Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ8ZDNY)

• DOT Name: Ena/VASP-like protein (EVL)
• Synonyms: Ena/vasodilator-stimulated phosphoprotein-like
• Gene Name: EVL
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Liver cirrhosis
  Liver failure
  Breast neoplasm
  Plasma cell myeloma
• UniProt ID: EVL_HUMAN
• Pfam ID: PF08776 ; PF00568
• Sequence:
  MSEQSICQARASVMVYDDTSKKWVPIKPGQQGFSRINIYHNTASNTFRVVGVKLQDQQVV
  INYSIVKGLKYNQATPTFHQWRDARQVYGLNFASKEEATTFSNAMLFALNIMNSQEGGPS
  SQRQVQNGPSPDEMDIQRRQVMEQHQQQRQESLERRTSATGPILPPGHPSSAASAPVSCS
  GPPPPPPPPVPPPPTGATPPPPPPLPAGGAQGSSHDESSMSGLAAAIAGAKLRRVQRPED
  ASGGSSPSGTSKSDANRASSGGGGGGLMEEMNKLLAKRRKAASQSDKPAEKKEDESQMED
  PSTSPSPGTRAASQPPNSSEAGRKPWERSNSVEKPVSSILSRTPSVAKSPEAKSPLQSQP
  HSRMKPAGSVNDMALDAFDLDRMKQEILEEVVRELHKVKEEIIDAIRQELSGISTT
• Function: Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. EVL enhances actin nucleation and polymerization.
• KEGG Pathway: Rap1 sig.ling pathway (hsa04015)
• Reactome Pathway:
  Signaling by ROBO receptors (R-HSA-376176)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Generation of second messenger molecules (R-HSA-202433)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[4]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[5]
Liver failure	DISLGEL6	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[6]
Plasma cell myeloma	DIS0DFZ0	moderate	Posttranslational Modification	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Ena/VASP-like protein (EVL) affects the response to substance of Methotrexate.	[21]

1 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 Ena/VASP-like protein (EVL).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ena/VASP-like protein (EVL).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ena/VASP-like protein (EVL).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ena/VASP-like protein (EVL).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ena/VASP-like protein (EVL).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ena/VASP-like protein (EVL).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ena/VASP-like protein (EVL).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ena/VASP-like protein (EVL).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ena/VASP-like protein (EVL).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ena/VASP-like protein (EVL).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ena/VASP-like protein (EVL).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ena/VASP-like protein (EVL).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Ena/VASP-like protein (EVL).	[20]

References

• [1] Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis.PLoS Med. 2008 May 27;5(5):e114. doi: 10.1371/journal.pmed.0050114.
• [2] DNA Methylation Analysis Using Droplet Digital PCR.Methods Mol Biol. 2018;1768:363-383. doi: 10.1007/978-1-4939-7778-9_21.
• [3] MethyLight droplet digital PCR for detection and absolute quantification of infrequently methylated alleles.Epigenetics. 2015;10(9):803-9. doi: 10.1080/15592294.2015.1068490. Epub 2015 Jul 17.
• [4] Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
• [5] Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis.Hepatology. 2017 Oct;66(4):1219-1231. doi: 10.1002/hep.29267. Epub 2017 Aug 26.
• [6] EVL (Ena/VASP-like) expression is up-regulated in human breast cancer and its relative expression level is correlated with clinical stages.Oncol Rep. 2008 Apr;19(4):1015-20.
• [7] Epigenetic silencing of EVL/miR-342 in multiple myeloma.Transl Res. 2018 Feb;192:46-53. doi: 10.1016/j.trsl.2017.11.005. Epub 2017 Nov 23.
• [8] 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.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] 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.
• [12] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [13] 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.
• [14] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [15] 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.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [18] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.