Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT21ALNF)

• DOT Name: EPM2A-interacting protein 1 (EPM2AIP1)
• Synonyms: Laforin-interacting protein
• Gene Name: EPM2AIP1
• Related Disease: Lafora disease
• UniProt ID: EPMIP_HUMAN
• Pfam ID: PF18658
• Sequence:
  MWMTPKRSKMEVDEALVFRPEWTQRYLVVEPPEGDGALCLVCRRLIVATRERDVRRHYEA
  EHEYYERYVADGERAALVERLRQGDLPVASFTPEERAARAGLGLCRLLALKGRGWGEGDF
  VYQCMEVLLREVLPEHVSVLQGVDLSPDITRQRILSIDRNLRNQLFNRARDFKAYSLALD
  DQAFVAYENYLLVFIRGVGPELEVQEDLLTIINLTHHFSVGALMSAILESLQTAGLSLQR
  MVGLTTTHTLRMIGENSGLVSYMREKAVSPNCWNVIHYSGFLHLELLSSYDVDVNQIINT
  ISEWIVLIKTRGVRRPEFQTLLTESESEHGERVNGRCLNNWLRRGKTLKLIFSLRKEMEA
  FLVSVGATTVHFSDKQWLCDFGFLVDIMEHLRELSEELRVSKVFAAAAFDHICTFEVKLN
  LFQRHIEEKNLTDFPALREVVDELKQQNKEDEKIFDPDRYQMVICRLQKEFERHFKDLRF
  IKKDLELFSNPFNFKPEYAPISVRVELTKLQANTNLWNEYRIKDLGQFYAGLSAESYPII
  KGVACKVASLFDSNQICEKAFSYLTRNQHTLSQPLTDEHLQALFRVATTEMEPGWDDLVR
  ERNESNP
• Tissue Specificity: Expressed in heart, brain, placenta, liver, pancreas, kidney and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lafora disease	DIS83JHH	Limited	Biomarker	[1]

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 EPM2A-interacting protein 1 (EPM2AIP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[8]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[9]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[10]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of EPM2A-interacting protein 1 (EPM2AIP1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of EPM2A-interacting protein 1 (EPM2AIP1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of EPM2A-interacting protein 1 (EPM2AIP1).	[11]

References

• [1] Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy.Hum Mol Genet. 2004 Jun 1;13(11):1117-29. doi: 10.1093/hmg/ddh130. Epub 2004 Apr 21.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.