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P67774

- PP2AA_BOVIN

UniProt

P67774 - PP2AA_BOVIN

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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

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.

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. 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
Complete GO annotation...

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.

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
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 isoform
PRO_0000058838Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei307 – 3071Phosphotyrosine
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.
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.

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP67774.
SMRiP67774. Positions 2-296.

Family & Domainsi

Sequence similaritiesi

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 85 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

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