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Protein

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

Gene

Ppp2ca

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 SGOL2 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 similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi57 – 571Manganese 1By similarity
Metal bindingi59 – 591Manganese 1By similarity
Metal bindingi85 – 851Manganese 1By similarity
Metal bindingi85 – 851Manganese 2By similarity
Metal bindingi117 – 1171Manganese 2By similarity
Active sitei118 – 1181Proton donorBy similarity
Metal bindingi167 – 1671Manganese 2By similarity
Metal bindingi241 – 2411Manganese 2By similarity

GO - Molecular functioni

  1. enzyme binding Source: RGD
  2. ion channel binding Source: RGD
  3. metal ion binding Source: UniProtKB-KW
  4. protein antigen binding Source: RGD
  5. protein complex binding Source: RGD
  6. protein C-terminus binding Source: RGD
  7. protein dimerization activity Source: MGI
  8. protein domain specific binding Source: RGD
  9. protein heterodimerization activity Source: UniProtKB
  10. protein kinase B binding Source: RGD
  11. protein kinase binding Source: RGD
  12. protein phosphatase 2A binding Source: RGD
  13. protein phosphatase binding Source: RGD
  14. protein serine/threonine phosphatase activity Source: RGD
  15. tau protein binding Source: RGD

GO - Biological processi

  1. cardiac ventricle development Source: RGD
  2. cellular response to calcium ion Source: RGD
  3. cellular response to cytokine stimulus Source: RGD
  4. cellular response to ethanol Source: RGD
  5. cellular response to follicle-stimulating hormone stimulus Source: RGD
  6. cellular response to glucose stimulus Source: RGD
  7. cellular response to insulin stimulus Source: RGD
  8. cellular response to steroid hormone stimulus Source: RGD
  9. heart development Source: RGD
  10. meiotic cell cycle Source: UniProtKB-KW
  11. mesoderm development Source: Ensembl
  12. negative regulation of calcium ion transmembrane transporter activity Source: RGD
  13. negative regulation of epithelial to mesenchymal transition Source: Ensembl
  14. negative regulation of protein phosphorylation Source: RGD
  15. negative regulation of transcription factor import into nucleus Source: RGD
  16. negative regulation of transcription from RNA polymerase II promoter Source: RGD
  17. positive regulation of apoptotic process Source: RGD
  18. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
  19. positive regulation of protein dephosphorylation Source: RGD
  20. positive regulation of protein phosphatase type 2A activity Source: RGD
  21. positive regulation of protein serine/threonine kinase activity Source: Ensembl
  22. protein dephosphorylation Source: RGD
  23. protein heterotrimerization Source: MGI
  24. regulation of protein autophosphorylation Source: MGI
  25. regulation of protein catabolic process Source: MGI
  26. regulation of protein phosphorylation Source: MGI
  27. regulation of receptor activity Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Meiosis

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_275313. Initiation of Nuclear Envelope Reformation.
REACT_285685. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_289020. Degradation of beta-catenin by the destruction complex.
REACT_295236. Cyclin A/B1 associated events during G2/M transition.
REACT_297490. ERK/MAPK targets.
REACT_297906. Separation of Sister Chromatids.
REACT_302790. ERKs are inactivated.
REACT_305922. CTLA4 inhibitory signaling.
REACT_306841. Integration of energy metabolism.
REACT_307725. Spry regulation of FGF signaling.
REACT_309382. S33 mutants of beta-catenin aren't phosphorylated.
REACT_309779. PP2A-mediated dephosphorylation of key metabolic factors.
REACT_313998. MASTL Facilitates Mitotic Progression.
REACT_314194. APC truncation mutants have impaired AXIN binding.
REACT_316496. Resolution of Sister Chromatid Cohesion.
REACT_318496. T41 mutants of beta-catenin aren't phosphorylated.
REACT_320469. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
REACT_320639. S45 mutants of beta-catenin aren't phosphorylated.
REACT_321501. S37 mutants of beta-catenin aren't phosphorylated.
REACT_331147. misspliced GSK3beta mutants stabilize beta-catenin.
REACT_338831. Mitotic Prometaphase.
REACT_341164. AXIN missense mutants destabilize the destruction complex.
REACT_341833. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_342181. Glycolysis.
REACT_345474. Beta-catenin phosphorylation cascade.
REACT_347117. Cyclin D associated events in G1.
REACT_348359. DARPP-32 events.
REACT_350048. truncations of AMER1 destabilize the destruction complex.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3380. Ppp2ca.

Subcellular locationi

  1. Cytoplasm By similarity
  2. Nucleus By similarity
  3. Chromosomecentromere By similarity
  4. Cytoplasmcytoskeletonspindle pole By similarity

  5. Note: In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles. Centromeric localization requires the presence of SGOL2 (By similarity).By similarity

GO - Cellular componenti

  1. chromosome, centromeric region Source: UniProtKB-SubCell
  2. cytosol Source: RGD
  3. extracellular vesicular exosome Source: Ensembl
  4. neuron projection Source: RGD
  5. nucleus Source: UniProtKB-SubCell
  6. plasma membrane Source: Ensembl
  7. postsynaptic density Source: RGD
  8. protein phosphatase type 2A complex Source: Ensembl
  9. spindle pole Source: UniProtKB-SubCell
  10. terminal bouton Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 309309Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformPRO_0000058843Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei307 – 3071PhosphotyrosineBy similarity
Modified residuei309 – 3091Leucine methyl esterBy similarity

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 (By similarity).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).By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiP63331.
PRIDEiP63331.

2D gel databases

World-2DPAGE0004:P63331.

PTM databases

PhosphoSiteiP63331.

Expressioni

Gene expression databases

GenevestigatoriP63331.

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, SGOL1 and SGOL2. 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 (By similarity). Interacts with BTBD10 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ANP32AP396872EBI-7050205,EBI-359234From a different organism.
Dpysl2P479422EBI-7050205,EBI-917570
TIPRLO756633EBI-7050205,EBI-1054735From a different organism.

Protein-protein interaction databases

BioGridi246804. 2 interactions.
IntActiP63331. 8 interactions.
MINTiMINT-199689.

Structurei

3D structure databases

ProteinModelPortaliP63331.
SMRiP63331. Positions 2-309.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0639.
GeneTreeiENSGT00550000074618.
HOGENOMiHOG000172696.
HOVERGENiHBG000216.
InParanoidiP63331.
KOiK04382.
OMAiWIENLMA.
OrthoDBiEOG74N5H2.
PhylomeDBiP63331.
TreeFamiTF105559.

Family and domain databases

Gene3Di3.60.21.10. 1 hit.
InterProiIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamiPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSiPR00114. STPHPHTASE.
SMARTiSM00156. PP2Ac. 1 hit.
[Graphical view]
SUPFAMiSSF56300. SSF56300. 1 hit.
PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P63331-1 [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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16043 mRNA. Translation: CAA34166.1.
X14159 mRNA. Translation: CAB42983.1.
M33114 mRNA. Translation: AAA41904.1.
BC070914 mRNA. Translation: AAH70914.1.
BC072531 mRNA. Translation: AAH72531.1.
PIRiS06592. PART2A.
RefSeqiNP_058735.1. NM_017039.2.
XP_008772116.1. XM_008773894.1.
UniGeneiRn.1271.

Genome annotation databases

EnsembliENSRNOT00000007621; ENSRNOP00000007621; ENSRNOG00000005389.
GeneIDi103694903.
24672.
KEGGirno:103694903.
rno:24672.
UCSCiRGD:3380. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16043 mRNA. Translation: CAA34166.1.
X14159 mRNA. Translation: CAB42983.1.
M33114 mRNA. Translation: AAA41904.1.
BC070914 mRNA. Translation: AAH70914.1.
BC072531 mRNA. Translation: AAH72531.1.
PIRiS06592. PART2A.
RefSeqiNP_058735.1. NM_017039.2.
XP_008772116.1. XM_008773894.1.
UniGeneiRn.1271.

