Affinage

PPP2R5D

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform · UniProt Q14738

Length
602 aa
Mass
70.0 kDa
Annotated
2026-06-10
48 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP2R5D encodes B56δ, a substrate-specifying regulatory subunit that assembles with the PP2A scaffold (A) and catalytic (C) subunits into a heterotrimeric holoenzyme directing protein dephosphorylation across neuronal signaling, cell-cycle control, and developmental programs (PMID:17301223, PMID:26168268). Holoenzyme activity is gated by upstream phosphorylation: PKA and PKC phosphorylate B56δ at Ser566/Ser573 to raise catalytic efficiency by lowering the apparent Km and reducing inhibitory phosphorylation of the C subunit (PMID:17301223, PMID:20423611, PMID:29294329), a regulatory logic explained structurally by intrinsically disordered B56δ termini that fold against the holoenzyme core to impose dual autoinhibition of both the active site and the substrate-binding groove, relieved by these activating phosphorylation events (PMID:38150499). Through this holoenzyme, B56δ dephosphorylates a wide substrate set with distinct physiological outputs—DARPP-32 Thr75 in dopaminergic signaling (PMID:17301223), Cdc25 to license mitotic entry (PMID:17110335), the CDK5 activator p35 governing GSK3β-dependent tau phosphorylation (PMID:21482799), tyrosine hydroxylase Ser40 controlling dopamine synthesis (PMID:22046270), Bcl-2 Ser70 (PMID:25082878), C/EBPβ during adipogenesis (PMID:25152162), eNOS Ser116 (PMID:26255574), and liprin-α1 Ser763, where dephosphorylation suppresses liquid-liquid phase separation (PMID:38948786, PMID:40484382). B56δ also nucleates non-canonical complexes, partnering with PPM1G to relocalize it and dephosphorylate α-catenin Ser641 at adherens junctions (PMID:31432583). Loss of B56δ inactivates GSK3β control of c-Myc, driving spontaneous hepatocellular carcinoma in knockout mice (PMID:28967903), and B56δ is genetically required with B56γ for cardiac outflow tract development (PMID:35415460). De novo missense mutations in PPP2R5D cause an intellectual disability and macrocephaly syndrome through a dominant-negative mechanism, impairing A/C-subunit binding and/or SLiM-dependent substrate recruitment and producing hyperactivation of AKT-mTOR-RPS6 and GSK3β-c-Myc signaling (PMID:26168268, PMID:33482199, PMID:36216457, PMID:37572851).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established B56δ-PP2A as a cell-cycle checkpoint effector by identifying how it relieves 14-3-3 sequestration of Cdc25 to control mitotic entry.

    Evidence Xenopus cell-free extract and cell-based assays with phosphosite mapping, dominant-negative and rescue experiments

    PMID:17110335

    Open questions at the time
    • Did not resolve how DNA-damage checkpoints physically activate the B56δ holoenzyme
    • Human in vivo relevance not addressed
  2. 2007 High

    Showed that B56δ phosphorylation is an activating switch, linking PKA phosphorylation of Ser566 to increased phosphatase activity and DARPP-32 dephosphorylation in neurons.

    Evidence In vitro kinase assay, site-directed mutagenesis, HEK293 cotransfection, striatal slice phosphorylation assays

    PMID:17301223

    Open questions at the time
    • Structural basis of phosphorylation-induced activation unknown at this stage
    • Full substrate repertoire untested
  3. 2010 Medium

    Quantified the activating mechanism, showing PKA phosphorylation of Ser566 lowers holoenzyme Km roughly tenfold and decreases inhibitory C-subunit Tyr307 phosphorylation.

    Evidence In vitro kinase assay, mutagenesis, kinetic analysis with forskolin in HEK293 cells

    PMID:20423611

    Open questions at the time
    • Single lab, limited validation
    • Roles of additional sites Ser53/68/81 in vivo not resolved
  4. 2011 High

    Connected B56δ loss to neurodegenerative tau pathology via an indirect p35/CDK5/GSK3β cascade, and to dopamine synthesis control via tyrosine hydroxylase Ser40.

    Evidence Ppp2r5d knockout mouse with in vitro dephosphorylation assays; PKC kinase assay with RNAi and dopamine measurement in N27 cells

    PMID:21482799 PMID:22046270

    Open questions at the time
    • Direct versus indirect substrate relationships partly inferred
    • TH study from single lab
  5. 2014 High

    Revealed that post-translational modification can selectively disassemble the holoenzyme, with peroxynitrite nitration of B56δ Tyr289 blocking A/C recruitment while sparing substrate binding to stabilize Bcl-2.

