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Symbol PPP3CA contributors: mct - updated : 18-05-2016
HGNC name protein phosphatase 3, catalytic subunit, alpha isozyme
HGNC id 9314
Corresponding disease
IECEE epileptic encephalopathy, infantile or early childhood
Location 4q24      Physical location : 101.944.586 - 102.268.628
Synonym name
  • protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform (calcineurin A alpha)
  • calcineurin A alpha
  • Synonym symbol(s) CALNA, CALN, CCN1, CNA1, PPP2B
    TYPE functioning gene
    STRUCTURE 324.04 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    ADH4 4q21-q24 alcohol dehydrogenase 4 (class II), pi polypeptide LOC359806 4q24 PCNA pseudogene p1PCNA ADH6 4q21-q25 alcohol dehydrogenase 6 (class V) ADH1A 4q21-q23 alcohol dehydrogenase 1A (class I), alpha polypeptide ADH1B 4q21-q23 alcohol dehydrogenase IB (class I), beta polypeptide ADH1C 4q21-q23 alcohol dehydrogenase 1C (class I), gamma polypeptide ADH7 4q23-q24 alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide DKFZP434G072 4q23 hypothetical protein DKFZp434G072 MGC27034 4q23 hypothetical protein MGC27034 MTP 4q24 microsomal triglyceride transfer protein (large polypeptide, 88kDa) LOC285556 4q23 hypothetical protein LOC285556 DAPP1 4q25-q27 dual adaptor of phosphotyrosine and 3-phosphoinositides MAP2K1IP1 4q24-q26 mitogen-activated protein kinase kinase 1 interacting protein 1 FLJ14281 4q23 hypothetical protein FLJ14281 H2AFZ 4q24 H2A histone family, member Z LOC256880 4q23 hypothetical LOC256880 LOC115265 EMCN 4q23 endomucin PPP3CA 4q21-q24 protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform (calcineurin A alpha) LOC90024 4q24 hypothetical LOC90024 BANK1 4q23 B-cell scaffold protein with ankyrin repeats 1 SLC39A8 4q22-q24 solute carrier family 39 (zinc transporter), member 8 NFKB1 4q24 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) MANBA 4q22-q25 mannosidase, beta A, lysosomal UBE2D3 4q22.2 ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast) LOC150159 4q24 CG10806-like
    TRANSCRIPTS type messenger
    text alternatively spliced transcripts (Giri, Guerini)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 4676 63 521 - 2008 17478429
    13 - 4646 - 511 - 2008 17478429
    12 - 4520 - 469 - 2008 17478429
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumear   highly
    Nervousnerve   highly
    Reproductivemale systemprostate  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • a catalytic domain followed by the DSCR1-binding region
  • a binding domain for calcineurin B subunit and for calmodulin, CaM binding region (CaMBR)
  • the C terminal autoinhibitory peptide (AID), that is 52 AAs C-terminal to the CaMBR
    interspecies ortholog to murine Ppp3ca
    homolog to C.elegans co2f4.2
  • PPP family of phosphatase
  • PP-2b subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • calmodulin dependent serine/threonine phosphatase 2B, catalytic subunit
  • involved in osteoclast regulation
  • playing a role in the calmodulin activation of calcineurin
  • regulating bone formation through an effect on osteoblast differentiation
  • may regulate the kinase activity of CDK4 in a cell cycle-dependent manner and may be an important component of the negative regulation of CDK4
  • participates in regulation of AQP2 expression, phosphorylation, and function
  • its activation is required for lytic granule exocytosis but it is not the sole Ca2+-dependent step
  • only Ca(2+)-dependent serine/threonine-specific protein phosphatase and is considered a potential regulator of many intracellular signaling events
  • is required for expression of inflammatory factors, and reveal a novel process of calcineurin-mediated activation of NFKB1
  • activation promotes apoptosis of glomerular podocytes
  • CAMK2D and PPP3CA provide likely a switch-like mechanism that controls Ca-dependent LIMK1, SSH1 and CFL1 activation, and subsequently actin cytoskeletal reorganization
  • is an important regulator of SLC6A4 activity in the adult brain
  • is a calmodulin-activated, serine/threonine phosphatase that is necessary for cardiac, vasculature, and nervous system development, as well as learning and memory, skeletal muscle growth, and immune system activation
  • affect a series of signalling pathways and exert a proapoptotic effect in cardiomyocytes
  • novel role of calcineurin in suppressing adaptive autophagy during oxidative stress by downregulating the AMPK signalling pathway
  • likely a negative feedback of cooperative action of CALM1, GAP43, and PPP3CA on P/Q and L-type channels activity
  • involved in synaptic vesicle recycling, in epilepsy and neurodevelopmental disorders, further strengthening the role of synaptic vesicle cycle dysregulation in epilepsy
  • in the brain plays an important role in synaptic transmission via regulation of the signaling response to calcium ions
    EDF1/CALM1/PPP3CA/NFATC1 pathway
    a component
  • composed of a compoment being the catalytic subunit and the b component confering calcium sensibility
  • calcineurin is a heterodimer of a 58- to 64-kDa catalytic subunit, calcineurin A (PPP3CA), and a 19-kDa regulatory subunit, calcineurin B (PPP3R1)
    small molecule metal binding,
  • Ca2+
  • protein
  • RCAN1
  • RCAN2
  • PPP3CA and PPP3CB binding to EIF2AK3 enhances inhibition of protein translation to allow the cell time to recover
  • PPP3CA may improve endothelial barrier function by interaction with PPP1R12A and activating myosin phosphatase (MP) through PPP1R12A(pThr696) dephosphorylation, thereby affecting actin polymerization and decreasing myosin phosphorylation
  • physical association of SLC6A4 with PPP3CA is promoted by PPP3CA activity
  • CALM1 binds PPP3CA regulatory domain (RD) and causes a conformational change that removes PPP3CA autoinhibitory domain (AID) from its catalytic site, activating PPP3CA
  • prolonged oxidative stress-induced activation of PPP3CA contributes to the attenuation of adaptive AMP-activated protein kinase (AMPK) signalling and inhibits autophagy in cardiomyocytes
  • lysosomal calcium signalling is linked to both PPP3CA regulation and autophagy induction, identifying the lysosome as a hub for the signalling pathways that regulate cellular homeostasis
  • lysosomal Ca2+ release through MCOLN1 activates PPP3CA, which binds and dephosphorylates &
  • 8203;TFEB, thus promoting its nuclear translocation
    cell & other
    activated by calmodulin
    Other calcium dependent
    corresponding disease(s) IECEE
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in the diabetic kidney
    Susceptibility to cardiac hypertrophy
    Variant & Polymorphism
    Candidate gene
    Therapy target
    transgenic mice overexpressing a truncated form of the murine calcineurin A-alpha catalytic subunit under the control of the CaMKII alpha promoter
  • transgenic mice expressing the calcineurin inhibitory domains of either calcineurin-binding protein 1 or A kinase-anchoring protein 79