P63331 (PP2AA_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

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.
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.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Chromosome › centromere By similarity. 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. Centromeric localization requires the presence of SGOL2 By similarity.
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 By similarity. 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 By similarity.
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	Acetylation 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 electronic annotation. Source: Compara 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 Inferred from direct assay PubMed 16519540. Source: RGD protein heterotrimerization Inferred from mutant phenotype PubMed 19029245. Source: MGI regulation of protein autophosphorylation Inferred from mutant phenotype PubMed 19029245. Source: MGI regulation of protein catabolic process Inferred from mutant phenotype PubMed 19029245. Source: MGI regulation of receptor activity Inferred from mutant phenotype PubMed 19029245. Source: MGI
Cellular_component	chromosome, centromeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara protein phosphatase type 2A complex Inferred from electronic annotation. Source: Compara 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 Inferred from direct assay PubMed 16519540. Source: RGD
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_0000058843
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	4	1	N6-acetyllysine By similarity
	Modified residue	307	1	Phosphotyrosine By similarity
	Modified residue	309	1	Leucine methyl ester By similarity

Sequences

	Sequence		Length	Mass (Da)
	P63331 [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]	"Nucleotide sequence of a rat heart cDNA encoding the isotype alpha of the catalytic subunit of protein phosphatase 2A." Posas F., Arino J. Nucleic Acids Res. 17:8369-8369(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	"Molecular cloning of cDNA for the catalytic subunit of rat liver type 2A protein phosphatase, and detection of high levels of expression of the gene in normal and cancer cells." Kitagawa Y., Tahira T., Ikeda I., Kikuchi K., Tsuiki S., Sugimura T., Nagao M. Biochim. Biophys. Acta 951:123-129(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"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]. Tissue: Heart and Lung.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X16043 mRNA. Translation: CAA34166.1. X14159 mRNA. Translation: CAB42983.1. M33114 mRNA. Translation: AAA41904.1. BC070914 mRNA. Translation: AAH70914.1. BC072531 mRNA. Translation: AAH72531.1.
IPI	IPI00200391.
PIR	PART2A. S06592.
RefSeq	NP_058735.1. NM_017039.2.
UniGene	Rn.1271.
3D structure databases
ProteinModelPortal	P63331.
SMR	P63331. Positions 6-293.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-199689.
PTM databases
PhosphoSite	P63331.
2D gel databases
World-2DPAGE	0004:P63331.
Proteomic databases
PaxDb	P63331.
PRIDE	P63331.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000007621; ENSRNOP00000007621; ENSRNOG00000005389.
GeneID	24672.
KEGG	rno:24672.
UCSC	RGD:3380. rat.
Organism-specific databases
CTD	5515.
RGD	3380. Ppp2ca.
Phylogenomic databases
eggNOG	COG0639.
GeneTree	ENSGT00550000074618.
HOGENOM	HOG000172696.
HOVERGEN	HBG000216.
InParanoid	P63331.
KO	K04382.
OMA	TFNHANR.
OrthoDB	EOG4Q58PR.
Enzyme and pathway databases
Reactome	REACT_113568. Metabolism.
Gene expression databases
Genevestigator	P63331.
GermOnline	ENSRNOG00000005389. Rattus norvegicus.
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	P63331.
NextBio	295524.

Entry information

Entry name

PP2AA_RAT

Accession

Primary (citable) accession number: P63331
Secondary accession number(s): O88591, P13353

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program