Affinage

PTPN23

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

Length
1636 aa
Mass
179.0 kDa
Annotated
2026-04-28
47 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN23 (HD-PTP) is a catalytically inactive pseudophosphatase that functions as a central ESCRT pathway adaptor, coordinating the transfer of ubiquitinated cargo from early endosomal sorting machinery to multivesicular body intraluminal vesicles for lysosomal degradation. Its Bro1 domain adopts an open, extended conformation that simultaneously engages ESCRT-0 (STAM2), ESCRT-I (TSG101), and ESCRT-III (CHMP4B), bridging these complexes in a non-redundant manner to sort receptors including EGFR, integrins, death receptors (TNFR1), and ubiquitinated tau aggregates via endosomal microautophagy (PMID:18434552, PMID:23477725, PMID:28831121, PMID:40197510, PMID:39609437). Beyond endosomal sorting, PTPN23 is required for tubule fission at the trans-Golgi network during constitutive secretion, for dystrophin-glycoprotein complex assembly and T-tubule patterning in cardiomyocytes, and for endosomal PI3KC2α/AKT2 signaling via WNK3-mediated phosphorylation of PI3KC2α (PMID:41848521, PMID:38214189, PMID:39841180). Homozygous Ptpn23 knockout is embryonic lethal, and haploinsufficiency predisposes to lung adenoma, B-cell lymphoma, and lipodystrophy through impaired endosomal maturation and cholesterol trafficking (PMID:19378249, PMID:27210750, PMID:39155850).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2006 Medium

    Identification of HD-PTP's physical interaction partners (CHMP4B, TSG101, ALG-2, endophilin A1) established it as a Bro1-domain protein engaged with multiple ESCRT components, raising the question of how it coordinates them.

    Evidence Yeast two-hybrid and Strep-pulldown in HEK293T cells

    PMID:17174262

    Open questions at the time
    • Functional significance of individual interactions untested
    • No structural information on binding interfaces
    • Redundancy with ALIX unexplored
  2. 2008 High

    Demonstration that HD-PTP is required for MVB cargo sorting via its Bro1 domain–CHMP4B interaction established its non-redundant role in endosomal trafficking, resolving whether it was merely an ALIX paralog.

    Evidence RNAi depletion, retroviral chimera sorting assay, domain-mutant rescue, electron microscopy in human cells

    PMID:18434552

    Open questions at the time
    • Mechanism of cargo handoff from ESCRT-0 to ESCRT-III unknown
    • Relationship to ESCRT-II pathway unresolved
  3. 2009 High

    Enzymatic analysis proved HD-PTP is catalytically inactive as a tyrosine phosphatase due to a conserved active-site divergence, redefining it as a pseudophosphatase whose growth-suppressor function is phosphatase-independent.

    Evidence DiFMUP enzymatic assay, active-site back-mutation restoring activity, colony growth assay in cancer lines

    PMID:19340315

    Open questions at the time
    • Whether the PTP domain retains any non-canonical enzymatic activity
    • Structural basis of pseudophosphatase mechanism
  4. 2009 High

    Homozygous Ptpn23 knockout causing embryonic lethality at E9.5 demonstrated that HD-PTP is essential for mammalian development, not just cultured-cell trafficking.

    Evidence Beta-geo insertion knockout mouse, embryonic lethality assessment

    PMID:19378249

    Open questions at the time
    • Which specific developmental pathway fails
    • Whether lethality is due to endosomal, signaling, or other functions
  5. 2011 High

    PTPN23 loss was shown to activate SRC and β-catenin, drive E-cadherin internalization and EMT in mammary cells, linking its endosomal sorting function to suppression of invasive phenotypes.

    Evidence RNAi screen, substrate phosphorylation analysis, SRC inhibitor epistasis in mammary epithelial cells

    PMID:21724833

    Open questions at the time
    • Whether PTPN23 acts directly on SRC given its catalytic inactivity
    • Relevance in primary tumors in vivo
  6. 2013 High

    The cargo handoff mechanism was elucidated: HD-PTP Bro1 domain engages STAM2 (ESCRT-0) and CHMP4B (ESCRT-III) competitively at overlapping sites, with UBPY/USP8 recruitment enabling ESCRT-0 displacement, explaining how cargo transitions between ESCRT complexes.

