Details of Drug Off-Target (DOT)

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

• DOT Name: ERI1 exoribonuclease 2 (ERI2)
• Synonyms: EC 3.1.-.-; Exonuclease domain-containing protein 1
• Gene Name: ERI2
• UniProt ID: ERI2_HUMAN
• PDB ID: 7N8V; 7N8W
• EC Number: 3.1.-.-
• Pfam ID: PF00929 ; PF06839
• Sequence:
  MATKRLARQLGLIRRKSIAPANGNLGRSKSKQLFDYLIVIDFESTCWNDGKHHHSQEIIE
  FPAVLLNTSTGQIDSEFQAYVQPQEHPILSEFCMELTGIKQAQVDEGVPLKICLSQFCKW
  IHKIQQQKNIIFATGISEPSASEVKLCAFVTWSDWDLGVCLEYECKRKQLLKPVFLNSWI
  DLRATYKLFYRRKPKGLSGALQEVGIEFSGREHSGLDDSRNTALLAWKMIRDGCVMKITR
  SLNKVPTKKNFSILARNLNTIQVEEMSACNISIQGPSIYNKEPKNIINPHEKVQMKSICA
  NSPIKAQQDQLQVKNNIKASLHNVKSSLPLFNTKSSTSVGQLQSPTLNSPIYMQKQGKNE
  HLAFNTKSKASTVGSELVLVSTTVPTVHHVSDLEMSSTLDCLPVLADWEDVVLLPASQPE
  ENVDCTVPISDSDLEISFNSGERLMVLKELEMSSHENFGDIEETPQKSETSKSIVYKSPH
  TTIYNVKEAKDPGSDISAFKLPEHKSSTFNRVNANMSHPLVLGKHPLLSGGTKRNPCSPQ
  AFPPAKKQPFTIHEEKPTSSDCSPVRSSSWRRLPSILTSTVNLQEPWKSGKMTPPLCKCG
  RRSKRLVVSNNGPNHGKVFYCCPIGKYQENRKCCGYFKWEQTLQKERANSMVPSHSTGGL
  TFSSPETSHICDRNLSISTKNSLRLRPSMRN

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of ERI1 exoribonuclease 2 (ERI2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ERI1 exoribonuclease 2 (ERI2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ERI1 exoribonuclease 2 (ERI2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ERI1 exoribonuclease 2 (ERI2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ERI1 exoribonuclease 2 (ERI2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of ERI1 exoribonuclease 2 (ERI2).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of ERI1 exoribonuclease 2 (ERI2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ERI1 exoribonuclease 2 (ERI2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ERI1 exoribonuclease 2 (ERI2).	[12]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of ERI1 exoribonuclease 2 (ERI2).	[13]

3 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 ERI1 exoribonuclease 2 (ERI2).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of ERI1 exoribonuclease 2 (ERI2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ERI1 exoribonuclease 2 (ERI2).	[11]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.