Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEI347F)

• DOT Name: ETS-related transcription factor Elf-2 (ELF2)
• Synonyms: E74-like factor 2; New ETS-related factor
• Gene Name: ELF2
• Related Disease:
  Cerebellar ataxia
  Juvenile idiopathic arthritis
  Neoplasm
  T-cell leukaemia
  Visceral leishmaniasis
  Acute myelogenous leukaemia
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: ELF2_HUMAN
• Pfam ID: PF12310 ; PF00178
• Sequence:
  MTSAVVDSGGTILELSSNGVENQEESEKVSEYPAVIVEPVPSARLEQGYAAQVLVYDDET
  YMMQDVAEEQEVETENVETVEASVHSSNAHCTDKTIEAAEALLHMESPTCLRDSRSPVEV
  FVPPCVSTPEFIHAAMRPDVITETVVEVSTEESEPMDTSPIPTSPDSHEPMKKKKVGRKP
  KTQQSPISNGSPELGIKKKPREGKGNTTYLWEFLLDLLQDKNTCPRYIKWTQREKGIFKL
  VDSKAVSKLWGKHKNKPDMNYETMGRALRYYYQRGILAKVEGQRLVYQFKDMPKNIVVID
  DDKSETCNEDLAGTTDEKSLERVSLSAESLLKAASSVRSGKNSSPINCSRAEKGVARVVN
  ITSPGHDASSRSPTTTASVSATAAPRTVRVAMQVPVVMTSLGQKISTVAVQSVNAGAPLI
  TSTSPTTATSPKVVIQTIPTVMPASTENGDKITMQPAKIITIPATQLAQCQLQTKSNLTG
  SGSINIVGTPLAVRALTPVSIAHGTPVMRLSMPTQQASGQTPPRVISAVIKGPEVKSEAV
  AKKQEHDVKTLQLVEEKPADGNKTVTHVVVVSAPSAIALPVTMKTEGLVTCEK
• Function: Isoform 1 transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter.; Isoform 2 may function in repression of RUNX1-mediated transactivation.
• Tissue Specificity: Expressed in all fetal and adult tissues examined. Among fetal tissues, highest levels of expression detected in heart, lung, liver and kidney, and lower levels in brain. Among adult tissues, highest levels of expression detected in heart, placenta, lung, skeletal muscle, spleen, thymus, testis and ovary. Moderate expression in prostate, small intestine, kidney, liver and pancreas, and weak expression in colon, brain and peripheral blood lymphocytes.
• Reactome Pathway: RUNX1 regulates transcription of genes involved in BCR signaling (R-HSA-8939245)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Strong	Altered Expression	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[4]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[6]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[7]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of ETS-related transcription factor Elf-2 (ELF2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ETS-related transcription factor Elf-2 (ELF2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ETS-related transcription factor Elf-2 (ELF2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ETS-related transcription factor Elf-2 (ELF2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ETS-related transcription factor Elf-2 (ELF2).	[12]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of ETS-related transcription factor Elf-2 (ELF2).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of ETS-related transcription factor Elf-2 (ELF2).	[14]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of ETS-related transcription factor Elf-2 (ELF2).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ETS-related transcription factor Elf-2 (ELF2).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ETS-related transcription factor Elf-2 (ELF2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of ETS-related transcription factor Elf-2 (ELF2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ETS-related transcription factor Elf-2 (ELF2).	[16]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of ETS-related transcription factor Elf-2 (ELF2).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ETS-related transcription factor Elf-2 (ELF2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ETS-related transcription factor Elf-2 (ELF2).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of ETS-related transcription factor Elf-2 (ELF2).	[19]

References

• [1] Clinical and Functional Characterization of a Missense ELF2 Variant in a CANVAS Family.Front Genet. 2018 Mar 23;9:85. doi: 10.3389/fgene.2018.00085. eCollection 2018.
• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance.Oncotarget. 2016 Apr 19;7(16):22448-59. doi: 10.18632/oncotarget.7988.
• [4] Elf-2, a rhombotin-2 binding ets transcription factor: discovery and potential role in T cell leukemia.Leukemia. 1997 Jan;11(1):86-96. doi: 10.1038/sj.leu.2400516.
• [5] Immunogenicity and Protective Efficacy of T-Cell Epitopes Derived From Potential Th1 Stimulatory Proteins of Leishmania (Leishmania) donovani.Front Immunol. 2019 Feb 28;10:288. doi: 10.3389/fimmu.2019.00288. eCollection 2019.
• [6] The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases.Leuk Res. 2003 May;27(5):387-92. doi: 10.1016/s0145-2126(02)00214-x.
• [7] MiR-409-3p regulates cell proliferation and tumor growth by targeting E74-like factor 2 in osteosarcoma.FEBS Open Bio. 2017 Jan 27;7(3):348-357. doi: 10.1002/2211-5463.12177. eCollection 2017 Mar.
• [8] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [9] 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.
• [10] 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.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [13] 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.
• [14] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [15] Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther. 2005 Feb;4(2):233-41.
• [16] 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.
• [17] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [18] 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.
• [19] 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.
• [20] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.