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P67774

- PP2AA_BOVIN

UniProt

P67774 - PP2AA_BOVIN

Protein

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

Gene

PPP2CA

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 86 (01 Oct 2014)
      Sequence version 1 (11 Oct 2004)
      Previous versions | rss
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    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. metal ion binding Source: UniProtKB-KW
    2. phosphoprotein phosphatase activity Source: UniProtKB-KW
    3. protein heterodimerization activity Source: UniProtKB

    GO - Biological processi

    1. meiotic nuclear division Source: UniProtKB-KW
    2. mesoderm development Source: Ensembl
    3. negative regulation of epithelial to mesenchymal transition Source: Ensembl
    4. positive regulation of protein serine/threonine kinase activity Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Meiosis

    Keywords - Ligandi

    Manganese, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_202853. Spry regulation of FGF signaling.
    REACT_203739. Degradation of beta-catenin by the destruction complex.
    REACT_205490. DARPP-32 events.
    REACT_209545. Resolution of Sister Chromatid Cohesion.
    REACT_209873. disassembly of the destruction complex and recruitment of AXIN to the membrane.
    REACT_212572. PP2A-mediated dephosphorylation of key metabolic factors.
    REACT_212887. Separation of Sister Chromatids.
    REACT_213811. CTLA4 inhibitory signaling.
    REACT_217101. Integration of energy metabolism.
    REACT_217581. Beta-catenin phosphorylation cascade.
    REACT_218138. Cyclin D associated events in G1.
    REACT_220398. ERKs are inactivated.
    REACT_223514. Initiation of Nuclear Envelope Reformation.
    REACT_224007. Cyclin A/B1 associated events during G2/M transition.
    REACT_224187. Glycolysis.
    REACT_224304. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
    REACT_225310. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
    REACT_226850. ERK/MAPK targets.

    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
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 7

    Subcellular locationi

    Cytoplasm. Nucleus By similarity. Chromosomecentromere By similarity. Cytoplasmcytoskeletonspindle pole By similarity
    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: Ensembl
    3. nucleus Source: UniProtKB-SubCell
    4. plasma membrane Source: Ensembl
    5. protein phosphatase type 2A complex Source: Ensembl
    6. spindle pole Source: UniProtKB-SubCell

    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_0000058838Add
    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
    The N-terminus is blocked.

    Keywords - PTMi

    Methylation, Phosphoprotein

    Proteomic databases

    PaxDbiP67774.
    PRIDEiP67774.

    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

    Protein-protein interaction databases

    BioGridi159582. 1 interaction.
    IntActiP67774. 4 interactions.
    MINTiMINT-203725.

    Structurei

    3D structure databases

    ProteinModelPortaliP67774.
    SMRiP67774. Positions 2-296.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG0639.
    GeneTreeiENSGT00550000074618.
    HOGENOMiHOG000172696.
    HOVERGENiHBG000216.
    InParanoidiP67774.
    KOiK04382.
    OMAiQVKTLCD.
    OrthoDBiEOG74N5H2.
    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.

    P67774-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDEKVFTKEL 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):35,594
    Last modified:October 11, 2004 - v1
    Checksum:iC602291F78F34555
    GO

    Sequence cautioni

    The sequence AAA30695.1 differs from that shown. Reason: Frameshift at position 294.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X52554 mRNA. Translation: CAA36789.1.
    M16968 mRNA. Translation: AAA30695.1. Frameshift.
    X72858 mRNA. Translation: CAA51381.1.
    BC147979 mRNA. Translation: AAI47980.1.
    PIRiA28029.
    S10371.
    RefSeqiNP_851374.1. NM_181031.2.
    UniGeneiBt.34380.

    Genome annotation databases

    EnsembliENSBTAT00000000596; ENSBTAP00000000596; ENSBTAG00000000469.
    GeneIDi282320.
    KEGGibta:282320.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X52554 mRNA. Translation: CAA36789.1 .
    M16968 mRNA. Translation: AAA30695.1 . Frameshift.
    X72858 mRNA. Translation: CAA51381.1 .
    BC147979 mRNA. Translation: AAI47980.1 .
    PIRi A28029.
    S10371.
    RefSeqi NP_851374.1. NM_181031.2.
    UniGenei Bt.34380.

    3D structure databases

    ProteinModelPortali P67774.
    SMRi P67774. Positions 2-296.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 159582. 1 interaction.
    IntActi P67774. 4 interactions.
    MINTi MINT-203725.

    Chemistry

    BindingDBi P67774.
    ChEMBLi CHEMBL3862.

    Proteomic databases

    PaxDbi P67774.
    PRIDEi P67774.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000000596 ; ENSBTAP00000000596 ; ENSBTAG00000000469 .
    GeneIDi 282320.
    KEGGi bta:282320.

    Organism-specific databases

    CTDi 5515.

    Phylogenomic databases

    eggNOGi COG0639.
    GeneTreei ENSGT00550000074618.
    HOGENOMi HOG000172696.
    HOVERGENi HBG000216.
    InParanoidi P67774.
    KOi K04382.
    OMAi QVKTLCD.
    OrthoDBi EOG74N5H2.
    TreeFami TF105559.

    Enzyme and pathway databases

    Reactomei REACT_202853. Spry regulation of FGF signaling.
    REACT_203739. Degradation of beta-catenin by the destruction complex.
    REACT_205490. DARPP-32 events.
    REACT_209545. Resolution of Sister Chromatid Cohesion.
    REACT_209873. disassembly of the destruction complex and recruitment of AXIN to the membrane.
    REACT_212572. PP2A-mediated dephosphorylation of key metabolic factors.
    REACT_212887. Separation of Sister Chromatids.
    REACT_213811. CTLA4 inhibitory signaling.
    REACT_217101. Integration of energy metabolism.
    REACT_217581. Beta-catenin phosphorylation cascade.
    REACT_218138. Cyclin D associated events in G1.
    REACT_220398. ERKs are inactivated.
    REACT_223514. Initiation of Nuclear Envelope Reformation.
    REACT_224007. Cyclin A/B1 associated events during G2/M transition.
    REACT_224187. Glycolysis.
    REACT_224304. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
    REACT_225310. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
    REACT_226850. ERK/MAPK targets.

    Miscellaneous databases

    NextBioi 20806117.

    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. Tang P.M., de Paoli-Roach A.A.
      Submitted (MAR-1990) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Aortic smooth muscle.
    2. "Molecular cloning and sequence analysis of the catalytic subunit of bovine type 2A protein phosphatase."
      Green D.D., Yang S.-I., Mumby M.C.
      Proc. Natl. Acad. Sci. U.S.A. 84:4880-4884(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Chen S., Boynton A.
      Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    4. NIH - Mammalian Gene Collection (MGC) project
      Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Hereford.
      Tissue: Fetal muscle.
    5. "Protein phosphatase 2A catalytic subunit is methyl-esterified at its carboxyl terminus by a novel methyltransferase."
      Lee J., Stock J.
      J. Biol. Chem. 268:19192-19195(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 42-48 AND 284-308, METHYLATION AT LEU-309.
      Tissue: Brain.
    6. "Autophosphorylation-activated protein kinase phosphorylates and inactivates protein phosphatase 2A."
      Guo H., Damuni Z.
      Proc. Natl. Acad. Sci. U.S.A. 90:2500-2504(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION.

    Entry informationi

    Entry nameiPP2AA_BOVIN
    AccessioniPrimary (citable) accession number: P67774
    Secondary accession number(s): A6QLI7, P05323, P13197
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 11, 2004
    Last sequence update: October 11, 2004
    Last modified: October 1, 2014
    This is version 86 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, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3