    Evidence Competition binding assays, reciprocal Co-IPs, domain-mutant analysis, EGFR sorting readout

    PMID:23477725

    Open questions at the time
    • Kinetics and directionality of the handoff in cells
    • Whether additional regulators control the switch
  7. 2015 High

    HD-PTP was positioned as a non-canonical ESCRT pathway component that bypasses ESCRT-II entirely, bridging ESCRT-I directly to ESCRT-III for ILV formation, resolving a long-standing question about ESCRT-II requirement.

    Evidence Systematic RNAi epistasis across all ESCRT complexes, MHC-I surface measurement, rescue with WT and mutant HD-PTP

    PMID:26221024

    Open questions at the time
    • Whether both canonical (ESCRT-II) and HD-PTP-dependent pathways operate simultaneously on the same endosome
    • Structural basis for ESCRT-II bypass
  8. 2016 High

    Crystal structures of HD-PTP Bro1 with STAM2 revealed the atomic basis for ESCRT-0 selectivity: Thr145 uniquely enables STAM2 binding in opposite orientation to CHMP4B, explaining why ALIX and Brox cannot substitute.

    Evidence X-ray crystallography, site-directed mutagenesis, binding assays

    PMID:26866605

    Open questions at the time
    • Full-length structural model not available
    • How proline-rich region–SH3 interaction cooperates with Bro1 binding
  9. 2016 High

    In vivo haploinsufficiency studies showed that Ptpn23 heterozygosity predisposes to lung adenoma and B-cell lymphoma through impaired integrin β1 endosomal sorting, establishing HD-PTP as a haploinsufficient tumor suppressor.

    Evidence Ptpn23+/− mouse, tumor monitoring, Myc-driven lymphoma acceleration, integrin recycling assays

    PMID:27210750

    Open questions at the time
    • Specific integrin trafficking step affected
    • Whether human PTPN23 haploinsufficiency phenocopies mouse
  10. 2017 High

    SAXS and hydrodynamic analyses revealed that HD-PTP's ESCRT-binding region is constitutively open and extended (unlike compact ALIX), explaining its ability to simultaneously engage ESCRT-0, -I, and -III — a key architectural distinction.

    Evidence SAXS, analytical ultracentrifugation, SEC, binding assays with partners

    PMID:28831121

    Open questions at the time
    • Whether conformational changes occur upon cargo engagement
    • No high-resolution full-length structure
  11. 2017 High

    Structures of HD-PTP Bro1 with SARA and endofin revealed a second hydrophobic pocket unique to HD-PTP that explains high-affinity binding by TGFβ/BMP signaling endosome adaptors, expanding HD-PTP's role beyond cargo sorting to signaling regulation.

    Evidence X-ray crystallography of multiple complexes, mutagenesis, affinity analysis

    PMID:28602823

    Open questions at the time
    • Functional consequence of SARA/endofin competition with CHMP4B in signaling contexts
    • In vivo validation of TGFβ/BMP pathway regulation via HD-PTP
  12. 2019 High

    HD-PTP was found to be required for ephrin-B2:EphB2 receptor clustering and Src-family kinase activation, preventing premature receptor degradation — revealing a role upstream of receptor signaling rather than solely in degradative sorting.

    Evidence BioID proximity labeling, Co-IP, RNAi, cell collapse assay, chick in vivo axon guidance

    PMID:31420572

    Open questions at the time
    • Whether HD-PTP directly scaffolds EphB2 or acts indirectly via endosomal recycling
    • Generalizability to other receptor tyrosine kinases beyond EGFR/EphB2
  13. 2021 High

    Endofin was shown to bridge ESCRT-0 (Hrs) to HD-PTP, promoting lysosomal delivery of EGFR and integrin α5; disruption of this bridge sustains surface receptor signaling, revealing an additional layer of ESCRT-0–HD-PTP cooperation.

    Evidence BioID, reciprocal Co-IP, RNAi, receptor surface density and lysosomal delivery assays, interaction-deficient mutant complementation

    PMID:34761192

    Open questions at the time
    • Temporal ordering of endofin versus direct STAM2 engagement
    • Stoichiometry of the endofin–HD-PTP–ESCRT-0 complex
  14. 2022 High

    Direct binding of HD-PTP Bro1 domain to the HAV VP1 pX export signal, non-redundantly with ALIX, demonstrated that viruses co-opt HD-PTP for quasi-enveloped release, extending its ESCRT function to pathogen egress.

