Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ANQLQ)

• DOT Name: COMM domain-containing protein 10 (COMMD10)
• Gene Name: COMMD10
• Related Disease:
  Bipolar disorder
  Colitis
  Colorectal carcinoma
  Inflammatory bowel disease
  Schizophrenia
  Asthma
  Chronic obstructive pulmonary disease
  Bladder transitional cell carcinoma
  Clear cell renal carcinoma
  Neoplasm
• UniProt ID: COMDA_HUMAN
• PDB ID: 8ESD; 8F2R; 8F2U
• Pfam ID: PF07258 ; PF21672
• Sequence:
  MAVPAALILRESPSMKKAVSLINAIDTGRFPRLLTRILQKLHLKAESSFSEEEEEKLQAA
  FSLEKQDLHLVLETISFILEQAVYHNVKPAALQQQLENIHLRQDKAEAFVNTWSSMGQET
  VEKFRQRILAPCKLETVGWQLNLQMAHSAQAKLKSPQAVLQLGVNNEDSKSLEKVLVEFS
  HKELFDFYNKLETIQAQLDSLT
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Colitis	DISAF7DD	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Asthma	DISW9QNS	moderate	Biomarker	[4]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[4]
Bladder transitional cell carcinoma	DISNL46A	Limited	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]

9 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 COMM domain-containing protein 10 (COMMD10).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of COMM domain-containing protein 10 (COMMD10).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of COMM domain-containing protein 10 (COMMD10).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 10 (COMMD10).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of COMM domain-containing protein 10 (COMMD10).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of COMM domain-containing protein 10 (COMMD10).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of COMM domain-containing protein 10 (COMMD10).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of COMM domain-containing protein 10 (COMMD10).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of COMM domain-containing protein 10 (COMMD10).	[14]

References

• [1] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [2] Impaired COMMD10-Mediated Regulation of Ly6C(hi) Monocyte-Driven Inflammation Disrupts Gut Barrier Function.Front Immunol. 2018 Nov 14;9:2623. doi: 10.3389/fimmu.2018.02623. eCollection 2018.
• [3] FMNL2 destabilises COMMD10 to activate NF-B pathway in invasion and metastasis of colorectal cancer.Br J Cancer. 2017 Oct 10;117(8):1164-1175. doi: 10.1038/bjc.2017.260. Epub 2017 Aug 17.
• [4] Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.Eur Respir J. 2014 Oct;44(4):860-72. doi: 10.1183/09031936.00001914. Epub 2014 Jul 3.
• [5] Expression profile and bioinformatics analysis of COMMD10 in BALB/C mice and human.Cancer Gene Ther. 2020 Apr;27(3-4):216-225. doi: 10.1038/s41417-019-0087-9. Epub 2019 Feb 21.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [14] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.