Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTNU8RK)

• DOT Name: Transcription and mRNA export factor ENY2 (ENY2)
• Synonyms: Enhancer of yellow 2 transcription factor homolog
• Gene Name: ENY2
• Related Disease:
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Neoplasm
  Type-1/2 diabetes
• UniProt ID: ENY2_HUMAN
• PDB ID: 4DHX
• Pfam ID: PF10163
• Sequence:
  MVVSKMNKDAQMRAAINQKLIETGERERLKELLRAKLIECGWKDQLKAHCKEVIKEKGLE
  HVTVDDLVAEITPKGRALVPDSVKKELLQRIRTFLAQHASL
• Function: Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes. The transcription regulatory histone acetylation (HAT) complex SAGA is a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[4]

13 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 Transcription and mRNA export factor ENY2 (ENY2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription and mRNA export factor ENY2 (ENY2).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[12]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Transcription and mRNA export factor ENY2 (ENY2).	[17]

References

• [1] Integration of whole-genome sequencing and functional screening identifies a prognostic signature for lung metastasis in triple-negative breast cancer.Int J Cancer. 2019 Nov 15;145(10):2850-2860. doi: 10.1002/ijc.32329. Epub 2019 Apr 29.
• [2] Subdivision of molecularly-classified groups by new gene signatures in breast cancer patients.Oncol Rep. 2012 Dec;28(6):2255-63. doi: 10.3892/or.2012.2018. Epub 2012 Sep 5.
• [3] ATXN7L3 and ENY2 Coordinate Activity of Multiple H2B Deubiquitinases Important for Cellular Proliferation and Tumor Growth.Mol Cell. 2016 May 19;62(4):558-71. doi: 10.1016/j.molcel.2016.03.030. Epub 2016 Apr 28.
• [4] Sus1/ENY2: a multitasking protein in eukaryotic gene expression.Crit Rev Biochem Mol Biol. 2012 Nov-Dec;47(6):556-68. doi: 10.3109/10409238.2012.730498. Epub 2012 Oct 12.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [13] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [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.