    Evidence Recombinant protein binding, biotin-tagged peptide Co-IP, RNAi, super-resolution microscopy, mutational analysis

    PMID:35969644

    Open questions at the time
    • Whether other non-enveloped viruses exploit HD-PTP
    • Structural basis of pX–Bro1 interaction
  15. 2023 High

    WDR4-mediated CUL4 ubiquitination of PTPN23 targets it for proteasomal degradation, identifying an upstream negative regulator that suppresses EGFR/c-MET lysosomal trafficking and sustains oncogenic signaling in NSCLC.

    Evidence Ubiquitylome mass spectrometry, ubiquitination assay, proteasome inhibitor rescue, receptor trafficking assay

    PMID:37821451

    Open questions at the time
    • Specific ubiquitination sites on PTPN23
    • Whether WDR4 regulation is tissue-specific
  16. 2024 High

    Cardiomyocyte-specific Ptpn23 knockout revealed a non-endosomal function: interaction with α-actinin and dystrophin to assemble the dystrophin-glycoprotein complex at costameres, required for T-tubule formation and cardiac function.

    Evidence Cre/LoxP conditional KO, AAV9 mosaic mutagenesis, glycerol-gradient fractionation, TEM, T-tubule imaging

    PMID:38214189

    Open questions at the time
    • Whether the DGC-assembly role uses the Bro1 domain or another region
    • Mechanism by which PTPN23 promotes DGC assembly
  17. 2024 High

    NAP1–PTPN23 interaction was shown to facilitate TNFR1 endosomal sorting; PTPN23 loss traps death and toll-like receptors in endosomes, activating NF-κB, apoptosis, necroptosis, and pyroptosis, revealing HD-PTP as a gatekeeper against inflammatory cell death.

    Evidence CRISPR screen in AML cells, BioID, receptor trafficking assay, cell death pathway activation assays

    PMID:39609437

    Open questions at the time
    • Whether PTPN23 directly sorts TNFR1 or acts via NAP1-dependent recruitment
    • In vivo validation of inflammatory phenotype
  18. 2024 High

    Hypomorphic HD-PTP mice revealed that impaired endosomal maturation causes defective cholesterol trafficking (decreased plasma membrane, increased lysosomal cholesterol), reducing EGFR trans-autophosphorylation and causing lipodystrophy — linking HD-PTP to lipid homeostasis.

    Evidence Hypomorphic mouse model, cholesterol fractionation, EGFR signaling assays, WAT histology

    PMID:39155850

    Open questions at the time
    • Which cholesterol transporter or sensor is affected
    • Whether cholesterol defect is primary or secondary to endosomal maturation failure
  19. 2025 High

    A genome-wide CRISPR screen identified PTPN23 as the critical adaptor bridging ESCRT-I to ESCRT-III for endosomal microautophagy (microaggrephagy) of ubiquitinated tau aggregates, a pathway independent of macroautophagy and CMA.

    Evidence Genome-wide CRISPR KO screen, ESCRT interaction assays, tau aggregate clearance assay, UBAP1 mutant analysis

    PMID:40197510

    Open questions at the time
    • Whether other protein aggregates use the same HD-PTP-dependent microautophagy
    • Structural details of tau–ESCRT-I–HD-PTP–ESCRT-III assembly
  20. 2025 High

    PTPN23 was found to promote PI3KC2α activity via WNK3-mediated phosphorylation, generating endosomal PI(3,4)P2 and activating AKT2, establishing a signaling-scaffolding function beyond its canonical cargo-sorting role.

    Evidence In vitro kinase assay, PI(3,4)P2 measurement, AKT2 assay, melanocyte-specific Ptpn23 KO mouse, tumor growth assays

    PMID:39841180

    Open questions at the time
    • Whether PI3KC2α activation requires HD-PTP's ESCRT interactions or is independent
    • How WNK3 is recruited to HD-PTP
  21. 2026 High

    Identification of PTPN23 on trans-Golgi carriers and its requirement for post-Golgi tubule fission (with CHMP1/VPS4) established a new non-endosomal location and function in constitutive secretion.

