PP2A (PPP2R1A)

PP2A (PPP2R1A)

[PP2A](/entities/pp2a) (Protein Phosphatase 2A) is a major serine/threonine phosphatase that regulates numerous cellular processes including cell cycle progression, [apoptosis](/entities/apoptosis), metabolism, and signal transduction. The PP2A holoenzyme consists of a catalytic subunit (PPP2CA or PPP2CB), a structural A subunit (PPP2R1A or PPP2R1B), and a regulatory B subunit that determines substrate specificity.

Gene Overview

<div class="infobox infobox-gene">
| Property | Value |
|----------|-------|
| Gene Symbol | PPP2R1A |
| Full Name | Protein Phosphatase 2 Scaffold Subunit A Alpha |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 5518 |
| OMIM | 605983 |
| Ensembl | ENSG00000114825 |
| UniProt | P30153 |
| Associated Diseases | Alzheimer's disease, cancer, intellectual disability |
</div>

Overview

PPP2R1A is a human gene whose product pPP2R1A encodes the alpha isoform of the structural A subunit of PP2A, which serves as a scaffold for assembly of the heterotrimeric phosphatase complex[@xu2006]:. Variants in PPP2R1A have been implicated in Alzheimer's Disease, Neurodegeneration, Cancer. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Normal Function

PPP2R1A encodes the alpha isoform of the structural A subunit of PP2A, which serves as a scaffold for assembly of the heterotrimeric phosphatase complex[@xu2006]:

PP2A (PPP2R1A)

[PP2A](/entities/pp2a) (Protein Phosphatase 2A) is a major serine/threonine phosphatase that regulates numerous cellular processes including cell cycle progression, [apoptosis](/entities/apoptosis), metabolism, and signal transduction. The PP2A holoenzyme consists of a catalytic subunit (PPP2CA or PPP2CB), a structural A subunit (PPP2R1A or PPP2R1B), and a regulatory B subunit that determines substrate specificity.

Gene Overview

<div class="infobox infobox-gene">
| Property | Value |
|----------|-------|
| Gene Symbol | PPP2R1A |
| Full Name | Protein Phosphatase 2 Scaffold Subunit A Alpha |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 5518 |
| OMIM | 605983 |
| Ensembl | ENSG00000114825 |
| UniProt | P30153 |
| Associated Diseases | Alzheimer's disease, cancer, intellectual disability |
</div>

Overview

PPP2R1A is a human gene whose product pPP2R1A encodes the alpha isoform of the structural A subunit of PP2A, which serves as a scaffold for assembly of the heterotrimeric phosphatase complex[@xu2006]:. Variants in PPP2R1A have been implicated in Alzheimer's Disease, Neurodegeneration, Cancer. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Normal Function

PPP2R1A encodes the alpha isoform of the structural A subunit of PP2A, which serves as a scaffold for assembly of the heterotrimeric phosphatase complex[@xu2006]:

Signal Transduction

• Kinase/Phosphatase Balance: PP2A antagonizes numerous kinases including AKT, ERK, and GSK3β
• Second Messenger Dephosphorylation: Regulates cAMP, Ca²⁺, and DAG signaling
• Receptor Signaling: Modulates insulin, Wnt, and Notch pathways

Cell Cycle Regulation

• Mitotic Entry: PP2A prevents premature mitotic entry by dephosphorylating CDK substrates
• Checkpoint Control: Essential for DNA damage checkpoint recovery
• Chromosome Segregation: Regulates spindle assembly checkpoint

Metabolic Regulation

• Glycogen Metabolism: PP2A dephosphorylates glycogen synthase
• Lipid Metabolism: Modulates acetyl-CoA carboxylase and fatty acid synthase
• [mTOR](/mechanisms/mtor-signaling-pathway) Signaling: PP2A negatively regulates mTORC1 activity

Disease Associations

Alzheimer's Disease

• Tau Pathology: PP2A activity is reduced in AD brains, leading to hyperphosphorylated tau[@liu2005]
• GSK3β Dysregulation: Reduced PP2A allows excessive GSK3β activity
• Amyloid Effects: [Aβ](/proteins/amyloid-beta) oligomers inhibit PP2A activity
• Therapeutic Target: PP2A activators are being explored as AD treatment

Neurodegeneration

• Parkinson's Disease: PP2A dysregulation affects [α-synuclein](/proteins/alpha-synuclein) phosphorylation
• HD: Altered PP2A activity contributes to neuronal dysfunction

Cancer

• Oncogenic Mutations: PPP2R1A is mutated in endometrial and other cancers[@hahn2012]
• Tumor Suppressor: PP2A restrains oncogenic signaling

Expression Pattern

PPP2R1A is ubiquitously expressed with high levels in:

• Brain ([cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum)
• Heart, liver, kidney
• Proliferating cells

Therapeutic Implications

Drug Development

• PP2A Activators: FTY720 (fingolimod) and other small molecules activate PP2A
• B subunit modulators: Targeting specific B subunits for tissue-specific effects

Research Directions

• Restoring PP2A activity to correct tau hyperphosphorylation
• Understanding PP2A dysfunction in specific neurodegenerative subtypes
• Developing brain-penetrant PP2A activators

Cross-Links

• [Tau (MAPT)](/proteins/tau) - Substrate
• [GSK3B](/genes/gsk3b) - Kinase antagonist
• [AKT](/genes/akt1) - Kinase substrate
• [Alzheimer's Disease](/diseases/alzheimers-disease) - Disease link

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)

External Links

• [Ensembl: ENSG00000114825](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000114825)
• [NCBI Gene: PPP2R1A](https://www.ncbi.nlm.nih.gov/gene/?term=PPP2R1A)
• [GeneCards: PPP2R1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PPP2R1A)
• [OMIM: PPP2R1A](https://omim.org/search?search=PPP2R1A)
• [Allen Brain Atlas: PPP2R1A](https://human.brain-map.org/microarray/search/show?search_term=PPP2R1A)

References

Pathway Context

Pathway Diagram

The following diagram shows the key molecular relationships involving PP2A (PPP2R1A) discovered through SciDEX knowledge graph analysis: