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FLASH GENE
Symbol PPP3CA contributors: mct - updated : 18-05-2016
HGNC name protein phosphatase 3, catalytic subunit, alpha isozyme
HGNC id 9314
RNA
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
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumear   highly
Nervousnerve   highly
Reproductivemale systemprostate  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral   
cells
SystemCellPubmedSpeciesStageRna symbol
Skeletonosteoblast
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 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
  • HOMOLOGY
    interspecies ortholog to murine Ppp3ca
    homolog to C.elegans co2f4.2
    Homologene
    FAMILY
  • PPP family of phosphatase
  • PP-2b subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    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)
  • INTERACTION
    DNA
    RNA
    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
    REGULATION
    activated by calmodulin
    Other calcium dependent
    ASSOCIATED DISORDERS
    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
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    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