    Evidence SOD1 knockdown, Tyr289 mutagenesis, holoenzyme assembly Co-IP, Bcl-2 phospho-immunoblot in lymphoma cells

    PMID:25082878

    Open questions at the time
    • Generality of nitration regulation across tissues unknown
  6. 2015 Medium

    Extended the substrate landscape to metabolic and vascular programs through C/EBPβ dephosphorylation in adipogenesis and eNOS Ser116 dephosphorylation in endothelial NO release.

    Evidence Co-IP, knockdown, adipogenesis assays; dominant-negative B56δ, phospho-immunoblot and NO measurement in endothelial cells

    PMID:25152162 PMID:26255574

    Open questions at the time
    • Both single-lab studies
    • Direct holoenzyme-substrate engagement not structurally defined
  7. 2015 High

    Defined the dominant-negative disease mechanism, showing de novo mutations in a conserved acidic loop uncouple B56δ from A/C binding and cause GSK3β hyperphosphorylation.

    Evidence Reciprocal Co-IP, phosphatase activity assays, mutant overexpression, GSK3β immunoblot across 16 patients

    PMID:26168268

    Open questions at the time
    • Endogenous-level consequences not yet tested
    • Downstream signaling network not mapped
  8. 2017 Medium

    Tied B56δ to tumor suppression in vivo, with knockout livers developing hepatocellular carcinoma alongside GSK3β and c-Myc Ser62 hyperphosphorylation; also confirmed Ser573 as a β-adrenergic activation site in cardiomyocytes.

    Evidence Ppp2r5d KO mouse with phospho-immunoblot, IHC, RNA-seq; phosphate-affinity gels and S573A mutant in adult rat ventricular myocytes

    PMID:28967903 PMID:29294329

    Open questions at the time
    • Single-lab studies
    • Causal chain from GSK3β to tumorigenesis not fully dissected
  9. 2019 High

    Uncovered a non-canonical role, in which B56δ partners with PPM1G to relocalize it and dephosphorylate α-catenin Ser641 for adherens junction assembly.

    Evidence Co-IP, subcellular fractionation/live imaging, in vitro phosphatase assay, knockdown/rescue migration assays

    PMID:31432583

    Open questions at the time
    • Stoichiometry and structural basis of the PPM1G-B56δ complex unknown
    • Whether PP2A C subunit participates unclear
  10. 2021 High

    Resolved how disease variants drive growth signaling using endogenous CRISPR-edited cells, linking E420K B56δ to an AKT interaction and constitutive AKT-mTOR-RPS6 activation; double KO with B56γ showed an essential role in heart development.

    Evidence CRISPR base editing of E420K, phosphoproteomics, PPP2R5D-AKT Co-IP, rapamycin rescue; CRISPR/Cas9n double-KO mouse with cardiac anatomy analysis

    PMID:33482199 PMID:35415460

    Open questions at the time
    • Whether AKT is a direct dephosphorylation substrate not fully established
    • Redundancy logic between B56δ and B56γ not molecularly defined
  11. 2022 Medium

    Systematically mapped variant biochemistry, separating A/C-binding defects from SLiM-dependent substrate-binding defects and correlating them with phenotype severity; also identified a host-factor role in HCV replication.

    Evidence Co-IP binding assays across variants with clinical correlation in 76 patients; Co-IP, colocalization and KO/complementation HCV replication assays

    PMID:35836293 PMID:36216457

    Open questions at the time
    • Mechanism by which NS5B exploits B56δ unknown
    • Binding-assay severity correlation is associative
  12. 2023 High

    Provided the structural and mechanistic basis of regulation, showing disordered B56δ arms create dual autoinhibition spanning activation sites and disease residues, with variants increasing activity and mitotic errors; computational modeling implicated an Arg89-Glu198 salt bridge disrupted by E198K.

    Evidence Cryo-EM structure determination with in vitro phosphorylation and mitotic error assays; QM/ONIOM active-site modeling

    PMID:37377738 PMID:38150499

    Open questions at the time
    • QM modeling lacks experimental validation (Low confidence)
    • How specific variants quantitatively shift substrate selectivity not fully resolved
  13. 2025 High

    Established liprin-α1 as a SLiM-recruited substrate whose Ser763 dephosphorylation suppresses liquid-liquid phase separation and promotes heterodimerization, with E420K B56δ failing to restrain this LLPS.

