Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOVHLU9)

• DOT Name: Copper homeostasis protein cutC homolog (CUTC)
• Gene Name: CUTC
• Related Disease: Leigh syndrome
• UniProt ID: CUTC_HUMAN
• PDB ID: 3IWP
• Pfam ID: PF03932
• Sequence:
  MKRQGASSERKRARIPSGKAGAANGFLMEVCVDSVESAVNAERGGADRIELCSGLSEGGT
  TPSMGVLQVVKQSVQIPVFVMIRPRGGDFLYSDREIEVMKADIRLAKLYGADGLVFGALT
  EDGHIDKELCMSLMAICRPLPVTFHRAFDMVHDPMAALETLLTLGFERVLTSGCDSSALE
  GLPLIKRLIEQAKGRIVVMPGGGITDRNLQRILEGSGATEFHCSARSTRDSGMKFRNSSV
  AMGASLSCSEYSLKVTDVTKVRTLNAIAKNILV
• Function: May play a role in copper homeostasis. Can bind one Cu(1+) per subunit.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leigh syndrome	DISWQU45	moderate	Genetic Variation	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Copper homeostasis protein cutC homolog (CUTC) affects the response to substance of Fluorouracil.	[15]

13 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 Copper homeostasis protein cutC homolog (CUTC).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Copper homeostasis protein cutC homolog (CUTC).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Copper homeostasis protein cutC homolog (CUTC).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Copper homeostasis protein cutC homolog (CUTC).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Copper homeostasis protein cutC homolog (CUTC).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Copper homeostasis protein cutC homolog (CUTC).	[3]

References

• [1] Leigh syndrome associated with a novel mutation in the COX15 gene.J Pediatr Endocrinol Metab. 2016 Jun 1;29(6):741-4. doi: 10.1515/jpem-2015-0396.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.