Details of Drug Off-Target (DOT)

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

• DOT Name: COMM domain-containing protein 4 (COMMD4)
• Gene Name: COMMD4
• Related Disease: Non-small-cell lung cancer
• UniProt ID: COMD4_HUMAN
• PDB ID: 8F2R; 8F2U
• Pfam ID: PF07258 ; PF21672
• Sequence:
  MRFRFCGDLDCPDWVLAEISTLAKMSSVKLRLLCSQVLKELLGQGIDYEKILKLTADAKF
  ESGDVKATVAVLSFILSSAAKHSVDGESLSSELQQLGLPKEHAASLCRCYEEKQSPLQKH
  LRVCSLRMNRLAGVGWRVDYTLSSSLLQSVEEPMVHLRLEVAAAPGTPAQPVAMSLSADK
  FQVLLAELKQAQTLMSSLG
• Function: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF-kappa-B.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Neddylation (R-HSA-8951664)

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	Altered Expression	[1]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of COMM domain-containing protein 4 (COMMD4).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 4 (COMMD4).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of COMM domain-containing protein 4 (COMMD4).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COMM domain-containing protein 4 (COMMD4).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of COMM domain-containing protein 4 (COMMD4).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of COMM domain-containing protein 4 (COMMD4).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of COMM domain-containing protein 4 (COMMD4).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of COMM domain-containing protein 4 (COMMD4).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of COMM domain-containing protein 4 (COMMD4).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of COMM domain-containing protein 4 (COMMD4).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of COMM domain-containing protein 4 (COMMD4).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of COMM domain-containing protein 4 (COMMD4).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of COMM domain-containing protein 4 (COMMD4).	[10]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] 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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.