    Evidence MS interactomics, phospho-MS with antibody validation, SLiM mutagenesis, KO and E420K knock-in cells, LLPS imaging, Co-IP

    PMID:38948786 PMID:40484382

    Open questions at the time
    • Physiological consequence of liprin-α1 LLPS dysregulation in patient neurons not shown
    • Whether LLPS control generalizes to other B56δ substrates unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how individual disease variants convert B56δ's dual-autoinhibited holoenzyme into specific gain- versus loss-of-function outputs on distinct substrates, and how these reconcile into the unified ID-macrocephaly-tumor phenotype.
  • No structure of disease-variant holoenzyme bound to substrate
  • Tissue-specific substrate selectivity not mapped
  • Direct versus indirect status of several substrates (AKT) unconfirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2
Partners
AKTC/EBPΒNS5BPPIL1L LIPRIN-Α1 (PPFIA1)PPM1GPPP2CAPPP2R1A
Complex memberships
PP2A holoenzyme (A-C-B56δ heterotrimer)PPM1G-B56δ complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PKA phosphorylates the B56δ (PPP2R5D) regulatory subunit of PP2A at Ser-566, which increases the overall phosphatase activity of the PP2A-B56δ/A/C heterotrimer in vitro and in vivo. The B56δ-containing PP2A complex dephosphorylates DARPP-32 at Thr-75, thereby mediating cAMP/PKA-dependent regulation of dopaminergic signaling in striatal neurons. In vitro kinase assay, site-directed mutagenesis (Ser-566 phosphorylation sites), cotransfection in HEK293 cells, striatal slice phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 17301223
2006 PP2A/B56δ phosphatase complex dephosphorylates Cdc25 at T138 (Xenopus numbering), a site distinct from the inhibitory Ser287, thereby reducing Cdc25 affinity for 14-3-3 proteins and enabling 14-3-3 release to promote mitotic entry. DNA-responsive checkpoints activate PP2A/B56δ complexes, identifying B56δ as a central checkpoint effector. Xenopus cell-free extract and cell-based assays, immunoprecipitation, phosphorylation site mapping, dominant-negative and rescue experiments Cell High 17110335
2011 In Ppp2r5d knockout mice, tau becomes progressively hyperphosphorylated at pathological epitopes in restricted brain areas. The mechanism is indirect: PP2A-B56δ (PP2A-T61δ) dephosphorylates p35 (the CDK5 activator), and its absence leads to p35 hyperphosphorylation and degradation, thereby reducing CDK5 activity. Loss of CDK5 activity results in decreased phosphorylation of GSK3β at Ser-9, increasing GSK3β activity and causing tau hyperphosphorylation. Ppp2r5d knockout mouse model, in vitro dephosphorylation assays, immunohistochemistry, kinase activity assays, behavioral testing Proceedings of the National Academy of Sciences of the United States of America High 21482799
2015 De novo missense mutations in PPP2R5D within a conserved acidic loop render mutant B56δ deficient in binding the PP2A A and C subunits, uncoupling it from phosphatase activity. This dominant-negative effect results in hyperphosphorylation of the B56δ-regulated substrate GSK3β in cells overexpressing mutant subunits. Co-immunoprecipitation for A/C subunit binding, phosphatase activity assays, overexpression of mutant subunits in cells, GSK3β phosphorylation immunoblot The Journal of clinical investigation High 26168268
2014 B56δ is the specific PP2A regulatory subunit mediating dephosphorylation of Bcl-2 at Ser70. Peroxynitrite-mediated nitration of B56δ at Tyr289 inhibits recruitment of the PP2A catalytic core (A and C subunits) to the B56δ complex while preserving B56δ binding to phospho-Ser70-Bcl-2, thereby preventing Bcl-2 dephosphorylation and stabilizing its antiapoptotic activity. Genetic knockdown of SOD1, co-immunoprecipitation, site-specific mutagenesis of B56δ Tyr289, PP2A holoenzyme assembly assays, Bcl-2 phosphorylation immunoblot Blood High 25082878
2011 Protein kinase C phosphorylates a key regulatory site in B56δ, activating the B56δ-containing PP2A heterotrimer, which then dephosphorylates Ser40 of tyrosine hydroxylase. RNAi knockdown of B56δ in N27 cells increases dopamine synthesis, confirming that PP2A-B56δ-mediated TH dephosphorylation reduces TH activity. In vitro kinase assay, RNAi knockdown, dopamine synthesis measurement, phosphorylation assays in cell lines PloS one Medium 22046270
