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Protein

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

Gene

PPP2CA

Organism
Bos taurus (Bovine)
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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Meiosis

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_273363. Spry regulation of FGF signaling.
REACT_280353. Cyclin D associated events in G1.
REACT_281157. ERK/MAPK targets.
REACT_285394. ERKs are inactivated.
REACT_289700. Beta-catenin phosphorylation cascade.
REACT_290141. Resolution of Sister Chromatid Cohesion.
REACT_291730. Separation of Sister Chromatids.
REACT_293088. Initiation of Nuclear Envelope Reformation.
REACT_297209. Degradation of beta-catenin by the destruction complex.
REACT_301041. DARPP-32 events.
REACT_301593. PP2A-mediated dephosphorylation of key metabolic factors.
REACT_302171. Cyclin A/B1 associated events during G2/M transition.
REACT_306084. Mitotic Prometaphase.
REACT_315039. Integration of energy metabolism.
REACT_317928. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_325678. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
REACT_333435. Glycolysis.
REACT_340957. CTLA4 inhibitory signaling.
REACT_354112. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_362588. RHO GTPases Activate Formins.

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 Componenti: Chromosome 7

Subcellular locationi

GO - Cellular componenti

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_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). Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity).By similarity

Protein-protein interaction databases

BioGridi159582. 1 interaction.
IntActiP67774. 4 interactions.
MINTiMINT-203725.
STRINGi9913.ENSBTAP00000000596.

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.
OMAiWIENLMA.
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

        10         20         30         40         50
MDEKVFTKEL 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):35,594
Last modified:October 11, 2004 - v1
Checksum:iC602291F78F34555
GO

Sequence cautioni

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi159582. 1 interaction.
IntActiP67774. 4 interactions.
MINTiMINT-203725.
STRINGi9913.ENSBTAP00000000596.

Chemistry

BindingDBiP67774.
ChEMBLiCHEMBL3862.

Proteomic databases

PaxDbiP67774.
PRIDEiP67774.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5515.

Phylogenomic databases

eggNOGiCOG0639.
GeneTreeiENSGT00550000074618.
HOGENOMiHOG000172696.
HOVERGENiHBG000216.
InParanoidiP67774.
KOiK04382.
OMAiWIENLMA.
OrthoDBiEOG74N5H2.
TreeFamiTF105559.

Enzyme and pathway databases

ReactomeiREACT_273363. Spry regulation of FGF signaling.
REACT_280353. Cyclin D associated events in G1.
REACT_281157. ERK/MAPK targets.
REACT_285394. ERKs are inactivated.
REACT_289700. Beta-catenin phosphorylation cascade.
REACT_290141. Resolution of Sister Chromatid Cohesion.
REACT_291730. Separation of Sister Chromatids.
REACT_293088. Initiation of Nuclear Envelope Reformation.
REACT_297209. Degradation of beta-catenin by the destruction complex.
REACT_301041. DARPP-32 events.
REACT_301593. PP2A-mediated dephosphorylation of key metabolic factors.
REACT_302171. Cyclin A/B1 associated events during G2/M transition.
REACT_306084. Mitotic Prometaphase.
REACT_315039. Integration of energy metabolism.
REACT_317928. Inhibition of replication initiation of damaged DNA by RB1/E2F1.
REACT_325678. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
REACT_333435. Glycolysis.
REACT_340957. CTLA4 inhibitory signaling.
REACT_354112. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_362588. RHO GTPases Activate Formins.

Miscellaneous databases

NextBioi20806117.
PROiP67774.

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. 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 AT TYR-307.

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: June 24, 2015
This is version 93 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

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.