Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0N3WL9)

• DOT Name: Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11)
• Gene Name: COX11
• Related Disease:
  Breast cancer
  Breast carcinoma
  Male breast carcinoma
  Mitochondrial complex IV deficiency, nuclear type 23
• UniProt ID: COX11_HUMAN
• Pfam ID: PF04442
• Sequence:
  MGGLWRPGWRCVPFCGWRWIHPGSPTRAAERVEPFLRPEWSGTGGAERGLRWLGTWKRCS
  LRARHPALQPPRRPKSSNPFTRAQEEERRRQNKTTLTYVAAVAVGMLGASYAAVPLYRLY
  CQTTGLGGSAVAGHASDKIENMVPVKDRIIKISFNADVHASLQWNFRPQQTEIYVVPGET
  ALAFYRAKNPTDKPVIGISTYNIVPFEAGQYFNKIQCFCFEEQRLNPQEEVDMPVFFYID
  PEFAEDPRMIKVDLITLSYTFFEAKEGHKLPVPGYN
• Function: Exerts its effect at some terminal stage of cytochrome c oxidase synthesis, probably by being involved in the insertion of the copper B into subunit I.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Male breast carcinoma	DISUNQ2Q	Disputed	Genetic Variation	[2]
Mitochondrial complex IV deficiency, nuclear type 23	DISZIW3D	Limited	Autosomal recessive	[3]

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 Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[11]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cytochrome c oxidase assembly protein COX11, mitochondrial (COX11).	[18]

References

• [1] Genetic Breast Cancer Susceptibility Variants and Prognosis in the Prospectively Randomized SUCCESS A Study.Geburtshilfe Frauenheilkd. 2017 Jun;77(6):651-659. doi: 10.1055/s-0042-113189. Epub 2017 Jun 28.
• [2] Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men.PLoS Genet. 2011 Sep;7(9):e1002290. doi: 10.1371/journal.pgen.1002290. Epub 2011 Sep 15.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen. 2007 Apr-May;48(3-4):179-89. doi: 10.1002/em.20245.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] 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.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.