Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHV25GG)

• DOT Name: Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1)
• Synonyms: Cytochrome c oxidase subunit VIIa-heart; Cytochrome c oxidase subunit VIIa-H; Cytochrome c oxidase subunit VIIa-muscle; Cytochrome c oxidase subunit VIIa-M
• Gene Name: COX7A1
• Related Disease:
  Adenocarcinoma
  Cytochrome-c oxidase deficiency disease
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Non-insulin dependent diabetes
• UniProt ID: CX7A1_HUMAN
• Pfam ID: PF02238
• Sequence:
  MQALRVSQALIRSFSSTARNRFQNRVREKQKLFQEDNDIPLYLKGGIVDNILYRVTMTLC
  LGGTVYSLYSLGWASFPRN
• Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Cardiac muscle contraction (hsa04260)
  Thermogenesis (hsa04714)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[12]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytochrome c oxidase subunit 7A1, mitochondrial (COX7A1).	[14]

References

• [1] Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells.Biochem Biophys Res Commun. 2017 Jan 22;482(4):713-719. doi: 10.1016/j.bbrc.2016.11.100. Epub 2016 Nov 17.
• [2] Assembly of nuclear DNA-encoded subunits into mitochondrial complex IV, and their preferential integration into supercomplex forms in patient mitochondria.FEBS J. 2009 Nov;276(22):6701-13. doi: 10.1111/j.1742-4658.2009.07384.x. Epub 2009 Oct 16.
• [3] COX7A1 suppresses the viability of human non-small cell lung cancer cells via regulating autophagy.Cancer Med. 2019 Dec;8(18):7762-7773. doi: 10.1002/cam4.2659. Epub 2019 Oct 30.
• [4] Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle.Diabetologia. 2008 Jul;51(7):1159-68. doi: 10.1007/s00125-008-1018-8. Epub 2008 May 17.
• [5] 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.
• [6] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Expression of cytochrome c oxidase subunits encoded by mitochondrial or nuclear DNA in the muscle of patients with zidovudine myopathy. J Neurol Sci. 1994 Sep;125(2):190-3. doi: 10.1016/0022-510x(94)90034-5.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.