Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHSX40F)

• DOT Name: Cytochrome c oxidase assembly factor 1 homolog (COA1)
• Synonyms: Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 15 kDa
• Gene Name: COA1
• Related Disease:
  Bone giant cell tumor
  CHARGE syndrome
  Neoplasm
• UniProt ID: COA1_HUMAN
• Pfam ID: PF08695
• Sequence:
  MMWQKYAGSRRSMPLGARILFHGVFYAGGFAIVYYLIQKFHSRALYYKLAVEQLQSHPEA
  QEALGPPLNIHYLKLIDRENFVDIVDAKLKIPVSGSKSEGLLYVHSSRGGPFQRWHLDEV
  FLELKDGQQIPVFKLSGENGDEVKKE
• Function: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. MITRAC complexes regulate both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. Required for assembly of mitochondrial respiratory chain complex I and complex IV. As part of the MCIA complex, required for efficient assembly of the mitochondrial complex I.
• KEGG Pathway: Thermogenesis (hsa04714)
• Reactome Pathway:
  Complex I biogenesis (R-HSA-6799198)
  Respiratory electron transport (R-HSA-611105)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone giant cell tumor	DIS0RGK9	Strong	Biomarker	[1]
CHARGE syndrome	DISKD3CW	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

10 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 Cytochrome c oxidase assembly factor 1 homolog (COA1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[4]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[9]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[13]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the methylation of Cytochrome c oxidase assembly factor 1 homolog (COA1).	[16]

References

• [1] MiR-127 and miR-376a act as tumor suppressors by invivo targeting of COA1 and PDIA6 in giant cell tumor of bone.Cancer Lett. 2017 Nov 28;409:49-55. doi: 10.1016/j.canlet.2017.08.029. Epub 2017 Sep 1.
• [2] The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline.Am J Pathol. 2012 Aug;181(2):626-41. doi: 10.1016/j.ajpath.2012.05.006. Epub 2012 May 29.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [10] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [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] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [16] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.