Affinage

PTPN3

Tyrosine-protein phosphatase non-receptor type 3 · UniProt P26045

Length
913 aa
Mass
104.0 kDa
Annotated
2026-06-10
45 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN3 (PTPH1) is a multidomain non-receptor protein tyrosine phosphatase that couples a PDZ-based substrate-recruitment module to a catalytic PTP domain, acting as both an enzyme and a scaffold across signaling, oncogenic, and viral contexts (PMID:7544351, PMID:25314968). Its N-terminal band 4.1/ERM domain directly modulates catalytic output and substrate selectivity, and the PDZ domain autoinhibits the catalytic domain through a connecting linker, an autoinhibition relieved when a PDZ-binding motif (PBM) ligand engages the PDZ domain (PMID:7544351, PMID:25314968, PMID:37200868). Through this PDZ-mediated recruitment PTPN3 dephosphorylates defined substrates: it traps and dephosphorylates VCP/p97 at its C-terminal tyrosines (PMID:10364224), dephosphorylates the stress kinase p38γ MAPK in a complex whose architecture and substrate specificity are defined by a glutamate-containing E-loop (PMID:20332238, PMID:25314968), dephosphorylates Eps15 to promote EGFR endocytosis and lysosomal degradation (PMID:25263444), and inhibits Src to limit DAAM1 Tyr652 phosphorylation, dimerization, and actin assembly (PMID:31406243). PTPN3 activity is reciprocally regulated by its partners: p38γ phosphorylates PTPN3 at Ser-459 in a Ras-controlled feedback loop, and 14-3-3β binds PTPN3 in a serine-phosphorylation-dependent manner (PMID:9341175, PMID:22730326). In cancer, PTPN3 exhibits context-dependent roles—it cooperates with p38γ and scaffolds HER2 to drive oncogenic growth and acts as a Ras effector (PMID:20332238, PMID:39803648), yet suppresses lung cancer proliferation and metastasis via Eps15/EGFR and Src/DAAM1 control (PMID:25263444, PMID:31406243). Independent of its phosphatase activity, PTPN3 stabilizes the TGF-β type I receptor by blocking Smurf2 binding, and the cholangiocarcinoma-associated L232R mutation disables this tumor-suppressive function (PMID:31304624). The PDZ domain also binds viral PBMs from HPV E6 (targeting PTPN3 for E6AP/proteasome-dependent degradation) and hepatitis B core protein, linking PTPN3 to viral pathogenesis (PMID:17166906, PMID:31092861, PMID:33441627). Genetic ablation of PTPN3 catalytic activity in mice leaves TCR signaling and T cell development intact, indicating its proposed role in negative TCR regulation is dispensable in vivo (PMID:17339465, PMID:19107198).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Established PTPN3 as a bona fide tyrosine phosphatase and showed that its N-terminal band 4.1 domain is not merely structural but tunes catalytic rate and substrate choice.

    Evidence In vitro enzymatic assays with purified protein, trypsin cleavage, and PKC phosphorylation

    PMID:7544351

    Open questions at the time
    • Physiological substrates not yet identified
    • Mechanism by which the N-terminal domain alters substrate selectivity unresolved
  2. 1997 High

    Identified phospho-serine-dependent 14-3-3β binding at two motifs as a regulatory input controlling PTPN3, framing the phosphatase as itself a regulated node.

    Evidence Yeast two-hybrid, in vitro reconstitution, site-directed mutagenesis of Ser359/Ser853, co-IP

    PMID:9341175

    Open questions at the time
    • Functional consequence of 14-3-3 binding for catalytic activity or localization not defined
    • Kinase generating the phospho-motifs in cells unclear
  3. 1999 High

    Defined VCP/p97 as a direct cellular substrate via substrate-trapping, linking PTPN3 catalytic activity to growth inhibition.

    Evidence Substrate-trapping double mutant, inducible expression in NIH3T3, phosphotyrosine blots

    PMID:10364224

    Open questions at the time
    • Downstream consequences of VCP dephosphorylation not mapped
    • Recruitment mechanism to VCP unknown
  4. 2003 Medium

    Cell-based assays nominated PTPN3 as a negative regulator of TCR-zeta and proximal T cell signaling.

