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MGP002392

UniProt Annotations

Entry Information
Gene Nameprotein phosphatase 2, catalytic subunit, alpha isozyme
Protein EntryPP2AA_HUMAN
UniProt IDP67775
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; Synonyms=PP2Acalpha1; IsoId=P67775-1; Sequence=Displayed; Name=2; Synonyms=PP2Acalpha2; IsoId=P67775-2; Sequence=VSP_044320; Note=Catalytically inactive, shows enhanced binding to IGBP1, and does not interact with the scaffolding subunit PPP2R1A.;
Catalytic Activity[a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate.
CofactorName=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:17055435}; Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:17055435};
FunctionPP2A 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 (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'. {ECO:0000250, ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:22613722, ECO:0000269|PubMed:9920888}.
InteractionP31749:AKT1; NbExp=5; IntAct=EBI-712311, EBI-296087; P39687:ANP32A; NbExp=2; IntAct=EBI-712311, EBI-359234; P03129:E7 (xeno); NbExp=3; IntAct=EBI-712311, EBI-866453; P04020:E7 (xeno); NbExp=2; IntAct=EBI-712311, EBI-7005254; P46695:IER3; NbExp=2; IntAct=EBI-712311, EBI-1748945; P78318:IGBP1; NbExp=10; IntAct=EBI-712311, EBI-1055954; Q61249:Igbp1 (xeno); NbExp=3; IntAct=EBI-712311, EBI-7002233; O14920:IKBKB; NbExp=3; IntAct=EBI-712311, EBI-81266; Q9Y6K9:IKBKG; NbExp=4; IntAct=EBI-712311, EBI-81279; Q969F8:KISS1R; NbExp=3; IntAct=EBI-712311, EBI-8481408; P97346:Nxn (xeno); NbExp=2; IntAct=EBI-712311, EBI-309684; P30153:PPP2R1A; NbExp=14; IntAct=EBI-712311, EBI-302388; P30154:PPP2R1B; NbExp=7; IntAct=EBI-712311, EBI-357094; Q9Y2T4:PPP2R2C; NbExp=3; IntAct=EBI-712311, EBI-1774058; Q15172:PPP2R5A; NbExp=3; IntAct=EBI-712311, EBI-641666; Q15173:PPP2R5B; NbExp=4; IntAct=EBI-712311, EBI-1369497; Q13362:PPP2R5C; NbExp=7; IntAct=EBI-712311, EBI-1266156; P28749:RBL1; NbExp=2; IntAct=EBI-712311, EBI-971402; Q08999:RBL2; NbExp=2; IntAct=EBI-712311, EBI-971439; Q04206:RELA; NbExp=6; IntAct=EBI-712311, EBI-73886; O43815:STRN; NbExp=3; IntAct=EBI-712311, EBI-1046642; O75663:TIPRL; NbExp=3; IntAct=EBI-712311, EBI-1054735; Q15645:TRIP13; NbExp=3; IntAct=EBI-712311, EBI-358993;
PtmPhosphorylation 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.
PtmReversibly 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. {ECO:0000269|PubMed:8206937}.
SimilarityBelongs to the PPP phosphatase family. PP-1 subfamily. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:16541025}. Nucleus {ECO:0000269|PubMed:16541025}. Chromosome, centromere {ECO:0000269|PubMed:16541025}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:16541025}. 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). {ECO:0000250}.
SubunitPP2A 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 (By similarity). Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity). Interacts with TP53, SGOL1 and SGOL2. Interacts with AXIN1; the interaction dephosphorylates AXIN1. Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3. Interacts with RAF1. Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination. Interacts with GSK3B (via C2 domain). {ECO:0000250, ECO:0000250|UniProtKB:P63330, ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:12473674, ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17055435, ECO:0000269|PubMed:17245430, ECO:0000269|PubMed:17485487, ECO:0000269|PubMed:18394995, ECO:0000269|PubMed:19818709, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20092282, ECO:0000269|PubMed:9647778, ECO:0000269|PubMed:9920888}.
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