Affinage

PTPN13

Tyrosine-protein phosphatase non-receptor type 13 · UniProt Q12923

Length
2485 aa
Mass
276.9 kDa
Annotated
2026-04-28
95 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTPN13 is a large, multi-domain non-receptor protein tyrosine phosphatase that functions as both a catalytic enzyme and a phosphatase-independent scaffold to negatively regulate oncogenic signaling, modulate immune cell differentiation, and maintain epithelial cell polarity. Its FERM domain binds PtdIns(4,5)P2 to anchor the protein at the apical plasma membrane of polarized epithelial cells, while five PDZ domains—subject to allosteric inter-domain regulation—recruit diverse substrates and scaffolding partners including APC, PTEN, ephrinB, TRIP6, and STAT proteins (PMID:10504335, PMID:12766187, PMID:17979300, PMID:29581186). Catalytically, PTPN13 directly dephosphorylates IRS-1, Her2/ErbB2, Src (pY419), STAT1/4/6, ephrinB ligands, TRIP6 (pY55), p85β, and c-Abl, thereby suppressing PI3K/Akt, Ras/MAPK, JAK/STAT, and Src signaling pathways to inhibit cell invasion, promote apoptosis, sustain intercellular junction integrity, and regulate CD4+ T helper cell differentiation (PMID:17638892, PMID:20501847, PMID:17306571, PMID:23604317, PMID:31938048, PMID:41486293). Independent of its phosphatase activity, PTPN13 anchors PTEN to the apical membrane to control apical domain size and sequesters IGF2BP1 to destabilize c-Myc mRNA (PMID:29581186, PMID:33051595).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Identification of PTPN13 as a novel multi-domain cytoplasmic PTP established the existence of a uniquely large phosphatase combining FERM, PDZ, and catalytic domains, raising the question of how each domain contributes to function.

    Evidence PCR-based cloning and in vitro phosphatase assay on 32P-myelin basic protein

    PMID:7929060

    Open questions at the time
    • No cellular substrates identified
    • Function of FERM and PDZ domains unknown
    • No in vivo data
  2. 1997 High

    Discovery that PDZ domains of PTPN13 bind specific C-terminal motifs (Fas, PARG1) established PTPN13 as a scaffolding hub capable of recruiting apoptotic receptors and Rho-regulatory GTPase-activating proteins.

    Evidence Peptide affinity chromatography with Fas C-terminus mutagenesis; yeast two-hybrid and in vitro GAP assay for PARG1

    PMID:9261095 PMID:9305890

    Open questions at the time
    • Functional consequence of Fas–PTPN13 interaction on apoptosis not demonstrated
    • In vivo relevance of PARG1 scaffolding unclear
  3. 1999 High

    Demonstrating that the FERM domain targets PTPN13 to the apical membrane of polarized epithelial cells resolved where PTPN13 operates and implied a role in epithelial polarity.

    Evidence Domain constructs in MDCK cells, immuno-EM, and FRAP showing dynamic apical localization

    PMID:10504335

    Open questions at the time
    • Lipid-binding mechanism of FERM domain not yet defined
    • Functional consequence of apical targeting on signaling not tested
  4. 2000 High

    High-affinity binding of PTPN13 PDZ2 to the tumor suppressor APC and to the focal adhesion protein TRIP6 expanded the interactome to include Wnt-pathway and cytoskeletal components.

    Evidence SPR (KD = 8.1 nM for APC), co-IP in COS cells, yeast two-hybrid for TRIP6

    PMID:10826496 PMID:10951583

    Open questions at the time
    • Functional significance of APC–PTPN13 interaction in Wnt signaling not established
    • No dephosphorylation of TRIP6 yet shown
  5. 2002 High

    NMR structure of PDZ2 and the discovery that PTPN13 dephosphorylates ephrinB ligands during reverse signaling provided both atomic-level insight into target selectivity and the first defined signaling pathway regulated by PTPN13 catalytic activity.

    Evidence NMR structure determination with peptide binding titration; co-IP and phosphorylation assays for ephrinB dephosphorylation

    PMID:11884147 PMID:11983165

    Open questions at the time
    • In vivo significance of ephrinB dephosphorylation in tissue patterning not shown
    • Structural basis of PDZ–ephrinB interaction not determined
  6. 2002 High

    Establishing that PTPN13 triggers apoptosis in breast cancer cells by dephosphorylating IRS-1 and suppressing the PI3K/Akt pathway identified the first direct substrate-to-phenotype link for PTPN13 in cancer.

    Evidence Antisense and overexpression in breast cancer cells with PI3K activity, Akt phosphorylation, and apoptosis assays

    PMID:12354757

    Open questions at the time
    • Specific IRS-1 phosphosites dephosphorylated not mapped
    • In vivo tumor suppression not yet demonstrated
  7. 2003 High

    Identification of PtdIns(4,5)P2-binding motifs within the FERM domain and PTPN13 localization to centrosomes/midbody during mitosis revealed dual membrane-targeting mechanisms and an unexpected role in cytokinesis.

    Evidence PIP2 mutation analysis, protein-lipid overlay for FERM-PIP2 binding; endogenous immunofluorescence at centrosomes/midbody, cytokinesis defect upon overexpression

    PMID:12529439 PMID:12766187

    Open questions at the time
    • Identity of cytokinesis-relevant substrates unknown
    • Mechanism linking FERM–actin binding to midbody function unclear
  8. 2007 High

    A burst of substrate identifications—IRS-1, Src pY419, TRIP6 pY55, STAT4/6, Her2/ErbB2—and the discovery of PDZ1-PDZ2 allosteric regulation established PTPN13 as a broad negative regulator of multiple oncogenic and immune signaling pathways with built-in selectivity control.

