Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOYAP3V)

• DOT Name: Elongin BC and Polycomb repressive complex 2-associated protein (EPOP)
• Synonyms: Proline-rich protein 28
• Gene Name: EPOP
• UniProt ID: EPOP_HUMAN
• Pfam ID: PF15223
• Sequence:
  METLCPAPRLAVPASPRGSPCSPTPRKPCRGTQEFSPLCLRALAFCALAKPRASSLGPGP
  GELAARSPVLRGPQAPLRPGGWAPDGLKHLWAPTGRPGVPNTAAGEDADVAACPRRGEEE
  EGGGGFPHFGVRSCAPPGRCPAPPHPRESTTSFASAPPRPAPGLEPQRGPAASPPQEPSS
  RPPSPPAGLSTEPAGPGTAPRPFLPGQPAEVDGNPPPAAPEAPAASPSTASPAPAAPGDL
  RQEHFDRLIRRSKLWCYAKGFALDTPSLRRGPERPPAKGPARGAAKKRRLPAPPPRTAQP
  RRPAPTLPTTSTFSLLNCFPCPPALVVGEDGDLKPASSLRLQGDSKPPPAHPLWRWQMGG
  PAVPEPPGLKFWGINMDES
• Function: Scaffold protein that serves as a bridging partner between the PRC2/EZH2 complex and the elongin BC complex: required to fine-tune the transcriptional status of Polycomb group (PcG) target genes in embryonic stem cells (ESCs). Plays a key role in genomic regions that display both active and repressive chromatin properties in pluripotent stem cells by sustaining low level expression at PcG target genes: acts by recruiting the elongin BC complex, thereby restricting excessive activity of the PRC2/EZH2 complex. Interaction with USP7 promotes deubiquitination of H2B at promoter sites. Acts as a regulator of neuronal differentiation.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

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 Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[8]

10 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 Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[5]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[6]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Elongin BC and Polycomb repressive complex 2-associated protein (EPOP).	[12]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.