PPP1CA: Protein Phosphatase 1 Catalytic Subunit Alpha
A key serine/threonine phosphatase regulating diverse cellular processes including cell cycle, metabolism, and signal transduction.
Gene Information Card
| Symbol | PPP1CA |
|---|---|
| Full Name | Protein Phosphatase 1 Catalytic Subunit Alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 5499 ncbi.nlm.nih.gov/gene/5499 |
| Ensembl ID | ENSG00000172531 |
| UniProt ID | P62136 |
| OMIM ID | 176875 |
| HGNC ID | 9281 |
| Aliases | PP-1A, PP1A, PPP1A, PP1alpha |
Description
PPP1CA encodes the catalytic subunit alpha of protein phosphatase 1 (PP1), a ubiquitous serine/threonine phosphatase that regulates numerous cellular processes including glycogen metabolism, cell cycle progression, muscle contraction, and neuronal signaling. PP1 holoenzymes consist of a catalytic subunit (PPP1CA, PPP1CB, or PPP1CC) bound to one or more regulatory subunits that determine substrate specificity and subcellular localization.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | PPP1CA overexpression promotes dephosphorylation of key cell cycle regulators, driving proliferation | PMID: 25609812 |
| Breast cancer | Altered PPP1CA expression correlates with poor prognosis; regulates estrogen receptor signaling | PMID: 21502544 |
| Prostate cancer | PPP1CA interacts with androgen receptor to modulate transcriptional activity | PMID: 18632636 |
| Colorectal cancer | PPP1CA upregulation linked to tumor progression via Wnt/β-catenin pathway | PMID: 27058443 |
| Neurodevelopmental disorders | PPP1CA mutations (e.g., p.Asp96Tyr) impair synaptic plasticity and learning | PMID: 29276005 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | High |
| Heart | 15.2 | High |
| Liver | 12.8 | Medium |
| Kidney | 14.1 | High |
| Lung | 11.3 | Medium |
| Skeletal muscle | 16.7 | High |
| Testis | 13.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | High expression |
| HeLa | 19.8 | High expression |
| HepG2 | 17.3 | High expression |
| MCF7 | 15.6 | Medium expression |
| A549 | 14.2 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asp96Tyr | Missense | Rare | Impaired catalytic activity; associated with intellectual disability |
| p.Arg74Cys | Missense | Rare | Reduced phosphatase activity; linked to neurodevelopmental delay |
| p.Thr320Ala | Missense | Somatic (cancer) | Loss of phosphorylation site; altered cell cycle regulation |
| p.Ser199Ala | Missense | Somatic (cancer) | Disrupts regulatory subunit binding; promotes proliferation |
| c.1A>G | Start loss | Rare | Loss of protein expression; severe developmental phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Asp96Tyr, p.Arg74Cys) reduce catalytic activity, impairing dephosphorylation of substrates like CREB and DARPP-32, leading to synaptic dysfunction and neurodevelopmental disorders.
Gain of Function (GOF)
Overexpression or activating mutations (e.g., p.Thr320Ala) enhance PP1 activity, promoting dephosphorylation of tumor suppressors (e.g., Rb) and driving cell cycle progression in cancers.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg74Cys) may act dominant-negatively by forming inactive holoenzymes with regulatory subunits, reducing overall PP1 activity in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine phosphatase activity | • phosphoprotein phosphatase activity |
| • metal ion binding | • protein binding |
| • enzyme regulator activity | • cell cycle |
| • signal transduction | • glycogen metabolic process |
| • regulation of transcription by RNA polymerase II | • synaptic signaling |
Pathways
• Glycogen metabolism (Reactome: R-HSA-70221)
• Cell cycle
• mitotic (Reactome: R-HSA-69278)
• Signaling by GPCR (Reactome: R-HSA-372790)
• CREB phosphorylation (Reactome: R-HSA-111933)
• PP1 regulatory network (KEGG: hsa04150)
Protein Summary
PPP1CA encodes the 37 kDa catalytic subunit alpha of protein phosphatase 1. The protein contains a conserved PP1 catalytic domain and is ubiquitously expressed. It forms holoenzymes with over 200 regulatory subunits, targeting it to specific substrates. Key functions include dephosphorylation of glycogen phosphorylase, Rb, and DARPP-32. Post-translational modifications (e.g., phosphorylation at Thr320) regulate its activity. Mutations are linked to neurodevelopmental disorders and multiple cancers.
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