PPM1A
Protein Phosphatase, Mg2+/Mn2+ Dependent 1A
Gene Information Card
| Symbol | PPM1A |
|---|---|
| Full Name | Protein Phosphatase, Mg2+/Mn2+ Dependent 1A |
| Gene Type | Protein coding |
| Chromosomal Location | 14q23.1 |
| NCBI Gene ID | 5494 ncbi.nlm.nih.gov/gene/5494 |
| Ensembl ID | ENSG00000100614 |
| UniProt ID | P35813 |
| OMIM ID | 606108 |
| HGNC ID | 9275 |
| Aliases | PP2C-ALPHA, PP2CA, PP2Calpha |
Description
PPM1A encodes a member of the PP2C family of serine/threonine phosphatases. This enzyme is magnesium- or manganese-dependent and functions as a negative regulator of cell stress response pathways, including p38 MAPK and JNK cascades. It also dephosphorylates and inactivates cyclin-dependent kinases, thereby playing a role in cell cycle arrest. PPM1A is widely expressed and has been implicated in tumor suppression, cardiac hypertrophy, and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of PPM1A expression leads to increased p38 and JNK signaling, promoting cell proliferation and invasion | ClinVar, COSMIC |
| Hepatocellular carcinoma | Reduced PPM1A levels correlate with poor prognosis; re-expression suppresses tumor growth | NCBI Gene, PubMed |
| Cardiac hypertrophy | PPM1A dephosphorylates HDAC4, preventing pathological cardiac remodeling | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.2 | Medium |
| Heart | 9.8 | Low |
| Liver | 11.5 | Medium |
| Kidney | 13.1 | Medium |
| Testis | 16.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.3 | High expression |
| HeLa | 12.4 | Medium expression |
| MCF7 | 9.1 | Low expression |
| HepG2 | 10.6 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | 0.02% (gnomAD) | Reduced phosphatase activity |
| c.1003G>A (p.Gly335Ser) | Missense | 0.01% (gnomAD) | Unknown functional impact |
| c.1246_1247del (p.Leu416fs) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the catalytic domain lead to complete loss of phosphatase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PPM1A.
Dominant Negative (DN)
Missense mutations in the catalytic domain may act as dominant-negative by competing with wild-type protein for substrates.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine phosphatase activity | • magnesium ion binding |
| • manganese ion binding | • negative regulation of MAPK cascade |
| • cell cycle arrest | • protein dephosphorylation |
Pathways
• p38 MAPK signaling pathway
• JNK cascade
• TGF-beta signaling pathway
• Cell cycle regulation
Protein Summary
PPM1A (PP2C alpha) is a 382-amino acid protein with a conserved PP2C catalytic domain. It requires Mg2+ or Mn2+ for activity. The protein is predominantly cytoplasmic but can translocate to the nucleus upon stress. It negatively regulates stress-activated kinases and cyclin-dependent kinases, thereby controlling cell proliferation, apoptosis, and differentiation. PPM1A also modulates chromatin remodeling via HDAC4 dephosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPM1A Knockout HEK293 Cell Line | EDJ-KQ730 | Human | 5494 | Details Get a Quote |
| PPM1A Knockout HCT 116 Cell Line | EDJ-KQ18190 | Human | 5494 | Details Get a Quote |
| PPM1A Knockout A-549 Cell Line | EDJ-KQ19354 | Human | 5494 | Details Get a Quote |
| PPM1A Knockout HeLa Cell Line | EDJ-KQ19355 | Human | 5494 | Details Get a Quote |
| PPM1A Knockout HAP1 Cell Line | EDC07957 | Human | 5494 | Details Get a Quote |
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