Protein Phosphatase 3 (Calcineurin A-alpha)
| Calcineurin (PPP3CA) | |
|---|---|
| Gene | [PPP3CA](/genes/ppp3ca) |
| UniProt ID | [P26448](https://www.uniprot.org/uniprot/P26448) |
| PDB Structures | 1TCO, 2J4R, 4ORO |
| Molecular Weight | 58.7 kDa (catalytic subunit) |
| Subcellular Localization | Cytoplasm, postsynaptic terminals, [dendritic spines](/mechanisms/dendritic-spines) |
| Protein Family | Serine/threonine protein phosphatase (PP2B) |
| Function | Calcium-dependent protein phosphatase, transcription regulation |
Calcineurin Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Calcineurin is a calcium/calmodulin-dependent serine/threonine phosphatase composed of[1]:
The catalytic subunit contains:
Calcineurin is a key mediator of calcium-dependent signaling:
Calcineurin is highly expressed in:
Calcineurin activity is dysregulated in AD[3]. The enzyme contributes to tau dephosphorylation and may promote NFT formation. Altered calcineurin affects synaptic plasticity.
Calcineurin modulates dopaminergic neuron survival. Dysregulation contributes to mitochondrial dysfunction and apoptosis.
Calcineurin is activated during ischemia and contributes to excitotoxic cell death. Calcineurin inhibitors provide neuroprotection in some contexts.
Calcineurin regulates neuronal excitability. Altered phosphatase activity contributes to seizure activity.
| Drug | Target | Clinical Use |
|---|---|---|
| Cyclosporine A | Calcineurin (via cyclophilin) | Immunosuppression |
| Tacrolimus | Calcineurin (via FKBP12) | Immunosuppression |
Note: These drugs do not cross the blood-brain barrier effectively.
Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000. ↩︎
Winder DG, et al. Calcineurin as a molecular probe in synaptic plasticity. Nature. 1999. ↩︎
Abdul HM, et al. Calcineurin in Alzheimer's disease. Nat Rev Neurosci. 2006. ↩︎