Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPVHOZ7)

• DOT Name: Protein C-ets-2 (ETS2)
• Gene Name: ETS2
• UniProt ID: ETS2_HUMAN
• PDB ID: 4BQA; 4MHV
• Pfam ID: PF00178 ; PF19525 ; PF02198
• Sequence:
  MNDFGIKNMDQVAPVANSYRGTLKRQPAFDTFDGSLFAVFPSLNEEQTLQEVPTGLDSIS
  HDSANCELPLLTPCSKAVMSQALKATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATN
  EFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLEQMIKENQEKTEDQYEE
  NSHLTSVPHWINSNTLGFGTEQAPYGMQTQNYPKGGLLDSMCPASTPSVLSSEQEFQMFP
  KSRLSSVSVTYCSVSQDFPGSNLNLLTNNSGTPKDHDSPENGADSFESSDSLLQSWNSQS
  SLLDVQRVPSFESFEDDCSQSLCLNKPTMSFKDYIQERSDPVEQGKPVIPAAVLAGFTGS
  GPIQLWQFLLELLSDKSCQSFISWTGDGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRG
  LRYYYDKNIIHKTSGKRYVYRFVCDLQNLLGFTPEELHAILGVQPDTED
• Function: Transcription factor activating transcription. Binds specifically the DNA GGAA/T core motif (Ets-binding site or EBS) in gene promoters and stimulates transcription.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway: Oncogene Induced Senescence (R-HSA-2559585)

Molecular Interaction Atlas (MIA) of This DOT

30 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 Protein C-ets-2 (ETS2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein C-ets-2 (ETS2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein C-ets-2 (ETS2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein C-ets-2 (ETS2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein C-ets-2 (ETS2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein C-ets-2 (ETS2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein C-ets-2 (ETS2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein C-ets-2 (ETS2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein C-ets-2 (ETS2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein C-ets-2 (ETS2).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein C-ets-2 (ETS2).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein C-ets-2 (ETS2).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein C-ets-2 (ETS2).	[12]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Protein C-ets-2 (ETS2).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Protein C-ets-2 (ETS2).	[14]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Protein C-ets-2 (ETS2).	[15]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Protein C-ets-2 (ETS2).	[16]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Protein C-ets-2 (ETS2).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein C-ets-2 (ETS2).	[7]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Protein C-ets-2 (ETS2).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein C-ets-2 (ETS2).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein C-ets-2 (ETS2).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein C-ets-2 (ETS2).	[22]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Protein C-ets-2 (ETS2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein C-ets-2 (ETS2).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein C-ets-2 (ETS2).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein C-ets-2 (ETS2).	[25]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Protein C-ets-2 (ETS2).	[26]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Protein C-ets-2 (ETS2).	[27]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Protein C-ets-2 (ETS2).	[28]

2 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 decreases the methylation of Protein C-ets-2 (ETS2).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein C-ets-2 (ETS2).	[23]

References

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• [9] 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.
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• [13] Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis. 2006 May;27(5):916-24. doi: 10.1093/carcin/bgi312. Epub 2005 Dec 16.
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• [16] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [17] Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Res. 2007 Mar 1;67(5):1988-96. doi: 10.1158/0008-5472.CAN-06-3066.
• [18] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [19] 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.
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• [23] 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.
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• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [26] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
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• [28] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.