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FLASH GENE
Symbol PPP2CA contributors: mct/npt/pgu - updated : 29-01-2019
HGNC name protein phosphatase 2, catalytic subunit, alpha isozyme
HGNC id 9299
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • C terminal carboxyl group methylated by carboxyl methyltransferase
    • HOMOLOGY
    Homologene
    FAMILY
  • PPP phosphatase family
  • PP-1 subfamily
    • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    basic FUNCTION
  • protein phosphatase 2A, catalytic subunit playing a pivotal role in gastrulation and neurulation in mouse
  • antagonizing CDC2/CCNB1complex which regulates the G2-M transition in the cell cycle
  • function as tumor suppressor protein, and important physiological regulator of cell growth and of cellular stress signaling
  • appears to function as an endogenous regulator of SPHK1 phosphorylation
  • interacts with epithelial tight junctions and negatively regulates the integrity of the tight junction
  • in the absence of netrin-1, recruitment of PPP2CA to UNC5B allows the activation of DAPK1 via a PPP2CA-mediated dephosphorylation and this mechanism is involved in angiogenesis regulation
  • by promoting the inflammatory capacity of T cells, catalytic subunit of PP2A (PP2Ac) dysregulation contributes to the pathogenesis of systemic lupus erythematosus (SLE)
  • is a key negative regulator of phosphatidylinositol 3-kinase/AKT pathway
  • changes in PPP2CA activity due to methylation and tyrosine phosphorylation occur in sperm and these changes may play an important role in the regulation of sperm function
  • essential enzyme that is implicated as a tumor suppressor based on its central role in phosphorylation-dependent signaling pathways
  • PPP2CA is required for the function of T(reg) cells and the prevention of autoimmunity
  • major serine/threonine protein phosphatase, participating in multiple steps of meiosis
  • regulates kinetochore-microtubule attachment during meiosis I in oocyte
  • participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction
  • has a critical role in the proliferation and metastasis of osteosarcoma cells
  • plays a major role in maintaining cellular signaling homeostasis by dephosphorylation of a variety of signaling proteins and acts as a tumor suppressor
  • critical role for membrane-initiated ER signaling in metabolic homeostasis via the central action of PPP2CA
  • may act as an oncogene in the progression of colorectal cancer
  • importance of PPP2CA in neurodevelopmental processes and brain function
    • CELLULAR PROCESS cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with a 65kDa regulatory subunit
  • catalytic subunit of the ubiquitous Ser/Thr protein phosphatase PP2A could interact with the C-ter of KISS1R
  • STRIPAK contains the PPP2CA, the striatins (STRN, STRN3, STRN4), MOB4, FAM40A and FAM40B, the cerebral cavernous malformation 3 (CCM3) protein, and members of the germinal center kinase III family of Ste20 kinases
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating with IGBP1
  • with GRM3(by Cterminal cytoplasmic tail)
  • PPP2CA involvement is a molecular mechanism for FCAR ligand binding regulation, a key step in initiating an immune response
  • IGBP1 plays a required role in regulating the assembly and maintenance of adaptive PPP2CA phosphatase complexes
  • PPP2CA inhibiting IL23A production by suppressing the expression of the IL23A gene
  • in addition to PPP2CA, IGBP1 interacts with UBR5 and PABPC1, suggesting its involvement in multiple steps in the MTOR pathway that leads to translation initiation and cell-cycle progression
  • reduction of PPP2CA activity due to an enhanced IGBP1-PPP2CA interaction contributes directly to chemical carcinogen-induced tumorigenesis
  • STRN, STRN32, STRN4 binds directly to PPP2CA and PDCD10
  • IGBP1 interacts with MID1, a microtubule-associated ubiquitin E3 ligase that appears to regulate the function of PPP2CA
  • SEMA3A elevates endothelial cell permeability through PPP2CA inactivation
  • GSK3B can inhibit PPP2CA by increasing the inhibitory L309-demethylation involving upregulation of PPME1 and inhibition of LCMT1
  • CABP4 is dephosphorylated by PPP2CA in the retina
  • NMNAT2 affects MAPT phosphorylation by regulating PPP2CA activity
  • role for MID1 in the regulation of IGBP1 that is likely to impact the stability and activity level of PPP2CA
  • IGBP1 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PPP2CA) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible UBR5
  • SIK2 attenuates the association of the PPP2CA repressor, the protein phosphatase methylesterase-1 (PPME1), thus preserving the methylation status of the PPP2CA catalytic subunit
  • in addition to recruiting PPP2CA to dephosphorylate cohesin and CDCA5, SGO1 physically shields cohesin from WAPL
  • MID1 catalyze the polyubiquitination of IGBP1, a protein regulator of protein phosphatase 2A (PPP2CA)
  • STK36 ubiquitination and cleavage is one of the key elements connecting the MID1-PPP2CA protein complex with GLI3 activity control
  • CIP2A interact with Protein phosphatase 2 (PPP2CA) to stabilize MYC and prevent its degradation
  • PPFIA1 functioned with PPP2CA to promote the dephosphorylation of KIF7, triggering KIF7 localization to the tips of primary cilia and promoting GLI transcriptional activity
  • PPME1 affects the activity of PPP2CA by demethylating PP2Ac, but also by directly binding to the phosphatase active site, suggesting loss of PPME1 in cells would enhance PPP2CA activity
  • a significant fraction of total PPP6C is associated with IGBP1, whereas a minimal fraction of total PPP2CA is associated with IGBP1
  • RAB9A, competes with the catalytic subunit PPP2CA in binding to PPP2R1A, which has an important role in controlling the PPP2CA catalytic activity, compromised in several solid tumors and leukemias
  • regulation of protein phosphatase 2A (PPP2CA) tumor suppressor function by PPME1
  • oncoprotein CIP2A is stabilized via interaction with tumor suppressor PPP2CA
  • PPP2CA regulated the stem cell factor (SCF)-induced activation of MAPK14/cofilin signaling pathway and subsequent migration of cardiac stem cells (CSCs) by interaction with MAPK14
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IDHE
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • prognostic marker in Colorectal cancer
    • Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    PPP2CA and its regulatory subunits may be a therapeutic target for Alzheimer's disease
    cancerdigestivecolon
    therapeutic target in Colorectal cancer
    cancerbone 
    its inhibition could potentially suppress the malignancy of osteosarcoma cells
    diabetetype 2 
    inhibition of hepatic PPP2CA may be a useful strategy for the treatment of insulin resistance syndrome
    ANIMAL & CELL MODELS
    double-transgenic Dom5/pR5 mice showed 7-fold increased numbers of hippocampal neurons that specifically phosphorylated the pathological S422 epitope of tau