    Evidence Reporter assays in Jurkat cells, substrate-trapping PTP library screen, transfection dephosphorylation assays

    PMID:10820377 PMID:14672952

    Open questions at the time
    • Overexpression-based; physiological relevance untested
    • ERM-domain contribution not mechanistically resolved
  5. 2009 High

    Genetic mouse models overturned the proposed T cell role, showing PTPN3 catalytic activity is dispensable for TCR signaling even with related phosphatases removed.

    Evidence Single, double (PTPN3/PTPN4) and triple (with PTPN13) knockout mice with comprehensive T cell phenotyping

    PMID:17339465 PMID:19107198

    Open questions at the time
    • Redundancy with non-tested phosphatases not excluded
    • Does not address non-immune functions
  6. 2002 High

    Defined the PDZ domain as a substrate/partner recruitment module by mapping PTPN3 to the TACE/ADAM17 C-terminal PBM and showing negative regulation of TNF-α shedding.

    Evidence Y2H, in vitro binding, reciprocal co-IP, shedding/ELISA functional assay

    PMID:12207026

    Open questions at the time
    • Whether TACE is dephosphorylated or only down-regulated in level unresolved
  7. 2007 Medium

    Extended PDZ-mediated partnering to the cardiac channel Nav1.5, with catalytic activity altering channel availability.

    Evidence Y2H, pull-down, co-expression electrophysiology with active vs inactive PTPN3

    PMID:16930557

    Open questions at the time
    • Direct dephosphorylation of Nav1.5 not demonstrated
    • In vivo cardiac relevance untested
  8. 2012 High

    Established a reciprocal PTPN3–p38γ oncogenic module: PTPN3 dephosphorylates p38γ while p38γ phosphorylates PTPN3 at Ser-459 under Ras control, defining a feedback circuit driving transformation.

    Evidence Y2H, co-IP, in vitro/in vivo phosphatase and kinase assays, proteomics, S459 mutagenesis, mouse xenograft

    PMID:20332238 PMID:22730326

    Open questions at the time
    • How S459 phosphorylation alters catalytic or scaffold function not fully defined
  9. 2014 High

    Resolved the structural basis of substrate specificity and PDZ-relieved autoinhibition, explaining how PDZ binding licenses catalysis toward activated p38γ.

    Evidence Hybrid X-ray/SAXS/cross-linking-MS of the PTPN3–p38γ complex with phosphatase assays

    PMID:25314968

    Open questions at the time
    • Generality of E-loop specificity to other substrates untested in this study
  10. 2014 High

    Revealed opposing cancer roles: phosphatase-independent VDR stabilization promotes breast cancer growth, ICC gain-of-function mutations enhance proliferation, while Eps15 dephosphorylation drives EGFR degradation to suppress lung cancer.

    Evidence Co-IP, knockdown/overexpression, phosphatase assays, ICC mutant (L232R/L384H) functional assays, Drosophila screen, xenograft

    PMID:21119599 PMID:24503127 PMID:25263444

    Open questions at the time
    • Tissue determinants of oncogenic vs tumor-suppressive behavior unresolved
    • VDR-stabilization mechanism not structurally defined
  11. 2019 High

    Expanded the phosphatase-independent scaffold function: PTPN3 stabilizes TβRI by blocking Smurf2, and separately controls Src–DAAM1 to restrain actin-driven metastasis, with ICC L232R abolishing TGF-β tumor suppression.

    Evidence Co-IP, receptor stability and Smad reporter assays, Src/phosphatase assays, DAAM1 Y652F rescue, metastasis model, L232R/phosphatase-dead mutants

    PMID:31304624 PMID:31406243

    Open questions at the time
    • How a single L232R mutation toggles between gain- and loss-of-function across pathways unresolved
  12. 2021 High

    Defined PTPN3 as a target of viral PBMs, structurally characterizing PDZ recognition of HPV E6, HBc, and TACE motifs and the linker-mediated autoinhibition independent of PBM binding.

    Evidence X-ray crystallography of PDZ–PBM complexes, PDZome screening, ITC/NMR, HPV E6/E6AP degradation assays, HBV infection assays, phosphatase assays with linker mutants

    PMID:17166906 PMID:30875834 PMID:31092861 PMID:33441627 PMID:37200868

    Open questions at the time
    • Functional impact of PTPN3 on HBV/HPV life cycle only partially defined
    • Why PBM binding does not relieve linker autoinhibition for non-p38γ ligands unclear
  13. 2024 Medium

    Positioned PTPN3 as a multi-kinase PDZ scaffold organizing HER2, p38γ, PBK and YAP1 to drive a transcriptional oncogenic program.

    Evidence Co-IP, PDZ binding assays, HER2 dephosphorylation, S459 phosphorylation, transcription assays, xenograft

    PMID:39803648

    Open questions at the time
    • Single lab; direct vs indirect assembly of the four-protein scaffold not fully dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTPN3 selects between phosphatase-dependent and scaffold (phosphatase-independent) modes in a given tissue, and what unifies its opposing tumor-promoting and tumor-suppressing outputs, remains unresolved.
  • No integrated model reconciling oncogenic vs tumor-suppressor activities
  • In vivo substrate repertoire beyond cancer cell models undefined
  • Endogenous regulatory inputs (14-3-3, S459) not connected to physiological outcomes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
DAAM1HER2 (ERBB2)P38Γ (MAPK12)SCN5A (NAV1.5)TACE (ADAM17)TGFBR1VCPVDR

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Purified PTPH1 exhibits protein tyrosine phosphatase activity toward myelin basic protein (MBP) and RCML substrates; phosphorylation by protein kinase C in vitro decreases Km without affecting Vmax. Removal of the N-terminal band 4.1 homology domain stimulates dephosphorylation of RCML but inhibits activity toward MBP, indicating that the N-terminal domain directly modulates catalytic function and substrate selectivity. In vitro enzymatic assay with purified baculovirus-expressed protein, limited trypsin cleavage, PKC phosphorylation assay The Journal of biological chemistry High 7544351
1997 PTPH1 associates with 14-3-3β in a serine phosphorylation-dependent manner. Two novel motifs (RSLS359VE and RVDS853EP) in PTPH1 were identified as major 14-3-3β binding sites; mutation of Ser359 and Ser853 to alanine significantly reduced association. The interaction was reconstituted in vitro with recombinant proteins, abolished by phosphatase treatment, and enhanced by Cdc25C-associated kinase treatment. Yeast two-hybrid screen, in vitro reconstitution with recombinant proteins, site-directed mutagenesis, co-immunoprecipitation from cell lines The Journal of biological chemistry High 9341175
1999 PTPH1 directly dephosphorylates VCP (p97/CDC48) in cells. A substrate-trapping mutant (D811A/Y676F double mutant) specifically trapped VCP in vivo and recognized the C-terminal tyrosines of VCP. Induction of wild-type PTPH1 caused specific dephosphorylation of VCP without altering the overall phosphotyrosine profile of cells. Wild-type PTPH1 expression dramatically inhibited cell growth, while a catalytically impaired mutant did not. Substrate-trapping mutagenesis (D811A, Y676F), in vitro substrate trapping from cell lysates, tetracycline-inducible expression in NIH3T3 cells, immunoprecipitation, phosphotyrosine western blot The Journal of biological chemistry High 10364224
2000 Expression of catalytically active PTPH1 in Jurkat T cells reduces TCR-induced activation of NFAT/AP-1 reporter genes, Erk2 MAP kinase, MEK, and JNK. Catalytically inactive PTPH1-CS had no effect. Deletion of the N-terminal ERM domain reduced the inhibitory effect, indicating the ERM domain contributes to PTPH1's function in T cell signaling. Transient transfection in Jurkat T cells, luciferase reporter assays, kinase activity assays, catalytically inactive mutant controls European journal of immunology Medium 10820377
2002 PTPH1 interacts with the cytoplasmic domain of TACE (ADAM17) via its PDZ domain binding to the C-terminal group I PDZ-binding motif of TACE (ending in cysteine). Co-expression of catalytically active PTPH1 reduces TACE protein levels and decreases phorbol ester-stimulated shedding of TNF-α compared to catalytically inactive PTPH1, identifying PTPH1 as a negative regulator of TACE. Yeast two-hybrid screen, in vitro binding assay, co-immunoprecipitation from eukaryotic cells, co-expression functional assay (TACE shedding), ELISA for TNF-α The Journal of biological chemistry High 12207026
2003 PTPH1 is the predominant phosphatase capable of complexing with phospho-TCR zeta in a substrate-trapping library screen of 47 human PTPs, and transfection assays confirmed PTPH1 directly dephosphorylates TCR zeta ITAMs. PTP substrate-trapping library (47 PTP catalytic domains), protein purification/chromatography, novel ELISA-based PTPase assay, transfection assays The Journal of biological chemistry Medium 14672952
2006 HPV E6 oncoproteins, in complex with E6AP ubiquitin ligase, associate with PTPN3 via binding of E6's C-terminus to the PDZ domain of PTPN3, leading to proteasome-dependent degradation of PTPN3 in vitro and in living cells. Degradation requires E6AP and the proteasome. In transduced keratinocytes, E6-conferred reduced growth factor requirement partially phenocopies PTPN3 knockdown. In vitro degradation assay, co-immunoprecipitation, proteasome inhibitor experiments, siRNA knockdown in keratinocytes Journal of virology High 17166906