    Evidence In vitro dephosphorylation and substrate-trapping for IRS-1/TRIP6; PTP-BL knockout mice for STAT4/6; siRNA screen and tumor mutant analysis for Her2; NMR/phage display for PDZ allostery

    PMID:17306571 PMID:17591779 PMID:17638892 PMID:17979300 PMID:17982484

    Open questions at the time
    • How allosteric PDZ regulation translates to substrate selectivity in vivo not tested
    • Whether STAT dephosphorylation is direct or scaffold-mediated not fully resolved
  9. 2007 High

    HPV16 E6-mediated degradation of PTPN13 provided direct evidence that PTPN13 loss is selected for during viral oncogenesis, enabling anchorage-independent growth.

    Evidence Co-IP, shRNA, E6 PDZBM mutant, soft-agar and in vivo xenograft invasion models with rescue

    PMID:18160445

    Open questions at the time
    • Mechanism of E6-induced PTPN13 degradation (proteasomal vs. other) not fully defined
  10. 2009 High

    Demonstrating that PTPN13 phosphatase activity suppresses Ras/RAF/MEK/ERK signaling and that 20% of HPV-negative HNSCCs harbor loss-of-function PTPN13 mutations linked the enzyme to a second major oncogenic pathway.

    Evidence Catalytic-mutant comparison, MEK inhibitor rescue, soft-agar assay, patient tumor sequencing

    PMID:19734941

    Open questions at the time
    • Direct MAPK pathway substrate of PTPN13 not identified in this study
    • Comprehensive PTPN13 mutation frequency across cancer types not established
  11. 2010 High

    Substrate-trapping identified Src pY419 as a direct PTPN13 substrate, and in vivo xenograft experiments showed that PTPN13 loss increases tumor growth and invasion through Src/FAK/p130cas hyperactivation.

    Evidence Substrate-trapping mutant co-IP, siRNA, Src/FAK phosphorylation assays, mouse xenograft

    PMID:20501847

    Open questions at the time
    • Whether PTPN13 dephosphorylates Src at the plasma membrane or in a specific compartment unknown
  12. 2013 High

    Discovery that PTPN13 dephosphorylates p85β at Tyr-655 to license its ubiquitylation by FBXL2 revealed a mechanism coupling phosphatase activity to PI3K subunit turnover and autophagy control.

    Evidence In vitro dephosphorylation, FBXL2 complex purification, ubiquitylation assay, autophagy readout

    PMID:23604317

    Open questions at the time
    • Whether this mechanism operates in all PI3K-dependent tissues not tested
    • Relative contribution of p85β vs. IRS-1 dephosphorylation to PI3K suppression unclear
  13. 2018 High

    CRISPR deletion established that PTPN13 anchors PTEN to the apical membrane independently of phosphatase activity, separating PTPN13's scaffolding from catalytic tumor suppressor functions.

    Evidence CRISPR knockout of PTPN13 and PTEN in polarized Ls174T:W4 cells, co-IP, brush border quantification

    PMID:29581186

    Open questions at the time
    • Which PDZ domain mediates PTEN anchoring in vivo not fully resolved
    • Whether PTEN anchoring contributes to tumor suppression in mouse models not tested
  14. 2020 High

    Transgenic mouse models with PTPN13 phosphatase domain deletion crossed to HER2-overexpressing mice demonstrated that PTPN13 catalytic activity maintains desmosomes and suppresses breast tumor invasiveness in vivo, with phosphoproteomics implicating junction-related substrates.

    Evidence Genetic mouse model, phosphoproteomics, desmosome immunofluorescence, xenograft

    PMID:31938048

    Open questions at the time
    • Specific desmosomal substrates directly dephosphorylated by PTPN13 not identified
    • Whether junction maintenance is Src-dependent or involves novel substrates unclear
  15. 2020 Medium

    A phosphatase-independent tumor-suppressive mechanism was uncovered: PTPN13 sequesters IGF2BP1 to promote c-Myc mRNA degradation, and HBx-driven DNMT3A methylation silences the PTPN13 promoter in HBV-related hepatocellular carcinoma.

    Evidence Co-IP (PTPN13-IGF2BP1, HBx-DNMT3A), ChIP of DNMT3A at PTPN13 promoter, c-Myc mRNA stability assay

    PMID:33051595

    Open questions at the time
    • Phosphatase-independent IGF2BP1 sequestration mechanism awaits independent replication
    • Structural basis of PTPN13-IGF2BP1 interaction unknown
  16. 2026 High

    APC loss in colorectal cancer frees PTPN13 to dephosphorylate STAT1, suppressing MHC-I expression and CD8+ T cell immunity; a competitive APC-derived peptide restores anti-tumor immunity and enhances anti-PD1 therapy, establishing PTPN13 as a targetable immune evasion mechanism.

    Evidence In vitro STAT1 dephosphorylation, co-IP, competitive peptide (APC11) binding, mouse CRC models with anti-PD1 combination

    PMID:41486293

    Open questions at the time
    • Whether APC11 peptide has off-target effects on other PDZ-containing proteins not assessed
    • Applicability beyond APC-mutant CRC not established
  17. 2026 High

    PDLIM4 was identified as a recruiter of PTPN13 to dephosphorylate STAT3/4/6 in T cells, with a disease-associated PDLIM4 SNP impairing PTPN13 binding and causing augmented Th differentiation, demonstrating adaptor-dependent substrate targeting.

