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Symbol PPP2CA contributors: mct/npt/pgu - updated : 29-01-2019
HGNC name protein phosphatase 2, catalytic subunit, alpha isozyme
HGNC id 9299
Corresponding disease
IDHE intellectual disability, hypotonia, epilepsy
Location 5q31.1      Physical location : 133.532.148 - 133.561.950
Synonym name
  • replication protein C
  • serine/threonine-protein phosphatase 2A catalytic subunit
  • alpha isoform
  • protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform
  • replication protein C
  • Synonym symbol(s) PP2CA, PP2A-C, RP-C,PP2A-alpha, PP2A
    TYPE functioning gene
    STRUCTURE 30.01 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D5S1766 - D5S2543 - D5S1429 - D5S1947 - D5S458 - D5S808 - D5S396 - PPP2CA - HSPA4 - D5S1697 - D5S1375 - D5S1391 - D5S816 - IL9 - TGFB1 - SMAD5 - D5S393 - D5S89 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2643 35.5 309 - 2017 29066346
    7 splicing 2694 - 244 - 2017 29066346
  • PPP2ACA2
  • is overexpressed in chronic lymphocytic leukemia patients
  • can be induced following serum withdrawal
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, pregnancy
  • C terminal carboxyl group methylated by carboxyl methyltransferase
  • PPP phosphatase family
  • PP-1 subfamily
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
    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
    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
    small molecule
  • 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
  • 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)
  • CIP2A interact with Protein phosphatase 2 (PPP2CA) to stabilize MYC and prevent its degradation
  • 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
    corresponding disease(s) IDHE
    Variant & Polymorphism
    Candidate gene
  • prognostic marker in Colorectal cancer
  • Therapy target
    PPP2CA and its regulatory subunits may be a therapeutic target for Alzheimer's disease
    therapeutic target in Colorectal cancer
    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
    double-transgenic Dom5/pR5 mice showed 7-fold increased numbers of hippocampal neurons that specifically phosphorylated the pathological S422 epitope of tau