Affinage

PTPN4

Tyrosine-protein phosphatase non-receptor type 4 · UniProt P29074

Length
926 aa
Mass
105.9 kDa
Annotated
2026-04-28
40 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN4 is a non-receptor protein tyrosine phosphatase that functions as a signal-modulating enzyme in synaptic plasticity, innate immunity, and growth control, with its catalytic activity gated by an intramolecular PDZ–phosphatase autoinhibitory mechanism. The PDZ domain directly inhibits phosphatase activity through an inter-domain linker containing a conserved hydrophobic patch; binding of C-terminal PDZ ligands—including glutamate receptor subunits GluN2A and GluRδ2, p38γ MAPK, and high-risk HPV E6 oncoproteins—relieves this autoinhibition and activates catalysis (PMID:25158884, PMID:28801650, PMID:27246854, PMID:35089587). Identified substrates include TRAM, whose dephosphorylation suppresses TRIF-dependent TLR4/IRF3 signaling and IFN-β production (PMID:25825441); pSTAT3-Tyr705, whose dephosphorylation restrains STAT3-driven tumor proliferation (PMID:31025789, PMID:37747937); and CrkI, whose dephosphorylation inhibits cell migration (PMID:23666597). In Purkinje neurons, PTPN4 is required for cerebellar long-term depression and motor learning, and its FERM domain directs localization to dendritic spines where it regulates NMDA receptor phosphorylation (PMID:17953619, PMID:30238967, PMID:33158444).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Establishing that PTPN4 is membrane/cytoskeleton-associated and subject to proteolytic activation answered how the phosphatase is regulated post-translationally: calpain cleavage within the PEST-containing intermediate domain activates catalytic activity 4–8-fold, linking calcium signaling to PTPN4 function in platelets.

    Evidence Subcellular fractionation, recombinant protein calpain/trypsin cleavage assays, and calpain inhibitor treatment in human platelets

    PMID:8910369

    Open questions at the time
    • Whether calpain activation of PTPN4 occurs in neurons or immune cells
    • Identity of platelet substrates dephosphorylated by activated PTPN4
  2. 1996 Medium

    Demonstrating that PTPN4 overexpression suppresses cell growth and anchorage-independent colony formation—partially independent of catalytic activity—established that PTPN4 functions as a growth suppressor with both enzymatic and scaffolding contributions.

    Evidence Stable COS-7 lines expressing wild-type or catalytically inactive C→S mutant PTPN4, soft-agar assays

    PMID:8917530

    Open questions at the time
    • The non-catalytic mechanism of growth inhibition was not identified
    • Relevance to endogenous expression levels unknown
  3. 2000 High

    Identification of glutamate receptors GluRδ2 and GluN2B as PDZ-domain-dependent interactors of PTPN4 placed the phosphatase at postsynaptic sites and suggested a role in modulating excitatory neurotransmission.

    Evidence Yeast two-hybrid, co-immunoprecipitation from brain tissue and cultured cells, PDZ domain binding assays

    PMID:10748123

    Open questions at the time
    • Whether PTPN4 directly dephosphorylates GluRδ2 or GluN2B was not demonstrated
    • Functional consequence of the interaction on synaptic transmission was not tested
  4. 2006 Medium

    Drosophila Ptpmeg mutant analysis revealed that PTPN4-family phosphatase activity is essential for axon projection and that the FERM domain has a distinct, selective role in axon stabilization, providing the first in vivo genetic evidence for domain-specific functions.

    Evidence Drosophila loss-of-function mutants, domain-specific transgenic rescue, mosaic analysis of mushroom body neurons

    PMID:17138662

    Open questions at the time
    • Mammalian axon guidance roles not tested
    • Cell-autonomous versus non-cell-autonomous substrates not identified
  5. 2007 High

    PTPN4 knockout mice demonstrated that the phosphatase is required for cerebellar long-term depression and motor learning, converting the receptor-interaction data into a defined physiological function at identified synapses.

    Evidence PTPN4 KO mice, rotarod and eyeblink conditioning behavior, electrophysiology at parallel fiber–Purkinje cell synapses

    PMID:17953619

    Open questions at the time
    • The specific synaptic substrate(s) mediating LTD impairment were not identified
    • Whether hippocampal synaptic plasticity is also affected was not examined
  6. 2008 Medium

    Substrate-trapping identified TCR ζ-chain ITAMs as PTPN4 substrates, but genetic ablation of PTPN4 alone or together with PTPN3 and PTPN13 revealed complete dispensability for T cell signaling, establishing functional redundancy in the immune compartment.

    Evidence Substrate-trapping co-IP, single/double/triple KO mice, T cell development and cytokine assays

    PMID:18614237 PMID:19107198

    Open questions at the time
    • Identity of the compensating phosphatase(s) in T cells
    • Whether PTPN4 contributes to T cell signaling under stress or infection conditions
  7. 2014 High

    Reconstitution of the PDZ–phosphatase bidomain revealed that catalytic activity is autoinhibited by the PDZ domain in a compact conformation, and that PDZ ligand binding relieves this inhibition—establishing the core allosteric mechanism governing PTPN4 activation.

    Evidence AUC, SAXS, NMR of the bidomain construct, in vitro phosphatase assays ± PDZ ligands

    PMID:25158884

    Open questions at the time
    • Full-length structural context including the FERM domain was not resolved
    • Quantitative coupling between ligand affinity and activation extent was not fully defined
  8. 2015 High

    Identification of TRAM as a PTPN4 substrate in macrophages demonstrated that the phosphatase negatively regulates innate immune signaling by specifically suppressing TRIF-dependent IRF3 activation and IFN-β production downstream of TLR4.

    Evidence Co-IP, tyrosine phosphorylation assays, PTPN4 overexpression/knockdown in macrophages, IRF3 and IFN-β reporter assays

    PMID:25825441

    Open questions at the time
    • Whether PDZ-ligand-dependent activation is required for TRAM dephosphorylation in cells
    • Role in other TLR pathways not tested
  9. 2016 High

    Crystal structures of the PTPN4-PDZ/p38γ complex and enzymatic assays showed that p38γ is both the highest-affinity endogenous PDZ ligand and a direct substrate (activation-loop dephosphorylation), unifying the allosteric activation and substrate-recognition functions of the PDZ domain.

    Evidence X-ray crystallography, ITC, in vitro phosphatase assays on p38γ activation-loop phosphopeptides

    PMID:27246854

    Open questions at the time
    • In vivo validation of p38γ as a PTPN4 substrate in a physiological setting
    • Whether other MAPKs are similarly regulated
  10. 2017 Medium

    Mutagenesis of the conserved hydrophobic patch in the PDZ–phosphatase inter-domain linker pinpointed the molecular element mediating autoinhibition and ligand-dependent activation, refining the allosteric model to a specific structural element.

    Evidence Site-directed mutagenesis of linker residues, kinetic phosphatase assays

    PMID:28801650

    Open questions at the time
    • No full-length structure showing linker conformation in autoinhibited state
    • Contribution of FERM domain to regulation not addressed
  11. 2018 Medium

    A de novo FERM-domain missense variant (p.Leu72Ser) was shown to abolish PTPN4 localization to dendritic spines, linking the FERM domain to subcellular targeting and implicating PTPN4 dysfunction in neurodevelopmental disease.

    Evidence Transfection of WT/mutant PTPN4 in mouse hippocampal neurons, confocal imaging

    PMID:30238967

    Open questions at the time
    • Functional synaptic consequence of mislocalization not measured
    • Number of patients carrying this variant is very small
  12. 2019 Medium

    Identification of STAT3-Tyr705 as a direct PTPN4 substrate established a tumor-suppressive axis: loss of PTPN4 in colorectal cancer derepresses STAT3 transcriptional activity and accelerates tumor growth.

    Evidence Co-IP, pSTAT3 dephosphorylation assay, PTPN4 overexpression/knockdown, xenograft model

    PMID:31025789

    Open questions at the time
    • Whether PDZ-dependent activation is required for STAT3 dephosphorylation
    • Contribution of other PTPN4 substrates to growth suppression
  13. 2020 Medium

    Discovery that NSPA/MARCH8 ubiquitinates PTPN4 targeting it for degradation, and that PTPN4 accumulation in NSPA-KO mice causes NMDAR removal from PSDs and impaired hippocampal LTP, revealed ubiquitin-dependent turnover as a key regulatory layer and extended PTPN4's synaptic role beyond the cerebellum.

    Evidence Cell-based ubiquitination assay, NSPA-KO mouse synaptic fractionation, LTP electrophysiology, behavioral memory assays

    PMID:33158444

    Open questions at the time
    • Whether NSPA-mediated and MARCH8-mediated ubiquitination are redundant or context-specific
    • Direct substrate identity at hippocampal synapses not fully defined
  14. 2022 High

    Crystal structures of the PTPN4-PDZ domain bound to high-risk HPV E6 C-terminal peptides revealed the structural basis of viral hijacking of PTPN4 and showed that multiple oncogenic HPV genotypes converge on PTPN4-PDZ binding, suggesting a conserved viral immune/growth evasion strategy.

    Evidence X-ray crystallography, ITC with HPV16/18/31/33/45 E6 peptides

    PMID:35089587

    Open questions at the time
    • Functional consequence of HPV E6–PTPN4 interaction on phosphatase activity or cell signaling not tested in cells
    • Whether E6 binding activates or sequesters PTPN4 in vivo unknown
  15. 2023 Medium

    MARCH8 was identified as an E3 ligase promoting PTPN4 ubiquitination and degradation, and loss of PTPN4 activated STAT3 signaling to drive pancreatic cancer growth and metastasis, extending the PTPN4–STAT3 tumor-suppressive axis to a second cancer type and identifying an upstream regulatory E3.

    Evidence Ubiquitination assay, co-IP, PTPN4 overexpression/knockdown in pancreatic cancer cells, xenograft model

    PMID:37747937

    Open questions at the time
    • Whether MARCH8 ubiquitinates PTPN4 at the same sites as NSPA
    • Structural basis of MARCH8–PTPN4 interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of PTPN4 integrating FERM, PDZ, and phosphatase domains has not been determined, leaving unknown how the FERM domain coordinates with PDZ-dependent allosteric regulation and subcellular targeting to control substrate access in vivo.
  • No full-length atomic structure
  • Mechanism by which FERM domain directs dendritic spine localization is structurally uncharacterized
  • In vivo substrates responsible for cerebellar LTD remain unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
CRKGRID2GRIN2AGRIN2BMAPK12MARCH8STAT3TICAM2

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PTPN4 (PTPMEG) interacts with glutamate receptor delta2 (GluRδ2) and NMDA receptor GluRε1 (GluN2B) via its PDZ domain binding to the C-terminal PDZ target sequences of these receptors; additionally, PTPN4 enhances Fyn-mediated tyrosine phosphorylation of GluRε1 in a PTPase activity-dependent manner Yeast two-hybrid screening, co-immunoprecipitation from cultured cells and brain tissue, PDZ domain binding assay The Journal of biological chemistry High 10748123
1996 PTPN4 (PTPMEG) is primarily localized to the membrane and cytoskeletal fractions of cells; it is phosphorylated on serine and threonine residues within an intermediate domain (aa 386–503) containing PEST sequences and proline-rich motifs; proteolytic cleavage by calpain in this region activates the phosphatase 4–8-fold; in platelets, thrombin and calcium ionophore stimulation triggers calpain-mediated proteolysis and activation of PTPN4 Subcellular fractionation, recombinant protein expression (Sf9 and COS-7 cells), trypsin/calpain cleavage assays, immunoprecipitation from human platelets, calpain inhibitor (calpeptin) treatment The Journal of biological chemistry High 8910369
1996 Overexpression of PTPN4 in COS-7 cells reduces cell growth rate, lowers saturation density, and inhibits anchorage-independent colony formation; the catalytically inactive C→S mutant also inhibits proliferation and colony formation, though less potently, suggesting both enzymatic and non-enzymatic mechanisms; endogenous PTPN4 is localized to membrane and cytoskeletal fractions Stable COS-7 cell lines overexpressing wild-type and active-site C→S mutant PTPN4, soft-agar colony formation assay, subcellular fractionation Proceedings of the National Academy of Sciences of the United States of America Medium 8917530
2007 PTPN4 knockout mice show impaired motor learning (accelerated rotarod), impaired cerebellar delay eyeblink conditioning, and significantly attenuated long-term depression (LTD) at parallel fiber–Purkinje cell synapses, establishing that PTPN4 tyrosine dephosphorylation events are required for cerebellar synaptic plasticity and motor learning; developmental climbing fiber elimination and basal synaptic properties are unaffected PTPN4 knockout mouse generation, behavioral testing (rotarod, eyeblink conditioning), electrophysiology (LTD at PF-PC synapses) The European journal of neuroscience High 17953619
2011 The PTPN4 PDZ domain binds peptides mimicking C-terminal sequences of known ligands (e.g., GluN2A C-terminus, rabies virus G protein); crystal structures of PTPN4-PDZ complexed with two different peptides define the structural determinants of binding; intracellular delivery of high-affinity PDZ ligand peptides induces glioblastoma cell death, and killing efficiency correlates with PDZ binding affinity Crystal structure determination of PTPN4-PDZ/peptide complexes, binding affinity measurements, intracellular peptide delivery assays in glioblastoma cells Structure (London, England : 1993) High 22000519
2015 PTPN4 directly dephosphorylates TRAM (TICAM2) on tyrosine residues upon TLR4 activation, thereby inhibiting cytoplasmic translocation of TRAM, disrupting TRAM–TRIF interaction, and specifically suppressing TRIF-dependent IRF3 activation and IFN-β production downstream of TLR4 Co-immunoprecipitation, tyrosine phosphorylation assays, overexpression/knockdown of PTPN4 in macrophages, IRF3 activation and IFN-β reporter assays Journal of immunology (Baltimore, Md. : 1950) High 25825441
2008 PTPN4 substrate-trapping mutants complex with TCR ζ-chain ITAMs and can dephosphorylate ITAM phosphotyrosines; substrate-trapping derivative augments basal and TCR-induced NF-κB activation; however, PTPN4-deficient mice show no defect in T cell development, TCR signaling, ITAM phosphorylation, or immune responses, indicating functional redundancy with other phosphatases in T cells Substrate-trapping mutant co-immunoprecipitation, PTPN4-deficient mouse generation, T cell signaling assays, NF-κB reporter assay Molecular immunology Medium 18614237
2008 PTPN4 and PTPN3 are both dispensable for TCR signal transduction; PTPN4/PTPN3 double-KO and PTPN4/PTPN3/PTPN13 triple-KO mice show normal T cell development, cytokine production, and Th1/Th2/Th17 differentiation, establishing genetic epistasis that these three FERM-PDZ PTPs do not redundantly control TCR signaling PTPN4-deficient, double-KO, and triple-KO mouse generation; T cell development, proliferation, cytokine, and differentiation assays PloS one Medium 19107198
2013 PTPN4 interacts with CrkI via the SH3 domain of CrkI and the proline-rich region (aa 462–468) of PTPN4; overexpression of PTPN4 reduces CrkI tyrosine phosphorylation and inhibits CrkI-mediated cell proliferation and migration; PTPN4 knockdown enhances CrkI-mediated cell growth and motility Yeast two-hybrid, GST pull-down, co-immunoprecipitation, co-localization, overexpression/siRNA knockdown with proliferation and wound-healing assays Cellular & molecular biology letters Medium 23666597
2014 The PDZ domain of PTPN4 inhibits its own phosphatase catalytic activity through an intramolecular interaction; binding of a PDZ ligand releases this autoinhibition and restores catalytic activity; the two-domain PDZ–phosphatase construct adopts a predominant compact conformation in solution as shown by AUC, SAXS, and NMR Analytical ultracentrifugation, small-angle X-ray scattering, NMR spectroscopy, in vitro phosphatase activity assays with and without PDZ ligands The FEBS journal High 25158884
2016 PTPN4 PDZ domain forms a tight complex with the C-terminal sequence of p38γ MAPK; crystal structure of PTPN4-PDZ bound to the p38γ C-terminus reveals molecular basis of recognition; p38γ C-terminus has the highest affinity among known endogenous PTPN4-PDZ ligands; binding of the p38γ C-terminal peptide to the PDZ domain abolishes the catalytic autoinhibition of PTPN4, enabling efficient dephosphorylation of the p38γ activation loop Crystal structure determination, isothermal titration calorimetry, in vitro phosphatase activity assays, intracellular peptide delivery (cell death assay) The Journal of biological chemistry High 27246854
2017 The inter-domain linker connecting the PTPN4 PDZ domain and phosphatase domain contains a conserved patch of hydrophobic residues that mediates the PDZ-related autoinhibition and PDZ-ligand-dependent activation of phosphatase activity; mutations in this linker patch disrupt PTPN4 bidomain regulation without affecting PDZ ligand binding affinity Comparative sequence analysis, site-directed mutagenesis of linker residues, kinetic phosphatase activity assays Scientific reports Medium 28801650
2019 PTPN4 directly interacts with STAT3 and dephosphorylates pSTAT3 at Tyr705; loss of PTPN4 in colorectal/rectal cancer cells promotes STAT3 transcriptional activity and tumor growth, both in vitro and in vivo Co-immunoprecipitation, phosphatase assay (pSTAT3 Tyr705), PTPN4 overexpression and knockdown with cell growth and xenograft assays Cancer science Medium 31025789
2018 A de novo missense variant in the FERM domain of PTPN4 (p.Leu72Ser) causes loss of PTPN4 localization to dendritic spines in mouse hippocampal neurons without affecting overall neuronal expression, linking PTPN4 spine localization to neurodevelopmental phenotype Transfection of wild-type and mutant human PTPN4 in mouse hippocampal neurons, confocal imaging of dendritic spine localization Clinical genetics Medium 30238967
2006 Drosophila Ptpmeg (ortholog of PTPN4/PTPN3) regulates axonal projection establishment and stabilization in the central brain; phosphatase activity is essential for both mushroom body α and β lobe formation; the FERM domain is selectively required for preventing α lobe retraction but not β lobe overextension; Ptpmeg acts non-cell-autonomously in MB or EB neurons, implicating it in cell-cell signaling Drosophila ptpmeg loss-of-function mutants, neuronal rescue experiments, domain-specific transgenes (phosphatase-dead, FERM mutants), mosaic analysis Development (Cambridge, England) Medium 17138662
2020 NSPA (neuronal surface P antigen) ubiquitinates PTPMEG (mouse PTPN4 ortholog), targeting it for proteasomal degradation; in NSPA-KO mice, PTPMEG accumulates at postsynaptic densities, leading to reduced tyrosine phosphorylation of GluN2B (Tyr1472 endocytic signal) and selective removal of GluN2A and GluN2B NMDAR subunits from PSDs, impairing hippocampal LTP and memory Cell-based ubiquitination assay, immunoblot of synaptic fractions, NSPA-KO mouse electrophysiology (LTP), behavioral memory assays, GluN2B pTyr1472 immunoblot BMC biology Medium 33158444
2022 HPV16 E6 oncoprotein C-terminal PDZ-binding motif directly binds the PDZ domain of PTPN4; crystal structure and ITC measurements show that hydrophobic interactions (Leu158 of E6) and hydrogen bond networks sustain the complex; high-risk HPV genotypes 16, 18, 31, 33, and 45 all bind PTPN4 PDZ with comparable affinities X-ray crystallography of PTPN4-PDZ/HPV E6 peptide complex, isothermal titration calorimetry Journal of microbiology (Seoul, Korea) High 35089587
2023 E3 ubiquitin ligase MARCH8 promotes PTPN4 protein degradation via ubiquitination; loss of PTPN4 activates STAT3 phosphorylation (pSTAT3 Tyr705) and its transcriptional activity, promoting pancreatic cancer growth and metastasis Ubiquitination assay, co-immunoprecipitation, PTPN4 overexpression/knockdown in pancreatic cancer cells, xenograft in vivo model, western blot for pSTAT3 Pancreas Medium 37747937
2025 KPNA5 recognizes nuclear localization signals (NLS) in PTPN4 and mediates its nuclear transport; nuclear PTPN4 inhibits STAT3 phosphorylation and downstream signaling in ovarian cancer cells Co-immunoprecipitation, overexpression/knockdown studies in ovarian cancer cells, xenograft model, western blot for pSTAT3, NLS mapping Cancer medicine Low 40145330

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor delta 2 and epsilon subunits. The Journal of biological chemistry 76 10748123
2019 miR-181c-5p Exacerbates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4. Oxidative medicine and cellular longevity 51 31178952
1996 The properties of the protein tyrosine phosphatase PTPMEG. The Journal of biological chemistry 49 8910369
2022 MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis. Experimental & molecular medicine 47 36042375
2007 Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression. The European journal of neuroscience 42 17953619
2011 Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death. Structure (London, England : 1993) 41 22000519
2015 Phosphatase PTPN4 preferentially inhibits TRIF-dependent TLR4 pathway by dephosphorylating TRAM. Journal of immunology (Baltimore, Md. : 1950) 31 25825441
1996 The effect of overexpression of the protein tyrosine phosphatase PTPMEG on cell growth and on colony formation in soft agar in COS-7 cells. Proceedings of the National Academy of Sciences of the United States of America 29 8917530
2019 Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer. Cancer science 24 31025789
2008 The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of dephosphorylating the TCR ITAMs and regulating NF-kappaB, is dispensable for T cell development and/or T cell effector functions. Molecular immunology 23 18614237
2016 Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ. The Journal of biological chemistry 22 27246854
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
2016 MicroRNA-183 promotes migration and invasion of CD133(+)/CD326(+) lung adenocarcinoma initiating cells via PTPN4 inhibition. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 26951513
2006 Ptpmeg is required for the proper establishment and maintenance of axon projections in the central brain of Drosophila. Development (Cambridge, England) 21 17138662
2014 Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain. The FEBS journal 20 25158884
2022 Crocin induces ROS-mediated papillary thyroid cancer cell apoptosis by modulating the miR-34a-5p/PTPN4 axis in vitro. Toxicology and applied pharmacology 16 35085590
2020 Inhibition of microRNA-15b-5p Attenuates the Progression of Oral Squamous Cell Carcinoma via Modulating the PTPN4/STAT3 Axis. Cancer management and research 16 33149666
2013 PTPN4 negatively regulates CrkI in human cell lines. Cellular & molecular biology letters 16 23666597
2006 PTPN3 and PTPN4 tyrosine phosphatase expression in human gastric adenocarcinoma. Anticancer research 16 16619586
2018 Neurodevelopmental phenotype caused by a de novo PTPN4 single nucleotide variant disrupting protein localization in neuronal dendritic spines. Clinical genetics 15 30238967
2014 Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype. European journal of human genetics : EJHG 15 25424712
2023 CircDLGAP4 induces autophagy and improves endothelial cell dysfunction in atherosclerosis by targeting PTPN4 with miR-134-5p. Environmental toxicology 12 37615249
2017 Regulation of the Human Phosphatase PTPN4 by the inter-domain linker connecting the PDZ and the phosphatase domains. Scientific reports 11 28801650
2023 Exosomes from circRNA-Ptpn4 can modify ADSC treatment and repair nerve damage caused by cerebral infarction by shifting microglial M1/M2 polarization. Molecular and cellular biochemistry 10 37632638
2022 Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein. Journal of microbiology (Seoul, Korea) 10 35089587
2020 Neuronal surface P antigen (NSPA) modulates postsynaptic NMDAR stability through ubiquitination of tyrosine phosphatase PTPMEG. BMC biology 10 33158444
2000 Molecular cloning and characterization of a protein tyrosine phosphatase enriched in testis, a putative murine homologue of human PTPMEG. Gene 9 11054567
2021 miR-16-5p Regulates PTPN4 and Affects Cardiomyocyte Apoptosis and Autophagy Induced by Hypoxia/Reoxygenation. Evidence-based complementary and alternative medicine : eCAM 8 34306144
2024 LncRNA SH3BP5-AS1 promotes hepatocellular carcinoma progression by sponging miR-6838-5p and activation of PTPN4. Aging 7 38761175
2023 E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4. Pancreas 7 37747937
2021 PTPN4 germline variants result in aberrant neurodevelopment and growth. HGG advances 6 34527963
2024 circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood-brain barrier integrity and cognitive function in uremic encephalopathy. Cell biology and toxicology 3 38630149
2025 KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus. Cancer medicine 2 40145330
2025 Circ_0001084/miR-181c-5p/PTPN4 Axis Mitigates Cardiomyocyte Injury by Modulating the TLR4/NF-κB Pathway: Insights into Therapeutic Potential for Myocardial Reperfusion Injury. Journal of inflammation research 1 39871962
2025 Effect of the PTPN4/TRAM/TLR4 Signaling Pathway on Angiogenesis Mediated by Rab27a-regulated miR-17-5p Secretion in Breast Cancer Exosomes. The American journal of the medical sciences 1 40456466
2016 Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma. Computational biology and chemistry 1 27923202
2026 Major clinical improvement in a boy with developmental disabilities and a PTPN4 mutation with intensive re-education and an enriched environment in a day care hospital: a case report. Journal of medical case reports 0 41776703
2025 GnRH-driven FSH synthesis and secretion are modulated through circ-ptpn4 ceRNA sequestration of let-7b-5p miRNA, which negatively controls ELK1 expression. Theriogenology 0 41289789
2025 Circular RNA PTPN4 Contributes to Blood-Brain Barrier Disruption during Early Epileptogenesis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41391036
2023 Inhibition of microRNA-15b-5p Attenuates the Progression of Oral Squamous Cell Carcinoma via Modulating the PTPN4/STAT3 Axis [Retraction]. Cancer management and research 0 37693220