Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0S09B3)

DOT Name Tyrosine-protein phosphatase non-receptor type 18 (PTPN18)
Synonyms EC 3.1.3.48; Brain-derived phosphatase
Gene Name PTPN18
Related Disease
Endometrial cancer ( )
Endometrial carcinoma ( )
Gastrointestinal stromal tumour ( )
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome ( )
Hepatocellular carcinoma ( )
UniProt ID
PTN18_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2OC3; 4GFU; 4GFV; 4NND
EC Number
3.1.3.48
Pfam ID
PF00102
Sequence
MSRSLDSARSFLERLEARGGREGAVLAGEFSDIQACSAAWKADGVCSTVAGSRPENVRKN
RYKDVLPYDQTRVILSLLQEEGHSDYINGNFIRGVDGSLAYIATQGPLPHTLLDFWRLVW
EFGVKVILMACREIENGRKRCERYWAQEQEPLQTGLFCITLIKEKWLNEDIMLRTLKVTF
QKESRSVYQLQYMSWPDRGVPSSPDHMLAMVEEARRLQGSGPEPLCVHCSAGCGRTGVLC
TVDYVRQLLLTQMIPPDFSLFDVVLKMRKQRPAAVQTEEQYRFLYHTVAQMFCSTLQNAS
PHYQNIKENCAPLYDDALFLRTPQALLAIPRPPGGVLRSISVPGSPGHAMADTYAVVQKR
GAPAGAGSGTQTGTGTGTGARSAEEAPLYSKVTPRAQRPGAHAEDARGTLPGRVPADQSP
AGSGAYEDVAGGAQTGGLGFNLRIGRPKGPRDPPAEWTRV
Function Differentially dephosphorylate autophosphorylated tyrosine kinases which are known to be overexpressed in tumor tissues.
Tissue Specificity Expressed in brain, colon and several tumor-derived cell lines.
Reactome Pathway
Interleukin-37 signaling (R-HSA-9008059 )
Downregulation of ERBB2 signaling (R-HSA-8863795 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Endometrial cancer DISW0LMR Strong Biomarker [1]
Endometrial carcinoma DISXR5CY Strong Biomarker [1]
Gastrointestinal stromal tumour DIS6TJYS Strong Biomarker [2]
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome DIS7E15X Strong Genetic Variation [3]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [12]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [16]
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9 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 Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [8]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [9]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [10]
Selenium DM25CGV Approved Selenium increases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [13]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tyrosine-protein phosphatase non-receptor type 18 (PTPN18). [15]
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⏷ Show the Full List of 9 Drug(s)

References

1 Downregulation of PTPN18 can inhibit proliferation and metastasis and promote apoptosis of endometrial cancer.Clin Exp Pharmacol Physiol. 2019 Aug;46(8):734-742. doi: 10.1111/1440-1681.13098. Epub 2019 May 30.
2 miR-125a-5p regulation increases phosphorylation of FAK that contributes to imatinib resistance in gastrointestinal stromal tumors.Exp Cell Res. 2018 Oct 1;371(1):287-296. doi: 10.1016/j.yexcr.2018.08.028. Epub 2018 Aug 24.
3 PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders.Immunol Rev. 2009 Mar;228(1):312-24. doi: 10.1111/j.1600-065X.2008.00747.x.
4 Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma.Cell Physiol Biochem. 2018;46(6):2335-2346. doi: 10.1159/000489625. Epub 2018 May 4.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
8 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.
9 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.
10 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
11 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.
12 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.
13 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.
14 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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 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.