2010 PKA phosphorylates PPP2R5D at Ser-53, Ser-68, Ser-81, and Ser-566 in vitro, but Ser-566 is the dominant in vivo phosphorylation site upon forskolin stimulation. Phosphorylation of PPP2R5D by PKA reduces the apparent Km of PP2A holoenzyme from 11.25 μM to 1.175 μM, increasing catalytic efficiency. Phosphorylation also decreases inhibitory Tyr-307 phosphorylation on the PP2A catalytic C subunit. In vitro kinase assay, site-directed mutagenesis of phosphorylation sites, kinetic analysis in HEK293 cells with forskolin, phospho-immunoblot BMB reports Medium 20423611
2017 β-Adrenergic receptor stimulation induces PKA-mediated phosphorylation of B56δ at Ser573 in adult rat ventricular cardiomyocytes. A non-phosphorylatable S573A mutant B56δ fails to increase PP2A catalytic activity in response to isoprenaline, demonstrating that Ser573 phosphorylation is required for β-AR-stimulated PP2A activation in cardiomyocytes. Phosphate-affinity SDS-PAGE, adenoviral transduction with WT and S573A mutant B56δ-GFP, co-immunoprecipitation with A/C subunits, PP2A activity assay, phosphoproteomics immunoblotting in ARVMs Journal of molecular and cellular cardiology Medium 29294329
2019 PPM1G (a PPM-family phosphatase) forms a novel holoenzyme complex with B56δ (PPP2R5D). B56δ promotes relocalization of PPM1G from the nucleus to the cytoplasm. The PPM1G-B56δ complex dephosphorylates α-catenin at Ser641 in the cytoplasm, which is required for proper adherens junction assembly and prevention of aberrant cell migration. Co-immunoprecipitation, subcellular fractionation/live imaging for relocalization, in vitro phosphatase assay on α-catenin, knockdown/rescue experiments for cell migration and junction assembly EMBO reports High 31432583
2015 B56δ-containing PP2A directly binds C/EBPβ and dephosphorylates it during early adipogenesis. This dephosphorylation is required for C/EBPβ degradation, which allows subsequent expression of PPARγ and C/EBPα and completion of adipogenesis. Co-immunoprecipitation of B56δ with C/EBPβ, okadaic acid inhibition, knockdown of specific B56 subunits, adipogenesis induction assay, immunoblotting for adipogenic transcription factors Biochimica et biophysica acta Medium 25152162
2015 B56δ-containing PP2A dephosphorylates eNOS at Ser116. Aphidicolin-induced DNA damage increases B56δ-Ser566 phosphorylation, activating PP2A-B56δ, which dephosphorylates eNOS-Ser116 and contributes to NO release in endothelial cells. Dominant-negative B56δ blocks both Ser116 dephosphorylation and NO production. Dominant-negative B56δ overexpression, okadaic acid inhibition, phospho-immunoblot for eNOS-Ser116 and B56δ-Ser566, NO measurement in bovine aortic endothelial cells Nitric oxide : biology and chemistry Medium 26255574
2021 A CRISPR-base-edited E420K heterozygous variant of PPP2R5D in HEK293 cells reveals a direct interaction between PPP2R5D and AKT, leading to constitutively active AKT-mTOR signaling, increased cell size, and uncoordinated cellular growth. Rapamycin reduces cell size and RPS6 hyperphosphorylation in E420K variant cells. CRISPR single-base editing to introduce E420K variant, quantitative phosphoproteomics (TMT-LC-MS3), co-immunoprecipitation of PPP2R5D-AKT, rapamycin treatment, cell size measurement The Journal of biological chemistry High 33482199
2017 Loss of PP2A-B56δ in knockout mice leads to spontaneous hepatocellular carcinoma, associated with c-Myc Ser62 hyperphosphorylation and GSK3β Ser9 hyperphosphorylation in non-cancerous B56δ-null livers, indicating that B56δ-driven GSK3β inactivation controls c-Myc activity as a tumor suppressive mechanism. Ppp2r5d knockout mouse model, targeted immunoblotting, immunohistochemistry, RNA sequencing, phospho-specific antibodies for c-Myc Ser62 and GSK3β Ser9 Oncogene Medium 28967903
2022 PPP2R5D interacts specifically with HCV NS5B RNA-dependent RNA polymerase (but not HCV Core or NS3), colocalizes with NS5B in the endoplasmic reticulum, and is required for HCV replication. Knockout of PPP2R5D abolishes HCV infection in Huh7.5 cells, and re-expression restores infection. Co-immunoprecipitation, colocalization by imaging, PPP2R5D knockout and knockdown with complementation, HCV replicon replication assay Virology journal Medium 35836293
