Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P63330

- PP2AA_MOUSE

UniProt

P63330 - PP2AA_MOUSE

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (11 Oct 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

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

    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

    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 1 Publication. Nucleus By similarity. Chromosomecentromere 1 Publication. 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.By similarity

    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

    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 isoformPRO_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.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

    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.By similarity

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

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

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti31 – 311L → P in AAD12587. (PubMed:9920888)Curated
    Sequence conflicti73 – 731G → V in AAD12587. (PubMed:9920888)Curated

    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 100 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