Protein: Protein phosphatase 3 catalytic subunit alpha (EC 3.1.3.16) (CAM-PRP catalytic subunit) (Calcineurin A alpha) (Calmodulin-dependent calcineurin A subunit alpha isoform) (CNA alpha) (Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform) (P63328)
Organism: Mus musculus (Mouse)
Function: Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Many of the substrates contain a PxIxIT motif and/or a LxVP motif (By similarity). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (By similarity). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (By similarity). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (By similarity). Dephosphorylates and inactivates transcription factor ELK1 (By similarity). Dephosphorylates DARPP32 (By similarity). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (By similarity). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function. Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration. Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands. Required for calcineurin activity and homosynaptic depotentiation in the hippocampus. Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation. Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation. Positively regulates osteoclast differentiation, potentially via NFATC1 signaling. May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling. Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB. Required for antigen-specific T-cell proliferation response.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:16286645, ECO:0000269|PubMed:16968888}. Cell membrane {ECO:0000250|UniProtKB:Q08209}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q08209}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P63329}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P63329}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q08209}. Note=Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle. Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation. {ECO:0000250|UniProtKB:P63329, ECO:0000250|UniProtKB:Q08209}.
Interaction partners:
- Calcineurin subunit B type 1
- Calmodulin-like protein 3
- Calmodulin 5
- Calmodulin-1
- Calmodulin-4
- Calmodulin-like protein 4
- Nuclear factor of activated T-cells, cytoplasmic 1
- Calcineurin subunit B type 2
- Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform
- Nuclear factor of activated T-cells, cytoplasmic 3
Sequence:
MSEPKAIDPKLSTTDRVVKAVPFPPSHRLTAKEVFDNDGKPRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFGNEKTQEHFTHNTVRGCSYFYSYPAVCDFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHPYWLPNFMDVFTWSLPFVGEKVTEMLVNVLNICSDDELGSEEDGFDGATAAARKEVIRNKIRAIGKMARVFSVLREESESVLTLKGLTPTGMLPSGVLSGGKQTLQSATVEAIEADEAIKGFSPQHKITSFEEAKGLDRINERMPPRRDAMPSDANLNSINKALASETNGTDSNGSNSSNIQ