2023 Cryo-EM structures of the PP2A-B56δ holoenzyme reveal that long intrinsically disordered regions (IDRs) at B56δ N- and C-termini fold against each other and the holoenzyme core, forming a closed latent conformation with dual autoinhibition of the phosphatase active site and the substrate-binding groove. This interface spans >190 Å, harbors activation phosphorylation sites and essentially all ID-associated mutation residues. ID mutations increase holoenzyme activity and alter phosphorylation rates; severe variants significantly increase mitotic duration and error rates. Single-particle cryo-EM structure determination, in vitro phosphorylation assays, mitotic duration and error rate measurements in cells with disease variants Proceedings of the National Academy of Sciences of the United States of America High 38150499
2023 Quantum mechanical calculations on the PP2A(PPP2R5D)/phosphoserine system indicate that bidentate Arg89-substrate binding is critical for optimal catalytic function, yielding ΔH‡ = +15.5 kcal/mol vs +18.8 kcal/mol when Arg89 is engaged in a salt bridge with B56δ Glu198. The pathogenic E198K mutation replaces the acidic Glu198 with a positively charged Lys, disrupting this salt bridge and altering the catalytic mechanism. Quantum-based hybrid ONIOM(UB3LYP/6-31G(d):UPM7) computational modeling of 39-residue active-site models Frontiers in cell and developmental biology Low 37377738
2023 PPP2R5D/PP2A-B56δ interacts with liprin-α1 through a canonical short linear interaction motif (SLiM) in liprin-α1's N-terminal dimerization domain. Loss of this interaction (SLiM mutation or PPP2R5D KO) results in increased liprin-α1 phosphorylation at Ser763 and promotes liprin-α1 liquid-liquid phase separation (LLPS). The E420K disease variant of PPP2R5D compromises suppression of liprin-α1 LLPS. MS-based interactomics, co-immunoprecipitation, SLiM mutagenesis, PPP2R5D KO cells, GFP-liprin-α1 LLPS imaging, phospho-mass spectrometry bioRxivpreprint Medium 38948786
2025 PPP2R5D-PP2A holoenzyme inhibits liprin-α1 LLPS by dephosphorylating liprin-α1 at multiple Ser/Thr sites including Ser763. The phospho-mimetic S763E mutant is sufficient to drive liprin-α1 LLPS. The E420K PPP2R5D disease variant increases liprin-α1 Ser763 phosphorylation and promotes LLPS. The interaction also promotes liprin-α1/β1 heterodimerization, which opposes LLPS. Mass spectrometry phospho-analysis, phospho-specific antibody validation, SLiM mutagenesis, PPP2R5D KO and E420K knock-in cells, LLPS imaging, liprin-α1/β1 co-immunoprecipitation The Journal of biological chemistry High 40484382
2022 Functional characterization of PPP2R5D missense variants shows that pathogenic variants cause impaired PP2A A/C-subunit binding, decreased SLiM-dependent substrate binding, or both. The most severe clinical phenotypes associate with variants that completely lose one of these binding properties while retaining the other, supporting a dominant-negative disease mechanism. The p.Glu198Lys variant shows the highest C-binding defect. Co-immunoprecipitation for A/C subunit binding, SLiM-dependent substrate binding assays, correlation with clinical phenotype severity in 76 patients Journal of medical genetics Medium 36216457
2021 Double knockout of Ppp2r5d (B56δ) and Ppp2r5c (B56γ) in mice causes arrest of fetal development around E12 and results in a single cardiac outflow vessel instead of separate aorta and pulmonary artery, demonstrating a genetic interaction between B56δ and B56γ that is required for heart development. Neither single knockout alone is lethal. CRISPR/Cas9n knockout mouse generation, genetic epistasis (double KO), embryonic lethal phenotype analysis, cardiac anatomy assessment FASEB bioAdvances Medium 35415460
2023 Quantitative phosphoproteomics of CRISPR-edited E198K and E420K PPP2R5D variant HEK293 cells reveals hyperphosphorylation of RPS6 as a shared signaling alteration, mediated through converging mTORC1/p70S6K activation. E420K shows AKT-dependent mTORC1 activation while E198K shows AKT-independent ERK-dependent activation. Rapamycin and the S6K inhibitor LY2584702 suppress RPS6 hyperphosphorylation. CRISPR-PRIME editing for E198K variant, global quantitative proteomics and phosphoproteomics, rapamycin and kinase inhibitor treatments, immunoblotting The Journal of biological chemistry Medium 37572851

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56delta subunit. Proceedings of the National Academy of Sciences of the United States of America 232 17301223
2006 Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell 162 17110335
2015 B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability. The Journal of clinical investigation 108 26168268
2011 Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3beta. Proceedings of the National Academy of Sciences of the United States of America 103 21482799
2014 Ser70 phosphorylation of Bcl-2 by selective tyrosine nitration of PP2A-B56δ stabilizes its antiapoptotic activity. Blood 81 25082878
2015 Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth. Human molecular genetics 75 25972378
2015 De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism. Neurogenetics 74 26576547
1996 Assignment of human protein phosphatase 2A regulatory subunit genes b56alpha, b56beta, b56gamma, b56delta, and b56epsilon (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2 --> p12. Genomics 58 8812429
2017 Loss of protein phosphatase 2A regulatory subunit B56δ promotes spontaneous tumorigenesis in vivo. Oncogene 46 28967903
2020 Early-Onset Parkinsonism Is a Manifestation of the PPP2R5D p.E200K Mutation. Annals of neurology 45 32743835
2020 PPP2R5D-Related Intellectual Disability and Neurodevelopmental Delay: A Review of the Current Understanding of the Genetics and Biochemical Basis of the Disorder. International journal of molecular sciences 41 32074998
2021 A disorder-related variant (E420K) of a PP2A-regulatory subunit (PPP2R5D) causes constitutively active AKT-mTOR signaling and uncoordinated cell growth. The Journal of biological chemistry 35 33482199
2022 Clinical, neuroimaging and molecular characteristics of PPP2R5D-related neurodevelopmental disorders: an expanded series with functional characterisation and genotype-phenotype analysis. Journal of medical genetics 25 36216457
2011 Protein kinase C-dependent dephosphorylation of tyrosine hydroxylase requires the B56δ heterotrimeric form of protein phosphatase 2A. PloS one 22 22046270
2017 β-Adrenergic regulation of cardiac type 2A protein phosphatase through phosphorylation of regulatory subunit B56δ at S573. Journal of molecular and cellular cardiology 21 29294329
2019 PPM1G forms a PPP-type phosphatase holoenzyme with B56δ that maintains adherens junction integrity. EMBO reports 19 31432583
2023 B56δ long-disordered arms form a dynamic PP2A regulation interface coupled with global allostery and Jordan's syndrome mutations. Proceedings of the National Academy of Sciences of the United States of America 18 38150499
2023 Quantitative proteomics and phosphoproteomics of PP2A-PPP2R5D variants reveal deregulation of RPS6 phosphorylation via converging signaling cascades. The Journal of biological chemistry 17 37572851
2010 Phosphorylation on the PPP2R5D B regulatory subunit modulates the biochemical properties of protein phosphatase 2A. BMB reports 16 20423611
2021 Growth arrest of PPP2R5C and PPP2R5D double knockout mice indicates a genetic interaction and conserved function for these PP2A B subunits. FASEB bioAdvances 13 35415460
2003 Expression of the B56delta subunit of protein phosphatase 2A and Mea1 in mouse spermatogenesis. Identification of a new B56gamma subunit (B56gamma4) specifically expressed in testis. Cytogenetic and genome research 10 15051958
2021 A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype. BioMed research international 8 33628804
2022 Rare missense variants in the PPP2R5D gene associated with Parkinson's disease in the Han Chinese population. Neuroscience letters 7 35257824
2022 A novel nonsense mutation in PPP2R5D is associated with neurodevelopmental disorders and shows incomplete penetrance in a Chinese pedigree. Clinical neurology and neurosurgery 6 36403339
2021 PPP2R5D-Related Neurodevelopmental Disorder or Developmental and Epileptic Encephalopathy?: A Novel Phenotypic Description and Review of Published Cases. Neuropediatrics 6 34448180
