Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT10OKOF)

DOT Name Receptor-type tyrosine-protein phosphatase eta (PTPRJ)
Synonyms Protein-tyrosine phosphatase eta; R-PTP-eta; EC 3.1.3.48; Density-enhanced phosphatase 1; DEP-1; HPTP eta; Protein-tyrosine phosphatase receptor type J; R-PTP-J; CD antigen CD148
Gene Name PTPRJ
Related Disease
Hereditary nonpolyposis colon cancer ( )
Colorectal cancer ( )
UniProt ID
PTPRJ_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2CFV; 2DLE; 2NZ6; 7U01; 7U08
EC Number
3.1.3.48
Pfam ID
PF00041 ; PF18861 ; PF00102
Sequence
MKPAAREARLPPRSPGLRWALPLLLLLLRLGQILCAGGTPSPIPDPSVATVATGENGITQ
ISSTAESFHKQNGTGTPQVETNTSEDGESSGANDSLRTPEQGSNGTDGASQKTPSSTGPS
PVFDIKAVSISPTNVILTWKSNDTAASEYKYVVKHKMENEKTITVVHQPWCNITGLRPAT
SYVFSITPGIGNETWGDPRVIKVITEPIPVSDLRVALTGVRKAALSWSNGNGTASCRVLL
ESIGSHEELTQDSRLQVNISGLKPGVQYNINPYLLQSNKTKGDPLGTEGGLDASNTERSR
AGSPTAPVHDESLVGPVDPSSGQQSRDTEVLLVGLEPGTRYNATVYSQAANGTEGQPQAI
EFRTNAIQVFDVTAVNISATSLTLIWKVSDNESSSNYTYKIHVAGETDSSNLNVSEPRAV
IPGLRSSTFYNITVCPVLGDIEGTPGFLQVHTPPVPVSDFRVTVVSTTEIGLAWSSHDAE
SFQMHITQEGAGNSRVEITTNQSIIIGGLFPGTKYCFEIVPKGPNGTEGASRTVCNRTVP
SAVFDIHVVYVTTTEMWLDWKSPDGASEYVYHLVIESKHGSNHTSTYDKAITLQGLIPGT
LYNITISPEVDHVWGDPNSTAQYTRPSNVSNIDVSTNTTAATLSWQNFDDASPTYSYCLL
IEKAGNSSNATQVVTDIGITDATVTELIPGSSYTVEIFAQVGDGIKSLEPGRKSFCTDPA
SMASFDCEVVPKEPALVLKWTCPPGANAGFELEVSSGAWNNATHLESCSSENGTEYRTEV
TYLNFSTSYNISITTVSCGKMAAPTRNTCTTGITDPPPPDGSPNITSVSHNSVKVKFSGF
EASHGPIKAYAVILTTGEAGHPSADVLKYTYEDFKKGASDTYVTYLIRTEEKGRSQSLSE
VLKYEIDVGNESTTLGYYNGKLEPLGSYRACVAGFTNITFHPQNKGLIDGAESYVSFSRY
SDAVSLPQDPGVICGAVFGCIFGALVIVTVGGFIFWRKKRKDAKNNEVSFSQIKPKKSKL
IRVENFEAYFKKQQADSNCGFAEEYEDLKLVGISQPKYAAELAENRGKNRYNNVLPYDIS
RVKLSVQTHSTDDYINANYMPGYHSKKDFIATQGPLPNTLKDFWRMVWEKNVYAIIMLTK
CVEQGRTKCEEYWPSKQAQDYGDITVAMTSEIVLPEWTIRDFTVKNIQTSESHPLRQFHF
TSWPDHGVPDTTDLLINFRYLVRDYMKQSPPESPILVHCSAGVGRTGTFIAIDRLIYQIE
NENTVDVYGIVYDLRMHRPLMVQTEDQYVFLNQCVLDIVRSQKDSKVDLIYQNTTAMTIY
ENLAPVTTFGKTNGYIA
Function
Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2. Plays a role in cell adhesion, migration, proliferation and differentiation. Involved in vascular development. Regulator of macrophage adhesion and spreading. Positively affects cell-matrix adhesion. Positive regulator of platelet activation and thrombosis. Negative regulator of cell proliferation. Negative regulator of PDGF-stimulated cell migration; through dephosphorylation of PDGFR. Positive regulator of endothelial cell survival, as well as of VEGF-induced SRC and AKT activation; through KDR dephosphorylation. Negative regulator of EGFR signaling pathway; through EGFR dephosphorylation. Enhances the barrier function of epithelial junctions during reassembly. Negatively regulates T-cell receptor (TCR) signaling. Upon T-cell TCR activation, it is up-regulated and excluded from the immunological synapses, while upon T-cell-antigen presenting cells (APC) disengagement, it is no longer excluded and can dephosphorylate PLCG1 and LAT to down-regulate prolongation of signaling ; [Isoform 2]: Activates angiogenesis and cell migration. Downregulates the expression of the endothelial adhesion molecules ICAM1 and VCAM1.
Tissue Specificity
Expressed in the promyelocytic cell line HL-60, the granulocyte-macrophage colony-stimulating factor-dependent leukemic cell line F-36P, and the IL3 and erythropoietin-dependent leukemic cell line F-36E. Expressed predominantly in epithelial cells and lymphocytes. Enhanced expression at high cell density.; [Isoform 2]: Expressed in the brain.
KEGG Pathway
Adherens junction (hsa04520 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Negative regulation of MET activity (R-HSA-6807004 )
Negative regulation of FLT3 (R-HSA-9706369 )
Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hereditary nonpolyposis colon cancer DISPA49R Limited Autosomal dominant [1]
Colorectal cancer DISNH7P9 No Known Unknown [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [3]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [9]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [8]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [10]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [12]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [14]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of Receptor-type tyrosine-protein phosphatase eta (PTPRJ). [15]
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⏷ Show the Full List of 11 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
3 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.
4 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.
5 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.
6 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
7 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.
8 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
9 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.
10 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
11 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
12 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
13 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
14 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.
15 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.