P63330 (PP2AA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Short name=PP2A-alpha
EC=3.1.3.16

Gene names

Name:

Ppp2ca

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Protein existence	Evidence 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 phosphoprotein + H2O = a protein + 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. Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination By similarity. Ref.8
Subcellular location	Cytoplasm. Nucleus By similarity. Chromosome › centromere. Cytoplasm › cytoskeleton › spindle 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 process	Meiosis
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Nucleus
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Methylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	meiosis 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: Compara positive regulation of protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara 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 receptor activity Inferred from sequence orthology PubMed 19029245. Source: MGI
Cellular_component	chromosome, centromeric region Inferred from direct assay Ref.9. Source: UniProtKB cytosol Inferred from direct assay PubMed 12885400. 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_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 309	309	Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform		PRO_0000058840
Sites
	Active site	118	1	Proton donor By similarity
	Metal binding	57	1	Iron By similarity
	Metal binding	59	1	Iron By similarity
	Metal binding	85	1	Iron By similarity
	Metal binding	85	1	Manganese By similarity
	Metal binding	117	1	Manganese By similarity
	Metal binding	167	1	Manganese By similarity
	Metal binding	241	1	Manganese By similarity
Amino acid modifications
	Modified residue	307	1	Phosphotyrosine
	Modified residue	309	1	Leucine methyl ester
Experimental info
	Mutagenesis	307	1	Y → Q: Loss of trimeric subunit ABC assembly. Ref.7
	Mutagenesis	309	1	L → A: Loss of binding to PP2A B-alpha regulatory subunit. Ref.7
	Sequence conflict	31	1	L → P in AAD12587. Ref.2
	Sequence conflict	73	1	G → V in AAD12587. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P63330 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: 8DC11276E6DF9E33	FASTA	309	35,608
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00120374.
RefSeq	NP_062284.1. NM_019411.4.
UniGene	Mm.260288.
3D structure databases
ProteinModelPortal	P63330.
SMR	P63330. Positions 6-293.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63330. 7 interactions.
STRING	10090.ENSMUSP00000020608.
PTM databases
PhosphoSite	P63330.
Proteomic databases
PaxDb	P63330.
PRIDE	P63330.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020608; ENSMUSP00000020608; ENSMUSG00000020349.
GeneID	19052.
KEGG	mmu:19052.
UCSC	uc007ivb.1. mouse.
Organism-specific databases
CTD	5515.
MGI	MGI:1321159. Ppp2ca.
Phylogenomic databases
eggNOG	COG0639.
GeneTree	ENSGT00550000074618.
HOGENOM	HOG000172696.
HOVERGEN	HBG000216.
InParanoid	P63330.
KO	K04382.
OMA	TFNHANR.
OrthoDB	EOG4Q58PR.
Gene expression databases
Bgee	P63330.
Genevestigator	P63330.
GermOnline	ENSMUSG00000020349. Mus musculus.
Family and domain databases
InterPro	IPR004843. Metallo_PEstase_dom. IPR006186. Ser/Thr-sp_prot-phosphatase. [Graphical view]
Pfam	PF00149. Metallophos. 1 hit. [Graphical view]
PRINTS	PR00114. STPHPHTASE.
SMART	SM00156. PP2Ac. 1 hit. [Graphical view]
PROSITE	PS00125. SER_THR_PHOSPHATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P63330.
ChEMBL	CHEMBL2451.
ChiTaRS	PPP2CA. mouse.
NextBio	295524.
SOURCE	Search...

Entry information

Entry name

PP2AA_MOUSE

Accession

Primary (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 3, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program