P63331 · PP2AA_RAT

  • Protein
    Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
  • Gene
    Ppp2ca
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 SV40 large T antigen and p53/TP53. 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 (By similarity).
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 (By similarity).

Catalytic activity

Cofactor

Mn2+ (UniProtKB | Rhea| CHEBI:29035 )

Note: Binds 2 manganese ions per subunit.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site57Mn2+ 1 (UniProtKB | ChEBI)
Binding site59Mn2+ 1 (UniProtKB | ChEBI)
Binding site85Mn2+ 1 (UniProtKB | ChEBI)
Binding site85Mn2+ 2 (UniProtKB | ChEBI)
Binding site117Mn2+ 2 (UniProtKB | ChEBI)
Active site118Proton donor
Binding site167Mn2+ 2 (UniProtKB | ChEBI)
Binding site241Mn2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchromosome, centromeric region
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular ComponentFAR/SIN/STRIPAK complex
Cellular Componentmembrane raft
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentprotein phosphatase type 2A complex
Cellular Componentprotein serine/threonine phosphatase complex
Cellular Componentspindle pole
Cellular Componentsynapse
Cellular Componentterminal bouton
Molecular Functionbeta-2 adrenergic receptor binding
Molecular Functionenzyme binding
Molecular FunctionGABA receptor binding
Molecular Functionidentical protein binding
Molecular Functionmetal ion binding
Molecular Functionmyosin phosphatase activity
Molecular Functionprotein antigen binding
Molecular Functionprotein domain specific binding
Molecular Functionprotein heterodimerization activity
Molecular Functionprotein kinase B binding
Molecular Functionprotein kinase binding
Molecular Functionprotein phosphatase 2A binding
Molecular Functionprotein phosphatase binding
Molecular Functionprotein serine/threonine phosphatase activity
Molecular Functionprotein tyrosine phosphatase activity
Molecular Functionprotein-containing complex binding
Molecular Functiontau protein binding
Molecular Functiontransmembrane transporter binding
Biological Processcardiac ventricle development
Biological Processcellular response to calcium ion
Biological Processcellular response to cytokine stimulus
Biological Processcellular response to ethanol
Biological Processcellular response to follicle-stimulating hormone stimulus
Biological Processcellular response to glucose stimulus
Biological Processcellular response to insulin stimulus
Biological Processcellular response to steroid hormone stimulus
Biological Processheart development
Biological Processmeiotic cell cycle
Biological Processmesoderm development
Biological Processmitotic cell cycle
Biological Processnegative regulation of epithelial to mesenchymal transition
Biological Processnegative regulation of glycolytic process through fructose-6-phosphate
Biological Processnegative regulation of hippo signaling
Biological Processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processnegative regulation of protein import into nucleus
Biological Processnegative regulation of protein phosphorylation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of microtubule binding
Biological Processpositive regulation of NLRP3 inflammasome complex assembly
Biological Processpositive regulation of protein dephosphorylation
Biological Processregulation of G1/S transition of mitotic cell cycle
Biological Processregulation of protein autophosphorylation
Biological Processregulation of protein catabolic process
Biological Processregulation of protein phosphorylation
Biological Processregulation of signaling receptor activity
Biological Processresponse to lead ion
Biological ProcessT cell homeostasis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
  • EC number
  • Short names
    PP2A-alpha

Gene names

    • Name
      Ppp2ca

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P63331
  • Secondary accessions
    • O88591
    • P13353

Proteomes

Organism-specific databases

Subcellular Location

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

Keywords

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000588431-309Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Modified residue307Phosphotyrosine
Modified residue309Leucine methyl ester

Post-translational modification

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 (By similarity).
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 (By similarity).
Polyubiquitinated, leading to its degradation by the proteasome.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with the PP2A A subunit PPP2R1A (By similarity).
Interacts (via C-terminus) with PTPA (By similarity).
Interacts with NXN; the interaction is direct (By similarity).
Interacts with KCTD20 (By similarity).
Interacts with BTBD10 (By similarity).
Interacts with SGO1 and SGO2. Interacts with TP53. Interacts with AXIN1; the interaction dephosphorylates AXIN1. Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3. Interacts with RAF1. Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination. Interacts with GSK3B (via C2 domain). Interacts with MFHAS1; retains PPP2CA into the cytoplasm and excludes it from the nucleus. Interacts with PABIR1/FAM122A. Interacts with ADCY8; interaction is phosphatase activity-dependent; antagonizes interaction between ADCY8 and calmodulin. Interacts with CRTC3 (when phosphorylated at 'Ser-391'). Interacts with SPRY2; the interaction is inhibited by TESK1 interaction with SPRY2, possibly by vesicular sequestration of SPRY2. Interacts with TRAF3IP3. Interacts with AMBRA1 (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3. Forms a complex with AMBRA1 and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (By similarity).
Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26 (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
XENO P63331ANP32A P396872EBI-7050205, EBI-359234
BINARY P63331Dpysl2 P479422EBI-7050205, EBI-917570
XENO P63331TIPRL O756633EBI-7050205, EBI-1054735

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Belongs to the PPP phosphatase family. PP-1 subfamily.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    309
  • Mass (Da)
    35,608
  • Last updated
    2004-10-11 v1
  • Checksum
    8DC11276E6DF9E33
MDEKLFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRAHQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHVTRRTPDYFL

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X16043
EMBL· GenBank· DDBJ
CAA34166.1
EMBL· GenBank· DDBJ
mRNA
X14159
EMBL· GenBank· DDBJ
CAB42983.1
EMBL· GenBank· DDBJ
mRNA
M33114
EMBL· GenBank· DDBJ
AAA41904.1
EMBL· GenBank· DDBJ
mRNA
BC070914
EMBL· GenBank· DDBJ
AAH70914.1
EMBL· GenBank· DDBJ
mRNA
BC072531
EMBL· GenBank· DDBJ
AAH72531.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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