Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEN03BM)

• DOT Name: ETS translocation variant 3 (ETV3)
• Synonyms: ETS domain transcriptional repressor PE1; PE-1; Mitogenic Ets transcriptional suppressor
• Gene Name: ETV3
• Related Disease:
  Cardiac failure
  Cardiovascular disease
  Congestive heart failure
  Depression
  High blood pressure
  Liver cirrhosis
  Non-insulin dependent diabetes
  Obstructive sleep apnea
  Prostate carcinoma
  Prostate neoplasm
  Follicular lymphoma
  Small lymphocytic lymphoma
  Breast cancer
  Breast carcinoma
  Obesity
  Post-traumatic stress disorder
  Prostate cancer
  Type-1/2 diabetes
• UniProt ID: ETV3_HUMAN
• Pfam ID: PF00178
• Sequence:
  MKAGCSIVEKPEGGGGYQFPDWAYKTESSPGSRQIQLWHFILELLQKEEFRHVIAWQQGE
  YGEFVIKDPDEVARLWGRRKCKPQMNYDKLSRALRYYYNKRILHKTKGKRFTYKFNFNKL
  VMPNYPFINIRSSGVVPQSAPPVPTASSRFHFPPLDTHSPTNDVQPGRFSASSLTASGQE
  SSNGTDRKTELSELEDGSAADWRRGVDPVSSRNAIGGGGIGHQKRKPDIMLPLFARPGMY
  PDPHSPFAVSPIPGRGGVLNVPISPALSLTPTIFSYSPSPGLSPFTSSSCFSFNPEEMKH
  YLHSQACSVFNYHLSPRTFPRYPGLMVPPLQCQMHPEESTQFSIKLQPPPVGRKNRERVE
  SSEESAPVTTPTMASIPPRIKVEPASEKDPESLRQSAREKEEHTQEEGTVPSRTIEEEKG
  TIFARPAAPPIWPSVPISTPSGEPLEVTEDSEDRPGKEPSAPEKKEDALMPPKLRLKRRW
  NDDPEARELSKSGKFLWNGSGPQGLATAAADA
• Function: Transcriptional repressor that contribute to growth arrest during terminal macrophage differentiation by repressing target genes involved in Ras-dependent proliferation. Represses MMP1 promoter activity.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[1]
Depression	DIS3XJ69	Strong	Biomarker	[3]
High blood pressure	DISY2OHH	Strong	Biomarker	[4]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[6]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[9]
Follicular lymphoma	DISVEUR6	moderate	Genetic Variation	[10]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[10]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[11]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[11]
Obesity	DIS47Y1K	Limited	Biomarker	[12]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[13]
Prostate cancer	DISF190Y	Limited	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[14]

4 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 ETS translocation variant 3 (ETV3).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ETS translocation variant 3 (ETV3).	[19]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of ETS translocation variant 3 (ETV3).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of ETS translocation variant 3 (ETV3).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ETS translocation variant 3 (ETV3).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ETS translocation variant 3 (ETV3).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of ETS translocation variant 3 (ETV3).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ETS translocation variant 3 (ETV3).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of ETS translocation variant 3 (ETV3).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ETS translocation variant 3 (ETV3).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of ETS translocation variant 3 (ETV3).	[24]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of ETS translocation variant 3 (ETV3).	[26]

References

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• [2] Cardiorespiratory fitness as a predictor of short-term and lifetime estimated cardiovascular disease risk.Scand J Med Sci Sports. 2019 Sep;29(9):1402-1413. doi: 10.1111/sms.13468. Epub 2019 Jun 6.
• [3] A high exercise workload of ?0 METS predicts a low risk of significant ischemia and cardiac events in older adults.J Nucl Cardiol. 2020 Oct;27(5):1486-1496. doi: 10.1007/s12350-018-1376-7. Epub 2018 Jul 26.
• [4] Prediction of incident hypertension and arterial stiffness using the non-insulin-based metabolic score for insulin resistance (METS-IR) index.J Clin Hypertens (Greenwich). 2019 Aug;21(8):1063-1070. doi: 10.1111/jch.13614. Epub 2019 Jul 18.
• [5] The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: A study in the Swedish AMORIS cohort.Int J Cancer. 2017 Sep 15;141(6):1148-1160. doi: 10.1002/ijc.30818. Epub 2017 Jun 21.
• [6] Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors.Atherosclerosis. 2019 Nov;290:87-93. doi: 10.1016/j.atherosclerosis.2019.09.016. Epub 2019 Sep 25.
• [7] Diet associated with exercise improves baroreflex control of sympathetic nerve activity in metabolic syndrome and sleep apnea patients.Sleep Breath. 2019 Mar;23(1):143-151. doi: 10.1007/s11325-018-1675-x. Epub 2018 Jun 11.
• [8] Meta-analysis of metabolic syndrome and prostate cancer.Prostate Cancer Prostatic Dis. 2017 Jun;20(2):146-155. doi: 10.1038/pcan.2017.1. Epub 2017 Feb 21.
• [9] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [10] A new method to detect loss of heterozygosity using cohort heterozygosity comparisons.BMC Cancer. 2010 May 12;10:195. doi: 10.1186/1471-2407-10-195.
• [11] Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes.Breast Cancer Res Treat. 2013 Feb;138(1):37-45. doi: 10.1007/s10549-013-2408-2. Epub 2013 Jan 18.
• [12] The role of bioactives in energy metabolism and metabolic syndrome.Proc Nutr Soc. 2019 Aug;78(3):340-350. doi: 10.1017/S0029665119000545. Epub 2019 Apr 10.
• [13] Incentivizing attendance to prolonged exposure for PTSD with opioid use disorder patients: A randomized controlled trial.J Consult Clin Psychol. 2017 Jul;85(7):689-701. doi: 10.1037/ccp0000208. Epub 2017 Apr 17.
• [14] The impact of diabetes mellitus on the clinical phenotype of hypertrophic cardiomyopathy.Eur Heart J. 2019 Jun 1;40(21):1671-1677. doi: 10.1093/eurheartj/ehy625.
• [15] 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.
• [16] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [17] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [18] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [23] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [24] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [25] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [26] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.