    Evidence Co-IP, PDLIM4 knockout T cells, STAT phosphorylation assays, LIM domain mutagenesis, Th differentiation assays

    PMID:42028851

    Open questions at the time
    • Whether PDLIM4 recruits PTPN13 to STAT substrates in non-immune cell types unknown
    • Structural basis of PDLIM4 LIM–PTPN13 interaction not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the identity of direct desmosomal/junction substrates, the structural basis of full-length PTPN13 autoinhibition and inter-domain allosteric regulation, and whether PTPN13's diverse functions can be pharmacologically separated to exploit its tumor-suppressive or immune-potentiating activities.
  • No full-length structure or cryo-EM model exists
  • Desmosomal substrates not identified
  • Pharmacological activators or targeted degraders not developed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 14 GO:0060090 molecular adaptor activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005815 microtubule organizing center 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1500931 Cell-Cell communication 1
Partners
APCIGF2BP1PDLIM4PRK2PTENSDCCAG3TAPP1TRIP6

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 PTPN13 (PTPL1) was identified as a novel cytoplasmic protein tyrosine phosphatase with a PTP domain, a FERM domain (band 4.1 homology), five GLGF/PDZ repeats, and a leucine zipper motif; its catalytic activity was confirmed by dephosphorylation of 32P-labeled myelin basic protein in vitro. PCR-based cloning, in vitro phosphatase assay with MBP substrate The Journal of biological chemistry High 7929060
1997 The PDZ2 and PDZ4 domains of PTPN13 bind with high affinity to the C-terminal tail of Fas/CD95; the three C-terminal residues (SLV) of Fas are necessary and sufficient for high-affinity interaction with both PDZ2 and PDZ4. Peptide binding assay (affinity chromatography), systematic mutagenesis of Fas C-terminus The Journal of biological chemistry High 9261095
1997 PTPN13 PDZ4 domain interacts with the C-terminal four residues of PARG1 (PTPL1-associated RhoGAP 1), a novel 150-kDa protein whose GAP domain is active on Rho, Rac, and Cdc42 in vitro (preferring Rho), suggesting PTPN13 can scaffold a potent negative regulator of Rho signaling. Yeast two-hybrid, in vitro GAP activity assay, pulldown The Journal of biological chemistry High 9305890
1998 PTPN13 PDZ2 and PDZ4 domains interact with the LIM domain of the adaptor protein RIL; the RIL LIM domain is phosphorylated on tyrosine in vivo and is dephosphorylated in vitro by the PTPN13 PTP domain, establishing RIL-LIM as a direct substrate. Yeast two-hybrid, in vitro phosphatase assay, co-immunoprecipitation, immunohistochemistry Molecular biology of the cell High 9487134
1999 PTPN13 PDZ1 domain binds to the N-terminal ankyrin repeats of IκBα; expression of dominant-negative PTPN13 leads to tyrosine phosphorylation of IκBα, indicating PTPN13 dephosphorylates IκBα and thereby modulates NF-κB activation under oxidative stress. Yeast two-hybrid, co-immunoprecipitation in HeLa cells, dominant-negative expression The Biochemical journal Medium 9882613
1999 The FERM domain of PTPN13 is necessary and sufficient for targeting the protein to the apical membrane of polarized epithelial (MDCK) cells; this apical confinement is dynamic (as shown by FRAP, with full redistribution within 20 min via a cytosolic pool) and the PTP domains mediate homotypic interactions. Transient expression of domain constructs in MDCK cells, immuno-electron microscopy, FRAP, yeast two-hybrid Journal of cell science High 10504335
2000 PTPN13 PDZ2 (but not the alternatively spliced PDZ2b with a 5-aa insertion) binds the extreme C-terminus of the tumor suppressor APC with nanomolar affinity (KD = 8.1 nM); in vivo interaction confirmed by co-precipitation in COS cells and co-localization at cell extensions and nucleus in epithelial cells. Yeast two-hybrid, surface plasmon resonance, co-precipitation in COS cells, immunofluorescence in MDCK cells Oncogene High 10951583
2000 PTPN13 PDZ2 domain interacts with the zyxin-related focal adhesion protein TRIP6 (via its third LIM domain and C-terminus); co-precipitation and co-localization of TRIP6 with PTP-BL at F-actin structures in epithelial cells links PTPN13 to actin-based subcellular complexes. Yeast two-hybrid, co-immunoprecipitation in transfected epithelial cells, immunofluorescence European journal of cell biology Medium 10826496
2001 PTPN13 PDZ3 domain interacts with the C-terminus of the Rho effector kinase PRK2; a conserved C-terminal cysteine of PRK2 is indispensable for the interaction; the two proteins co-localize at lamellipodia in HeLa cells, linking PTPN13 to actin cytoskeleton regulation. Yeast two-hybrid, co-immunoprecipitation in HeLa cells, immunofluorescence, mutagenesis of PRK2 C-terminus FEBS letters Medium 11356191
2002 PTPN13 (PTP-BL) is recruited to ephrinB expression domains with delayed kinetics following EphB receptor engagement, dephosphorylates phospho-ephrinB ligands, and serves as part of a phosphotyrosine/SFK → PDZ-signaling switch during reverse signaling. Co-immunoprecipitation, phosphorylation assays in transfected cells, dominant-negative PTPN13 expression Molecular cell High 11983165
