Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2BZTSU)

• DOT Name: EMILIN-3 (EMILIN3)
• Synonyms: EMILIN-5; Elastin microfibril interface-located protein 3; Elastin microfibril interfacer 3; Elastin microfibril interface-located protein 5; Elastin microfibril interfacer 5
• Gene Name: EMILIN3
• Related Disease:
  Neoplasm
  Neoplasm of esophagus
• UniProt ID: EMIL3_HUMAN
• Pfam ID: PF07546
• Sequence:
  MGRRRLLVWLCAVAALLSGAQARGTPLLARPAPPGASRYSLYTTGWRPRLRPGPHKALCA
  YVVHRNVTCILQEGAESYVKAEYRQCRWGPKCPGTVTYRTVLRPKYKVGYKTVTDLAWRC
  CPGFTGKRCPEHLTDHGAASPQLEPEPQIPSGQLDPGPRPPSYSRAAPSPHGRKGPGLFG
  ERLERLEGDVQRLAQTYGTLSGLVASHEDPNRMTGGPRAPAVPVGFGVIPEGLVGPGDRA
  RGPLTPPLDEILSKVTEVSNTLQTKVQLLDKVHGLALGHEAHLQRLREAPPSPLTSLALL
  EEYVDRRLHRLWGSLLDGFEQKLQGVQSECDLRVQEVRRQCEEGQAASRRLHQSLDGREL
  ALRQELSQLGSQLQGLSVSGRGSCCGQLALINARMDGLERALQAVTETQRGPGAPAGDEL
  TRLSAAMLEGGVDGLLEGLETLNGTEGGARGCCLRLDMGGWGVGGFGTMLEERVQSLEER
  LATLAGELSHDSASPGRSARPLVQTELAVLEQRLVSLETSCTPSTTSAILDSLVAEVKAW
  QSRSEALLRQVASHAALLQQLNGTVAEVQGQLAEGTGSSLQGEITLLKVNLNSVSKSLTG
  LSDSVSQYSDAFLAANTSLDERERKVEAEVQAIQEQVSSQGSRLQAGHRQVLNLRGELEQ
  LKAGVAKVASGLSRCQDTAQKLQHTVGHFDQRVAQVEGACRRLGLLAAGLDSLPTEPLRP
  REGLWSHVDQLNRTLAQHTQDIARLRDDLLDCQAQLAEQVRPGQAN
• Reactome Pathway: Molecules associated with elastic fibres (R-HSA-2129379)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[2]

1 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 EMILIN-3 (EMILIN3).	[3]

8 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 EMILIN-3 (EMILIN3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of EMILIN-3 (EMILIN3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of EMILIN-3 (EMILIN3).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of EMILIN-3 (EMILIN3).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of EMILIN-3 (EMILIN3).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of EMILIN-3 (EMILIN3).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of EMILIN-3 (EMILIN3).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of EMILIN-3 (EMILIN3).	[11]

References

• [1] Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas.Cell Physiol Biochem. 2018;47(1):428-439. doi: 10.1159/000489954. Epub 2018 May 18.
• [2] Preparation and characterization of a novel monoclonal antibody specific to human EMILIN-5 protein.Hybridoma (Larchmt). 2007 Dec;26(6):417-21. doi: 10.1089/hyb.2007.0528.
• [3] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.