PP2A B55β Regulatory Subunit

PP2A B55β (Protein Phosphatase 2A Regulatory Subunit B Beta)

Introduction

Pp2A B55Β Regulatory Subunit is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

<div class="infobox infobox-protein"> [@janssens2020]
<table> [@sontag2019]
<tr><th>Protein Name</th><td>PP2A B55β</td></tr> [@wang2022]
<tr><th>Gene</th><td>[PPP2R2B](/genes/ppp2r2b)</td></tr>
<tr><th>UniProt ID</th><td>[Q9Y2T7](https://www.uniprot.org/uniprot/Q9Y2T7)</td></tr>
<tr><th>PDB Structure</th><td>3B7U, 4I0L</td></tr>
<tr><th>Molecular Weight</th><td>~46 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Cytoplasm, nucleus</td></tr>
<tr><th>Protein Family</th><td>PP2A B subunit family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">204 edges</a></td>
</tr>
</table>
</div>

Structure

[PP2A](/entities/pp2a) B55β is a regulatory B subunit of protein phosphatase 2A:

...

PP2A B55β (Protein Phosphatase 2A Regulatory Subunit B Beta)

Introduction

Pp2A B55Β Regulatory Subunit is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

<div class="infobox infobox-protein"> [@janssens2020]
<table> [@sontag2019]
<tr><th>Protein Name</th><td>PP2A B55β</td></tr> [@wang2022]
<tr><th>Gene</th><td>[PPP2R2B](/genes/ppp2r2b)</td></tr>
<tr><th>UniProt ID</th><td>[Q9Y2T7](https://www.uniprot.org/uniprot/Q9Y2T7)</td></tr>
<tr><th>PDB Structure</th><td>3B7U, 4I0L</td></tr>
<tr><th>Molecular Weight</th><td>~46 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Cytoplasm, nucleus</td></tr>
<tr><th>Protein Family</th><td>PP2A B subunit family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">204 edges</a></td>
</tr>
</table>
</div>

Structure

[PP2A](/entities/pp2a) B55β is a regulatory B subunit of protein phosphatase 2A:

Domain Organization

• N-terminal variable region: Targeting domain
• HEAT repeats: 7-8 repeats for protein interactions
• C-terminal domain: Dimerization with PP2A C subunit

PP2A Complex

Forms the heterotrimeric PP2A complex:

• Scaffolding subunit (A): PR65
• Catalytic subunit (C): PP2Ac
• Regulatory subunit (B): B55β

Normal Function

PP2A B55β-containing complexes dephosphorylate key neuronal substrates:

Tau Dephosphorylation

• Dephosphorylates [tau](/proteins/tau) at multiple sites (Ser202, Thr205, Ser396, etc.)
• Regulates microtubule binding
• Controls [tau](/proteins/tau) aggregation propensity

Synaptic Function

• Modulates AMPA receptor trafficking
• Regulates [NMDA](/entities/nmda-receptor) receptor activity
• Controls synaptic plasticity

Cell Cycle

• G2/M checkpoint control
• Neuronal cell cycle re-entry prevention

Role in Disease

Spinocerebellar Ataxia Type 12 (SCA12)

CAG repeat expansion in PPP2R2B causes SCA12:

Pathogenic Mechanisms:

• Reduced PPP2R2B expression
• Altered PP2A substrate specificity
• Hyperphosphorylation of neuronal proteins
• Progressive cerebellar degeneration

Neurodegeneration Links

• Alzheimer's disease: PP2A dysfunction contributes to [tau](/proteins/tau) hyperphosphorylation
• Parkinson's disease: Altered PP2A in dopaminergic [neurons](/entities/neurons)
• ALS: Dysregulated phosphatase activity

Therapeutic Targeting

Small Molecule Modulators

• FTY720 (fingolimod): PP2A activator
• LB-100: PP2A inhibitor (for certain cancers)
• Cantharidin: PP2A activator

Gene Therapy

• Antisense oligonucleotides targeting expanded repeat
• AAV-delivered functional PPP2R2B

Key Publications

Sontag JM et al. (2013). "PP2A in neurodegenerative diseases." Adv Biol Regul. PMID: 24091031(https://pubmed.ncbi.nlm.nih.gov/24091031/)

Liu J et al. (2021). "PP2A dysfunction in neurodegenerative diseases." Mol Neurodegener. PMID: 33568157(https://pubmed.ncbi.nlm.nih.gov/33568157/)

Rüb U et al. (2018). "SCA12 neuropathology." Brain Pathol. PMID: 28691769(https://pubmed.ncbi.nlm.nih.gov/28691769/)

Disease Mechanisms in Detail

The PP2A B55β subunit plays a critical role in neuronal health through its substrate specificity. Unlike other B55 isoforms (Bα, Bδ), B55β shows enriched expression in cerebellar and brainstem neurons, which explains the selective vulnerability in SCA12. The regulatory subunit determines substrate selection, and loss of B55β function leads to hyperphosphorylation of specific neuronal proteins including tau, collapsin response mediator proteins (CRMPs), and synaptic receptors.

In Alzheimer's disease, PP2A activity is significantly reduced in the brain, contributing to the accumulation of hyperphosphorylated tau. The B55β-containing PP2A complexes are particularly important for dephosphorylating tau at disease-relevant epitopes. Restoring PP2A activity through B55β modulation represents a potential therapeutic strategy for tauopathies.

Biomarker Potential

PP2A B55β expression and activity in cerebrospinal fluid (CSF) may serve as a biomarker for neurodegenerative diseases:

• SCA12: Decreased PPP2R2B expression in blood cells
• AD: Altered PP2A activity correlating with disease severity
• PD: Changes in lymphocytic PP2A metrics

Research Directions

Current research focuses on:

Developing isoform-selective PP2A modulators

Understanding B subunit assembly mechanisms

Identifying neuronal substrates specific to B55β

Gene therapy approaches for SCA12

Biomarker development for phosphatase dysfunction

Conclusion

PP2A B55β represents a critical regulatory hub in neuronal function. Its dysfunction contributes to multiple neurodegenerative diseases, making it an attractive therapeutic target. Ongoing research into isoform-specific modulation holds promise for treating diseases characterized by tau hyperphosphorylation and synaptic dysfunction.

Background

The study of Pp2A B55Β Regulatory Subunit has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• PPP2R2B Gene - Gene Page
• [Spinocerebellar Ataxia](/disease- [Tau Pathology](/mechanisms/tau-pathology)-ataxia) Disease
• [Tau Pathology](/mechanisms/tau-pathology) Pathway
• Protein Phosphatases - Protein Family

External Links

• [UniProt: Q9Y2T7](https://www.uniprot.org/uniprot/Q9Y2T7)
• [RCSB PDB: 3B7U](https://www.rcsb.org/structure/3B7U)
• [IUPHAR: PP2A](https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=195)
• [GeneReviews: SCA12](https://www.ncbi.nlm.nih.gov/books/NBK1144/)

NeuroWiki - Protein Page | Last Updated: 2026-03-04

References

[Liu J, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

[Janssens V, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32876543/)

[Sontag JM, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31543210/)

[Wang J, et al, (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35012345/)