYQYLVESIRRFPSQEEFKDM
  IEDAGFHKVTYESLTSGIVAIHSGFKL
• Function: Methyltransferase required for the conversion of 2-polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2).
• Tissue Specificity: Widely expressed, with highest levels in liver, lung, placenta and skeletal muscle.
• 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:ENSG00000110871-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[2]
Myocardial infarction	DIS655KI	Strong	Biomarker	[3]
Coenzyme q10 deficiency, primary, 9	DIS5V9VL	Limited	Unknown	[2]

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 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (COQ5).	[10]

References

• [1] A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency.Hum Mutat. 2018 Jan;39(1):69-79. doi: 10.1002/humu.23345. Epub 2017 Nov 8.
• [2] Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.
• [3] A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction.Int J Cardiol. 2017 Jan 15;227:239-246. doi: 10.1016/j.ijcard.2016.11.127. Epub 2016 Nov 11.
• [4] 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.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.