Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP0961M)

DOT Name Cytochrome c oxidase subunit 5A, mitochondrial (COX5A)
Synonyms Cytochrome c oxidase polypeptide Va
Gene Name COX5A
Related Disease
Acute myocardial infarction ( )
Adenoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal adenoma ( )
Colorectal carcinoma ( )
Esophageal squamous cell carcinoma ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Leigh syndrome ( )
Lung adenocarcinoma ( )
Nasopharyngeal carcinoma ( )
Neoplasm ( )
Pancreatic ductal carcinoma ( )
Parkinson disease ( )
Pulmonary arterial hypertension ( )
Schizophrenia ( )
Squamous cell carcinoma ( )
Type-1/2 diabetes ( )
Asthma ( )
Carcinoma ( )
Chronic obstructive pulmonary disease ( )
Gastric cancer ( )
Melanoma ( )
Mitochondrial disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Cytochrome-c oxidase deficiency disease ( )
Arthritis ( )
Coronary heart disease ( )
Epithelial ovarian cancer ( )
High blood pressure ( )
Lung cancer ( )
Lung carcinoma ( )
Mitochondrial complex 4 deficiency, nuclear type 20 ( )
Non-small-cell lung cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Rheumatoid arthritis ( )
Stomach cancer ( )
UniProt ID
COX5A_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5Z62
Pfam ID
PF02284
Sequence
MLGAALRRCAVAATTRADPRGLLHSARTPGPAVAIQSVRCYSHGSQETDEEFDARWVTYF
NKPDIDAWELRKGINTLVTYDMVPEPKIIDAALRACRRLNDFASTVRILEVVKDKAGPHK
EIYPYVIQELRPTLNELGISTPEELGLDKV
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 )
Reactome Pathway
Respiratory electron transport (R-HSA-611105 )
Cytoprotection by HMOX1 (R-HSA-9707564 )
TP53 Regulates Metabolic Genes (R-HSA-5628897 )
BioCyc Pathway
MetaCyc:HS11312-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myocardial infarction DISE3HTG Strong Biomarker [1]
Adenoma DIS78ZEV Strong Biomarker [2]
Adult glioblastoma DISVP4LU Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Cardiovascular disease DIS2IQDX Strong Biomarker [7]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [8]
Colon cancer DISVC52G Strong Biomarker [9]
Colon carcinoma DISJYKUO Strong Biomarker [9]
Colorectal adenoma DISTSVHM Strong Genetic Variation [10]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [11]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [12]
Glioblastoma multiforme DISK8246 Strong Altered Expression [3]
Glioma DIS5RPEH Strong Altered Expression [13]
Hepatocellular carcinoma DIS0J828 Strong Genetic Variation [14]
Leigh syndrome DISWQU45 Strong Genetic Variation [15]
Lung adenocarcinoma DISD51WR Strong Altered Expression [16]
Nasopharyngeal carcinoma DISAOTQ0 Strong Biomarker [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Pancreatic ductal carcinoma DIS26F9Q Strong Altered Expression [19]
Parkinson disease DISQVHKL Strong Genetic Variation [20]
Pulmonary arterial hypertension DISP8ZX5 Strong Biomarker [21]
Schizophrenia DISSRV2N Strong Biomarker [20]
Squamous cell carcinoma DISQVIFL Strong Biomarker [22]
Type-1/2 diabetes DISIUHAP Strong Biomarker [23]
Asthma DISW9QNS moderate Altered Expression [24]
Carcinoma DISH9F1N moderate Altered Expression [25]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [26]
Gastric cancer DISXGOUK moderate Biomarker [27]
Melanoma DIS1RRCY moderate Biomarker [28]
Mitochondrial disease DISKAHA3 moderate Biomarker [29]
Prostate cancer DISF190Y moderate Biomarker [30]
Prostate carcinoma DISMJPLE moderate Biomarker [30]
Cytochrome-c oxidase deficiency disease DISK7N3G Supportive Autosomal recessive [31]
Arthritis DIST1YEL Limited Biomarker [32]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [33]
Epithelial ovarian cancer DIS56MH2 Limited Altered Expression [34]
High blood pressure DISY2OHH Limited Biomarker [35]
Lung cancer DISCM4YA Limited Genetic Variation [36]
Lung carcinoma DISTR26C Limited Genetic Variation [36]
Mitochondrial complex 4 deficiency, nuclear type 20 DISIY7IA Limited Autosomal recessive [37]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [38]
Ovarian cancer DISZJHAP Limited Altered Expression [34]
Ovarian neoplasm DISEAFTY Limited Altered Expression [34]
Rheumatoid arthritis DISTSB4J Limited Biomarker [39]
Stomach cancer DISKIJSX Limited Biomarker [27]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Cytochrome c oxidase subunit 5A, mitochondrial (COX5A) affects the response to substance of Doxorubicin. [50]
Arsenic DMTL2Y1 Approved Cytochrome c oxidase subunit 5A, mitochondrial (COX5A) affects the response to substance of Arsenic. [51]
Vinblastine DM5TVS3 Approved Cytochrome c oxidase subunit 5A, mitochondrial (COX5A) affects the response to substance of Vinblastine. [50]
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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 Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [40]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [41]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [42]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [43]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [44]
Zidovudine DM4KI7O Approved Zidovudine decreases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [45]
Capsaicin DMGMF6V Approved Capsaicin increases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [46]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [47]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [48]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Cytochrome c oxidase subunit 5A, mitochondrial (COX5A). [49]
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⏷ Show the Full List of 10 Drug(s)

