PPP2R1A Gene

PPP2R1A

title: PPP2R1A Gene

PPP2R1A — Protein Phosphatase 2 Regulatory Subunit A Alpha

Overview

PPP2R1A encodes the regulatory subunit A alpha of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in the brain. [PP2A](/entities/pp2a) is crucial for [tau](/proteins/tau) dephosphorylation, and its dysfunction is implicated in Alzheimer's disease and other tauopathies. [@xu2020]

Introduction

PPP2R1A (Protein Phosphatase 2 Regulatory Subunit A Alpha) encodes the alpha isoform of the structural/regulatory subunit A of PP2A. PP2A is one of the most abundant protein phosphatases in eukaryotic cells and plays essential roles in regulating various cellular processes, including signal transduction, cell cycle progression, and tau phosphorylation dynamics in [neurons](/entities/neurons).

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | PPP2R1A |
| Full Name | Protein Phosphatase 2 Regulatory Subunit A Alpha |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 5518 |
| OMIM ID | 616981 |
| Ensembl ID | ENSG00000101162 |
| UniProt ID | P46821 |
| Encoded Protein | PP2A subunit A (PR65-alpha) |
| Associated Diseases | Alzheimer's disease, breast cancer, tauopathies |

</div>

Function

PPP2R1A encodes the alpha isoform of the PP2A subunit A, which serves as a scaffold for assembling the PP2A holoenzyme.

...

PPP2R1A

title: PPP2R1A Gene

PPP2R1A — Protein Phosphatase 2 Regulatory Subunit A Alpha

Overview

PPP2R1A encodes the regulatory subunit A alpha of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in the brain. [PP2A](/entities/pp2a) is crucial for [tau](/proteins/tau) dephosphorylation, and its dysfunction is implicated in Alzheimer's disease and other tauopathies. [@xu2020]

Introduction

PPP2R1A (Protein Phosphatase 2 Regulatory Subunit A Alpha) encodes the alpha isoform of the structural/regulatory subunit A of PP2A. PP2A is one of the most abundant protein phosphatases in eukaryotic cells and plays essential roles in regulating various cellular processes, including signal transduction, cell cycle progression, and tau phosphorylation dynamics in [neurons](/entities/neurons).

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | PPP2R1A |
| Full Name | Protein Phosphatase 2 Regulatory Subunit A Alpha |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 5518 |
| OMIM ID | 616981 |
| Ensembl ID | ENSG00000101162 |
| UniProt ID | P46821 |
| Encoded Protein | PP2A subunit A (PR65-alpha) |
| Associated Diseases | Alzheimer's disease, breast cancer, tauopathies |

</div>

Function

PPP2R1A encodes the alpha isoform of the PP2A subunit A, which serves as a scaffold for assembling the PP2A holoenzyme.

Key normal physiological functions include:

• Tau dephosphorylation — PP2A dephosphorylates tau at multiple pathological sites (Ser202, Thr205, Ser396, Ser404)
• Signal transduction — Regulates various signaling pathways including PI3K/Akt, MAPK, and Wnt
• Cell cycle control — Essential for cell cycle progression
• Synaptic plasticity — Regulates [NMDA receptor](/entities/nmda-receptor) function and [LTP](/mechanisms/long-term-potentiation)
• [Apoptosis](/entities/apoptosis) — Modulates apoptotic pathways

Disease Associations

Alzheimer's Disease (AD)

PP2A dysfunction is a hallmark of AD:

• Reduced PP2A activity — PP2A activity decreased in AD brain
• Tau hyperphosphorylation — Loss of PP2A contributes to NFT formation
• Synaptic deficits — PP2A regulates synaptic proteins
• Therapeutic target — PP2A activators in development for AD treatment
• Genetic variants — PPP2R1A variants associated with AD risk

Other Tauopathies

• Progressive supranuclear palsy — PP2A dysfunction contributes to tau pathology
• Frontotemporal dementia — Altered PP2A in FTLD-Tau

Cancer

• Oncogenic role — PPP2R1A mutations in various cancers
• PP2A inhibition — Tumor suppressor function of PP2A

Expression

PPP2R1A exhibits widespread expression:

• High expression — Brain ([cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum), testis, blood
• Cellular localization — Cytosolic, associated with membranes
• Isoforms — Two isoforms (alpha and beta) with tissue-specific distribution
• Neuronal importance — Critical for neuronal function due to extensive phosphorylation

Key Publications

[Liu et al., PP2A in Alzheimer's disease (2023)](https://doi.org/10.1016/j.neurobiolaging.2023.01.008)

[Sontag & Sontag, PP2A and tau pathology (2022)](https://doi.org/10.1093/brain/awab456)

[Ruediger et al., PPP2R1A mutations in disease (2021)](https://doi.org/10.1038/s41588-021-00956-0)

[Xu et al., PP2A activator for AD therapy (2020)](https://doi.org/10.1038/s41591-020-0945-z)

Cross-links

• [Tau protein](/proteins/tau) — PP2A dephosphorylates tau
• [Alzheimer's disease](/diseases/alzheimers-disease) — Associated disease
• [Protein phosphatases](/mechanisms/protein-phosphorylation) — PP2A in phosphorylation
• [PP2A](/proteins/pp2a-protein) — Related protein

Background

The study of Ppp2R1A Gene 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

• [Neurodegenerative Diseases](/)
• [Genes](/genes)
• [Proteins](/proteins)
• [Mechanisms](/mechanisms)

External Links

• [NCBI Gene Database](https://www.ncbi.nlm.nih.gov/gene)
• [UniProt Protein Database](https://www.uniprot.org/)
• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)

References

Liu R, et al, PP2A in Alzheimer's disease (2023)

Sontag JM, Sontag E, PP2A and tau pathology (2022)

Ruediger R, et al, PPP2R1A mutations in disease (2021)

Xu Y, et al, PP2A activator for AD therapy (2020)