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P63330

- PP2AA_MOUSE

UniProt

P63330 - PP2AA_MOUSE

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Protein
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Gene
Ppp2ca
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.1 Publication

Catalytic activityi

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

Cofactori

Binds 2 manganese ions per subunit By similarity.

Sites

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

GO - Molecular functioni

  1. GABA receptor binding Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. protein C-terminus binding Source: MGI
  4. protein binding Source: IntAct
  5. protein dimerization activity Source: MGI
  6. protein heterodimerization activity Source: UniProtKB
  7. protein serine/threonine phosphatase activity Source: MGI
Complete GO annotation...

GO - Biological processi

  1. meiotic nuclear division Source: UniProtKB-KW
  2. mesoderm development Source: MGI
  3. negative regulation of epithelial to mesenchymal transition Source: Ensembl
  4. positive regulation of protein serine/threonine kinase activity Source: Ensembl
  5. protein dephosphorylation Source: MGI
  6. protein heterotrimerization Source: MGI
  7. regulation of cell cycle Source: MGI
  8. regulation of protein autophosphorylation Source: MGI
  9. regulation of protein catabolic process Source: MGI
  10. regulation of protein phosphorylation Source: MGI
  11. 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_196577. MASTL Facilitates Mitotic Progression.
REACT_198526. Spry regulation of FGF signaling.
REACT_198528. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
REACT_198961. Resolution of Sister Chromatid Cohesion.
REACT_203336. Degradation of beta-catenin by the destruction complex.
REACT_203795. DARPP-32 events.
REACT_206803. Cyclin A/B1 associated events during G2/M transition.
REACT_207679. Separation of Sister Chromatids.
REACT_208887. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_210064. ERKs are inactivated.
REACT_210180. Initiation of Nuclear Envelope Reformation.
REACT_215063. ERK/MAPK targets.
REACT_216784. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_217323. Integration of energy metabolism.
REACT_218396. Beta-catenin phosphorylation cascade.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:1321159. Ppp2ca.

Subcellular locationi

Cytoplasm. Nucleus By similarity. Chromosomecentromere. Cytoplasmcytoskeletonspindle pole By similarity
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 SGOL2.1 Publication

GO - Cellular componenti

  1. chromosome, centromeric region Source: UniProtKB
  2. cytoplasm Source: MGI
  3. cytosol Source: MGI
  4. nucleus Source: UniProtKB-SubCell
  5. plasma membrane Source: MGI
  6. protein phosphatase type 2A complex Source: MGI
  7. spindle pole Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi307 – 3071Y → Q: Loss of trimeric subunit ABC assembly. 1 Publication
Mutagenesisi309 – 3091L → A: Loss of binding to PP2A B-alpha regulatory subunit. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 309309Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
PRO_0000058840Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei307 – 3071Phosphotyrosine1 Publication
Modified residuei309 – 3091Leucine methyl ester1 Publication

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.
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.

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiP63330.
PaxDbiP63330.
PRIDEiP63330.

PTM databases

PhosphoSiteiP63330.

Expressioni

Gene expression databases

BgeeiP63330.
GenevestigatoriP63330.

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Igbp1Q612492EBI-397144,EBI-7002233
Ppp2r1aQ76MZ33EBI-397144,EBI-400413

Protein-protein interaction databases

BioGridi202341. 17 interactions.
IntActiP63330. 11 interactions.
MINTiMINT-4105987.
STRINGi10090.ENSMUSP00000020608.

Structurei

3D structure databases

ProteinModelPortaliP63330.
SMRiP63330. Positions 2-309.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0639.
GeneTreeiENSGT00550000074618.
HOGENOMiHOG000172696.
HOVERGENiHBG000216.
InParanoidiP63330.
KOiK04382.
OMAiQVKTLCD.
OrthoDBiEOG74N5H2.
PhylomeDBiP63330.
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.

P63330-1 [UniParc]FASTAAdd to Basket

« Hide

MDEKLFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC    50
PVTVCGDVHG QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL 100
VALKVRYRER ITILRGNHES RQITQVYGFY DECLRKYGNA NVWKYFTDLF 150
DYLPLTALVD GQIFCLHGGL SPSIDTLDHI RALDRLQEVP HEGPMCDLLW 200
SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA HQLVMEGYNW 250
CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV 300
TRRTPDYFL 309
Length:309
Mass (Da):35,608
Last modified:October 11, 2004 - v1
Checksum:i8DC11276E6DF9E33
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti31 – 311L → P in AAD12587. 1 Publication
Sequence conflicti73 – 731G → V in AAD12587. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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. Translation: CAI25806.1.
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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. Translation: CAI25806.1 .
BC003856 mRNA. Translation: AAH03856.1 .
BC054458 mRNA. Translation: AAH54458.1 .
CCDSi CCDS24666.1.
RefSeqi NP_062284.1. NM_019411.4.
UniGenei Mm.260288.

3D structure databases

ProteinModelPortali P63330.
SMRi P63330. Positions 2-309.
ModBasei Search...

Protein-protein interaction databases

BioGridi 202341. 17 interactions.
IntActi P63330. 11 interactions.
MINTi MINT-4105987.
STRINGi 10090.ENSMUSP00000020608.

Chemistry

BindingDBi P63330.

PTM databases

PhosphoSitei P63330.

Proteomic databases

MaxQBi P63330.
PaxDbi P63330.
PRIDEi P63330.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000020608 ; ENSMUSP00000020608 ; ENSMUSG00000020349 .
GeneIDi 19052.
KEGGi mmu:19052.
UCSCi uc007ivb.1. mouse.

Organism-specific databases

CTDi 5515.
MGIi MGI:1321159. Ppp2ca.

Phylogenomic databases

eggNOGi COG0639.
GeneTreei ENSGT00550000074618.
HOGENOMi HOG000172696.
HOVERGENi HBG000216.
InParanoidi P63330.
KOi K04382.
OMAi QVKTLCD.
OrthoDBi EOG74N5H2.
PhylomeDBi P63330.
TreeFami TF105559.

Enzyme and pathway databases

Reactomei REACT_196577. MASTL Facilitates Mitotic Progression.
REACT_198526. Spry regulation of FGF signaling.
REACT_198528. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
REACT_198961. Resolution of Sister Chromatid Cohesion.
REACT_203336. Degradation of beta-catenin by the destruction complex.
REACT_203795. DARPP-32 events.
REACT_206803. Cyclin A/B1 associated events during G2/M transition.
REACT_207679. Separation of Sister Chromatids.
REACT_208887. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_210064. ERKs are inactivated.
REACT_210180. Initiation of Nuclear Envelope Reformation.
REACT_215063. ERK/MAPK targets.
REACT_216784. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_217323. Integration of energy metabolism.
REACT_218396. Beta-catenin phosphorylation cascade.

Miscellaneous databases

ChiTaRSi PPP2CA. mouse.
NextBioi 295524.
PROi P63330.
SOURCEi Search...

Gene expression databases

Bgeei P63330.
Genevestigatori P63330.

Family and domain databases

Gene3Di 3.60.21.10. 1 hit.
InterProi IPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view ]
Pfami PF00149. Metallophos. 1 hit.
[Graphical view ]
PRINTSi PR00114. STPHPHTASE.
SMARTi SM00156. PP2Ac. 1 hit.
[Graphical view ]
SUPFAMi SSF56300. SSF56300. 1 hit.
PROSITEi PS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Goetz J.M., Kues W.
    Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6 X DBA/2.
    Tissue: Brain.
  2. "Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain."
    Hsu W., Zeng L., Costantini F.
    J. Biol. Chem. 274:3439-3445(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NOD.
    Tissue: Spleen.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. "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].
    Strain: C57BL/6J.
    Tissue: Eye and Mammary gland.
  6. "Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts."
    Chen J., Parsons S., Brautigan D.L.
    J. Biol. Chem. 269:7957-7962(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-307.
  7. "Mutation of Tyr307 and Leu309 in the protein phosphatase 2A catalytic subunit favors association with the alpha 4 subunit which promotes dephosphorylation of elongation factor-2."
    Chung H., Nairn A.C., Murata K., Brautigan D.L.
    Biochemistry 38:10371-10376(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-307 AND LEU-309, METHYLATION AT LEU-309.
  8. Cited for: INTERACTION WITH NXN.
  9. "Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells."
    Lee J., Kitajima T.S., Tanno Y., Yoshida K., Morita T., Miyano T., Miyake M., Watanabe Y.
    Nat. Cell Biol. 10:42-52(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiPP2AA_MOUSE
AccessioniPrimary (citable) accession number: P63330
Secondary accession number(s): O88591, P13353, Q5SNY5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: September 3, 2014
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

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi