Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3IZ61B)

• DOT Name: COMM domain-containing protein 9 (COMMD9)
• Gene Name: COMMD9
• Related Disease: Non-small-cell lung cancer
• UniProt ID: COMD9_HUMAN
• PDB ID: 4NKN; 4OE9; 6BP6; 8ESD; 8F2R; 8F2U
• Pfam ID: PF07258 ; PF20923
• Sequence:
  MAALTAEHFAALQSLLKASSKDVVRQLCQESFSSSALGLKKLLDVTCSSLSVTQEEAEEL
  LQALHRLTRLVAFRDLSSAEAILALFPENFHQNLKNLLTKIILEHVSTWRTEAQANQISL
  PRLVDLDWRVDIKTSSDSISRMAVPTCLLQMKIQEDPSLCGDKPSISAVTVELSKETLDT
  MLDGLGRIRDQLSAVASK
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]

9 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 COMM domain-containing protein 9 (COMMD9).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of COMM domain-containing protein 9 (COMMD9).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of COMM domain-containing protein 9 (COMMD9).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 9 (COMMD9).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COMM domain-containing protein 9 (COMMD9).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of COMM domain-containing protein 9 (COMMD9).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of COMM domain-containing protein 9 (COMMD9).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of COMM domain-containing protein 9 (COMMD9).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of COMM domain-containing protein 9 (COMMD9).	[11]

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 COMM domain-containing protein 9 (COMMD9).	[9]

References

• [1] COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer.Cell Signal. 2017 Jan;30:59-66. doi: 10.1016/j.cellsig.2016.11.016. Epub 2016 Nov 19.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [9] 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.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.