FEATURES

FAMILY

DESCRIPTION

Also known as PP2BA_HUMAN, PPP3CA, CALNA, CNA. 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). Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B) (PubMed:8524402, PubMed:12218175, PubMed:12357034, PubMed:17498738, PubMed:22343722, PubMed:23468591, PubMed:27974827). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CA/calcineurin A, calcineurin B and calmodulin (By similarity). Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B (PubMed:8524402, PubMed:12218175, PubMed:12357034, PubMed:17498738, PubMed:22343722, PubMed:23468591, PubMed:27974827). Interacts (via calmodulin-binding domain) with CALM1/calmodulin; the interaction depends on calmodulin binding to Ca(2+) (PubMed:18384083, Ref.33, PubMed:19404396, PubMed:25144868). Forms a complex composed of MYOZ2 and ACTN1 (By similarity). Within the complex interacts with MYOZ2 (PubMed:11114196). Interacts with MYOZ1 (PubMed:11114196). Interacts with MYOZ3 (PubMed:11842093). Interacts with CIB1; the interaction increases upon cardiomyocyte hypertrophy (By similarity). Interacts with CHP1 and CHP2 (By similarity). Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (PubMed:15454081, PubMed:30611118). Interacts with DNM1L; the interaction dephosphorylates DNM1L and promotes its translocation to mitochondria (PubMed:18838687). Interacts with CMYA5; this interaction represses calcineurin activity in muscle (By similarity). Interacts (constitutively active form) with SYNPO2 (PubMed:17923693). Interacts with scaffold protein AKAP5 (via IAIIIT motif); the interaction recruits PPP3CA to the plasma membrane following L-type Ca(2+)-channel activation (PubMed:22343722). Interacts with NFATC2 (PubMed:26248042). Interacts with RCAN3 (PubMed:26248042). Interacts with PPIA (PubMed:12218175, PubMed:12357034). Interacts with RCAN1 (PubMed:12809556). Interacts with UNC119 (By similarity). Interacts with C16orf74 (via PxIxIT motif, when phosphorylated on 'Thr-44') (PubMed:28881575). Interacts (via N-terminus) with MAP3K14/NIK (via C-terminus and kinase domain) (By similarity). Interacts with TRAF3 (By similarity). Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558).

EXTERNAL LINKS

PPP3CA

Protein phosphatase 3 catalytic subunit alpha

PPP3CA

Molecular Synopsis