2006 PTPH1 interacts with the cardiac voltage-gated sodium channel Nav1.5 via the PDZ domain of PTPH1 binding to the PDZ-binding motif in the C-terminus of Nav1.5. Co-expression of catalytically active PTPH1 shifts the Nav1.5 availability relationship toward hyperpolarized potentials, while inactive PTPH1 or the tyrosine kinase Fyn does the opposite, indicating that tyrosine phosphorylation destabilizes the inactivated state of Nav1.5. Yeast two-hybrid screen (cardiac cDNA library), pull-down assay, co-expression in HEK293 cells with electrophysiology Biochemical and biophysical research communications Medium 16930557
2007 Mice lacking catalytically active PTPN3 (gene-trapped and gene-targeted strains) show normal TCR signal transduction, T cell development, cytokine production, and proliferation, demonstrating that PTPN3 phosphatase activity is dispensable for negative regulation of TCR signaling in primary T cells in vivo. Gene trap and gene targeting in mice, flow cytometry, T cell activation assays, cytokine ELISA, proliferation assays Journal of immunology High 17339465
2008 PTPN3 and PTPN4 double-deficient mice, as well as PTPN3/PTPN4/PTPN13 triple-deficient mice, show normal T cell development, TCR-induced cytokine synthesis, proliferation, and Th1/Th2/Th17 differentiation, establishing that PTPN3 and PTPN4 are dispensable for TCR signal transduction even in the absence of related phosphatases. Generation of single, double, and triple knockout mice; T cell development, activation, and differentiation assays PloS one High 19107198
2010 PTPH1 is a specific phosphatase for p38γ MAPK through PDZ-mediated binding; yeast two-hybrid screening and in vitro/in vivo analyses confirmed the interaction. PTPH1 dephosphorylates p38γ, and their complex formation is required for cooperative oncogenic activity in Ras-dependent malignant growth in vitro and in mice. Yeast two-hybrid screen, in vitro binding assay, co-immunoprecipitation, phosphatase assay, cell transformation assays, mouse xenograft Cancer research High 20332238
2010 PTPH1 stimulates breast cancer growth by binding vitamin D receptor (VDR) and increasing cytoplasmic accumulation of VDR, leading to mutual stabilization of PTPH1 and VDR. This oncogenic activity is independent of PTPH1's phosphatase activity but dependent on its ability to increase VDR protein expression. Co-immunoprecipitation, siRNA knockdown, overexpression in breast cancer cell lines, subcellular fractionation, cell proliferation assays Oncogene Medium 21119599
2012 p38γ MAPK phosphorylates its phosphatase PTPH1 at Ser-459 in vitro and in vivo through their complex formation, as identified by unbiased proteomics. This phosphorylation is regulated by Ras signaling and is important for Ras, p38γ, and PTPH1 oncogenic activity as well as stress-induced cell growth/death responses. Unbiased proteomic/mass spectrometric identification of phosphorylation, in vitro kinase assay, in vivo phosphorylation assay, site-directed mutagenesis (S459), genetic and pharmacological pathway analyses The Journal of biological chemistry High 22730326
2014 Somatic gain-of-function mutations in PTPN3 (including L232R and L384H) found in intrahepatic cholangiocarcinoma alter phosphatase activity and further increase cell proliferation, colony formation, and migration beyond wild-type PTPN3 when expressed in ICC cell lines. Whole exome sequencing, transgenic expression of mutant PTPN3 in cholangiocarcinoma cell lines, cell proliferation/colony/migration assays, phosphatase activity assay Gastroenterology Medium 24503127
2014 PTPN3 dephosphorylates Eps15 (EGFR pathway substrate 15), promoting EGFR lipid raft-mediated endocytosis and lysosomal degradation. Depletion of PTPN3 impairs EGFR degradation and enhances lung cancer cell proliferation and tumorigenicity, while PTPN3 and an Eps15 phosphorylation-deficient mutant suppress cell growth and migration in vitro and tumor xenograft growth in vivo. Drosophila genetic screen, PTPN3 knockdown/overexpression in lung cancer cells, phosphatase assay with Eps15 substrate, endocytosis assays, xenograft mouse model Oncogene High 25263444