2002 NMR solution structure of PTPN13 PDZ2 was determined; PDZ2 displays a canonical fold with a unique extended flexible loop (L1) at the base of the binding pocket; PDZ2 binds the C-terminus of RIL (with non-canonical E-x-V motif) but does not bind the murine Fas C-terminus, clarifying target selectivity. NMR structure determination, 15N relaxation, peptide binding titration Journal of molecular biology High 11884147
2002 PTPN13 (PTPL1/FAP-1) triggers apoptosis in human breast cancer cells by inhibiting the IRS-1/PI3K/Akt survival pathway; antisense abrogation of PTPN13 abolished 4-hydroxytamoxifen-induced apoptosis, and overexpression of PTPN13 reduced PI3K activity (~80%), Akt activation (~55%), and IRS-1 tyrosine phosphorylation (~65%). Stable antisense transfection, timed PTPN13 expression, PI3K activity assay, Akt phosphorylation assay, TUNEL/nucleosome ELISA for apoptosis The Journal of biological chemistry High 12354757
2003 PTPN13 FERM domain is necessary and sufficient for targeting the phosphatase to the apical plasma membrane (dorsal microvilli) of HeLa cells; two PtdIns(4,5)P2-binding motifs within the FERM domain mediate membrane binding, demonstrated by mutation of both sites and protein-lipid overlay assays. Overexpression of full-length vs. domain constructs in HeLa cells, PtdIns(4,5)P2 mutation analysis, protein-lipid overlay, cell fractionation, neomycin masking experiment Journal of cell science High 12766187
2003 PTPN13 (PTPL1) associates with the PtdIns(3,4)P2-binding adaptor TAPP1 (and TAPP2) primarily through its PDZ1 domain; this interaction maintains PTPL1 in the cytoplasm under basal conditions, and following H2O2 stimulation (which generates PtdIns(3,4)P2), the PTPL1-TAPP1 complex translocates to the plasma membrane; TAPP1 knockdown enhances PKB activation after IGF1 stimulation. Co-immunoprecipitation of endogenous proteins, GST pulldown, subcellular fractionation, siRNA knockdown, Akt phosphorylation assay The Biochemical journal High 14516276
2003 PTPN13 (PTP-BL) localizes to centrosomes and the spindle midzone during mitosis, and concentrates at the midbody during cytokinesis; overexpression of wild-type or phosphatase-inactive PTPN13 causes defects in cytokinesis and generation of multinucleate cells; the FERM domain co-sediments with F-actin and an N-terminal splicing variant (182-aa insertion) targets PTPN13 to the midbody and centrosome. Immunofluorescence of endogenous protein, co-sedimentation with F-actin and microtubules, overexpression of WT and catalytically-inactive mutants, analysis of multinucleation Molecular biology of the cell High 12529439
2004 Crystal structure of the PTPN13 catalytic domain at 1.8 Å resolution revealed a standard PTP fold with an additional N-terminal helix and a second positively charged pocket near the active site reminiscent of PTP1B's second phosphotyrosine binding site; PTPN13, like PTP1B, dephosphorylates a bis-phosphorylated insulin receptor peptide more efficiently than a monophosphorylated one; the M2307T tumor mutation near the active site cysteine significantly reduces phosphatase activity. X-ray crystallography (1.8 Å), in vitro phosphatase assay with insulin receptor peptides, mutagenesis of tumor-derived mutations The Journal of biological chemistry High 15611135
2007 PTPN13 directly dephosphorylates IRS-1, thereby blocking the IRS-1/PI3K/Akt signaling pathway and inducing apoptosis; shown by in vitro dephosphorylation of IRS-1 by PTPN13, dominant-negative PTPN13 preventing IRS-1 dephosphorylation, and siRNA confirming PTPL1's crucial role in IRS-1 dephosphorylation in cells. In vitro phosphatase assay with immunoprecipitated IRS-1, dominant-negative PTPN13 expression, siRNA knockdown, PI3K/Akt activity assays, apoptosis assays Cancer research High 17638892
2007 PTPN13 negatively regulates Her2/ErbB2 by dephosphorylating the Her2 signaling domain; growth factor-induced phosphorylation of PTPN13 is required for this dephosphorylation (negative feedback); tumor-derived PTPN13 mutations reduce its phosphatase activity and elevate Her2 oncogenic signaling and cell invasiveness. siRNA phosphatase library screen, growth factor stimulation with phosphorylation assays, invasion assays, comparison of WT vs. tumor-mutant PTPN13 phosphatase activity Oncogene High 17982484
2007 PTPN13 dephosphorylates STAT proteins (STAT4 and STAT6) in vitro and in vivo; PTP-BL deficiency leads to increased and prolonged STAT4/STAT6 activation in CD4+ T cells, resulting in enhanced Th1 and Th2 differentiation. In vitro dephosphorylation assay, PTP-BL knockout mouse model, flow cytometry for Th1/Th2 differentiation, STAT phosphorylation measurements Immunity High 17306571
2007 PTPN13 dephosphorylates phosphotyrosine-55 of TRIP6 in vitro and inhibits LPA-induced TRIP6 tyrosine phosphorylation in cells; this requires a direct protein-protein interaction and PTPN13 phosphatase activity, resulting in inhibition of TRIP6-Crk association and LPA-induced cell migration. In vitro phosphatase assay (dephosphorylation of pTyr-55 TRIP6), co-immunoprecipitation, TRIP6 focal adhesion dynamics, cell migration assays The Journal of biological chemistry High 17591779
2007 HPV16 E6 oncoprotein interacts with PTPN13 via its PDZ binding motif and induces loss of PTPN13 protein; PTPN13 loss allows anchorage-independent growth and synergizes with Ras(v12) for invasive growth in vivo; restoring PTPN13 expression reverses anchorage-independent growth. Co-immunoprecipitation, shRNA knockdown, E6 PDZBM mutant, soft-agar assay, in vivo xenograft invasion model, rescue experiment Journal of virology High 18160445
2008 ICSBP/IRF8 represses PTPN13 transcription by binding a cis element in the proximal PTPN13 promoter; this interaction requires phosphorylation of conserved tyrosine residues in the ICSBP IRF domain and increases during myeloid differentiation, thereby reducing Fap-1 (PTPN13) levels and sensitizing cells to Fas-induced apoptosis. CpG island microarray chromatin immunoprecipitation, luciferase reporter, ChIP, ICSBP mutants, Fas apoptosis assays The Journal of biological chemistry High 18195016
2009 PTPN13 phosphatase activity inhibits Ras/RAF/MEK/ERK (MAP kinase) signaling; wild-type PTPN13 suppresses MAPK signaling in cells overexpressing ErbB2, EGFR, or H-Ras(V12), while a catalytically-inactive PTPN13 does not; MEK inhibitor U0126 blocks anchorage-independent growth in PTPN13-null cells; 20% of HPV-negative HNSCCs harbor PTPN13 phosphatase mutations that fail to inhibit MAPK signaling. Co-transfection of WT vs. catalytically-inactive PTPN13, MAPK phosphorylation assays, MEK inhibitor rescue, soft-agar assay, sequencing of patient tumors Oncogene High 19734941
2010 PTPN13 directly dephosphorylates Src at tyrosine 419 (activating phosphorylation), established by substrate-trapping experiments; PTPN13 silencing increases pY419-Src, activating downstream FAK and p130cas; PTPN13 loss increases tumor growth and invasion in vivo. Substrate-trapping mutant PTPN13, co-immunoprecipitation, siRNA knockdown, Src/FAK/p130cas phosphorylation assays, mouse xenograft tumor model, invasion assay Cancer research High 20501847
2007 PTPN13 (PTPL1) interacts with TRPM2 calcium channel via PDZ domain binding; PTPN13 co-expression reduces TRPM2 tyrosine phosphorylation and inhibits H2O2/TNFα-induced calcium influx and cell death; PTPN13 knockdown increases TRPM2 phosphorylation and susceptibility to oxidative stress-induced death. PDZ domain array blot, co-immunoprecipitation, GST pulldown, PTPN13 overexpression/siRNA knockdown, intracellular calcium measurement, cell viability assays American journal of physiology. Cell physiology Medium 17251321
2012 The serologically defined colon cancer antigen-3 (SDCCAG3) forms a complex with PTPN13 at the midbody during cytokinesis; both proteins regulate cytokinesis, as overexpression or downregulation of SDCCAG3 causes multinucleation; SDCCAG3 also interacts with ArfGAP GIT1, linking PTPN13 complex to vesicular trafficking during cell division. Co-immunoprecipitation, immunofluorescence localization, overexpression/RNAi of SDCCAG3, multinucleation quantification Oncogene Medium 23108400
2012 PTPN13 regulates a signaling complex involving ErbB2, Src kinase, and EphrinB1 in breast cancer; EphrinB1 (a PTPN13 substrate) interacts with ErbB2; Src mediates EphrinB1 phosphorylation and subsequent MAP kinase signaling; decreased PTPN13 function enhances this signaling. Co-immunoprecipitation, localization studies, EphrinB1 phosphorylation assays, PTPN13 siRNA knockdown, MAP kinase assays PloS one Medium 22279592
2013 PTPN13 (PTPL1) dephosphorylates p85β regulatory subunit of PI3K at Tyr-655 (adjacent to its degron), enabling p85β binding to the F-box protein FBXL2 and subsequent ubiquitylation and proteasomal degradation; this mechanism controls PI3K signaling cascade and, when defective, promotes autophagy. Purification of FBXL2 complex, co-immunoprecipitation, ubiquitylation assay, p85β phosphorylation assays, PTPL1 knockdown, in vitro dephosphorylation, autophagy readout Nature cell biology High 23604317
2012 Valosin-containing protein (VCP/p97) was identified as a direct substrate of PTPN13 by substrate-trapping mass spectrometry; VCP tyrosine phosphorylation may be important for its midbody localization during cytokinesis. Substrate-trapping PTPN13 mutant, mass spectrometry, co-immunoprecipitation, overexpression and localization studies Experimental cell research Medium 23018179
2014 PTPN13 PDZ2 domain binds the C-terminal PDZ-binding motif of PTEN in a manner dependent on the PDZ1-PDZ2 interdomain arrangement; yeast two-hybrid and GST pull-down with mutational analysis of PTEN PDZ-BM define binding specificity. Yeast two-hybrid, GST pulldown, mutational analysis of PTEN C-terminal PDZ-binding motif Methods (San Diego, Calif.) Medium 25448478
2017 PTPN13 is a PDZ-binding partner of calpain-2 and is cleaved/inactivated by calpain-2, generating stable breakdown products (P13BPs); PTPN13 dephosphorylates and inhibits c-Abl; following TBI, calpain-2 activation cleaves PTPN13, activates c-Abl, and triggers tau tyrosine phosphorylation and tau oligomer accumulation; calpain-2 inhibitor post-TBI blocks this pathway. Co-immunoprecipitation (calpain-2/PTPN13), in vitro calpain cleavage assay, c-Abl phosphorylation assays, calpain-2 selective inhibitor treatment in TBI mouse model, tau oligomer quantification Scientific reports High 28924170
2018 NMR solution structure of PTPN13 PDZ3 domain (apo and in complex with PRK2 C-terminus) reveals that PDZ3 binds the five C-terminal amino acids of PRK2 in the canonical β-groove, with P0 (Cys) and P-2 (Asp) side chains facing the groove and P-1 (Trp) and P-3 (Ala) pointing away — providing a structural basis for class III ligand recognition. Multidimensional NMR spectroscopy (structure determination of apo and ligand-bound PDZ3) Journal of molecular biology High 30189200
