| Full Name | Protein Phosphatase, Mg2+/Mn2+ Dependent 1A |
|---|---|
| Gene Symbol | PPM1A |
| Chromosome | 14q23.1 |
| NCBI Gene ID | [5494](https://www.ncbi.nlm.nih.gov/gene/5494) |
| OMIM | [605663](https://omim.org/entry/605663) |
| Ensembl | [ENSG00000163209](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000163209) |
| UniProt | [P35813](https://www.uniprot.org/uniprot/P35813) |
| Encoded Protein | [PP2Cα protein](/proteins/ppm1a-protein) |
| Associated Diseases | Alzheimer's disease, Cancer, Cardiovascular disease |
PPM1A (Protein Phosphatase, Mg2+/Mn2+ Dependent 1A), also known as PP2Cα, encodes a member of the PPM family of serine/threonine protein phosphatases.[1] PPM1A plays critical roles in tau dephosphorylation, TGF-β signaling termination, and cellular stress responses.[2] In neurodegeneration, PPM1A activity is neuroprotective through its ability to counteract pathogenic tau hyperphosphorylation and modulate neuroinflammatory signaling pathways.
The PPM1A gene spans approximately 35 kb on chromosome 14q23.1 and contains 8 exons.[3] The encoded 382-amino acid protein:
Expression in the nervous system: PPM1A is ubiquitously expressed with high levels in brain, particularly in hippocampus, cortex, and cerebellum.[4] Neuronal expression is developmentally regulated, increasing with maturation.
PPM1A directly dephosphorylates tau protein:[5]
PPM1A dephosphorylates SMAD proteins:[6]
PPM1A inactivates MAPK pathway components:[7]
PPM1A modulates metabolic signaling:[8]
PPM1A dysfunction in AD:[9]
PPM1A relevance to other tauopathies:[10]
PPM1A acts as tumor suppressor:[11]
| Tissue | Expression Level | Notes |
|---|---|---|
| Hippocampus | High | Tau regulation, memory |
| Cerebral cortex | High | Cognitive function |
| Cerebellum | Moderate | Motor coordination |
| Brain microvasculature | Moderate | Endothelial function |
| Immune cells | Moderate | Inflammatory regulation |
| Variant | dbSNP | Effect | Clinical Relevance |
|---|---|---|---|
| rs2280729 | NCBI | Intronic | Expression quantitative trait locus |
| rs12462007 | NCBI | Intronic | Potential AD modifier |
| rs11623846 | NCBI | 5' UTR | Gene expression regulation |
Strategies to enhance PPM1A activity:[12]
Lammers T, Lavi S. Role of type 2C protein phosphatases in growth regulation. Oncogene. 2007. ↩︎
Numata T, et al. PPM1A in cellular stress responses. Biochim Biophys Acta. 2017. ↩︎
Travis SM, Welsh MJ. PPM1A gene structure and regulation. Genomics. 1997. ↩︎
Chen H, et al. PPM1A expression in brain regions. J Neurochem. 2018. ↩︎
Wang X, et al. PPM1A dephosphorylates tau protein. J Neurochem. 2018. ↩︎
Lin X, et al. PPM1A as a SMAD phosphatase. Cell. 2006. ↩︎
Takekawa M, et al. PPM1A inactivation of p38 and JNK. EMBO J. 1998. ↩︎
Garcia D, Shaw RJ. AMPK and PPM1A in metabolic regulation. Mol Cell. 2017. ↩︎
Wang AC, et al. PPM1A dysfunction in Alzheimer's disease. Neurobiol Aging. 2019. ↩︎
Liu SJ, et al. PPM1A and tauopathy pathology. Brain Res. 2016. ↩︎
Ofek P, et al. PPM1A as a tumor suppressor. Cell Cycle. 2011. ↩︎
Yang Y, et al. PPM1A activators as therapeutic candidates. J Med Chem. 2020. ↩︎