PPP2R2A: Protein Phosphatase 2 Regulatory Subunit B Alpha
A key regulator of PP2A holoenzyme specificity, implicated in cancer and neurological disorders.
Gene Information Card
| Symbol | PPP2R2A |
|---|---|
| Full Name | Protein Phosphatase 2 Regulatory Subunit B, Alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 8p21.2 |
| NCBI Gene ID | 5520 ncbi.nlm.nih.gov/gene/5520 |
| Ensembl ID | ENSG00000121966 |
| UniProt ID | P63151 |
| OMIM ID | 605997 |
| HGNC ID | 9304 |
| Aliases | B55A, B55alpha, PP2A-B55A, PR52A |
Description
PPP2R2A encodes the alpha isoform of the regulatory B55 subunit of protein phosphatase 2 (PP2A). PP2A is a major serine/threonine phosphatase that regulates diverse cellular processes including cell cycle, apoptosis, and signal transduction. The B55 subunit confers substrate specificity and subcellular localization to the PP2A holoenzyme. PPP2R2A is considered a tumor suppressor gene and is frequently deleted or mutated in various cancers.
Disease Associations
| Disease Name | Disease Description |
|---|---|
| Breast cancer | Loss of PPP2R2A expression reduces PP2A activity, promoting AKT and ERK signaling; genomic deletion at 8p21.2 is common. |
| Colorectal cancer | Somatic mutations and reduced expression of PPP2R2A impair PP2A-mediated dephosphorylation of oncogenic substrates. |
| Alzheimer disease | Dysregulation of PP2A (including B55 subunit) contributes to tau hyperphosphorylation. |
| Lung cancer | Frequent loss of heterozygosity at 8p21.2 leads to decreased PPP2R2A expression and increased cell proliferation. |
| Prostate cancer | PPP2R2A downregulation correlates with poor prognosis and enhanced PI3K/AKT signaling. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 23.5 | High |
| Heart | 12.1 | Medium |
| Liver | 8.4 | Medium |
| Lung | 6.2 | Low |
| Breast | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression |
| HeLa | 10.7 | Medium expression |
| MCF7 | 7.2 | Low expression |
| A549 | 6.5 | Low expression |
| HCT 116 | 9.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Mutation site | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <1% | Loss of start codon; likely loss of function |
| c.487C>T (p.Arg163Trp) | missense | <1% | Impaired substrate binding; reported in COSMIC |
| c.742G>A (p.Gly248Arg) | missense | <1% | Reduced PP2A activity; COSMIC |
| c.1045C>T (p.Arg349*) | nonsense | <1% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (nonsense, frameshift, missense affecting conserved residues) lead to reduced PP2A holoenzyme activity or stability, consistent with a tumor suppressor role.
Gain of Function (GOF)
No evidence of gain-of-function mutations in PPP2R2A.
Dominant Negative (DN)
Some missense mutations (e.g., Arg163Trp) may act in a dominant-negative manner by competing with wild-type B55 for PP2A core binding, but evidence is limited.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/5520 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PPP2R2A
Gene Ontology (GO)
| • GO:0000159 – protein phosphatase type 2A complex | • GO:0005515 – protein binding |
| • GO:0006470 – protein dephosphorylation | • GO:0019901 – protein kinase binding |
| • GO:0042802 – identical protein binding | • GO:0072542 – protein phosphatase activator activity |
Pathways
• hsa04110 – Cell cycle
• hsa04150 – mTOR signaling pathway
• hsa04010 – MAPK signaling pathway
• hsa04151 – PI3K-Akt signaling pathway
• hsa05010 – Alzheimer disease
Protein Summary
The PPP2R2A protein (B55 alpha) is a 447-amino acid regulatory subunit of PP2A. It contains a conserved B55 domain that mediates binding to the PP2A catalytic and scaffolding subunits. B55 alpha targets PP2A to specific substrates such as AKT, ERK, and tau, controlling their phosphorylation status. Loss of B55 alpha expression or function disrupts PP2A-mediated dephosphorylation, leading to sustained activation of oncogenic signaling pathways.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP2R2A Knockout HEK293 Cell Line | EDJ-KQ851 | Human | 5520 | Details Get a Quote |
| PPP2R2A Knockout HeLa Cell Line | EDJ-KQ18318 | Human | 5520 | Details Get a Quote |
| PPP2R2A Knockout A-549 Cell Line | EDJ-KQ19644 | Human | 5520 | Details Get a Quote |
| PPP2R2A Knockout HCT 116 Cell Line | EDJ-KQ19645 | Human | 5520 | Details Get a Quote |
| PPP2R2A (c.459+59A>C )Point Mutation in HAP1 Cell Line | EDC03583 | Human | 5520 | Details Get a Quote |
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