Affinage

Showing PTPN23 — HD-PTP is a alias.

PTPN23

Tyrosine-protein phosphatase non-receptor type 23 · UniProt Q9H3S7

Length
1636 aa
Mass
179.0 kDa
Annotated
2026-06-10
47 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN23/HD-PTP is a catalytically inactive pseudophosphatase that serves as a central coordinator of the ESCRT pathway, driving the endosomal sorting of ubiquitinated transmembrane cargo into multivesicular bodies for lysosomal degradation (PMID:18434552, PMID:19340315). Its Bro1 domain is the functional hub: it adopts an open, extended conformation optimal for simultaneous engagement of multiple ESCRT components (PMID:28831121), binding ESCRT-0 (STAM2 core, via a hydrophobic pocket that orients STAM2 oppositely to CHMP4B on Alix/Brox), ESCRT-I (TSG101), and ESCRT-III (CHMP4B), with overlapping binding sites enabling competitive handoff (PMID:23477725, PMID:17174262, PMID:26866605). PTPN23 recruits the deubiquitinase UBPY/USP8 and coordinately displaces ESCRT-0 in favor of ESCRT-III to transfer cargo such as EGFR (PMID:23477725), and it can act as a non-canonical substitute for ESCRT-II, bridging ESCRT-I directly to ESCRT-III for sorting of cargoes including MHC class I and ubiquitylated tau aggregates (PMID:26221024, PMID:40197510). Through this machinery PTPN23 governs the fate of diverse receptors — EGFR, integrins, death receptors (TNFR1) and TLRs, and neurotrophin receptors — thereby attenuating downstream signaling, suppressing invasion and tumorigenesis, and acting as a cell-death checkpoint (PMID:21724833, PMID:27210750, PMID:39609437, PMID:32079660). PTPN23 also functions beyond endosomes: it is essential for cardiac T-tubule formation, interacting with sarcomeric α-actinin and dystrophin to promote dystrophin-glycoprotein complex assembly at costameres (PMID:38214189), is required for constitutive secretion via tubule fission at the trans-Golgi network (PMID:41848521), and activates a WNK3–PI3KC2α–AKT2 endosomal survival axis independently of its catalytic activity (PMID:39841180). PTPN23 levels are controlled by WDR4–Cullin 4-mediated ubiquitination and proteasomal degradation, which restrains EGFR and c-MET turnover (PMID:37821451).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2008 High

    Established PTPN23 as a required factor for endosomal cargo sorting and MVB morphogenesis, defining its core cellular role and the indispensability of its Bro1 domain.

    Evidence RNAi depletion with domain-mutant rescue and EM/fluorescence imaging in mammalian cells

    PMID:18434552

    Open questions at the time
    • Did not resolve which ESCRT contacts are direct versus indirect
    • Catalytic status of the phosphatase domain not yet defined
  2. 2009 High

    Resolved the paradox of a phosphatase-named protein lacking enzymatic activity by showing PTPN23 is a catalytically dead pseudophosphatase whose biological activity is catalysis-independent.

    Evidence In vitro DiFMUP and phosphoinositide assays with catalytic back-mutation and colony formation assay

    PMID:19340315

    Open questions at the time
    • Did not establish what the divergent phosphatase domain does instead
    • No structural basis for the scaffolding function
  3. 2006 Medium

    Mapped the first Bro1-domain interaction network, distinguishing PTPN23 from Alix by Ca2+-independent TSG101 binding and lack of CIN85 interaction.

    Evidence Yeast two-hybrid and Strep-tag pulldowns from HEK293T lysates

    PMID:17174262

    Open questions at the time
    • Binding affinities and stoichiometry not quantified
    • Functional consequence of ALG-2 Ca2+-dependence untested
  4. 2013 High

    Built the mechanistic model of PTPN23 as a coordinator that hands EGFR cargo from ESCRT-0 to ESCRT-III, including recruitment of the deubiquitinase UBPY/USP8.

    Evidence Co-IP, pulldowns, competition assays, RNAi, and EGFR trafficking readouts

    PMID:23477725

    Open questions at the time
    • Temporal order of competition events on endosomes not directly visualized
    • Did not address cargoes other than EGFR
  5. 2011 High

    Connected PTPN23 endosomal function to tumor suppression by showing it controls E-cadherin trafficking and restrains SRC/β-catenin-driven invasion.