References

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16 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.
17 Correlation of the expressions of IGF1R-RACK1-STAT3 and Bcl-xl in nasopharyngeal carcinoma with the clinicopathological features and prognosis of nasopharyngeal carcinoma.J Cell Biochem. 2018 Feb;119(2):1931-1941. doi: 10.1002/jcb.26354. Epub 2017 Sep 18.
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19 CIP2A down regulation enhances the sensitivity of pancreatic cancer cells to gemcitabine.Oncotarget. 2016 Mar 22;7(12):14831-40. doi: 10.18632/oncotarget.7447.
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21 Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system.Br J Pharmacol. 2019 Apr;176(8):1038-1050. doi: 10.1111/bph.14167. Epub 2018 Apr 14.
22 ADAR1 overexpression is associated with cervical cancer progression and angiogenesis.Diagn Pathol. 2017 Jan 21;12(1):12. doi: 10.1186/s13000-017-0600-0.
23 Different Risk Profiles for the Postsurgical Prognosis of Gastric Cancer Patients with Different Blood Types: The FIESTA Study.J Cancer. 2018 Jul 30;9(16):2885-2894. doi: 10.7150/jca.25408. eCollection 2018.
24 IL-4/IFN- inflammatory cytokine profile induces a deficient regulation of the IL-1/IL-1RI/EP(2)/COX-2 pathway in nasal mucosa.Respir Med. 2019 Apr;150:136-140. doi: 10.1016/j.rmed.2019.03.008. Epub 2019 Mar 20.
25 Expression of methylation-modulated tumor-related genes in endoscopically resected early esophageal squamous neoplasia.Oncol Lett. 2017 Jul;14(1):737-742. doi: 10.3892/ol.2017.6196. Epub 2017 May 17.
26 Failed upregulation of TFAM protein and mitochondrial DNA in oxidatively deficient fibers of chronic obstructive pulmonary disease locomotor muscle.Skelet Muscle. 2016 Feb 18;6:10. doi: 10.1186/s13395-016-0083-9. eCollection 2016.
27 Tepoxalin a dual 5-LOX-COX inhibitor and erlotinib an EGFR inhibitor halts progression of gastric cancer in tumor xenograft mice.Am J Transl Res. 2018 Nov 15;10(11):3847-3856. eCollection 2018.
28 Inherited variation at MC1R and ASIP and association with melanoma-specific survival.Int J Cancer. 2015 Jun 1;136(11):2659-67. doi: 10.1002/ijc.29317. Epub 2014 Nov 26.
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30 COX-2 mediates pro-tumorigenic effects of PKC in prostate cancer.Oncogene. 2018 Aug;37(34):4735-4749. doi: 10.1038/s41388-018-0318-9. Epub 2018 May 16.
31 Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive. Hum Mutat. 2017 Jun;38(6):692-703. doi: 10.1002/humu.23210. Epub 2017 Mar 23.
32 LOX inhibitor HOEC interfered arachidonic acid metabolic flux in collagen-induced arthritis rats.Am J Transl Res. 2018 Aug 15;10(8):2542-2554. eCollection 2018.
33 Transition in the mechanism of flow-mediated dilation with aging and development of coronary artery disease.Basic Res Cardiol. 2017 Jan;112(1):5. doi: 10.1007/s00395-016-0594-x. Epub 2016 Dec 19.
34 Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E(2) in laying hen ovaries.Prostaglandins Leukot Essent Fatty Acids. 2013 Sep;89(4):179-87. doi: 10.1016/j.plefa.2013.08.001. Epub 2013 Aug 14.
35 Brain Prostaglandin D2 Increases Neurogenic Pressor Activity and Mean Arterial Pressure in Angiotensin II-Salt Hypertensive Rats.Hypertension. 2019 Dec;74(6):1499-1506. doi: 10.1161/HYPERTENSIONAHA.119.13175. Epub 2019 Oct 7.
36 Correlations of an Insertion/Deletion Polymorphism (rs10680577) in the RERT-lncRNA with the Susceptibility, Clinicopathological Features, and Prognosis of Lung Cancer.Biochem Genet. 2019 Feb;57(1):147-158. doi: 10.1007/s10528-018-9883-4. Epub 2018 Aug 2.
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38 Krppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer.Pathol Oncol Res. 2019 Jan;25(1):115-121. doi: 10.1007/s12253-017-0321-4. Epub 2017 Oct 6.
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40 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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42 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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44 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
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47 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
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49 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
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