P67774 (PP2AA_BOVIN) 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

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

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. 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. 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.
Sequence similarities	Belongs to the PPP phosphatase family. PP-1 subfamily.
Sequence caution	The sequence AAA30695.1 differs from that shown. Reason: Frameshift at position 294.

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 Direct protein sequencing 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
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 phosphoprotein phosphatase activity Inferred from electronic annotation. Source: UniProtKB-KW protein heterodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB
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_0000058838
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 Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P67774 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: C602291F78F34555	FASTA	309	35,594
	10 20 30 40 50 60 MDEKVFTKEL 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]	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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X52554 mRNA. Translation: CAA36789.1. M16968 mRNA. Translation: AAA30695.1. Frameshift. X72858 mRNA. Translation: CAA51381.1. BC147979 mRNA. Translation: AAI47980.1.
IPI	IPI00708693.
PIR	A28029. S10371.
RefSeq	NP_851374.1. NM_181031.2.
UniGene	Bt.34380.
3D structure databases
ProteinModelPortal	P67774.
ModBase	Search...
Protein-protein interaction databases
IntAct	P67774. 1 interaction.
MINT	MINT-203725.
Proteomic databases
PaxDb	P67774.
PRIDE	P67774.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000000596; ENSBTAP00000000596; ENSBTAG00000000469.
GeneID	282320.
KEGG	bta:282320.
Organism-specific databases
CTD	5515.
Phylogenomic databases
eggNOG	COG0639.
GeneTree	ENSGT00550000074618.
HOGENOM	HOG000172696.
HOVERGEN	HBG000216.
InParanoid	P67774.
KO	K04382.
OMA	TFNHANR.
OrthoDB	EOG4Q58PR.
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	P67774.
ChEMBL	CHEMBL3862.
NextBio	20806117.

Entry information

Entry name

PP2AA_BOVIN

Accession

Primary (citable) accession number: P67774
Secondary accession number(s): A6QLI7, P05323, P13197

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program