    Evidence RNAi loss-of-function screen, substrate phosphorylation assays, invasion assays, and SRC-inhibitor epistasis in mammary epithelial cells

    PMID:21724833

    Open questions at the time
    • Reconciliation with catalytic inactivity (substrate dephosphorylation claim) not addressed
    • Direct versus trafficking-mediated effects on substrates not separated
  6. 2015 High

    Demonstrated PTPN23 can substitute for ESCRT-II/VPS20 as a non-canonical ESCRT-I–ESCRT-III bridge, generalizing its adaptor role to virally ubiquitinated MHC class I.

    Evidence Systematic RNAi of individual ESCRT components with WT/mutant rescue and flow cytometry

    PMID:26221024

    Open questions at the time
    • Did not define when the non-canonical versus canonical route is selected
    • Structural basis of ESCRT-I bridging not resolved here
  7. 2016 High

    Provided the atomic basis for ESCRT-0 engagement, showing STAM2 binds the Bro1 hydrophobic pocket in an orientation opposite to CHMP4B with Thr145 as the determinant residue.

    Evidence X-ray crystallography of the Bro1–STAM2 complex with mutagenesis

    PMID:26866605

    Open questions at the time
    • Full-length complex architecture not captured
    • Dynamics of STAM2/CHMP4B exchange not directly observed
  8. 2016 High

    Linked PTPN23 dosage to in vivo tumor suppression and integrin recycling, validating its physiological role in restraining migration and invasion.

    Evidence Ptpn23+/- mouse tumor monitoring with integrin trafficking and migration assays

    PMID:27210750

    Open questions at the time
    • Cell-type origin of tumors not dissected
    • Direct integrin sorting mechanism in vivo not shown
  9. 2017 High

    Defined the conformational logic enabling simultaneous multi-ESCRT engagement, showing PTPN23 is extended and open unlike compact Alix.

    Evidence SAXS, hydrodynamic analysis, and binding assays with cellular partners

    PMID:28831121

    Open questions at the time
    • High-resolution full-length structure absent
    • Conformational regulation on membranes untested
  10. 2017 High

    Identified SARA and endofin as HD-PTP-specific Bro1 ligands competing with CHMP4 at the same site, revealing a unique neighboring pocket distinguishing PTPN23.

    Evidence Crystal structures of Bro1 with SARA, endofin, and three CHMP4 isoforms plus competition assays

    PMID:28602823

    Open questions at the time
    • Cellular role of SARA/endofin competition not resolved here
    • How competing ligands are ordered in time unknown
  11. 2021 High

    Placed endofin as a functional partner linking PTPN23 to ESCRT-0 (Hrs) for sorting of ubiquitinated integrin α5 and EGFR.

    Evidence BioID, co-IP, RNAi with mutant complementation, and receptor trafficking/migration assays

    PMID:34761192

    Open questions at the time
    • Whether endofin is universally required or cargo-selective unclear
    • Quantitative contribution versus direct STAM2/TSG101 routes not partitioned
  12. 2014 Medium

    Extended PTPN23 function to the nucleus, showing it shuttles and regulates SMN phosphorylation and Cajal body localization.

    Evidence Phosphatase RNAi screen, Cajal body accumulation assay, co-IP, phosphorylation analysis, fractionation

    PMID:25392300

    Open questions at the time
    • Mechanism linking endosomal scaffold to nuclear SMN regulation unknown
    • Whether effect is direct given catalytic inactivity unresolved
  13. 2007 Medium

    Implicated PTPN23 in adhesion signaling by showing it binds FAK and restrains FAK tyrosine phosphorylation and migration in endothelial cells.

    Evidence siRNA, co-IP, immunofluorescence, and migration assays

    PMID:17959146

    Open questions at the time
    • Direct dephosphorylation excluded by later catalytic-dead finding
    • Mechanism of FAK regulation (scaffold versus trafficking) unclear
  14. 2008 Medium

    Showed reciprocal regulation by Src, which phosphorylates and inhibits PTPN23, positioning it downstream of growth-factor signaling.

    Evidence Co-IP, in vitro phosphorylation, phosphatase activity assay, RNAi, Src inhibition

    PMID:18762272 PMID:18835089

    Open questions at the time
    • Reconciliation with catalytic inactivity of the PTP domain
    • Phosphosites on PTPN23 not mapped
  15. 2019 High

    Established a role in neuronal receptor signaling, showing PTPN23 sustains EphB2 clustering/activation and controls axon guidance.

