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Overview

Uniprot IDP63331
Protein NameSerine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Gene NamePpp2ca
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
41 KAKEILTKESNVQEV

Function

Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events. PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (By similarity). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate various proteins, such as AXIN1, p53/TP53, PIM3, WEE1. Activates RAF1 by dephosphorylating it at 'Ser-259'. Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint. Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC. Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (By similarity). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome. Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway. Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (By similarity). Catalyzes dephosphorylation of PIM3, promoting PIM3 ubiquitination and proteasomal degradation. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation. Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex. The INTAC complex drives premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: within the INTAC complex, PPP2CA catalyzes dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, thereby preventing transcriptional elongation (By similarity)

Protein Sequence

10 MDEKLFTKEL 20 DQWIEQLNEC 30 KQLSESQVKS 40 LCEKAKEILT 50 KESNVQEVRC 60 PVTVCGDVHG 70 QFHDLMELFR 80 IGGKSPDTNY 90 LFMGDYVDRG 100 YYSVETVTLL 110 VALKVRYRER 120 ITILRGNHES 130 RQITQVYGFY 140 DECLRKYGNA 150 NVWKYFTDLF 160 DYLPLTALVD 170 GQIFCLHGGL 180 SPSIDTLDHI 190 RALDRLQEVP 200 HEGPMCDLLW 210 SDPDDRGGWG 220 ISPRGAGYTF 230 GQDISETFNH 240 ANGLTLVSRA 250 HQLVMEGYNW 260 CHDRNVVTIF 270 SAPNYCYRCG 280 NQAAIMELDD 290 TLKYSFLQFD 300 PAPRRGEPHV TRRTPDYFL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0000775 chromosome, centromeric region
Biological Process GO:0051321 meiotic cell cycle
Biological Process GO:0007498 mesoderm development
Biological Process GO:0000278 mitotic cell cycle
Biological Process GO:1901020 negative regulation of calcium ion transmembrane transporter activity
Biological Process GO:0090090 negative regulation of canonical Wnt signaling pathway
Biological Process GO:0010719 negative regulation of epithelial to mesenchymal transition
Biological Process GO:1904539 negative regulation of glycolytic process through fructose-6-phosphate
Biological Process GO:0035331 negative regulation of hippo signaling
Biological Process GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process GO:0042308 negative regulation of protein import into nucleus
Biological Process GO:0001933 negative regulation of protein phosphorylation
Biological Process GO:0035970 peptidyl-threonine dephosphorylation
Biological Process GO:0035306 positive regulation of dephosphorylation
Biological Process GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
Biological Process GO:1900227 positive regulation of NLRP3 inflammasome complex assembly
Biological Process GO:0006470 protein dephosphorylation
Biological Process GO:2000045 regulation of G1/S transition of mitotic cell cycle
Biological Process GO:0031113 regulation of microtubule polymerization
Biological Process GO:0031952 regulation of protein autophosphorylation
Biological Process GO:0042176 regulation of protein catabolic process
Biological Process GO:0001932 regulation of protein phosphorylation
Biological Process GO:0010469 regulation of signaling receptor activity
Biological Process GO:0034243 regulation of transcription elongation by RNA polymerase II
Biological Process GO:0010288 response to lead ion
Biological Process GO:0160240 RNA polymerase II transcription initiation surveillance
Biological Process GO:0043029 T cell homeostasis
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0090443 FAR/SIN/STRIPAK complex
Cellular Component GO:0160232 INTAC complex
Cellular Component GO:0032039 integrator complex
Cellular Component GO:0045121 membrane raft
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0000159 protein phosphatase type 2A complex
Cellular Component GO:0000922 spindle pole
Cellular Component GO:0045202 synapse
Cellular Component GO:0043195 terminal bouton
Molecular Function GO:0031698 beta-2 adrenergic receptor binding
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0050811 GABA receptor binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0046872 metal ion binding
Molecular Function GO:0004721 phosphoprotein phosphatase activity
Molecular Function GO:1990405 protein antigen binding
Molecular Function GO:0019904 protein domain specific binding
Molecular Function GO:0046982 protein heterodimerization activity
Molecular Function GO:0043422 protein kinase B binding
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0051721 protein phosphatase 2A binding
Molecular Function GO:0019903 protein phosphatase binding
Molecular Function GO:0004722 protein serine/threonine phosphatase activity
Molecular Function GO:0004725 protein tyrosine phosphatase activity
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0180006 RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity
Molecular Function GO:0180007 RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity
Molecular Function GO:0180008 RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity
Molecular Function GO:0048156 tau protein binding
Molecular Function GO:0044325 transmembrane transporter binding
Biological Process GO:0003231 cardiac ventricle development
Biological Process GO:0071277 cellular response to calcium ion
Biological Process GO:0071345 cellular response to cytokine stimulus
Biological Process GO:0071361 cellular response to ethanol
Biological Process GO:0071372 cellular response to follicle-stimulating hormone stimulus
Biological Process GO:0071333 cellular response to glucose stimulus
Biological Process GO:0032869 cellular response to insulin stimulus
Biological Process GO:0071383 cellular response to steroid hormone stimulus
Biological Process GO:0007507 heart development

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.