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Protein

Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

Gene

Ppp2ca

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Activates RAF1 by dephosphorylating it at 'Ser-259' (By similarity).By similarity1 Publication

Miscellaneous

Double mutation Phe-307 and Gln-309 results in association of the PP2A C subunit with alpha-4 protein.

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Mn2+By similarityNote: Binds 2 manganese ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi57Manganese 1By similarity1
Metal bindingi59Manganese 1By similarity1
Metal bindingi85Manganese 1By similarity1
Metal bindingi85Manganese 2By similarity1
Metal bindingi117Manganese 2By similarity1
Active sitei118Proton donorBy similarity1
Metal bindingi167Manganese 2By similarity1
Metal bindingi241Manganese 2By similarity1

GO - Molecular functioni

  • GABA receptor binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • protein C-terminus binding Source: MGI
  • protein dimerization activity Source: MGI
  • protein heterodimerization activity Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processMeiosis
LigandManganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-MMU-1295596 Spry regulation of FGF signaling
R-MMU-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-MMU-180024 DARPP-32 events
R-MMU-195253 Degradation of beta-catenin by the destruction complex
R-MMU-196299 Beta-catenin phosphorylation cascade
R-MMU-198753 ERK/MAPK targets
R-MMU-202670 ERKs are inactivated
R-MMU-2467813 Separation of Sister Chromatids
R-MMU-2500257 Resolution of Sister Chromatid Cohesion
R-MMU-389513 CTLA4 inhibitory signaling
R-MMU-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-MMU-5663220 RHO GTPases Activate Formins
R-MMU-5673000 RAF activation
R-MMU-5675221 Negative regulation of MAPK pathway
R-MMU-6804757 Regulation of TP53 Degradation
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-68877 Mitotic Prometaphase
R-MMU-69231 Cyclin D associated events in G1
R-MMU-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-MMU-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (EC:3.1.3.16)
Short name:
PP2A-alpha
Gene namesi
Name:Ppp2ca
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1321159 Ppp2ca

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi307Y → Q: Loss of trimeric subunit ABC assembly. 1 Publication1
Mutagenesisi309L → A: Loss of binding to PP2A B-alpha regulatory subunit. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000588401 – 309Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformAdd BLAST309

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei307Phosphotyrosine1 Publication1
Modified residuei309Leucine methyl ester1 Publication1

Post-translational modificationi

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.1 Publication
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.1 Publication
May be monoubiquitinated by NOSIP.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP63330
MaxQBiP63330
PaxDbiP63330
PeptideAtlasiP63330
PRIDEiP63330

PTM databases

iPTMnetiP63330
PhosphoSitePlusiP63330

Expressioni

Gene expression databases

BgeeiENSMUSG00000020349
GenevisibleiP63330 MM

Interactioni

Subunit structurei

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 NXN; the interaction is direct. Interacts with TP53, SGO1 and SGO2. Interacts with AXIN1; the interaction dephosphorylates AXIN1 (By similarity). Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3 (By similarity). Interacts with RAF1. Interacts with GSK3B (via C2 domain) (By similarity). Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination (By similarity). Interacts with KCTD20 (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • GABA receptor binding Source: MGI
  • protein C-terminus binding Source: MGI
  • protein dimerization activity Source: MGI
  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi202341, 78 interactors
CORUMiP63330
IntActiP63330, 67 interactors
MINTiP63330
STRINGi10090.ENSMUSP00000020608

Structurei

3D structure databases

ProteinModelPortaliP63330
SMRiP63330
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0371 Eukaryota
COG0639 LUCA
GeneTreeiENSGT00550000074618
HOGENOMiHOG000172696
HOVERGENiHBG000216
InParanoidiP63330
KOiK04382
OMAiNKIFCPH
OrthoDBiEOG091G0B6S
PhylomeDBiP63330
TreeFamiTF105559

Family and domain databases

Gene3Di3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR006186 Ser/Thr-sp_prot-phosphatase
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit

Sequencei

Sequence statusi: Complete.

P63330-1 [UniParc]FASTAAdd to basket

« Hide

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

TRRTPDYFL
Length:309
Mass (Da):35,608
Last modified:October 11, 2004 - v1
Checksum:i8DC11276E6DF9E33
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31L → P in AAD12587 (PubMed:9920888).Curated1
Sequence conflicti73G → V in AAD12587 (PubMed:9920888).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076192 mRNA Translation: AAD12587.1
Z67745 mRNA Translation: CAA91558.1
AK076110 mRNA Translation: BAC36190.1
AK172644 mRNA Translation: BAE43111.1
AL935177 Genomic DNA No translation available.
BC003856 mRNA Translation: AAH03856.1
BC054458 mRNA Translation: AAH54458.1
CCDSiCCDS24666.1
RefSeqiNP_062284.1, NM_019411.4
UniGeneiMm.260288

Genome annotation databases

EnsembliENSMUST00000020608; ENSMUSP00000020608; ENSMUSG00000020349
GeneIDi19052
KEGGimmu:19052
UCSCiuc007ivb.1 mouse

Similar proteinsi

Entry informationi

Entry nameiPP2AA_MOUSE
AccessioniPrimary (citable) accession number: P63330
Secondary accession number(s): O88591, P13353, Q5SNY5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: May 23, 2018
This is version 133 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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