    Evidence BioID, co-IP, RNAi, collapse assay, in vivo chick motor neuron axon guidance

    PMID:31420572

    Open questions at the time
    • How PTPN23 promotes clustering rather than only degradation unclear
    • Direct versus ESCRT-mediated effect on EphB2 not separated
  16. 2020 Medium

    Identified PTPN23 as a regulator of neurotrophin receptor (p75NTR/TrkB) endocytic sorting through interaction with the dynein adaptor BICD1.

    Evidence BICD1 interactome MS, domain mapping, RNAi, fluorescence microscopy in motor neurons

    PMID:32079660

    Open questions at the time
    • Functional significance of BICD1 binding (non-cargo) undefined
    • Link to motor transport versus sorting not resolved
  17. 2024 High

    Revealed an unanticipated structural role in cardiac muscle, with PTPN23 required for T-tubule formation and DGC assembly at costameres via α-actinin and dystrophin interactions.

    Evidence Cardiomyocyte conditional/CRISPR knockout mice, AAV9 mosaics, fractionation, co-IP, EM, T-tubule imaging

    PMID:38214189

    Open questions at the time
    • Whether ESCRT activity underlies the costamere role unclear
    • Mechanism of membrane tubule shaping at Z-discs not defined
  18. 2024 High

    Defined PTPN23/ESCRT as a cell-death checkpoint by sorting death receptors and TLRs, with NAP1 facilitating TNFR1 endosomal sorting.

    Evidence CRISPR screen in AML cells, BioID, co-IP, receptor imaging, cell death assays

    PMID:39609437

    Open questions at the time
    • Whether NAP1 acts on cargoes beyond TNFR1 unknown
    • Selectivity of death-receptor versus other cargo sorting not resolved
  19. 2025 High

    Showed PTPN23 mediates endosomal microautophagy of tau aggregates by bridging TSG101-recognized polyubiquitinated tau to ESCRT-III, linking it to disease via UBAP1.

    Evidence Genome-wide CRISPR screen, co-IP, domain mapping, microscopy, tau degradation assay

    PMID:40197510

    Open questions at the time
    • In vivo relevance to tauopathy clearance not tested
    • Distinction between microautophagy and canonical ILV pathway not fully resolved
  20. 2025 High

    Uncovered a catalysis-independent signaling output: PTPN23 drives WNK3-dependent PI3KC2α phosphorylation to fuel PI(3,4)P2/AKT2 survival signaling at endosomes.

    Evidence RNAi/CRISPR, in vitro kinase assay, PI lipidomics, co-IP, mouse melanoma models

    PMID:39841180

    Open questions at the time
    • How PTPN23 induces WNK3 activity mechanistically unclear
    • Relationship of this axis to ESCRT sorting unresolved
  21. 2026 High

    Extended ESCRT-dependent PTPN23 function to the secretory pathway, showing it is required for trans-Golgi tubule fission and constitutive secretion.

    Evidence Post-Golgi carrier affinity-MS, pooled CRISPR screen, live-cell TGN imaging, secretion assays

    PMID:41848521

    Open questions at the time
    • Direct membrane-fission contacts at the TGN not defined
    • Whether the same Bro1 contacts operate at the Golgi unknown
  22. 2023 High

    Identified the upstream control of PTPN23 abundance, showing WDR4–Cullin 4 ubiquitinates PTPN23 to restrain EGFR/c-MET degradation.

    Evidence Ubiquitylome MS, co-IP, proteasome inhibition, degradation assays, competitive peptide

    PMID:37821451

    Open questions at the time
    • Physiological context regulating WDR4 activity unknown
    • Ubiquitination sites on PTPN23 not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTPN23's many roles — endosomal sorting, costamere assembly, TGN secretion, nuclear SMN regulation, and the catalysis-independent WNK3–PI3KC2α axis — are coordinated and selectively deployed in different tissues remains unresolved.
  • No unifying model linking endosomal scaffolding to non-endosomal functions
  • Tissue-specific partner repertoire not mapped
  • No human Mendelian disease directly attributed to PTPN23 in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005768 endosome 5 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-9609507 Protein localization 5 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
ACTN2CHMP4BDMDPI3KC2ASTAM2TSG101UBAP1USP8
Complex memberships
ESCRT machinerydystrophin-glycoprotein complex (DGC)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis; its Bro1 domain is essential for function, and ESCRT-III binding correlates with full biological activity. Depletion causes accumulation of ubiquitinated proteins on endosomal compartments and disrupts MVB morphogenesis. RNAi depletion in mammalian cells, RNAi-resistant rescue with HD-PTP mutants, fluorescence microscopy, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 18434552
2013 HD-PTP acts as a central coordinator of the ESCRT pathway for EGFR sorting: (1) the HD-PTP Bro1 domain binds the core domain of STAM2 (ESCRT-0), competed by CHMP4B (ESCRT-III) at an overlapping site; (2) a proline-rich peptide in HD-PTP binds the SH3 domain of STAM2; (3) HD-PTP recruits UBPY/USP8 to deubiquitinate EGFR, with UBPY interacting with HD-PTP-bound CHMP4B and with HD-PTP directly; concerted CHMP4B/UBPY recruitment displaces ESCRT-0 from cargo in favor of ESCRT-III. Co-immunoprecipitation, pulldown assays, RNAi depletion, fluorescence microscopy, EGFR trafficking assays Current biology : CB High 23477725
2011 PTPN23 suppression in mammary epithelial cells increases E-cadherin internalization, impairs early endosome trafficking of E-cadherin, elevates SRC and β-catenin activity, and promotes cell invasion. SRC, E-cadherin, and β-catenin were identified as direct substrates of PTPN23. Inhibition of SRC blocked the invasive effects of PTPN23 depletion. RNAi loss-of-function screen, shRNA knockdown, phosphorylation assays, migration/invasion assays, SRC inhibitor epistasis Genes & development High 21724833
2006 HD-PTP interacts with CHMP4b/Shax1 (ESCRT-III), TSG101 (ESCRT-I), endophilin A1, and ALG-2 via its Bro1 domain and proline-rich region. Interaction with ALG-2 is Ca2+-dependent; interaction with TSG101 is Ca2+-independent (unlike Alix). HD-PTP does not interact with CIN85. Yeast two-hybrid, Strep-tag pulldown from HEK293T cell lysates, Western blotting Archives of biochemistry and biophysics Medium 17174262
2009 HD-PTP is catalytically inactive as a tyrosine phosphatase due to evolutionary divergence of a key catalytic residue in its phosphatase domain; back-mutation of this residue restores tyrosine phosphatase activity. HD-PTP also lacks lipid phosphatase activity. Its colony growth reduction activity is independent of catalytic PTP activity. In vitro enzymatic assay using DiFMUP substrate and phosphoinositide phosphates, site-directed mutagenesis, colony formation assay PloS one High 19340315
2011 Myopic (Drosophila HD-PTP ortholog) regulates the Salvador/Warts/Hippo pathway by binding Yorkie via PPxY motifs interacting with Yorkie WW domains; Myopic colocalizes with Yorkie at endosomes and controls Yorkie endosomal association and protein levels, influencing expression of some Yorkie target genes. Genetic screen, co-immunoprecipitation, colocalization by fluorescence microscopy, in vivo Drosophila genetics Developmental cell Medium 21571226
2016 Haploinsufficiency of HD-PTP/PTPN23 in mice promotes tumor formation (lung adenoma, B cell lymphoma) and enhances integrin β1-dependent lymphoma survival and dissemination, consistent with a role of HD-PTP in attenuation of integrin recycling, cell migration, and invasion. Mouse Ptpn23+/- heterozygous knockout model, tumor monitoring, integrin trafficking assays, cell migration assays Cell reports High 27210750
2015 HD-PTP acts as an alternative to ESCRT-II and VPS20/CHMP6 as a link between ESCRT-I and ESCRT-III in the non-canonical ESCRT pathway used for sorting virally ubiquitinated (K63-linked) MHC class I into MVBs for lysosomal degradation. RNAi-mediated depletion of individual ESCRT proteins, rescue experiments with WT and mutant HD-PTP, flow cytometry for cell-surface MHC class I The Biochemical journal High 26221024
2016 Crystal structure of the HD-PTP Bro1 domain in complex with the STAM2 core region revealed that STAM2 binds the hydrophobic concave pocket of the Bro1 domain in the opposite orientation compared to CHMP4B binding to Alix/Brox. Thr145 of HD-PTP (vs. Lys151 of Alix) is a determinant residue enabling STAM2 binding; Alix- or Brox-mimicking mutations at this position abolish STAM2 interaction. X-ray crystallography, site-directed mutagenesis, binding assays PloS one High 26866605
2017 HD-PTP adopts an open and extended conformation (determined by SAXS and hydrodynamic analysis), optimal for simultaneous interactions with multiple ESCRTs, contrasting with the compact conformation of Alix. This open conformation is functionally competent for binding cellular ESCRT partners. Small angle X-ray scattering (SAXS), hydrodynamic analyses, binding assays with cellular partners Scientific reports High 28831121
2017 SARA and endofin bind with high affinity to the conserved hydrophobic region of the HD-PTP Bro1 domain (the same site as CHMP4/ESCRT-III) and compete with CHMP4 for this site. The interaction is specific to HD-PTP among Bro1 proteins due to a neighboring pocket unique to HD-PTP. Crystal structures of HD-PTPBro1 with SARA, endofin, and three CHMP4 isoforms were determined. X-ray crystallography, mutagenesis, binding/competition assays, co-immunoprecipitation Structure (London, England : 1993) High 28602823
2014 PTPN23/HD-PTP interacts with SMN and regulates SMN complex localization: PTPN23 knockdown reduces SMN accumulation in Cajal bodies and alters the phosphorylation pattern of SMN without affecting SMN complex assembly. PTPN23 shuttles between nucleus and cytoplasm. Systematic phosphatase RNAi screen, SMN-Cajal body accumulation assay, co-immunoprecipitation, phosphorylation analysis, subcellular fractionation/imaging Molecular biology of the cell Medium 25392300
2007 HD-PTP binds Focal Adhesion Kinase (FAK) in endothelial cells; this interaction is inhibited by bFGF treatment. In cells depleted of HD-PTP, FAK is hyperphosphorylated on tyrosine residues and localizes in focal adhesions at the leading edge, promoting cell migration. siRNA knockdown, co-immunoprecipitation, immunofluorescence, migration assay Biochemical and biophysical research communications Medium 17959146
2008 Src binds HD-PTP in endothelial cells; this interaction is enhanced by bFGF. Src phosphorylates HD-PTP on tyrosine residues, which inhibits HD-PTP's enzymatic (phosphatase) activity. HD-PTP does not modulate Src phosphorylation levels. Co-immunoprecipitation, in vitro phosphorylation assay, tyrosine phosphatase activity assay, RNAi, pharmacological Src inhibition The international journal of biochemistry & cell biology Medium 18762272
2008 In T24 bladder carcinoma cells, Src binds and phosphorylates HD-PTP on tyrosine residues upon EGF stimulation; FAK also binds and phosphorylates HD-PTP, reducing the HD-PTP–FAK interaction. HD-PTP depletion enhances FAK phosphorylation and its localization in focal complexes, promoting migration in a Src-dependent manner. RNAi, co-immunoprecipitation, phosphorylation assays, pharmacological Src inhibition, immunofluorescence, migration assay Cancer letters Medium 18835089
2019 HD-PTP is required for ephrin-B2:EphB2 signaling: HD-PTP associates with EphB2 (identified by BioID and confirmed by co-IP). HD-PTP loss attenuates ephrin-B2-induced EphB2 clustering and EphB2/Src family kinase activation, accelerates ligand-induced EphB2 degradation, and impairs axonal growth cone collapse and spinal motor neuron axon guidance in vivo. BioID proximity labeling, co-immunoprecipitation, RNAi knockdown, cell collapse assay, in vivo chick spinal motor neuron axon guidance Scientific reports High 31420572
2020 PTPN23 binds the N-terminus of the dynein adaptor BICD1 (not as canonical cargo); loss of PTPN23 leads to accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, identifying PTPN23 as a regulator of endocytic sorting of neurotrophin receptors in motor neurons. Proteomics/mass spectrometry of BICD1 interactome, molecular mapping, RNAi knockdown, fluorescence microscopy Journal of cell science Medium 32079660
2021 Endofin forms a complex with ESCRT constituents including HD-PTP and is required for HD-PTP/ESCRT-0-interdependent sorting of ubiquitinated transmembrane cargoes (integrin α5, EGFR). Mutants with impaired Endofin/HD-PTP association or cytosolic Endofin fail to restore EGFR lysosomal delivery. Endofin also promotes indirect interaction between Hrs (ESCRT-0) and HD-PTP. Proximity biotinylation (BioID), co-immunoprecipitation, RNAi depletion, complementation with mutants, receptor trafficking assays, cell migration assays iScience High 34761192
2022 HD-PTP Bro1 domain directly interacts with the HAV capsid pX export signal (confirmed by co-IP with recombinant proteins and biotin-tagged peptides). RNAi-mediated depletion of HD-PTP impedes quasi-enveloped HAV (eHAV) release. HD-PTP and ALIX activities are non-redundant and both required for eHAV release. Co-immunoprecipitation with recombinant proteins, biotin-tagged peptide pulldown, RNAi depletion, super-resolution fluorescence microscopy, quantitative virus release assay PLoS pathogens High 35969644
2023 WDR4-based Cullin 4 ubiquitin ligase ubiquitinates PTPN23, leading to its proteasomal degradation, thereby suppressing lysosomal trafficking and degradation of EGFR (WT, mutant) and c-MET. A competing peptide blocking PTPN23–WDR4 interaction restores EGFR/c-MET degradation. Unbiased ubiquitylome mass spectrometry, co-immunoprecipitation, proteasome inhibitor assays, receptor trafficking/degradation assays, competitive peptide intervention Cell death & disease High 37821451
2024 PTPN23 is essential for cardiac T-tubule formation and maintenance along Z-discs. PTPN23 interacts with sarcomeric α-actinin and dystrophin and promotes assembly of the dystrophin-glycoprotein complex (DGC) at costameres. Deletion of α-actinin alters PTPN23 subcellular localization; genetic inactivation of dystrophin causes similar T-tubule defects without affecting PTPN23 localization at Z-discs. Cardiomyocyte-specific Cre/LoxP and CRISPR/Cas9 knockout mice, AAV9-mediated mosaic mutagenesis, glycerol-gradient fractionation, co-immunoprecipitation, electron microscopy, T-tubule fluorescence staining Circulation High 38214189
2024 PTPN23-dependent ESCRT machinery functions as a cell death checkpoint: loss of PTPN23 causes accumulation of death receptors (TNFR1) and TLRs in endosomes, activating NF-κB, apoptotic, necroptotic, and pyroptotic pathways. NAK-associated protein 1 (NAP1) interacts with PTPN23 to facilitate endosomal sorting of TNFR1, sensitizing cells to TNF-α-induced cytotoxicity. CRISPR screen in AML cells, proximity-dependent biotin labeling (BioID), co-immunoprecipitation, receptor localization imaging, cell death assays Nature communications High 39609437
