PPP2R2A — Protein Phosphatase 2 Regulatory Subunit B55 Alpha

PPP2R2A — Protein Phosphatase 2 Regulatory Subunit B55 Alpha

Introduction

PPP2R2A — Protein Phosphatase 2 Regulatory Subunit B55 Alpha

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PPP2R2A — Protein Phosphatase 2 Regulatory Subunit B55 Alpha</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PPP2R2A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Protein Phosphatase 2 Regulatory Subunit B55 Alpha</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>8p21.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[5520](https://www.ncbi.nlm.nih.gov/gene/5520)</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>[601728](https://www.omim.org/entry/601728)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000156535](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000156535)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P63151](https://www.uniprot.org/uniprotkb/P63151)</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>447 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~52 kDa</td>
</tr>
<tr>
<td class="label">Substrate</td>
<td>Site</td>
</tr>
<tr>
<td class="label">Tau</td>
<td>Ser202, Thr205, Ser396</td>
</tr>
<tr>
<td class="label">[APP](/entities/app-protein)</td>
<td>Thr668</td>
</tr>
<tr>
<td class="label">Synapsin I</td>
<td>Ser9</td>
</tr>
<tr>
<td class="label">[NMDA Receptor](/entities/nmda-receptor)</td>
<td>Ser1323</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">ABT-737</td>
<td>Inhibits SET/I2PP2A</td>
</tr>
<tr>
<td class="label">FTY720 (Fingolimod)</td>
<td>Multiple mechanisms</td>
</tr>
<tr>
<td class="label">Saluben</td>
<td>Direct B55alpha interaction</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>

PPP2R2A (Protein Phosphatase 2 Regulatory Subunit B55 Alpha) encodes the B55alpha regulatory subunit of protein phosphatase 2A (PP2A), one of the most abundant serine/threonine phosphatases in the brain. Located at chromosome 8p21.2, PPP2R2A is essential for targeting [PP2A](/entities/pp2a) catalytic activity to specific substrates, including the microtubule-associated protein [tau](/proteins/tau) [1](https://www.ncbi.nlm.nih.gov/gene/5520).

Dysregulation of PPP2R2A and resulting PP2A dysfunction is a hallmark of Alzheimer's disease and other neurodegenerative disorders, making it a critical therapeutic target [2](https://doi.org/10.1016/j.tcb.2012.09.004).

Gene Overview

Molecular Function

PP2A-B55α Complex

PPP2R2A encodes the B55α (also known as PR55α) regulatory subunit that forms the PP2A-B55α holoenzyme with:

• PP2A catalytic subunit (PP2Ac/PPP2CA) — The catalytic core
• PP2A scaffolding subunit (PR65/A) — Structural platform

Substrate Targeting

The B55α subunit directs PP2A to dephosphorylate key neuronal substrates:

Tau Dephosphorylation

PP2A-B55α is the primary tau phosphatase in the brain, responsible for:

• Dephosphorylating pathogenic tau phospho-epitopes
• Restoring microtubule binding
• Preventing tau aggregation

Neuronal Function

Synaptic Plasticity

PP2A-B55α regulates synaptic plasticity through:

• [Long-term potentiation](/mechanisms/long-term-potentiation) (LTP) — Modulating NMDA receptor activity
• Long-term depression (LTD) — AMPA receptor internalization
• Synaptic protein turnover — Regulating synaptic scaffold proteins

Axonal Transport

The phosphatase complex regulates:

• Microtubule-based transport
• Kinesin/dynein function
• Synaptic vesicle trafficking

Neuronal Survival

PP2A-B55α activity protects neurons by:

• Dephosphorylating pro-apoptotic proteins (Bax, p53)
• Regulating Akt signaling
• Maintaining calcium homeostasis

Disease Associations

Alzheimer's Disease

PPP2R2A dysfunction in AD involves multiple mechanisms:

Parkinson's Disease

In PD, PP2A-B55α affects:

• [Alpha-synuclein](/proteins/alpha-synuclein) phosphorylation — At Ser129
• DJ-1 function — Oxidative stress response
• Mitochondrial dynamics — PGC-1α regulation

Cancer

PPP2R2A has complex roles in cancer:

• Functions as tumor suppressor in some contexts
• Mutations found in certain cancers
• PP2A inhibitors used as anticancer drugs

Therapeutic Implications

PP2A Activators

Several compounds are being developed to activate PP2A-B55α:

Tau-Directed Therapy

PP2A activation represents a direct approach to:

• Reduce tau phosphorylation
• Promote tau clearance
• Restore synaptic function

Biomarkers

PPP2R2A-related measurements may serve as:

• CSF biomarker for tau pathology
• Therapeutic response indicator
• Disease progression marker

Pathway Involvement

PPP2R2A participates in key signaling pathways:

See Also

• [Tau Protein](/proteins/tau)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Protein Phosphatase 2A](/mechanisms/protein-phosphatase-2a)
• [Tau Phosphorylation](/mechanisms/tau-phosphorylation)
• [GSK3B](/genes/gsk3b)
• [MAPT](/genes/mapt)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving PPP2R2A — Protein Phosphatase 2 Regulatory Subunit B55 Alpha discovered through SciDEX knowledge graph analysis: