Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH5BHUN)

• DOT Name: Epsin-2 (EPN2)
• Synonyms: EPS-15-interacting protein 2
• Gene Name: EPN2
• Related Disease: Schizophrenia
• UniProt ID: EPN2_HUMAN
• Pfam ID: PF01417
• Sequence:
  MTTSSIRRQMKNIVNNYSEAEIKVREATSNDPWGPSSSLMTEIADLTYNVVAFSEIMSMV
  WKRLNDHGKNWRHVYKALTLLDYLIKTGSERVAQQCRENIFAIQTLKDFQYIDRDGKDQG
  INVREKSKQLVALLKDEERLKAERAQALKTKERMAQVATGMGSNQITFGRGSSQPNLSTS
  HSEQEYGKAGGSPASYHGSPEASLCPQHRTGAPLGQSEELQPLSQRHPFLPHLGLASRPN
  GDWSQPCLTCDRAARATSPRVSSELEQARPQTSGEEELQLQLALAMSREVAEQEERLRRG
  DDLRLQMALEESRRDTVKIPKKKEHGSLPQQTTLLDLMDALPSSGPAAQKAEPWGPSAST
  NQTNPWGGPAAPASTSDPWPSFGTKPAASIDPWGVPTGATVQSVPKNSDPWAASQQPASS
  AGKRASDAWGAVSTTKPVSVSGSFELFSNLNGTIKDDFSEFDNLRTSKKTAESVTSLPSQ
  NNGTTSPDPFESQPLTVASSKPSSARKTPESFLGPNAALVNLDSLVTRPAPPAQSLNPFL
  APGAPATSAPVNPFQVNQPQPLTLNQLRGSPVLGTSTSFGPGPGVESMAVASMTSAAPQP
  ALGATGSSLTPLGPAMMNMVGSVGIPPSAAQATGTTNPFLL
• Function: Plays a role in the formation of clathrin-coated invaginations and endocytosis.
• Tissue Specificity: Highest expression is found in brain. Detected at lower levels in lung and liver.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Epsin-2 (EPN2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Epsin-2 (EPN2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Epsin-2 (EPN2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Epsin-2 (EPN2).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Epsin-2 (EPN2).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Epsin-2 (EPN2).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Epsin-2 (EPN2).	[7]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Epsin-2 (EPN2).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Epsin-2 (EPN2).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Epsin-2 (EPN2).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Epsin-2 (EPN2).	[10]

References

• [1] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [6] 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.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.