2014 The PTPN3–p38γ complex architecture was determined by a hybrid structural method (X-ray crystallography, SAXS, and chemical cross-linking/MS). A unique glutamic acid-containing loop (E-loop) of the PTPN3 phosphatase domain defines substrate specificity toward fully activated p38γ. The PDZ domain of PTPN3 stabilizes the active-state complex through binding the PDZ-binding motif of p38γ, alleviating autoinhibition of PTPN3 and enabling efficient tyrosine dephosphorylation. X-ray crystallography, small-angle X-ray scattering (SAXS), chemical cross-linking coupled to mass spectrometry, in vitro phosphatase assay Science signaling High 25314968
2019 PTPN3 interacts with Src and DAAM1 (formin-like actin regulator). PTPN3 inhibits Src activity and Src-mediated phosphorylation of DAAM1 Tyr652. Tyrosine phosphorylation of DAAM1 is required for DAAM1 homodimer formation and actin polymerization. Depletion of PTPN3 enhances lung cancer cell migration/invasion and metastasis via promoted actin filament assembly and focal adhesion dynamics; a DAAM1 phosphodeficient mutant rescues these effects. Co-immunoprecipitation, PTPN3 knockdown in lung cancer cells, Src kinase assay, site-directed mutagenesis of DAAM1 (Y652F), F-actin assembly assay, focal adhesion dynamics, mouse metastasis model Oncogene High 31406243
2019 PTPN3 stabilizes TGF-β type I receptor (TβRI) by attenuating the interaction between the E3 ubiquitin ligase Smurf2 and TβRI, thereby facilitating TGF-β-induced R-Smad phosphorylation and transcriptional responses. This function is independent of PTPN3's phosphatase activity. The ICC-associated L232R mutation disables this TGF-β signaling enhancement and abolishes tumor suppression. Co-immunoprecipitation, PTPN3 knockdown/overexpression, TβRI stability assay, Smad phosphorylation assay, luciferase reporter assay, phosphatase-dead mutant analysis, L232R mutant analysis The EMBO journal High 31304624
2019 The X-ray crystal structure of the PTPN3 PDZ domain in complex with the PDZ-binding motif (PBM) of HPV E6 was solved. The viral PBM and endogenous ligand p38γ bind the PDZ domain with similar affinities. PBM binding stabilizes the PDZ domain but does not impact the phosphatase catalytic regulation. X-ray crystallography, NMR chemical shift mapping, isothermal titration calorimetry/biophysical binding assays Scientific reports High 31092861
2019 HPV8 E6 protein binds PTPH1 and increases PTPH1 protein expression and phosphatase activity. PTPH1 suppression in immortalized keratinocytes reduces cell proliferation and reduces EGFR protein levels, suggesting PTPH1 supports EGFR-dependent keratinocyte proliferation. Co-immunoprecipitation, siRNA knockdown in keratinocytes, cell proliferation assay, western blot for EGFR Cells Medium 30875834
2021 PTPN3 PDZ domain binds the C-terminal PBM of hepatitis B virus core protein (HBc) within capsids or as homodimers; crystal structure of PTPN3-PDZ/HBc-PBM complex was solved, revealing a class I PDZ interaction despite atypical C-terminal cysteine in the PBM. Overexpression of PTPN3 significantly affects HBV infection in HepG2-NTCP cells. X-ray crystallography, pull-down assays, PDZ domain library screening, HBV infection assay in HepG2-NTCP cells, proteomics Scientific reports High 33441627
2023 The linker connecting the PDZ and phosphatase domains of PTPN3 is involved in autoinhibition of the phosphatase catalytic activity. Binding of PBMs to the PDZ domain does not impact this catalytic regulation. X-ray structures of complexes between PTPN3-PDZ and PBMs of HPV18 E6 and TACE were solved, revealing structural determinants of PBM recognition. X-ray crystallography, PDZome binding profile screening, phosphatase activity assay with linker mutants Frontiers in molecular biosciences Medium 37200868
2024 PTPH1 acts as a PDZ-domain scaffold for HER2 receptor tyrosine kinase, binding HER2, p38γ, PBK, and YAP1 via its PDZ domain. PTPH1 dephosphorylates HER2 and reciprocally increases HER2 protein expression. PTPH1 is phosphorylated at S459 by p38γ and/or PBK, regulating scaffold protein turnover. PTPH1 and HER2 cooperate to increase PBK and YAP1 transcription, and combinational inhibition of scaffold-kinases suppresses xenograft growth. Co-immunoprecipitation, PDZ domain binding assays, HER2 dephosphorylation assay, phosphorylation at S459, transcription assays, mouse xenograft model American journal of cancer research Medium 39803648

