Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNYDT6)

• DOT Name: Epsin-3 (EPN3)
• Synonyms: EPS-15-interacting protein 3
• Gene Name: EPN3
• Related Disease:
  Advanced cancer
  Adult glioblastoma
  Estrogen-receptor positive breast cancer
  Gastric adenocarcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: EPN3_HUMAN
• Pfam ID: PF01417 ; PF02809
• Sequence:
  MTTSALRRQVKNIVHNYSEAEIKVREATSNDPWGPPSSLMSEIADLTFNTVAFTEVMGML
  WRRLNDSGKNWRHVYKALTLLDYLLKTGSERVAHQCRENLYTIQTLKDFQYIDRDGKDQG
  VNVREKVKQVMALLKDEERLRQERTHALKTKERMALEGIGIGSGQLGFSRRYGEDYSRSR
  GSPSSYNSSSSSPRYTSDLEQARPQTSGEEELQLQLALAMSREEAEKPVPPASHRDEDLQ
  LQLALRLSRQEHEKEVRSWQGDGSPMANGAGAVVHHQRDREPEREERKEEEKLKTSQSSI
  LDLADIFVPALAPPSTHCSADPWDIPGFRPNTEASGSSWGPSADPWSPIPSGTVLSRSQP
  WDLTPMLSSSEPWGRTPVLPAGPPTTDPWALNSPHHKLPSTGADPWGASLETSDTPGGAS
  TFDPFAKPPESTETKEGLEQALPSGKPSSPVELDLFGDPSPSSKQNGTKEPDALDLGILG
  EALTQPSKEARACRTPESFLGPSASSLVNLDSLVKAPQVAKTRNPFLTGLSAPSPTNPFG
  AGEPGRPTLNQMRTGSPALGLAGGPVGAPLGSMTYSASLPLPLSSVPAGLTLPASVSVFP
  QAGAFAPQPLLPTPSSAGPRPPPPQTGTNPFL
• Tissue Specificity: Detected in migrating keratinocytes from wounded skin, but not in differentiating keratinocytes or in normal skin. Detected in chronic wounds, basal cell carcinoma and ulcerative colitis.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[1]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Epsin-3 (EPN3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Epsin-3 (EPN3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Epsin-3 (EPN3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Epsin-3 (EPN3).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Epsin-3 (EPN3).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Epsin-3 (EPN3).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Epsin-3 (EPN3).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Epsin-3 (EPN3).	[10]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Epsin-3 (EPN3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Epsin-3 (EPN3).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Epsin-3 (EPN3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Epsin-3 (EPN3).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Epsin-3 (EPN3).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Epsin-3 (EPN3).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Epsin-3 (EPN3).	[12]

References

• [1] Overexpression of Epsin3 enhances migration and invasion of glioma cells by inducing epithelialmesenchymal transition.Oncol Rep. 2018 Nov;40(5):3049-3059. doi: 10.3892/or.2018.6691. Epub 2018 Sep 10.
• [2] EPSIN 3, A Novel p53 Target, Regulates the Apoptotic Pathway and Gastric Carcinogenesis.Neoplasia. 2017 Mar;19(3):185-195. doi: 10.1016/j.neo.2016.12.010. Epub 2017 Jan 30.
• [3] Selective high-level expression of epsin 3 in gastric parietal cells, where it is localized at endocytic sites of apical canaliculi.Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21511-6. doi: 10.1073/pnas.1016390107. Epub 2010 Nov 29.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] 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.
• [9] 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.
• [10] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] 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.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.