Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI2VI8B)

• DOT Name: ELAV-like protein 3 (ELAVL3)
• Synonyms: Hu-antigen C; HuC; Paraneoplastic cerebellar degeneration-associated antigen; Paraneoplastic limbic encephalitis antigen 21
• Gene Name: ELAVL3
• Related Disease:
  Bladder transitional cell carcinoma
  Neoplasm
  Tarsal-carpal coalition syndrome
  Cerebellar disorder
  Crohn disease
  Gastric cancer
  Herpes simplex infection
  Interstitial cystitis
  Polycystic ovarian syndrome
  Stomach cancer
  Transitional cell carcinoma
  Urothelial carcinoma
  Nervous system inflammation
  Small-cell lung cancer
  Spinocerebellar ataxia type 3
• UniProt ID: ELAV3_HUMAN
• Pfam ID: PF00076
• Sequence:
  MVTQILGAMESQVGGGPAGPALPNGPLLGTNGATDDSKTNLIVNYLPQNMTQDEFKSLFG
  SIGDIESCKLVRDKITGQSLGYGFVNYSDPNDADKAINTLNGLKLQTKTIKVSYARPSSA
  SIRDANLYVSGLPKTMSQKEMEQLFSQYGRIITSRILVDQVTGVSRGVGFIRFDKRIEAE
  EAIKGLNGQKPLGAAEPITVKFANNPSQKTGQALLTHLYQSSARRYAGPLHHQTQRFRLD
  NLLNMAYGVKSPLSLIARFSPIAIDGMSGLAGVGLSGGAAGAGWCIFVYNLSPEADESVL
  WQLFGPFGAVTNVKVIRDFTTNKCKGFGFVTMTNYDEAAMAIASLNGYRLGERVLQVSFK
  TSKQHKA
• Function: RNA-binding protein that binds to AU-rich element (ARE) sequences of target mRNAs, including VEGF mRNA. May also bind poly-A tracts via RRM 3. May be involved in neuronal differentiation and maintenance. Plays a role in the stabilization of GAP43 mRNA and in spatial learning.
• Tissue Specificity: Brain specific.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder transitional cell carcinoma	DISNL46A	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Tarsal-carpal coalition syndrome	DISY90L2	Definitive	Altered Expression	[1]
Cerebellar disorder	DIS2O7WM	Strong	Altered Expression	[3]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[4]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[5]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[6]
Interstitial cystitis	DIS7CAJA	Strong	Biomarker	[7]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[8]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[5]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[9]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[9]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[10]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[10]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Biomarker	[11]

3 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 ELAV-like protein 3 (ELAVL3).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ELAV-like protein 3 (ELAVL3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ELAV-like protein 3 (ELAVL3).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ELAV-like protein 3 (ELAVL3).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of ELAV-like protein 3 (ELAVL3).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of ELAV-like protein 3 (ELAVL3).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ELAV-like protein 3 (ELAVL3).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ELAV-like protein 3 (ELAVL3).	[19]

References

• [1] Long noncoding RNA HOTAIR is a prognostic biomarker and inhibits chemosensitivity to doxorubicin in bladder transitional cell carcinoma.Cancer Chemother Pharmacol. 2016 Mar;77(3):507-13. doi: 10.1007/s00280-016-2964-3. Epub 2016 Jan 19.
• [2] Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells.J Biol Chem. 2019 Mar 1;294(9):3207-3218. doi: 10.1074/jbc.RA118.006682. Epub 2018 Dec 28.
• [3] Elavl3 regulates neuronal polarity through the alternative splicing of an embryo-specific exon in AnkyrinG.Neurosci Res. 2018 Oct;135:13-20. doi: 10.1016/j.neures.2018.03.008. Epub 2018 Mar 31.
• [4] The distinct features of microbial 'dysbiosis' of Crohn's disease do not occur to the same extent in their unaffected, genetically-linked kindred.PLoS One. 2017 Feb 21;12(2):e0172605. doi: 10.1371/journal.pone.0172605. eCollection 2017.
• [5] Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors.Mol Carcinog. 2015 Nov;54(11):1376-86. doi: 10.1002/mc.22213. Epub 2014 Sep 11.
• [6] Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells.Immunology. 2006 Feb;117(2):167-76. doi: 10.1111/j.1365-2567.2005.02275.x.
• [7] Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT/mTOR signaling pathway.Biochem Biophys Res Commun. 2018 Jan 1;495(1):546-552. doi: 10.1016/j.bbrc.2017.11.072. Epub 2017 Nov 11.
• [8] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [9] Expression of WWOX and FHIT is downregulated by exposure to arsenite in human uroepithelial cells.Toxicol Lett. 2013 Jul 4;220(2):118-25. doi: 10.1016/j.toxlet.2013.04.007. Epub 2013 Apr 22.
• [10] Antibody recognition and RNA binding of a neuronal nuclear autoantigen associated with paraneoplastic neurological syndromes and small cell lung carcinoma.J Neuroimmunol. 1999 Jan 1;93(1-2):37-44. doi: 10.1016/s0165-5728(98)00184-2.
• [11] Human Umbilical Cord Mesenchymal Stem Cells Protect Against SCA3 by Modulating the Level of 70 kD Heat Shock Protein.Cell Mol Neurobiol. 2018 Apr;38(3):641-655. doi: 10.1007/s10571-017-0513-1. Epub 2017 Jun 30.
• [12] 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.
• [13] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [14] 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.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [18] 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.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.