Ppp3ca
entrez
19055
canonical
uniprot
P63328
canonical
ensembl
ENSMUSG00000028161
resolver
ensp
ENSMUSP00000053101
resolver
ensp
ENSMUSP00000071040
resolver
genesymbol
Ppp3ca
resolver
genesymbol_syn
Calna
resolver
uniprot
B2RRX2
resolver
uniprot
P12816
resolver
uniprot
P20652
resolver
uniprot
Q3UCU1
resolver
uniprot
Q64135
resolver
uniprot_entry
PP2BA_MOUSE
resolver
uniprot_sec
B2RRX2
resolver
uniprot_sec
P12816
resolver
uniprot_sec
P20652
resolver
uniprot_sec
Q3UCU1
resolver
uniprot_sec
Q64135
resolver
activity_regulation
ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:26794871). 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:26794871). 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:26794871). 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:26794871). 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:26794871}.
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:26794871, PubMed:7791792). 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 (PubMed:15509543). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (PubMed:16735444). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (PubMed:21435446). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (PubMed:10200317). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (PubMed:19626032). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (PubMed:16286645). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (PubMed:16968888). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (PubMed:12773574). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (PubMed:26029823). Required for antigen-specific T-cell proliferation response (PubMed:8627154). 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:P63329, ECO:0000250|UniProtKB:Q08209, ECO:0000269|PubMed:10200317, ECO:0000269|PubMed:12773574, ECO:0000269|PubMed:15509543, ECO:0000269|PubMed:16286645, ECO:0000269|PubMed:16735444, ECO:0000269|PubMed:16968888, ECO:0000269|PubMed:19626032, ECO:0000269|PubMed:21435446, ECO:0000269|PubMed:26029823, ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:7791792, ECO:0000269|PubMed:8627154}.
uniprot
proteins
mass_dalton
58644
uniprot
proteins
mutagenesis
MUTAGEN 348..521; /note="Missing: Loss of catalytic activity. Loss of interaction with PPP3R1/calreticulin B and calmodulin."; /evidence="ECO:0000269|PubMed:26794871"; MUTAGEN 389..521; /note="Missing: Increases catalytic activity independently of calmodulin. Loss of interaction with calmodulin. Does not affect interaction with PPP3R1/calreticulin B."; /evidence="ECO:0000269|PubMed:26794871"; MUTAGEN 406..521; /note="Missing: Increases catalytic activity independently of calmodulin. Does not affect interaction with PPP3R1/calreticulin B and calmodulin."; /evidence="ECO:0000269|PubMed:26794871"; MUTAGEN 442..521; /note="Missing: Increases basal catalytic activity. Does not affect interaction with PPP3R1/calreticulin B and calmodulin."; /evidence="ECO:0000269|PubMed:26794871"; MUTAGEN 477; /note="D->N: Greatly reduces inhibition of calcineurin phosphatase activity."; /evidence="ECO:0000269|PubMed:7791792
uniprot
proteins
protein_family
PP-2B subfamily
uniprot
proteins
protein_family
PPP phosphatase family
uniprot
proteins
pubmed
10200317
uniprot
proteins
pubmed
11114196
uniprot
proteins
pubmed
12773574
uniprot
proteins
pubmed
12809556
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15509543
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16286645
uniprot
proteins
pubmed
16735444
uniprot
proteins
pubmed
16800626
uniprot
proteins
pubmed
16968888
uniprot
proteins
pubmed
19626032
uniprot
proteins
pubmed
20639889
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21427212
uniprot
proteins
pubmed
21435446
uniprot
proteins
pubmed
2162844
uniprot
proteins
pubmed
26029823
uniprot
proteins
pubmed
26794871
uniprot
proteins
pubmed
2848250
uniprot
proteins
pubmed
30611118
uniprot
proteins
pubmed
31696965
uniprot
proteins
pubmed
7791792
uniprot
proteins
pubmed
8077208
uniprot
proteins
pubmed
8627154
uniprot
proteins
sequence_length
521
uniprot
proteins
subcellular_location
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}.
uniprot
proteins