Ppp3ca
entrez
24674
canonical
uniprot
P63329
canonical
ensembl
ENSRNOG00000009882
resolver
ensp
ENSRNOP00000049674
resolver
ensp
ENSRNOP00000082751
resolver
ensp
ENSRNOP00000104489
resolver
genesymbol
Ppp3ca
resolver
genesymbol_syn
Calna
resolver
uniprot
P12816
resolver
uniprot
P20652
resolver
uniprot
Q6LDJ8
resolver
uniprot
Q9WUV7
resolver
uniprot
Q9Z1I5
resolver
uniprot_entry
PP2BA_RAT
resolver
uniprot_sec
P12816
resolver
uniprot_sec
P20652
resolver
uniprot_sec
Q6LDJ8
resolver
uniprot_sec
Q9WUV7
resolver
uniprot_sec
Q9Z1I5
resolver
activity_regulation
ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:1322410, PubMed:24018048). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:1322410, PubMed:24018048). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:1322410, PubMed:24018048). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:1322410, PubMed:24018048). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By similarity). {ECO:0000250|UniProtKB:P48452, ECO:0000269|PubMed:1322410, ECO:0000269|PubMed:24018048}.
uniprot
proteins
amino_acid_sequence
MSEPKAIDPKLSTTDRVVKAVPFPPSHRLTAKEVFDNDGKPRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFGNEKTQEHFTHNTVRGCSYFYSYPAVCDFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHPYWLPNFMDVFTWSLPFVGEKVTEMLVNVLNICSDDELGSEEDGFDGATAAARKEVIRNKIRAIGKMARVFSVLREESESVLTLKGLTPTGMLPSGVLSGGKQTLQSATVEAIEADEAIKGFSPQHKITSFEEAKGLDRINERMPPRRDAMPSDANLNSINKALASETNGTDSNGSNSSNIQ
uniprot
proteins
ec_number
3.1.3.16
uniprot
proteins
function
FUNCTION: Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:1322410, PubMed:24018048). 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 (PubMed:23699505). 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 (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T-cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (By similarity). Negatively regulates SLC9A1 activity (By similarity). {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:Q08209, ECO:0000269|PubMed:1322410, ECO:0000269|PubMed:23699505, ECO:0000269|PubMed:24018048}.
uniprot
proteins
mass_dalton
58644
uniprot
proteins
protein_family
PP-2B subfamily
uniprot
proteins
protein_family
PPP phosphatase family
uniprot
proteins
pubmed
10593895
uniprot
proteins
pubmed
11114196
uniprot
proteins
pubmed
1322410
uniprot
proteins
pubmed
1335233
uniprot
proteins
pubmed
18815128
uniprot
proteins
pubmed
2174876
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
23699505
uniprot
proteins
pubmed
24018048
uniprot
proteins
pubmed
2551293
uniprot
proteins
sequence_length
521
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q08209}. Cell membrane {ECO:0000250|UniProtKB:Q08209}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q08209}. Cell membrane, sarcolemma {ECO:0000269|PubMed:11114196}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:11114196}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q08209}. Note=Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle (PubMed:11114196). Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation (By similarity). {ECO:0000250|UniProtKB:Q08209, ECO:0000269|PubMed:11114196}.
uniprot
proteins