2018 PTPN13 (PTPL1) functions as an apical membrane anchor for PTEN, requiring a direct protein-protein interaction; this anchoring is necessary for PTEN's role in regulating apical membrane size in polarized intestinal epithelial cells; notably, PTPN13 phosphatase activity is dispensable for this scaffolding function. CRISPR/Cas9 deletion of PTPN13 and PTEN, co-immunoprecipitation, immunofluorescence, brush border phenotype quantification in Ls174T:W4 cells Molecular and cellular biology High 29581186
2019 The PTPN13 tandem PDZ2/3 domain allosterically modulates PDZ2 binding to APC; the presence of PDZ3 alters PDZ2's affinity for APC (12 C-terminal APC residues); PRK2 is a weak binding partner of PDZ2; NMR-based HADDOCK model of the PDZ2/3 tandem domain supports allosteric communication from PDZ3 to the PDZ2 ligand-binding site. Heteronuclear multidimensional NMR spectroscopy, NMR titration, HADDOCK molecular modeling BMC molecular and cell biology Medium 31286859
2020 PTPN13 inhibits cell motility and invasion via its phosphatase activity; phosphoproteomic analysis of breast cancer cells revealed that PTPN13 regulates intercellular junction-related proteins; in vivo, PTPN13 phosphatase activity deletion in HER2-overexpressing mice strongly increases breast tumor development and invasiveness associated with a loss of mesenchymal-to-epithelial transition phenotype and desmosome disruption. Transgenic mouse model (PTPN13 phosphatase domain deletion × HER2-overexpression), phosphoproteomics, gene ontology analysis, wound healing and invasion assays, immunofluorescence for cell junctions and desmosomes, xenograft model Theranostics High 31938048
2020 HBx protein promotes PTPN13 promoter methylation by upregulating and interacting with DNMT3A, which binds the PTPN13 promoter (-343 to -313 bp) to suppress transcription; PTPN13 inhibits tumor growth through competitive binding to IGF2BP1, reducing functional IGF2BP1 levels and promoting c-Myc mRNA degradation independent of PTPN13 phosphatase activity. Co-immunoprecipitation (HBx-DNMT3A, PTPN13-IGF2BP1), ChIP of DNMT3A at PTPN13 promoter, methylation analysis, overexpression/knockdown functional assays, c-Myc mRNA stability assay Oncogene Medium 33051595
2021 PTPN13 suppresses TGF-β1-induced epithelial-mesenchymal transition in lung cancer cells by counteracting canonical Smad2/3 and non-canonical p38 MAPK signaling pathways; immunoprecipitation demonstrated direct binding of PTPN13 to p38 MAPK, suggesting p38 MAPK is a direct substrate. siRNA knockdown, co-immunoprecipitation (PTPN13-p38 MAPK), Smad2/3 and p38 phosphorylation assays, cell migration/invasion assays, xenograft lung metastasis model Acta pharmacologica Sinica Medium 33536603
2025 PTPN13 modulates BCR signaling: PTPN13 and β-catenin are stabilized upon B-cell receptor activation; PTPN13 silencing reduces Bruton's tyrosine kinase (BTK) activation and β-catenin levels; pathogenic PTPN13 mutations (found in families with ALL/anemia/IBMF) impair the PTPN13-β-catenin interaction; PTPN13 co-immunoprecipitates with β-catenin. Co-immunoprecipitation (PTPN13-β-catenin), siRNA knockdown, BCR stimulation assays, BTK phosphorylation measurement, flow cytometry for CD25/CD38 markers Scientific reports Medium 41422331
2026 PTPN13 directly dephosphorylates STAT1, and loss of APC (common in CRC) leads to PTPN13-mediated STAT1 dephosphorylation, reducing MHC class I antigen presentation and CD8+ T cell infiltration; APC C-terminal 11-aa peptides (APC11) compete for PTPN13 binding, block PTPN13-STAT1 interaction, restore STAT1 phosphorylation and IRF1/MHC-I expression, and enhance anti-PD1 efficacy in vivo. Co-immunoprecipitation (PTPN13-STAT1), STAT1 phosphorylation assays, in vitro dephosphorylation, direct peptide binding assay, mouse CRC models, tumor-infiltrating lymphocyte quantification, combination anti-PD1 therapy Cell research High 41486293
2026 PDLIM4 recruits PTPN13 (PTP-BL) to dephosphorylate STAT3, STAT4, and STAT6 via PDLIM4's LIM domain interaction with PTPN13; a disease-associated nsSNP in PDLIM4 (Gly→Cys in LIM domain) reduces PDLIM4-PTPN13 binding and impairs STAT3 dephosphorylation; PDLIM4-deficient CD4+ T cells show augmented STAT phosphorylation and enhanced Th1, Th2, and Th17 differentiation. Co-immunoprecipitation, STAT phosphorylation assays, PDLIM4 knockout T cells, mutagenesis of PDLIM4 LIM domain, Th differentiation assays International immunology High 42028851
2007 PTPN13 allosteric regulation of PDZ2 binding specificity: PDZ1 directly contacts a surface on PDZ2 opposite the peptide-binding groove, causing long-range allosteric structural changes in the PDZ2 binding groove that alter its preference for class III-type ligands, as demonstrated by phage display library screening and structural NMR studies. Random C-terminal peptide λ phage display library screening, NMR structural studies of PDZ1-PDZ2 interaction Biochemistry High 17979300
2014 PTPN13 co-immunoprecipitates with β-catenin, co-localizes with β-catenin in megakaryocytic cell lines, regulates β-catenin phosphorylation and stability, and controls β-catenin transcriptional activity; PTPN13 silencing triggers megakaryocytic differentiation while overexpression inhibits it; PTPN13 is stabilized by Wnt signaling, placing it in the canonical Wnt/β-catenin pathway. Co-immunoprecipitation, co-localization, siRNA knockdown, β-catenin stability assays, differentiation assays in cell lines and murine hematopoietic progenitors Biochimica et biophysica acta Medium 25193362