    Evidence Affinity isolation of post-Golgi carriers with MS, pooled CRISPR-KO screen, tubule fission and cargo secretion assays

    PMID:41848521

    Open questions at the time
    • How PTPN23 is recruited to trans-Golgi versus endosomes
    • Whether the Bro1–CHMP4B interaction mediates Golgi fission or a distinct ESCRT-III complex is involved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive characterization at endosomes, the full-length structure of HD-PTP in complex with ESCRT components is unknown, the mechanism by which it is selectively recruited to distinct membrane compartments (endosome vs. trans-Golgi vs. costamere) remains unresolved, and whether its diverse non-endosomal functions (DGC assembly, PI3KC2α activation, secretion) employ ESCRT-dependent or ESCRT-independent mechanisms has not been systematically dissected.
  • No full-length HD-PTP structure with ESCRT partners
  • Compartment-selective recruitment mechanism unknown
  • Systematic dissection of ESCRT-dependent vs. -independent functions lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005768 endosome 9 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
BICD1CHMP4BNAP1STAM2TSG101USP8WDR4ZFYVE16
Complex memberships
ESCRT adaptor complex (HD-PTP–STAM2–TSG101–CHMP4B)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 HD-PTP/PTPN23 is required for endosomal cargo sorting to the lumen of multivesicular bodies (MVBs); the Bro1 domain is essential for this function, and ESCRT-III (CHMP4B) binding to the Bro1 domain correlates with full biological activity. Depletion causes accumulation of ubiquitinated proteins on endosomes and disrupted MVB morphogenesis. RNAi depletion, retroviral peptide chimera sorting assay, rescue with RNAi-resistant HD-PTP and domain mutants, electron microscopy of MVB morphology Proceedings of the National Academy of Sciences of the United States of America High 18434552
2013 HD-PTP coordinates EGFR transfer from ESCRT-0 to ESCRT-III: the Bro1 domain binds the core domain of STAM2 (ESCRT-0 subunit) at the same site competed by CHMP4B (ESCRT-III); a proline-rich region of HD-PTP binds the SH3 domain of STAM2; HD-PTP recruits UBPY/USP8 to facilitate EGFR deubiquitination; UBPY interacts with HD-PTP-bound CHMP4B and additionally with HD-PTP directly, enabling displacement of ESCRT-0 in favor of ESCRT-III. Co-immunoprecipitation, GST pulldown, competition binding assays, RNAi depletion with cargo-sorting readout, domain-mutant analysis Current biology : CB High 23477725
2011 PTPN23 suppresses cell invasion in mammary epithelial cells; loss of PTPN23 increases E-cadherin internalization, impairs early endosome trafficking, elevates SRC and β-catenin activity, and induces EMT. SRC, E-cadherin, and β-catenin were identified as direct substrates of PTPN23 phosphatase activity. SRC inhibition blocks the invasive phenotype caused by PTPN23 depletion. RNAi loss-of-function screen, shRNA knockdown, cell invasion assay, substrate identification by phosphorylation analysis, pharmacological SRC inhibition (SU6656) Genes & development High 21724833
2006 HD-PTP interacts with CHMP4b/Shax1, TSG101, endophilin A1, and ALG-2. Unlike Alix, HD-PTP binds TSG101 in a Ca2+-independent manner but interacts with ALG-2 Ca2+-dependently. Yeast two-hybrid, Strep-pulldown assays 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 an evolutionarily conserved divergence of a key active-site residue; back-mutation of this residue restores tyrosine phosphatase activity. Growth-suppressor activity is independent of catalytic PTP activity. Enzymatic assay with DiFMUP substrate, lipid phosphatase panel, active-site mutagenesis (back-mutation), colony growth assay in cancer cell lines PloS one High 19340315
2007 HD-PTP binds Focal Adhesion Kinase (FAK) and loss of HD-PTP causes FAK hyperphosphorylation on tyrosine residues and redistribution to focal adhesions at the leading edge, resulting in increased endothelial cell migration; bFGF treatment strongly inhibits the HD-PTP–FAK interaction. siRNA knockdown, migration assay, co-immunoprecipitation, phosphotyrosine immunoblotting, immunofluorescence localization Biochemical and biophysical research communications Medium 17959146
2008 Src binds HD-PTP; this interaction is enhanced by bFGF. Src phosphorylates HD-PTP on tyrosine residues, which inhibits HD-PTP enzymatic activity. Pharmacological or genetic inhibition of Src abrogates the migratory phenotype caused by HD-PTP depletion, placing HD-PTP downstream of Src in the regulation of endothelial motility. Co-immunoprecipitation, in vitro kinase assay, phosphatase activity assay, siRNA knockdown, Src inhibitor (SU6656), migration assay The international journal of biochemistry & cell biology Medium 18762272
2011 The Drosophila HD-PTP ortholog Myopic (Mop) binds the WW domains of the transcriptional coactivator Yorkie via PPxY motifs; Myopic colocalizes with Yorkie at endosomes and controls Yorkie endosomal association, protein levels, and expression of a subset of Yorkie target genes, establishing a role for endosomal trafficking in Hippo pathway regulation. Genetic screen, domain-mutant analysis (PPxY motifs), co-localization imaging at endosomes, genetic epistasis in Drosophila tissue Developmental cell High 21571226
2015 HD-PTP acts as an alternative to ESCRT-II and VPS20/CHMP6 in a non-canonical ESCRT pathway for MVB sorting of virally ubiquitinated MHC class I, bridging ESCRT-I and ESCRT-III subunits necessary for ILV formation. RNAi depletion of individual ESCRT subunits, cell surface MHC class I measurement, rescue experiments with wild-type and mutant HD-PTP 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 HD-PTP Bro1 in the opposite orientation to CHMP4B; Thr145 of HD-PTP (vs. Lys151 in Alix, Arg145 in Brox) is a key determinant enabling STAM2 binding, as Alix/Brox-mimicking mutations at this residue abolish the interaction. X-ray crystallography, site-directed mutagenesis, binding assay PloS one High 26866605
2017 Crystal structures of HD-PTP Bro1 in complex with SARA, endofin, and three CHMP4 isoforms showed that SARA/endofin bind the conserved CHMP4-binding hydrophobic pocket plus an additional neighboring pocket unique to HD-PTP, explaining their high-affinity HD-PTP-specific binding and competition with CHMP4; this links HD-PTP to TGFβ/BMP endosomal signaling regulation. X-ray crystallography, mutagenesis, binding/affinity analysis, Co-immunoprecipitation Structure (London, England : 1993) High 28602823
2017 Small-angle X-ray scattering and hydrodynamic analyses revealed that the entire ESCRT-binding region of HD-PTP adopts an open, extended conformation (in contrast to the compact Alix conformation), enabling simultaneous engagement of ESCRT-0, ESCRT-I, and ESCRT-III. Small-angle X-ray scattering (SAXS), analytical ultracentrifugation, size-exclusion chromatography, binding assays with cellular partners Scientific reports High 28831121
2014 PTPN23 interacts with SMN (Survival Motor Neuron) protein and is required for SMN accumulation in Cajal bodies; PTPN23 knockdown alters the phosphorylation pattern of SMN and impairs snRNP assembly without disrupting the SMN complex itself. PTPN23 shuttles between nucleus and cytoplasm. Systematic phosphatase RNAi screen, Cajal body immunofluorescence assay, Co-immunoprecipitation (SMN–PTPN23), phosphorylation analysis, live-cell nuclear/cytoplasmic shuttling assay Molecular biology of the cell Medium 25392300
2016 Haploinsufficiency of HD-PTP/PTPN23 predisposes mice to sporadic lung adenoma, B cell lymphoma, and accelerates Myc-driven lymphoma. Hemizygous loss increases integrin β1-dependent B cell survival and dissemination, consistent with a role for HD-PTP in attenuating integrin recycling. Ptpn23+/- mouse model, tumor incidence monitoring, Myc-driven lymphoma model, integrin recycling assays, cell migration/invasion assays Cell reports High 27210750
2009 Homozygous knockout of Ptpn23 in mice is lethal around embryonic day 9.5, demonstrating an essential developmental role; heterozygous mice are viable, and Ptpn23 expression is maintained throughout development and in adult epithelial tissues. Beta-geo insertion knockout mouse, X-gal staining for expression pattern, embryonic lethality assessment The International journal of developmental biology High 19378249
2018 The Drosophila HD-PTP ortholog Myopic, localized to early endosomes, selectively inhibits Ca2+-dependent and cAMP-dependent neuropeptide release from dense-core vesicles (DCVs) at the NMJ, without affecting small synaptic vesicle (SSV) exocytosis; this function does not require its interaction with ESCRT-III/CHMP4. Genetic gain- and loss-of-function in Drosophila NMJ, neuropeptide imaging, Ca2+ stimulation, cAMP stimulation, ESCRT-III interaction mutant analysis, early endosome localization imaging Proceedings of the National Academy of Sciences of the United States of America High 29378961
2019 HD-PTP is required for ephrin-B2-induced EphB2 clustering and Src family kinase activation; HD-PTP loss attenuates ephrin-B2:EphB2 collapse signaling and causes premature EphB2 degradation, linking HD-PTP to the earliest steps of Eph receptor signaling and to prevention of premature receptor depletion. BioID proximity labeling (EphB2 interactome), Co-immunoprecipitation, RNAi knockdown, cell collapse assay, chick in vivo axon guidance, EphB2 clustering imaging, kinase activation assay Scientific reports High 31420572
2020 PTPN23 binds the N-terminus of the dynein adaptor BICD1 (not as canonical cargo but as an adaptor); loss of PTPN23 causes accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like endosomal compartments, establishing PTPN23 as a regulator of neurotrophin receptor endocytic sorting in motor neurons. Proteomics/mass spectrometry of BICD1 interactome, Co-immunoprecipitation, domain mapping, RNAi knockdown in motor neurons, immunofluorescence of endosomal compartments Journal of cell science Medium 32079660
2021 Endofin forms a complex with HD-PTP and ESCRT constituents; Endofin promotes Hrs (ESCRT-0) indirect interaction with HD-PTP. Loss of Endofin or disruption of the Endofin–HD-PTP interaction impairs lysosomal delivery of EGFR and integrin α5, increasing their plasma membrane density and sustaining downstream signaling. Proximity biotinylation (BioID), Co-immunoprecipitation, RNAi depletion, receptor surface density assay, lysosomal delivery assay, complementation with wild-type and interaction-deficient mutants iScience High 34761192
2022 HD-PTP directly interacts through its Bro1 domain with a conserved pX export signal in the HAV VP1 capsid protein; both HD-PTP and ALIX are required non-redundantly for quasi-enveloped hepatitis A virus (eHAV) release in extracellular vesicles. RNAi depletion of either Bro1 domain protein impeded eHAV release. Co-immunoprecipitation with biotin-tagged peptides and recombinant proteins, RNAi depletion, super-resolution fluorescence microscopy co-localization, mutational analysis of export signal PLoS pathogens High 35969644
2023 WDR4, a substrate adaptor of Cullin 4 ubiquitin ligase, ubiquitinates PTPN23, targeting it for proteasomal degradation; this suppresses lysosomal trafficking and degradation of EGFR and c-MET, sustaining their oncogenic signaling in NSCLC. Ubiquitylome mass spectrometry, ubiquitination assay, proteasome inhibitor rescue, receptor trafficking assay, competing peptide experiment Cell death & disease High 37821451
2024 Ptpn23 interacts with sarcomeric α-actinin and dystrophin to promote assembly of the dystrophin-glycoprotein complex (DGC) at costameres; cardiomyocyte-specific Ptpn23 knockout causes disorganized cardiac T-tubules with enlarged diameters and progressive dilated cardiomyopathy. Deletion of α-actinin alters Ptpn23 subcellular localization. Ptpn23 acts cell-autonomously in T-tubule formation and maintenance. Cre/LoxP cardiomyocyte-specific knockout, CRISPR/Cas9, AAV9 mosaic somatic mutagenesis, glycerol-gradient fractionation, SDS-PAGE, T-tubule staining (MM 4-64, Di-8-ANEPPS, Cav3 immunofluorescence), transmission electron microscopy Circulation High 38214189
2024 NAK-associated protein 1 (NAP1) interacts with PTPN23 to facilitate endosomal sorting of TNFR1; loss of PTPN23 causes accumulation of death receptors (TNFR1) and toll-like receptors in endosomes, activating NF-κB, apoptotic, necroptotic, and pyroptotic pathways and sensitizing cells to TNF-α-induced cytotoxicity. CRISPR screen (AML cells), proximity-dependent biotin labeling (BioID), receptor trafficking assay, cell death pathway activation assays (NF-κB, apoptosis, necroptosis, pyroptosis), RNAi of ESCRT pathway genes Nature communications High 39609437
2025 PTPN23, identified by genome-wide CRISPR screen, acts as an adaptor bridging ESCRT-I (recognized ubiquitylated tau via TSG101 UEV domain) and ESCRT-III to mediate endosomal microautophagy (microaggrephagy) of ubiquitinated tau repeat domain aggregates, functioning independently of macroautophagy and CMA. Genome-wide CRISPR knockout screen, ESCRT-I/III interaction assays, ubiquitylated tau aggregate clearance assay, disease-associated UBAP1 mutant analysis The Journal of cell biology High 40197510
