Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6MIZ9)

• DOT Name: Testis-expressed protein 19 (TEX19)
• Gene Name: TEX19
• Related Disease:
  Advanced cancer
  Bladder cancer
  Epithelial ovarian cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: TEX19_HUMAN
• Pfam ID: PF15553
• Sequence:
  MCPPVSMRYEEEGMSYLYASWMYQLQHGDQLSICFTCFKAAFLDFKDLLESEDWEEDNWD
  PELMEHTEAESEQEGSSGMELSWGQSPGQPVQGGSEAWGPGTLAAAPEGLEDAGLDPHFV
  PTELWPQEAVPLGLGLEDADWTQGLPWRFEELLTCSHWPSFFPS
• Function: Required during spermatogenesis and placenta development, participating in the repression of retrotransposable elements and prevent their mobilization. Collaborates with the Piwi-interacting RNA (piRNA) pathway, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins. Interacts with Piwi proteins and directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Also during spermatogenesis, promotes, with UBR2, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis. Interacts with LINE-1 retrotransposon encoded LIRE1, stimulates LIRE1 polyubiquitination, mediated by UBR2, and degradation, inhibiting LINE-1 retrotransposon mobilization.
• Tissue Specificity: Expressed in testis. Expressed in undifferentiated embryonic stem cells.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[3]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[2]

2 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 Testis-expressed protein 19 (TEX19).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testis-expressed protein 19 (TEX19).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Testis-expressed protein 19 (TEX19).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Testis-expressed protein 19 (TEX19).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Testis-expressed protein 19 (TEX19).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Testis-expressed protein 19 (TEX19).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Testis-expressed protein 19 (TEX19).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Testis-expressed protein 19 (TEX19).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Testis-expressed protein 19 (TEX19).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Testis-expressed protein 19 (TEX19).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Testis-expressed protein 19 (TEX19).	[14]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Testis-expressed protein 19 (TEX19).	[15]

References

• [1] Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis.Mol Cancer. 2017 Apr 26;16(1):84. doi: 10.1186/s12943-017-0653-4.
• [2] Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.Tumour Biol. 2016 Jun;37(6):7757-65. doi: 10.1007/s13277-015-4567-8. Epub 2015 Dec 22.
• [3] TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.Life Sci. 2020 Jan 15;241:117171. doi: 10.1016/j.lfs.2019.117171. Epub 2019 Dec 13.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [11] Global gene expression analysis reveals novel transcription factors associated with long-term low-level exposure of EA.hy926 human endothelial cells to bisphenol A. Chem Biol Interact. 2023 Aug 25;381:110571. doi: 10.1016/j.cbi.2023.110571. Epub 2023 May 25.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [15] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.