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP-BL phosphatase. Molecular cell 258 11983165
1998 PDZ motifs in PTP-BL and RIL bind to internal protein segments in the LIM domain protein RIL. Molecular biology of the cell 131 9487134
1997 A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1. The Journal of biological chemistry 115 9305890
2007 The PDZ binding motif of human papillomavirus type 16 E6 induces PTPN13 loss, which allows anchorage-independent growth and synergizes with ras for invasive growth. Journal of virology 113 18160445
2013 FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade. Nature cell biology 109 23604317
1994 Cloning and characterization of PTPL1, a protein tyrosine phosphatase with similarities to cytoskeletal-associated proteins. The Journal of biological chemistry 93 7929060
2011 Curcumin suppresses human papillomavirus oncoproteins, restores p53, Rb, and PTPN13 proteins and inhibits benzo[a]pyrene-induced upregulation of HPV E7. Molecular carcinogenesis 88 21061268
2000 The Adenomatous Polyposis Coli-protein (APC) interacts with the protein tyrosine phosphatase PTP-BL via an alternatively spliced PDZ domain. Oncogene 74 10951583
2002 Structure, dynamics and binding characteristics of the second PDZ domain of PTP-BL. Journal of molecular biology 66 11884147
2000 The zyxin-related protein TRIP6 interacts with PDZ motifs in the adaptor protein RIL and the protein tyrosine phosphatase PTP-BL. European journal of cell biology 64 10826496
2007 Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signaling. Oncogene 60 17982484
2005 PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis. Oncogene 60 15782144
2009 Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway. Oncogene 59 19734941
2007 The putative tumor suppressor gene PTPN13/PTPL1 induces apoptosis through insulin receptor substrate-1 dephosphorylation. Cancer research 59 17638892
2002 Protein-tyrosine phosphatase PTPL1/FAP-1 triggers apoptosis in human breast cancer cells. The Journal of biological chemistry 56 12354757
2012 The nonreceptor-type tyrosine phosphatase PTPN13 is a tumor suppressor gene in non-small cell lung cancer. The American journal of pathology 54 22245727
2008 PTPL1: a large phosphatase with a split personality. Cancer metastasis reviews 54 18265946
1999 Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats. The Biochemical journal 53 9882613
2008 The interferon consensus sequence-binding protein (ICSBP/IRF8) represses PTPN13 gene transcription in differentiating myeloid cells. The Journal of biological chemistry 52 18195016
2007 Regulation of signal transducer and activator of transcription signaling by the tyrosine phosphatase PTP-BL. Immunity 49 17306571
2003 Membrane targeting of protein tyrosine phosphatase PTPL1 through its FERM domain via binding to phosphatidylinositol 4,5-biphosphate. Journal of cell science 49 12766187
2011 PTPN13/PTPL1: an important regulator of tumor aggressiveness. Anti-cancer agents in medicinal chemistry 48 21235435
2005 Kinetic folding mechanism of PDZ2 from PTP-BL. Protein engineering, design & selection : PEDS 48 16043447
1999 A FERM domain governs apical confinement of PTP-BL in epithelial cells. Journal of cell science 48 10504335
2007 An allosteric intramolecular PDZ-PDZ interaction modulates PTP-BL PDZ2 binding specificity. Biochemistry 47 17979300
1997 Characterization of the interactions between PDZ domains of the protein-tyrosine phosphatase PTPL1 and the carboxyl-terminal tail of Fas. The Journal of biological chemistry 46 9261095
2010 PTPL1/PTPN13 regulates breast cancer cell aggressiveness through direct inactivation of Src kinase. Cancer research 45 20501847
2003 The protein tyrosine phosphatase PTP-BL associates with the midbody and is involved in the regulation of cytokinesis. Molecular biology of the cell 45 12529439
2003 Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1. The Biochemical journal 45 14516276
2001 The protein kinase C-related kinase PRK2 interacts with the protein tyrosine phosphatase PTP-BL via a novel PDZ domain binding motif. FEBS letters 42 11356191
2007 Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1. American journal of physiology. Cell physiology 40 17251321
2009 Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers. Journal of cancer research and clinical oncology 36 19672627
2004 Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket. The Journal of biological chemistry 35 15611135
2020 Anti-oncogene PTPN13 inactivation by hepatitis B virus X protein counteracts IGF2BP1 to promote hepatocellular carcinoma progression. Oncogene 34 33051595
2004 Mild impairment of motor nerve repair in mice lacking PTP-BL tyrosine phosphatase activity. Physiological genomics 33 15226483
2020 Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer. Biomolecules 31 33322542
2012 The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis. Oncogene 29 23108400
1996 PTPN13, a fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3. Genomics 29 8824809
2007 PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration. The Journal of biological chemistry 27 17591779
2003 Cloning and characterization of mCRIP2, a mouse LIM-only protein that interacts with PDZ domain IV of PTP-BL. Genes to cells : devoted to molecular & cellular mechanisms 27 12839623
2003 Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas (hPTP1E): splicing-induced modulation of ligand specificity. Journal of molecular biology 27 14596806
2014 PTEN-PDZ domain interactions: binding of PTEN to PDZ domains of PTPN13. Methods (San Diego, Calif.) 26 25448478
2017 The tyrosine phosphatase PTPN13/FAP-1 links calpain-2, TBI and tau tyrosine phosphorylation. Scientific reports 24 28924170
2016 miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13. Oncotarget 24 27285768
2012 ErbB2, EphrinB1, Src kinase and PTPN13 signaling complex regulates MAP kinase signaling in human cancers. PloS one 24 22279592
2012 Accurate prediction of the dynamical changes within the second PDZ domain of PTP1e. PLoS computational biology 24 23209399
2009 Genetic polymorphisms in the PTPN13 gene and risk of squamous cell carcinoma of head and neck. Carcinogenesis 24 19892796
2021 PTPL1 suppresses lung cancer cell migration via inhibiting TGF-β1-induced activation of p38 MAPK and Smad 2/3 pathways and EMT. Acta pharmacologica Sinica 23 33536603
2004 A closed binding pocket and global destabilization modify the binding properties of an alternatively spliced form of the second PDZ domain of PTP-BL. Structure (London, England : 1993) 23 14725761
2017 Characterization and Functional Analysis of the Poplar Pectate Lyase-Like Gene PtPL1-18 Reveal Its Role in the Development of Vascular Tissues. Frontiers in plant science 22 28702042