2025 PTPN23 bridges ESCRT-I and ESCRT-III (instead of ESCRT-II) to mediate endosomal microautophagy of ubiquitylated tau (tauRD) aggregates. ESCRT-I subunit TSG101 recognizes polyubiquitinated tauRD via its UEV domain; PTPN23 acts as the adaptor linking ESCRT-I to ESCRT-III for microautophagic engulfment. A disease-associated UBAP1 mutation disrupts UBAP1–PTPN23 interaction and impairs tau clearance. Genome-wide CRISPR knockout screen, co-immunoprecipitation, domain mapping, fluorescence microscopy, tau aggregate degradation assay The Journal of cell biology High 40197510
2025 PTPN23 activates PI3KC2α by inducing WNK3-mediated phosphorylation of PI3KC2α at Ser329, enhancing PI3KC2α catalytic activity at endosomes, increasing PI(3,4)P2 production and subsequent AKT2 activation to support BRAF-mutant cancer cell survival. PTPN23 catalytic activity is not required for this function. RNAi/CRISPR knockdown, in vitro kinase assay, PI lipid mass spectrometry, co-immunoprecipitation, mouse melanoma models The Journal of experimental medicine High 39841180
2026 PTPN23 is required for constitutive secretion from the trans-Golgi network: loss of PTPN23 (and ESCRT subunits CHMP1 and VPS4) disrupts tubule fission from the trans-Golgi and impairs delivery of cargo to the plasma membrane, as well as constitutive secretion of soluble cargoes and endogenous hormones/antibodies in specialized cells. Affinity isolation of post-Golgi carriers with mass spectrometry, pooled CRISPR-KO screen, live-cell imaging of trans-Golgi tubules, cargo secretion assays The Journal of cell biology High 41848521
2012 HD-PTP undergoes calcium-dependent proteolytic degradation by calpains in T24 bladder carcinoma cells; calpain inhibition prevents this degradation and causes redistribution of HD-PTP to the cell periphery. Calpain inhibitor treatment, calcium manipulation, Western blotting, immunofluorescence Biochemical and biophysical research communications Medium 22510412
2006 HD-PTP protein is degraded via the proteasome system in response to FGF-2 in endothelial cells; VEGF does not affect HD-PTP protein levels. Proteasome inhibitor treatment, Western blotting, growth factor stimulation Frontiers in bioscience : a journal and virtual library Low 16720300
2024 A PTPN23 variant (rs6780013, p.Thr) binds EGFR and modulates its phosphorylation at Thr699, substantially inhibiting ESCC cell proliferation in vitro and in vivo. Co-immunoprecipitation, in vitro and in vivo proliferation assays, phosphorylation analysis Cancer letters Medium 38704135
2018 Myopic (HD-PTP/PTPN23 Drosophila ortholog) selectively inhibits activity-induced Ca2+-dependent neuropeptide (DCV) release at the NMJ without affecting small synaptic vesicle (SSV) release. This function does not require interaction with ESCRT-III protein CHMP4/Shrub. Presynaptic Myopic is abundant at early endosomes. Transgenic overexpression/knockdown in Drosophila NMJ, optical imaging of synaptic neuropeptide release, DCV counting, genetic rescue with CHMP4-interaction mutants Proceedings of the National Academy of Sciences of the United States of America Medium 29378961
2021 PTPN23 acts as a cofactor for HIV-1 Vpu-directed degradation of BST-2 and decrease of CD4 at the cell surface by supporting ESCRT-dependent sorting at multivesicular bodies; identified as part of the Vpu proximal proteome by APEX2 proximity labeling. APEX2 proximity proteomics, hierarchical clustering, RNAi depletion, flow cytometry for cell-surface protein levels PLoS pathogens Medium 34843601
2024 HD-PTP hypomorphic mice with reduced protein expression develop lipodystrophy, decreased receptor-mediated EGFR signaling in white adipose tissue (decreased trans-autophosphorylation and downstream effector activation despite normal EGF binding), decreased plasma membrane cholesterol, and increased lysosomal cholesterol, attributable to defective endosomal maturation and cholesterol trafficking. Hypomorphic mouse model, adipose tissue signaling assays, cholesterol fractionation, in vitro EGFR assays Journal of cell science Medium 39155850

