Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1UTJH4)

• DOT Name: COMM domain-containing protein 3 (COMMD3)
• Synonyms: Protein Bup; Protein PIL
• Gene Name: COMMD3
• Related Disease:
  B-cell neoplasm
  Adenocarcinoma
  Analgesia
  Major depressive disorder
  Metastatic prostate carcinoma
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: COMD3_HUMAN
• PDB ID: 8F2R; 8F2U
• Pfam ID: PF07258
• Sequence:
  MELSESVQKGFQMLADPRSFDSNAFTLLLRAAFQSLLDAQADEAVLDHPDLKHIDPVVLK
  HCHAAAATYILEAGKHRADKSTLSTYLEDCKFDRERIELFCTEYQNNKNSLEILLGSIGR
  SLPHITDVSWRLEYQIKTNQLHRMYRPAYLVTLSVQNTDSPSYPEISFSCSMEQLQDLVG
  KLKDASKSLERATQL
• 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: Widely expressed with highest expression in thymus.
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Analgesia	DISK3TVI	Strong	Biomarker	[3]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[4]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of COMM domain-containing protein 3 (COMMD3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of COMM domain-containing protein 3 (COMMD3).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of COMM domain-containing protein 3 (COMMD3).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of COMM domain-containing protein 3 (COMMD3).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of COMM domain-containing protein 3 (COMMD3).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of COMM domain-containing protein 3 (COMMD3).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of COMM domain-containing protein 3 (COMMD3).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COMM domain-containing protein 3 (COMMD3).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of COMM domain-containing protein 3 (COMMD3).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of COMM domain-containing protein 3 (COMMD3).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of COMM domain-containing protein 3 (COMMD3).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of COMM domain-containing protein 3 (COMMD3).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of COMM domain-containing protein 3 (COMMD3).	[15]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of COMM domain-containing protein 3 (COMMD3).	[17]

References

• [1] Comparative genome profiling across subtypes of low-grade B-cell lymphoma identifies type-specific and common aberrations that target genes with a role in B-cell neoplasia.Haematologica. 2008 May;93(5):670-9. doi: 10.3324/haematol.12221. Epub 2008 Mar 26.
• [2] COMMD3:BMI1 Fusion and COMMD3 Protein Regulate C-MYC Transcription: Novel Therapeutic Target for Metastatic Prostate Cancer.Mol Cancer Ther. 2019 Nov;18(11):2111-2123. doi: 10.1158/1535-7163.MCT-19-0150. Epub 2019 Aug 29.
• [3] Precision-guided long-acting analgesia by Gel-immobilized bupivacaine-loaded microsphere.Theranostics. 2018 May 23;8(12):3331-3347. doi: 10.7150/thno.25276. eCollection 2018.
• [4] Buprenorphine/samidorphan combination for the adjunctive treatment of major depressive disorder: results of a phase III clinical trial (FORWARD-3).Neuropsychiatr Dis Treat. 2019 Apr 4;15:795-808. doi: 10.2147/NDT.S199245. eCollection 2019.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.