3D structure databases

ProteinModelPortaliP63331.
SMRiP63331. Positions 2-309.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246804. 2 interactions.
IntActiP63331. 8 interactions.
MINTiMINT-199689.

PTM databases

PhosphoSiteiP63331.

2D gel databases

World-2DPAGE0004:P63331.

Proteomic databases

PaxDbiP63331.
PRIDEiP63331.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000007621; ENSRNOP00000007621; ENSRNOG00000005389.
GeneIDi103694903.
24672.
KEGGirno:103694903.
rno:24672.
UCSCiRGD:3380. rat.

Organism-specific databases

CTDi5515.
RGDi3380. Ppp2ca.

Phylogenomic databases

eggNOGiCOG0639.
GeneTreeiENSGT00550000074618.
HOGENOMiHOG000172696.
HOVERGENiHBG000216.
InParanoidiP63331.
KOiK04382.
OMAiWIENLMA.
OrthoDBiEOG74N5H2.
PhylomeDBiP63331.
TreeFamiTF105559.

Enzyme and pathway databases

ReactomeiREACT_275313. Initiation of Nuclear Envelope Reformation.
REACT_285685. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_289020. Degradation of beta-catenin by the destruction complex.
REACT_295236. Cyclin A/B1 associated events during G2/M transition.
REACT_297490. ERK/MAPK targets.
REACT_297906. Separation of Sister Chromatids.
REACT_302790. ERKs are inactivated.
REACT_305922. CTLA4 inhibitory signaling.
REACT_306841. Integration of energy metabolism.
REACT_307725. Spry regulation of FGF signaling.
REACT_309382. S33 mutants of beta-catenin aren't phosphorylated.
REACT_309779. PP2A-mediated dephosphorylation of key metabolic factors.
REACT_313998. MASTL Facilitates Mitotic Progression.
REACT_314194. APC truncation mutants have impaired AXIN binding.
REACT_316496. Resolution of Sister Chromatid Cohesion.
REACT_318496. T41 mutants of beta-catenin aren't phosphorylated.
REACT_320469. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
REACT_320639. S45 mutants of beta-catenin aren't phosphorylated.
REACT_321501. S37 mutants of beta-catenin aren't phosphorylated.
REACT_331147. misspliced GSK3beta mutants stabilize beta-catenin.
REACT_338831. Mitotic Prometaphase.
REACT_341164. AXIN missense mutants destabilize the destruction complex.
REACT_341833. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_342181. Glycolysis.
REACT_345474. Beta-catenin phosphorylation cascade.
REACT_347117. Cyclin D associated events in G1.
REACT_348359. DARPP-32 events.
REACT_350048. truncations of AMER1 destabilize the destruction complex.

Miscellaneous databases

NextBioi295524.
PROiP63331.

Gene expression databases

GenevestigatoriP63331.

Family and domain databases

Gene3Di3.60.21.10. 1 hit.
InterProiIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamiPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSiPR00114. STPHPHTASE.
SMARTiSM00156. PP2Ac. 1 hit.
[Graphical view]
SUPFAMiSSF56300. SSF56300. 1 hit.
PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Nucleotide sequence of a rat heart cDNA encoding the isotype alpha of the catalytic subunit of protein phosphatase 2A."
    Posas F., Arino J.
    Nucleic Acids Res. 17:8369-8369(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  2. "Molecular cloning of cDNA for the catalytic subunit of rat liver type 2A protein phosphatase, and detection of high levels of expression of the gene in normal and cancer cells."
    Kitagawa Y., Tahira T., Ikeda I., Kikuchi K., Tsuiki S., Sugimura T., Nagao M.
    Biochim. Biophys. Acta 951:123-129(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Heart and Lung.

Entry informationi

Entry nameiPP2AA_RAT
AccessioniPrimary (citable) accession number: P63331
Secondary accession number(s): O88591, P13353
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: April 29, 2015
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.