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 123 18434552
2013 Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB. Current biology : CB 97 23477725
2011 Identification of PTPN23 as a novel regulator of cell invasion in mammary epithelial cells from a loss-of-function screen of the 'PTP-ome'. Genes & development 65 21724833
2006 HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions. Archives of biochemistry and biophysics 55 17174262
2000 HD-PTP: A novel protein tyrosine phosphatase gene on human chromosome 3p21.3. Biochemical and biophysical research communications 50 11095967
2009 HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PloS one 48 19340315
2011 A screen for conditional growth suppressor genes identifies the Drosophila homolog of HD-PTP as a regulator of the oncoprotein Yorkie. Developmental cell 43 21571226
2016 Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer. Cell reports 41 27210750
2015 A non-canonical ESCRT pathway, including histidine domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC class I. The Biochemical journal 37 26221024
2009 Expression analysis and essential role of the putative tyrosine phosphatase His-domain-containing protein tyrosine phosphatase (HD-PTP). The International journal of developmental biology 31 19378249
2008 HD-PTP inhibits endothelial migration through its interaction with Src. The international journal of biochemistry & cell biology 29 18762272
2018 Dissecting the role of His domain protein tyrosine phosphatase/PTPN23 and ESCRTs in sorting activated epidermal growth factor receptor to the multivesicular body. Biochemical Society transactions 28 30190330
2007 The tyrosine phosphatase HD-PTP: A novel player in endothelial migration. Biochemical and biophysical research communications 26 17959146
2017 The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function. Scientific reports 24 28831121
2014 The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization. Molecular biology of the cell 24 25392300
2019 Phenotype and mutation expansion of the PTPN23 associated disorder characterized by neurodevelopmental delay and structural brain abnormalities. European journal of human genetics : EJHG 21 31395947
2017 Role of ESCRT component HD-PTP/PTPN23 in cancer. Biochemical Society transactions 21 28620046
2023 PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target. Cell death & disease 19 37821451
2016 Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0. PloS one 18 26866605
2020 The ESCRT-II Subunit EAP20/VPS25 and the Bro1 Domain Proteins HD-PTP and BROX Are Individually Dispensable for Herpes Simplex Virus 1 Replication. Journal of virology 17 31748394
2008 Inhibition of T24 human bladder carcinoma cell migration by RNA interference suppressing the expression of HD-PTP. Cancer letters 17 18835089
2022 Nonlytic cellular release of hepatitis A virus requires dual capsid recruitment of the ESCRT-associated Bro1 domain proteins HD-PTP and ALIX. PLoS pathogens 16 35969644
2017 Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARA/Endofin with HD-PTP. Structure (London, England : 1993) 15 28602823
2017 Mutations of PTPN23 in developmental and epileptic encephalopathy. Human genetics 15 29090338
2019 The endosomal sorting adaptor HD-PTP is required for ephrin-B:EphB signalling in cellular collapse and spinal motor axon guidance. Scientific reports 14 31420572
2024 Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex. Circulation 13 38214189
2021 Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes. iScience 12 34761192
2020 PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors. Journal of cell science 12 32079660
2018 Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release. Proceedings of the National Academy of Sciences of the United States of America 11 29378961
2006 Expression analysis and modulation by HIV-Tat of the tyrosine phosphatase HD-PTP. Journal of cellular biochemistry 10 16408268
2021 Transcriptome analysis reveals that hydrogen sulfide exposure suppresses cell proliferation and induces apoptosis through ciR-PTPN23/miR-15a/E2F3 signaling in broiler thymus. Environmental pollution (Barking, Essex : 1987) 9 34062439
2019 Loss of PTPN23 Promotes Proliferation and Epithelial-to-Mesenchymal Transition in Human Intestinal Cancer Cells. Inflammatory intestinal diseases 9 31768389
2018 Developmental epileptic encephalopathy with hypomyelination and brain atrophy associated with PTPN23 variants affecting the assembly of UsnRNPs. European journal of human genetics : EJHG 9 29899372
2006 The tyrosine phosphatase HD-PTP is regulated by FGF-2 through proteasome degradation. Frontiers in bioscience : a journal and virtual library 8 16720300
2021 Final Exon Frameshift Biallelic PTPN23 Variants Are Associated with Microcephalic Complex Hereditary Spastic Paraplegia. Brain sciences 5 34064836
2012 The tyrosine phosphatase HD-PTP (PTPN23) is degraded by calpains in a calcium-dependent manner. Biochemical and biophysical research communications 5 22510412
2025 ESCRT-I and PTPN23 mediate microautophagy of ubiquitylated tau aggregates. The Journal of cell biology 4 40197510
2024 PTPN23-dependent ESCRT machinery functions as a cell death checkpoint. Nature communications 4 39609437
2025 PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers. The Journal of experimental medicine 3 39841180
2021 A combined EM and proteomic analysis places HIV-1 Vpu at the crossroads of retromer and ESCRT complexes: PTPN23 is a Vpu-cofactor. PLoS pathogens 3 34843601
2024 PTPN23[Thr] variant reduces susceptibility and tumorigenesis in esophageal squamous cell carcinoma through dephosphorylation of EGFR. Cancer letters 2 38704135
2024 Loss of HD-PTP function results in lipodystrophy, defective cellular signaling and altered lipid homeostasis. Journal of cell science 2 39155850
2026 A PTPN23-dependent ESCRT pathway is essential for constitutive secretion in mammalian cells. The Journal of cell biology 1 41848521
2025 Intestinal epithelial PTPN23 is essential for gut barrier integrity and prevention of fatal bacterial translocation. Journal of Crohn's & colitis 1 39873381
2023 Loss of the endocytic tumor suppressor HD-PTP phenocopies LKB1 and promotes RAS-driven oncogenesis. bioRxiv : the preprint server for biology 1 36747658
2025 Microaggrephagy: an ESCRT-I-PTPN23-dependent pathway for MAPT/tau aggregate clearance. Autophagy 0 40574287
2010 Downregulation of HD-PTP by high magnesium concentration: novel insights into magnesium-induced endothelial migration. Magnesium research 0 20719712

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