2016 Tumour-suppressive role of PTPN13 in hepatocellular carcinoma and its clinical significance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 26801674
2014 PTPN13 regulates cellular signalling and β-catenin function during megakaryocytic differentiation. Biochimica et biophysica acta 19 25193362
2009 Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis. The international journal of biochemistry & cell biology 19 19782949
2005 Effects of LAR and PTP-BL phosphatase deficiency on adult mouse retinal cells activated by lens injury. The European journal of neuroscience 19 15932596
2012 Downregulation of protein tyrosine phosphatase PTPL1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells. Clinical & experimental metastasis 18 22274591
2020 PTPN13 induces cell junction stabilization and inhibits mammary tumor invasiveness. Theranostics 17 31938048
2015 PTPN13 and β-Catenin Regulate the Quiescence of Hematopoietic Stem Cells and Their Interaction with the Bone Marrow Niche. Stem cell reports 16 26344907
2020 Cancer-derived IgG involved in cisplatin resistance through PTP-BAS/Src/PDK1/AKT signaling pathway. Oral diseases 14 32730654
2013 PTPL1 and PKCδ contribute to proapoptotic signalling in prostate cancer cells. Cell death & disease 14 23559010
2013 The role of PTPN13 in invasion and metastasis of lung squamous cell carcinoma. Experimental and molecular pathology 14 23906871
2015 Promoter hypermethylation of PTPL1, PTPN6, DAPK, p16 and 5-azacitidine inhibits growth in DLBCL. Oncology reports 12 26498513
2004 The interaction of PTP-BL PDZ domains with RIL: an enigmatic role for the RIL LIM domain. Molecular biology reports 12 15663004
2024 METTL1/FOXM1 promotes lung adenocarcinoma progression and gefitinib resistance by inhibiting PTPN13 expression. Cancer medicine 11 38967523
2020 PTPN13 acts as a tumor suppressor in clear cell renal cell carcinoma by inactivating Akt signaling. Experimental cell research 10 32919955
2012 Valosin containing protein (VCP/p97) is a novel substrate for the protein tyrosine phosphatase PTPL1. Experimental cell research 10 23018179
2005 Redox-regulated affinity of the third PDZ domain in the phosphotyrosine phosphatase PTP-BL for cysteine-containing target peptides. The FEBS journal 10 15978037
2017 High PTPN13 expression in high grade serous ovarian carcinoma is associated with a better patient outcome. Oncotarget 9 29221157
2013 Stat3 inhibits PTPN13 expression in squamous cell lung carcinoma through recruitment of HDAC5. BioMed research international 9 24191246
2018 The Phosphatase PTPL1 Is Required for PTEN-Mediated Regulation of Apical Membrane Size. Molecular and cellular biology 8 29581186
2012 The leukemia-associated fusion protein Tel-platelet-derived growth factor receptor β (Tel-PdgfRβ) inhibits transcriptional repression of PTPN13 gene by interferon consensus sequence binding protein (Icsbp). The Journal of biological chemistry 8 22262849
2015 5-Azacitidine induces demethylation of PTPL1 and inhibits growth in non-Hodgkin lymphoma. International journal of molecular medicine 7 26133246
2008 Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas. Pathology 7 18038312
1996 The gene (PTPN13) encoding the protein tyrosine phosphatase PTP-BL/PTP-BAS is located in mouse chromosome region 5E/F and human chromosome region 4q21. Cytogenetics and cell genetics 7 8893825
2022 Protein tyrosine phosphatase PTPL1 suppresses lung cancer through Src/ERK/YAP1 signaling. Thoracic cancer 6 36193770
2021 Transcriptional regulation of miR-30a by YAP impacts PTPN13 and KLF9 levels and Schwann cell proliferation. The Journal of biological chemistry 6 34265306
2022 miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion. Biomedicines 5 36140249
2018 Molecular Basis of Class III Ligand Recognition by PDZ3 in Murine Protein Tyrosine Phosphatase PTPN13. Journal of molecular biology 5 30189200
2017 The PTPN13 Y2081D (T>G) (rs989902) polymorphism is associated with an increased risk of sporadic colorectal cancer. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 5 28504867
2023 PTPN13 Participates in the Regulation of Epithelial-Mesenchymal Transition and Platinum Sensitivity in High-Grade Serous Ovarian Carcinoma Cells. International journal of molecular sciences 4 37895093
2019 The binding affinity of PTPN13's tandem PDZ2/3 domain is allosterically modulated. BMC molecular and cell biology 4 31286859
2005 Subcellular localization and differentiation-induced redistribution of the protein tyrosine phosphatase PTP-BL in Neuroblastoma cells. Cellular and molecular neurobiology 4 16388334
2004 [PTPL1, a proapoptotic protein tyrosine phosphatase in breast cancers]. Bulletin du cancer 4 15242314
2023 Comprehensive analysis of the PTPN13 expression and its clinical implication in breast cancer. Neoplasma 3 36812232
2007 Sequence-specific (1)H, (13)C, and (15)N backbone assignment of the 28 kDa PDZ2/PDZ3 tandem domain of the protein tyrosine phosphatase PTP-BL. Biomolecular NMR assignments 3 19636852
2010 Sequence-specific 1H, 13C, and 15N assignment of the extended PDZ3 domain of the protein tyrosine phosphatase basophil-like PTP-BL. Biomolecular NMR assignments 2 20563762
2026 Targeting PTPN13 with 11-amino-acid peptides of C-terminal APC prevents immune evasion of colorectal cancer. Cell research 1 41486293
2025 Combined exome and RNA-seq analysis in patients with rare non-syndromic inherited brain arteriovenous malformation suggests a novel function for PTPN13 in arterial specification. Thrombosis research 1 41418676
2024 Arsenic disulfide promoted the demethylation of PTPL1 in diffuse large B cell lymphoma cells. PeerJ 1 38766487
2023 PTPN13 rs989902 and CHEK2 rs738722 are associated with esophageal cancer. Annals of medicine 1 38039548
2016 High-resolution crystal structure of the PDZ1 domain of human protein tyrosine phosphatase PTP-Bas. Biochemical and biophysical research communications 1 27544031
2026 PDLIM4 promotes dephosphorylation of STAT transcription factors by recruiting PTP-BL and inhibits Th1, Th2, and Th17 cell differentiation. International immunology 0 42028851
2026 Anti-SIA-cIgG enhances chemotherapy effectiveness through PTPN13-regulated tumor stemness in head and neck squamous cell carcinoma. Journal of translational internal medicine 0 42046805
2025 Altered PTPN13-β-catenin interaction by pathogenic mutations and involvement of this axis in B-cell receptor signalling. Scientific reports 0 41422331
2015 [Methylation Status of PTPL1 Gene in Non-Hodgkin's Lymphoma Cells]. Zhongguo shi yan xue ye xue za zhi 0 26708878
2014 [Expression and Significance of PTPL1 in Hematological Malignancies]. Zhongguo shi yan xue ye xue za zhi 0 25543508