2020 Differential Proteomic Analysis of Hepatocellular Carcinomas from Ppp2r5d Knockout Mice and Normal (Knockout) Livers. Cancer genomics & proteomics 6 33099469
2024 Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder. Clinical genetics 5 39169681
2022 PPP2R5D promotes hepatitis C virus infection by binding to viral NS5B and enhancing viral RNA replication. Virology journal 5 35836293
2014 Dephosphorylation of CCAAT/enhancer-binding protein β by protein phosphatase 2A containing B56δ is required at the early time of adipogenesis. Biochimica et biophysica acta 5 25152162
2024 The role of liprin-α1 phosphorylation in its liquid-liquid phase separation: regulation by PPP2R5D/PP2A holoenzyme. bioRxiv : the preprint server for biology 4 38948786
2015 B56δ subunit of protein phosphatase 2A decreases phosphorylation of endothelial nitric oxide synthase at serine 116: Mechanism underlying aphidicolin-stimulated NO production. Nitric oxide : biology and chemistry 4 26255574
2025 A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons. Stem cells (Dayton, Ohio) 3 39460716
2025 Hepatocyte-Derived Extracellular Vesicles Deliver miR-328-3p to Trigger PP2A-B56δ-Mediated p-NLRP3S295-Dependent Metaflammation in Macrophages upon Microcystin-LR Exposure. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 41255311
2023 Quantum-based modeling implies that bidentate Arg89-substrate binding enhances serine/threonine protein phosphatase-2A(PPP2R5D/PPP2R1A/PPP2CA)-mediated dephosphorylation. Frontiers in cell and developmental biology 3 37377738
2023 A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss of Ppp2r5d. Cancers 3 37627221
2003 Peas-Mea1-Ppp2r5d overlapping gene complex: a transposon mediated-gene formation in mammals. DNA research : an international journal for rapid publication of reports on genes and genomes 3 12755172
2025 Clinical-Genetic Approach to Conditions with Macrocephaly and ASD/Behaviour Abnormalities: Variants in PTEN and PPP2R5D Are the Most Recurrent Gene Mutations in a Patient-Oriented Diagnostic Strategy. Genes 2 40282429
2023 Quantitative proteomics and phosphoproteomics of PPP2R5D variants reveal deregulation of RPS6 phosphorylation through converging signaling cascades. bioRxiv : the preprint server for biology 2 37034727
2025 Pathogenic PPP2R5D variants disrupt neuronal development and neurite outgrowth in patient-derived neurons that are reversed by allele-specific knockdown. HGG advances 1 40340253
2025 The phosphatase activity of the PPP2R5D-PP2A holoenzyme modulates liprin-α1 liquid-liquid phase separation. The Journal of biological chemistry 1 40484382
2024 Thirteen New Patients of PPP2R5D Gene Mutation and the Fine Profile of Genotype-Phenotype Correlation Unraveling the Pathogenic Mechanism Underlying Macrocephaly Phenotype. Children (Basel, Switzerland) 1 39201832
2023 Extended regulation interface coupled to the allosteric network and disease mutations in the PP2A-B56δ holoenzyme. bioRxiv : the preprint server for biology 1 37066309
2023 An in-frame deletion affecting the critical acid loop of PPP2R5D is associated with a neonatal lethal form of PPP2R5D-related neurodevelopmental disorder. American journal of medical genetics. Part A 1 37248744
2026 Epirubicin Ameliorates Kidney Fibrosis by Inhibiting B56δ-Mediated Lipid Generation. Kidney diseases (Basel, Switzerland) 0 41767093
2025 Jordan syndrome due to PPP2R5D gene mutation: a report of two pediatric cases and literature review. Translational pediatrics 0 41367531
2024 PPP2R5D-Related Neurodevelopmental Disorder and Multiple Haemangiomas: A Novel Phenotypic Trait? Pediatric reports 0 39728742
2024 A guide to selecting high-performing antibodies for Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform (PPP2R5D) for use in Western Blot, immunoprecipitation and immunofluorescence. F1000Research 0 39935523
2023 Retracted: A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype. BioMed research international 0 38075329

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