Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7QEI2X)

DOT Name Testis-specific Y-encoded-like protein 5 (TSPYL5)
Synonyms TSPY-like protein 5
Gene Name TSPYL5
Related Disease
Gastric cancer ( )
Gastric neoplasm ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Epithelial ovarian cancer ( )
Glioma ( )
Hepatocellular carcinoma ( )
Neoplasm ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Lung cancer ( )
Lung carcinoma ( )
UniProt ID
TSYL5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00956
Sequence
MSGRSRGRKSSRAKNRGKGRAKARVRPAPDDAPRDPDPSQYQSLGEDTQAAQVQAGAGWG
GLEAAASAQLLRLGEEAACRLPLDCGLALRARAAGDHGQAAARPGPGKAASLSERLAADT
VFVGTAGTVGRPKNAPRVGNRRGPAGKKAPETCSTAGRGPQVIAGGRQKKGAAGENTSVS
AGEEKKEERDAGSGPPATEGSMDTLENVQLKLENMNAQADRAYLRLSRKFGQLRLQHLER
RNHLIQNIPGFWGQAFQNHPQLASFLNSQEKEVLSYLNSLEVEELGLARLGYKIKFYFDR
NPYFQNKVLIKEYGCGPSGQVVSRSTPIQWLPGHDLQSLSQGNPENNRSFFGWFSNHSSI
ESDKIVEIINEELWPNPLQFYLLSEGARVEKGKEKEGRQGPGKQPMETTQPGVSQSN
Function
Involved in modulation of cell growth and cellular response to gamma radiation probably via regulation of the Akt signaling pathway. Involved in regulation of p53/TP53. Suppresses p53/TP53 protein levels and promotes its ubiquitination; the function is dependent on USP7 and independent on MDM2. Proposed to displace p53/TP53 from interaction with USP7.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Gastric cancer DISXGOUK Definitive Posttranslational Modification [1]
Gastric neoplasm DISOKN4Y Definitive Posttranslational Modification [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Endometrial cancer DISW0LMR Strong Biomarker [5]
Endometrial carcinoma DISXR5CY Strong Biomarker [5]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [2]
Glioma DIS5RPEH Strong Posttranslational Modification [1]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [6]
Neoplasm DISZKGEW Strong Biomarker [7]
Obesity DIS47Y1K Strong Biomarker [8]
Ovarian cancer DISZJHAP Strong Biomarker [2]
Ovarian neoplasm DISEAFTY Strong Biomarker [2]
Prostate cancer DISF190Y Strong Biomarker [7]
Prostate carcinoma DISMJPLE Strong Altered Expression [7]
Prostate neoplasm DISHDKGQ Strong Altered Expression [7]
Lung cancer DISCM4YA Limited Biomarker [9]
Lung carcinoma DISTR26C Limited Biomarker [9]
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⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Testis-specific Y-encoded-like protein 5 (TSPYL5) decreases the response to substance of Arsenic. [17]
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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-specific Y-encoded-like protein 5 (TSPYL5). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Testis-specific Y-encoded-like protein 5 (TSPYL5). [14]
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5 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 Testis-specific Y-encoded-like protein 5 (TSPYL5). [11]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Testis-specific Y-encoded-like protein 5 (TSPYL5). [12]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Testis-specific Y-encoded-like protein 5 (TSPYL5). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Testis-specific Y-encoded-like protein 5 (TSPYL5). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Testis-specific Y-encoded-like protein 5 (TSPYL5). [16]
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References

1 Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric cancers.Lab Invest. 2008 Feb;88(2):153-60. doi: 10.1038/labinvest.3700706. Epub 2007 Dec 3.
2 Knockdown of miR-629 Inhibits Ovarian Cancer Malignant Behaviors by Targeting Testis-Specific Y-Like Protein 5.DNA Cell Biol. 2017 Dec;36(12):1108-1116. doi: 10.1089/dna.2017.3904. Epub 2017 Oct 3.
3 Network-based inference framework for identifying cancer genes from gene expression data.Biomed Res Int. 2013;2013:401649. doi: 10.1155/2013/401649. Epub 2013 Sep 1.
4 miR-19-5p Enhances Tumorigenesis in Human Colorectal Cancer Cells by Targeting TSPYL5.DNA Cell Biol. 2018 Jan;37(1):23-30. doi: 10.1089/dna.2017.3804. Epub 2017 Dec 14.
5 Expression of tumor suppressor genes related to the cell cycle in endometrial cancer patients.Adv Med Sci. 2016 Sep;61(2):317-324. doi: 10.1016/j.advms.2016.04.001. Epub 2016 Apr 13.
6 Hypermethylation of ACP1, BMP4, and TSPYL5 in Hepatocellular Carcinoma and Their Potential Clinical Significance.Dig Dis Sci. 2016 Jan;61(1):149-57. doi: 10.1007/s10620-015-3878-3. Epub 2015 Sep 19.
7 Testis specific Y-like 5: gene expression, methylation and implications for drug sensitivity in prostate carcinoma.BMC Cancer. 2017 Feb 24;17(1):158. doi: 10.1186/s12885-017-3134-7.
8 Modulation of genetic associations with serum urate levels by body-mass-index in humans.PLoS One. 2015 Mar 26;10(3):e0119752. doi: 10.1371/journal.pone.0119752. eCollection 2015.
9 MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53.Clin Cancer Res. 2017 Jul 15;23(14):3906-3917. doi: 10.1158/1078-0432.CCR-16-2530. Epub 2017 Feb 14.
10 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.
11 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
12 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.
13 High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
14 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.
15 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.
16 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.
17 Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility. Toxicol Appl Pharmacol. 2008 Jan 15;226(2):199-205. doi: 10.1016/j.taap.2007.09.004. Epub 2007 Sep 15.