2025 PTPN23 induces WNK3-mediated phosphorylation of PI3KC2α at serine 329, enhancing its catalytic activity; this promotes PI(3,4)P2 production at endosomes and AKT2 activation, supporting cell survival in BRAF-mutant cancer cells. PTPN23 silencing/knockout, in vitro kinase assay, PI(3,4)P2 measurement, AKT2 phosphorylation assay, melanocyte-specific Ptpn23 knockout mouse, in vivo tumor growth assays The Journal of experimental medicine High 39841180
2026 PTPN23 is essential for tubule fission from the trans-Golgi and constitutive secretion of soluble cargoes, hormones, and antibodies; loss of PTPN23 (or ESCRT subunits CHMP1 and VPS4) disrupts post-Golgi carrier fission and impairs cargo delivery to the plasma membrane. Affinity isolation of post-Golgi carriers with mass spectrometry, pooled CRISPR-KO screen, PTPN23 depletion, tubule fission assay, cargo secretion assay in specialized cells The Journal of cell biology High 41848521
2012 HD-PTP undergoes calcium-dependent proteasome-independent degradation by calpains in T24 bladder carcinoma cells; calpain inhibition with calpeptin causes redistribution of HD-PTP to the cell periphery. Calpain inhibitor treatment (calpeptin, ALLN), calcium manipulation, Western blotting, immunofluorescence localization Biochemical and biophysical research communications Medium 22510412
2006 FGF-2 (bFGF) induces HD-PTP protein degradation via the proteasome system in endothelial cells, while VEGF does not affect HD-PTP protein levels. Growth factor treatment, proteasome inhibitor rescue, Western blotting Frontiers in bioscience : a journal and virtual library Low 16720300
2024 In HD-PTP hypomorphic mice, loss of HD-PTP impairs endosomal maturation, leading to decreased plasma membrane cholesterol and increased lysosomal cholesterol accumulation (defective cholesterol trafficking), which reduces EGFR trans-autophosphorylation and downstream RAS/MAPK and PI3K/AKT signaling in white adipose tissue, causing lipodystrophy. Hypomorphic mouse model, lipid fractionation (cholesterol measurement), EGFR signaling assays (phosphorylation, EGF binding), proteomics, histology of WAT Journal of cell science High 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 121 18434552
2013 Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB. Current biology : CB 95 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 64 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 54 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 47 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 26 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 20 31395947
2017 Role of ESCRT component HD-PTP/PTPN23 in cancer. Biochemical Society transactions 20 28620046
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
2023 PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target. Cell death & disease 17 37821451
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 14 35969644
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
2017 Structural Basis for Specific Interaction of TGFβ Signaling Regulators SARA/Endofin with HD-PTP. Structure (London, England : 1993) 14 28602823
2017 Mutations of PTPN23 in developmental and epileptic encephalopathy. Human genetics 14 29090338
2024 Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex. Circulation 11 38214189
2021 Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes. iScience 11 34761192
2020 PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors. Journal of cell science 11 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 8 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 3 40197510
2024 PTPN23-dependent ESCRT machinery functions as a cell death checkpoint. Nature communications 3 39609437
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
2025 PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers. The Journal of experimental medicine 2 39841180
2024 PTPN23[Thr] variant reduces susceptibility and tumorigenesis in esophageal squamous cell carcinoma through dephosphorylation of EGFR. Cancer letters 2 38704135
2025 Intestinal epithelial PTPN23 is essential for gut barrier integrity and prevention of fatal bacterial translocation. Journal of Crohn's & colitis 1 39873381
2024 Loss of HD-PTP function results in lipodystrophy, defective cellular signaling and altered lipid homeostasis. Journal of cell science 1 39155850
2023 Loss of the endocytic tumor suppressor HD-PTP phenocopies LKB1 and promotes RAS-driven oncogenesis. bioRxiv : the preprint server for biology 1 36747658
2026 A PTPN23-dependent ESCRT pathway is essential for constitutive secretion in mammalian cells. The Journal of cell biology 0 41848521
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