PPP3CA
entrez
5530
canonical
uniprot
Q08209
canonical
ensembl
ENSG00000138814
resolver
ensp
ENSP00000320580
resolver
ensp
ENSP00000378322
resolver
ensp
ENSP00000378323
resolver
genesymbol
PPP3CA
resolver
genesymbol_syn
CALNA
resolver
genesymbol_syn
CNA
resolver
hgnc
HGNC:9314
resolver
uniprot
A0A0S2Z4B5
resolver
uniprot
A0A0S2Z4C6
resolver
uniprot
A1A441
resolver
uniprot
A8K3B7
resolver
uniprot
A8W6Z7
resolver
uniprot
A8W6Z8
resolver
uniprot
B5BUA2
resolver
uniprot
Q8TAW9
resolver
uniprot_entry
A0A0S2Z4B5_HUMAN
resolver
uniprot_entry
A0A0S2Z4C6_HUMAN
resolver
uniprot_entry
PP2BA_HUMAN
resolver
uniprot_sec
A1A441
resolver
uniprot_sec
A8K3B7
resolver
uniprot_sec
A8W6Z7
resolver
uniprot_sec
A8W6Z8
resolver
uniprot_sec
B5BUA2
resolver
uniprot_sec
Q8TAW9
resolver
activity_regulation
ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). 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+). 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. 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. 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 (PubMed:26248042, PubMed:30718414). {ECO:0000250|UniProtKB:P16298, ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:30718414}.
uniprot
proteins
amino_acid_sequence
MSEPKAIDPKLSTTDRVVKAVPFPPSHRLTAKEVFDNDGKPRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFGNEKTQEHFTHNTVRGCSYFYSYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHPYWLPNFMDVFTWSLPFVGEKVTEMLVNVLNICSDDELGSEEDGFDGATAAARKEVIRNKIRAIGKMARVFSVLREESESVLTLKGLTPTGMLPSGVLSGGKQTLQSATVEAIEADEAIKGFSPQHKITSFEEAKGLDRINERMPPRRDAMPSDANLNSINKALTSETNGTDSNGSNSSNIQ
uniprot
proteins
disease_involvement
DISEASE: Epileptic encephalopathy, infantile or early childhood, 1 (IECEE1) [MIM:617711]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE1 is an autosomal dominant condition with onset of seizures between the first weeks and first years of life. {ECO:0000269|PubMed:28942967, ECO:0000269|PubMed:29432562, ECO:0000269|PubMed:30254215}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development (ACCIID) [MIM:618265]: An autosomal dominant disease characterized by moderate to severe intellectual disability, craniosynostosis, cleft palate, micrognathia, arthrogryposis, and short stature. Some patients may present bone abnormalities and generalized seizures. {ECO:0000269|PubMed:29432562}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). 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 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). 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 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679). {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:P63329, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:17502104, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827, ECO:0000269|PubMed:30254215, ECO:0000269|PubMed:30611118, ECO:0000269|PubMed:30718414, ECO:0000269|PubMed:31375679, ECO:0000269|PubMed:33691586}.
uniprot
proteins
mass_dalton
58688
uniprot
proteins
mutagenesis
MUTAGEN 288; /note="Y->F: Partial loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341."; /evidence="ECO:0000269|PubMed:26248042"; MUTAGEN 288; /note="Y->N,A: Loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341."; /evidence="ECO:0000269|PubMed:26248042"; MUTAGEN 328..332; /note="Missing: Loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341."; /evidence="ECO:0000269|PubMed:26248042"; MUTAGEN 341; /note="Y->F: Resistant to cyclosporin A-mediated inhibition. Loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with N-288, A-228 or 328-V--R-332 DEL. Partial loss in Ca(2+)-mediated transcription factor NFAT activation; when associated with F-288."; /evidence="ECO:0000269|PubMed:26248042
uniprot
proteins
protein_family
PP-2B subfamily
uniprot
proteins
protein_family
PPP phosphatase family
uniprot
proteins
pubmed
11114196
uniprot
proteins
pubmed
11842093
uniprot
proteins
pubmed
12218175
uniprot
proteins
pubmed
12357034
uniprot
proteins
pubmed
12809556
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15454081
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15671020
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17498738
uniprot
proteins
pubmed
17502104
uniprot
proteins
pubmed
17923693
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18384083
uniprot
proteins
pubmed
18838687
uniprot
proteins
pubmed
19054851
uniprot
proteins
pubmed
19154138
uniprot
proteins
pubmed
19404396
uniprot
proteins
pubmed
20590401
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21647268
uniprot
proteins
pubmed
22343722
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23468591
uniprot
proteins
pubmed
25144868
uniprot
proteins
pubmed
26248042
uniprot
proteins
pubmed
27974827
uniprot
proteins
pubmed
28881575
uniprot
proteins
pubmed
28942967
uniprot
proteins
pubmed
29043977
uniprot
proteins
pubmed
29432562
uniprot
proteins
pubmed
30254215
uniprot
proteins
pubmed
30611118
uniprot
proteins
pubmed
30718414
uniprot
proteins
pubmed
31375679
uniprot
proteins
pubmed
33691586
uniprot
proteins
pubmed
34446558
uniprot
proteins
pubmed
41224739
uniprot
proteins
pubmed
8392375
uniprot
proteins
pubmed
8524402
uniprot
proteins
sequence_length
521
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:22343722}. Cell membrane {ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:28881575}; Peripheral membrane protein {ECO:0000269|PubMed:22343722}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P63329}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P63329}. Cell projection, dendritic spine {ECO:0000269|PubMed:22343722}. Note=Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle (By similarity). Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation (PubMed:22343722). {ECO:0000250|UniProtKB:P63329, ECO:0000269|PubMed:22343722}.
uniprot
proteins