Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIJ64B9)

• DOT Name: Cytochrome c oxidase assembly protein COX19 (COX19)
• Synonyms: hCOX19
• Gene Name: COX19
• Related Disease: Advanced cancer
• UniProt ID: COX19_HUMAN
• Pfam ID: PF06747
• Sequence:
  MSTAMNFGTKSFQPRPPDKGSFPLDHLGECKSFKEKFMKCLHNNNFENALCRKESKEYLE
  CRMERKLMLQEPLEKLGFGDLTSGKSEAKK
• Function: Required for the transduction of an SCO1-dependent redox signal from the mitochondrion to ATP7A to regulate cellular copper homeostasis. May be required for the assembly of mitochondrial cytochrome c oxidase.
• Tissue Specificity: Ubiquitously expressed. Highly expressed in skeletal muscle.
• KEGG Pathway: Thermogenesis (hsa04714)
• Reactome Pathway:
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]

5 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 protein COX19 (COX19).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cytochrome c oxidase assembly protein COX19 (COX19).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytochrome c oxidase assembly protein COX19 (COX19).	[4]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Cytochrome c oxidase assembly protein COX19 (COX19).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cytochrome c oxidase assembly protein COX19 (COX19).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytochrome c oxidase assembly protein COX19 (COX19).	[7]

References

• [1] Systematic expression analysis of the mitochondrial respiratory chain protein subunits identifies COX5B as a prognostic marker in clear cell renal cell carcinoma.Int J Urol. 2019 Sep;26(9):910-916. doi: 10.1111/iju.14040. Epub 2019 Jul 7.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.