PPP2CA

This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

Protein phosphatase 2 catalytic subunit alpha

PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (PubMed:22613722).
PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (PubMed:22613722).
Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity).
Can dephosphorylate SV40 large T antigen and p53/TP53 (PubMed:17245430).
Activates RAF1 by dephosphorylating it at 'Ser-259' (PubMed:10801873).
Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758).
Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (PubMed:25438055).
Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (PubMed:30513302).

Apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Ceramide metabolic process1 PublicationNAS:UniProtKB
Meiotic cell cycleIEA:UniProtKB-KW
Mesoderm developmentIEA:Ensembl
Mitotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of cell growth1 PublicationNAS:UniProtKB
Negative regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of protein kinase B signalingManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of tyrosine phosphorylation of STAT protein1 PublicationNAS:UniProtKB
Peptidyl-serine dephosphorylationManual Assertion Based On ExperimentTAS:ARUK-UCL
Peptidyl-threonine dephosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of microtubule bindingISS:ARUK-UCL
Positive regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Protein dephosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cell adhesion1 PublicationNAS:UniProtKB
Regulation of cell differentiation1 PublicationNAS:UniProtKB
Regulation of DNA replication1 PublicationNAS:UniProtKB
Regulation of G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of growth1 PublicationNAS:UniProtKB
Regulation of microtubule binding1 PublicationNAS:ARUK-UCL
Regulation of protein phosphorylation1 PublicationNAS:ARUK-UCL
Regulation of transcription, DNA-templated1 PublicationNAS:UniProtKB
Regulation of Wnt signaling pathway1 PublicationNAS:UniProtKB
Response to lead ionISS:ARUK-UCL
Response to organic substance1 PublicationNAS:UniProtKB
RNA splicing1 PublicationNAS:UniProtKB
Second-messenger-mediated signaling1 PublicationNAS:UniProtKB

Cytoplasm
Nucleus
Chromosome, centromere
Cytoplasm, cytoskeleton, spindle pole
In prometaphase cells, but not in anaphase cells, localizes at centromeres (PubMed:16541025).
During mitosis, also found at spindle poles (PubMed:16541025).
Centromeric localization requires the presence of SGO2 (By similarity).

Neurodevelopmental disorder and language delay with or without structural brain abnormalities (NEDLBA):
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay with onset in infancy and additional variable features including hypotonia, epilepsy, brain abnormalities such as ventriculomegaly and a small corpus callosum, and autism spectrum disorder.

Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization.
Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.
Polyubiquitinated, leading to its degradation by the proteasome.