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients. Gastroenterology 108 24503127
2002 Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1. The Journal of biological chemistry 94 12207026
1999 Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1. The Journal of biological chemistry 90 10364224
1997 Serine phosphorylation-dependent association of the band 4.1-related protein-tyrosine phosphatase PTPH1 with 14-3-3beta protein. The Journal of biological chemistry 87 9341175
2006 Degradation of tyrosine phosphatase PTPN3 (PTPH1) by association with oncogenic human papillomavirus E6 proteins. Journal of virology 80 17166906
2012 Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing. Genes, chromosomes & cancer 70 22334442
2010 PTPH1 dephosphorylates and cooperates with p38gamma MAPK to increase ras oncogenesis through PDZ-mediated interaction. Cancer research 66 20332238
2000 Cytoskeletal protein tyrosine phosphatase PTPH1 reduces T cell antigen receptor signaling. European journal of immunology 50 10820377
2003 PTPH1 is a predominant protein-tyrosine phosphatase capable of interacting with and dephosphorylating the T cell receptor zeta subunit. The Journal of biological chemistry 45 14672952
2014 Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation. Oncogene 42 25263444
2006 Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1. Biochemical and biophysical research communications 40 16930557
2010 PTPH1 cooperates with vitamin D receptor to stimulate breast cancer growth through their mutual stabilization. Oncogene 37 21119599
1995 Biochemical characterization of a human band 4.1-related protein-tyrosine phosphatase, PTPH1. The Journal of biological chemistry 26 7544351
2020 MicroRNA-574-5p in gastric cancer cells promotes angiogenesis by targeting protein tyrosine phosphatase non-receptor type 3 (PTPN3). Gene 25 31972307
2019 PTPN3 acts as a tumor suppressor and boosts TGF-β signaling independent of its phosphatase activity. The EMBO journal 25 31304624
2019 PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization. Oncogene 25 31406243
2012 p38γ Mitogen-activated protein kinase signals through phosphorylating its phosphatase PTPH1 in regulating ras protein oncogenesis and stress response. The Journal of biological chemistry 25 22730326
2008 The FERM and PDZ domain-containing protein tyrosine phosphatases, PTPN4 and PTPN3, are both dispensable for T cell receptor signal transduction. PloS one 22 19107198
2007 Normal TCR signal transduction in mice that lack catalytically active PTPN3 protein tyrosine phosphatase. Journal of immunology (Baltimore, Md. : 1950) 22 17339465
2020 PTPN3 Inhibits the Growth and Metastasis of Clear Cell Renal Cell Carcinoma via Inhibition of PI3K/AKT Signaling. Molecular cancer research : MCR 21 32169891
2014 Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain-modulated complex formation. Science signaling 21 25314968
2019 Structural and functional characterization of the PDZ domain of the human phosphatase PTPN3 and its interaction with the human papillomavirus E6 oncoprotein. Scientific reports 19 31092861
2016 Protein tyrosine phosphatase PTPN3 promotes drug resistance and stem cell-like characteristics in ovarian cancer. Scientific reports 19 27833130
2006 PTPN3 and PTPN4 tyrosine phosphatase expression in human gastric adenocarcinoma. Anticancer research 16 16619586
1995 Expression of PTPH1, a rat protein tyrosine phosphatase, is restricted to the derivatives of a specific diencephalic segment. Proceedings of the National Academy of Sciences of the United States of America 16 7644504
2019 Up-regulation of microRNA-497-5p inhibits colorectal cancer cell proliferation and invasion via targeting PTPN3. Bioscience reports 15 31350343
1996 Transfection of human ovarian cancer cells with the HER-2/neu receptor tyrosine kinase induces a selective increase in PTP-H1, PTP-1B, PTP-alpha expression. Gynecologic oncology 15 8626139
2021 PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor. Translational oncology 12 34134073
2019 PTPN3 expressed in activated T lymphocytes is a candidate for a non-antibody-type immune checkpoint inhibitor. Cancer immunology, immunotherapy : CII 12 31562536
2021 Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein. Scientific reports 11 33441627
1993 Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal-associated proteins. International journal of cancer 11 8253532
2016 PTPH1 promotes tumor growth and metastasis in human glioma. European review for medical and pharmacological sciences 8 27735041
2015 The molecular basis for the substrate specificity of protein tyrosine phosphatase PTPN3. Structure (London, England : 1993) 6 25862931
1994 Expression of cytoskeletal-associated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma. Journal of gastroenterology 6 7874267
2018 PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India: A retrospective study. Journal of cellular physiology 5 30189107
2022 Association of SNPs within PTPN3 gene with wool production and growth traits in a dual-purpose sheep population. Animal biotechnology 4 35192431
2023 Interactions of the protein tyrosine phosphatase PTPN3 with viral and cellular partners through its PDZ domain: insights into structural determinants and phosphatase activity. Frontiers in molecular biosciences 3 37200868
2023 PTPN3 inhibition contributes to the activation of the dendritic cell function to be a promising new immunotherapy target. Journal of cancer research and clinical oncology 3 37584709
2020 NFκB and TGFβ contribute to the expression of PTPN3 in activated human lymphocytes. Cellular immunology 3 33137650
2019 The Protein Tyrosine Phosphatase H1 PTPH1 Supports Proliferation of Keratinocytes and is a Target of the Human Papillomavirus Type 8 E6 Oncogene. Cells 3 30875834
2024 Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments. Journal of immunotherapy (Hagerstown, Md. : 1997) 1 38297883
2024 Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold. American journal of cancer research 1 39803648
2025 Elevated PTPN3 expression in type 2 diabetes mellitus: Insights from genetic and experimental analyses. Biomedical reports 0 39926046
2025 Clinicopathological correlation of PTPN3 expression in breast cancer and in silico drug screening against PTPN3 for therapeutics. Cancer genetics 0 40315635
2022 PTPN3 Could Βe a Therapeutic Target of Pancreatic Cancer. Anticancer research 0 35641270

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