Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P63330 (PP2AA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

Short name=PP2A-alpha
EC=3.1.3.16
Gene names
Name:Ppp2ca
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length309 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9

Catalytic activity

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

Cofactor

Binds 1 iron ion per subunit By similarity.

Binds 1 manganese ion per subunit By similarity.

Subunit structure

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. Ref.8

Subcellular location

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. Ref.9

Post-translational modification

Reversibly methyl esterified on Leu-309. Carboxyl methylation may play a role in holoenzyme assembly, enhancing the affinity of the PP2A core enzyme for some, but not all, regulatory subunits. It varies during the cell cycle.

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.

Miscellaneous

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

Sequence similarities

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

Ontologies

Keywords
   Biological processMeiosis
   Cellular componentCentromere
Chromosome
Cytoplasm
Cytoskeleton
Nucleus
   LigandIron
Manganese
Metal-binding
   Molecular functionHydrolase
Protein phosphatase
   PTMMethylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmeiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mesoderm development

Inferred from mutant phenotype PubMed 9770493. Source: MGI

negative regulation of epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

protein dephosphorylation

Traceable author statement PubMed 9882488. Source: MGI

protein heterotrimerization

Inferred from sequence orthology PubMed 19029245. Source: MGI

regulation of cell cycle

Traceable author statement PubMed 9770493. Source: MGI

regulation of protein autophosphorylation

Inferred from sequence orthology PubMed 19029245. Source: MGI

regulation of protein catabolic process

Inferred from sequence orthology PubMed 19029245. Source: MGI

regulation of protein phosphorylation

Inferred from sequence orthology PubMed 19029245. Source: MGI

regulation of receptor activity

Inferred from sequence orthology PubMed 19029245. Source: MGI

   Cellular_componentchromosome, centromeric region

Inferred from direct assay Ref.9. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 10781942PubMed 9882488. Source: MGI

cytosol

Inferred from direct assay PubMed 12885400PubMed 23840384. Source: MGI

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 10781942. Source: MGI

protein phosphatase type 2A complex

Inferred from direct assay PubMed 16717086. Source: MGI

spindle pole

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionGABA receptor binding

Inferred from direct assay PubMed 16754670. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein C-terminus binding

Inferred from physical interaction Ref.2. Source: MGI

protein dimerization activity

Inferred from sequence orthology PubMed 19029245. Source: MGI

protein heterodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine phosphatase activity

Traceable author statement PubMed 9770493. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Igbp1Q612492EBI-397144,EBI-7002233
Ppp2r1aQ76MZ33EBI-397144,EBI-400413

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 309309Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
PRO_0000058840

Sites

Active site1181Proton donor By similarity
Metal binding571Iron By similarity
Metal binding591Iron By similarity
Metal binding851Iron By similarity
Metal binding851Manganese By similarity
Metal binding1171Manganese By similarity
Metal binding1671Manganese By similarity
Metal binding2411Manganese By similarity

Amino acid modifications

Modified residue3071Phosphotyrosine
Modified residue3091Leucine methyl ester

Experimental info

Mutagenesis3071Y → Q: Loss of trimeric subunit ABC assembly. Ref.7
Mutagenesis3091L → A: Loss of binding to PP2A B-alpha regulatory subunit. Ref.7
Sequence conflict311L → P in AAD12587. Ref.2
Sequence conflict731G → V in AAD12587. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P63330 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: 8DC11276E6DF9E33

FASTA30935,608
        10         20         30         40         50         60 
MDEKLFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG 

        70         80         90        100        110        120 
QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYRER ITILRGNHES 

       130        140        150        160        170        180 
RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI 

       190        200        210        220        230        240 
RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA 

       250        260        270        280        290        300 
HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV 


TRRTPDYFL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
[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.
[8]"Interaction of nucleoredoxin with protein phosphatase 2A."
Lechward K., Sugajska E., de Baere I., Goris J., Hemmings B.A., Zolnierowicz S.
FEBS Lett. 580:3631-3637(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_062284.1. NM_019411.4.
UniGeneMm.260288.

3D structure databases

ProteinModelPortalP63330.
SMRP63330. Positions 2-309.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202341. 17 interactions.
IntActP63330. 11 interactions.
MINTMINT-4105987.
STRING10090.ENSMUSP00000020608.

Chemistry

BindingDBP63330.

PTM databases

PhosphoSiteP63330.

Proteomic databases

PaxDbP63330.
PRIDEP63330.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020608; ENSMUSP00000020608; ENSMUSG00000020349.
GeneID19052.
KEGGmmu:19052.
UCSCuc007ivb.1. mouse.

Organism-specific databases

CTD5515.
MGIMGI:1321159. Ppp2ca.

Phylogenomic databases

eggNOGCOG0639.
GeneTreeENSGT00550000074618.
HOGENOMHOG000172696.
HOVERGENHBG000216.
InParanoidP63330.
KOK04382.
OMALMACKQL.
OrthoDBEOG74N5H2.
PhylomeDBP63330.
TreeFamTF105559.

Gene expression databases

BgeeP63330.
GenevestigatorP63330.

Family and domain databases

InterProIPR004843. Calcineurin-like_PHP_apaH.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSPR00114. STPHPHTASE.
SMARTSM00156. PP2Ac. 1 hit.
[Graphical view]
PROSITEPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP2CA. mouse.
NextBio295524.
PROP63330.
SOURCESearch...

Entry information

Entry namePP2AA_MOUSE
AccessionPrimary (citable) accession number: P63330
Secondary accession number(s): O88591, P13353, Q5SNY5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: April 16, 2014
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot