ID   PP2AA_MOUSE             Reviewed;         309 AA.
AC   P63330; O88591; P13353; Q5SNY5;
DT   11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2004, sequence version 1.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform;
DE            Short=PP2A-alpha;
DE            EC=3.1.3.16 {ECO:0000250|UniProtKB:P67775};
GN   Name=Ppp2ca;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6 X DBA/2; TISSUE=Brain;
RA   Goetz J.M., Kues W.;
RL   Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9920888; DOI=10.1074/jbc.274.6.3439;
RA   Hsu W., Zeng L., Costantini F.;
RT   "Identification of a domain of Axin that binds to the serine/threonine
RT   protein phosphatase 2A and a self-binding domain.";
RL   J. Biol. Chem. 274:3439-3445(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=NOD; TISSUE=Spleen;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Eye, and Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PHOSPHORYLATION AT TYR-307.
RX   PubMed=7510677; DOI=10.1016/s0021-9258(17)37144-2;
RA   Chen J., Parsons S., Brautigan D.L.;
RT   "Tyrosine phosphorylation of protein phosphatase 2A in response to growth
RT   stimulation and v-src transformation of fibroblasts.";
RL   J. Biol. Chem. 269:7957-7962(1994).
RN   [7]
RP   MUTAGENESIS OF TYR-307 AND LEU-309, AND METHYLATION AT LEU-309.
RX   PubMed=10441131; DOI=10.1021/bi990902g;
RA   Chung H., Nairn A.C., Murata K., Brautigan D.L.;
RT   "Mutation of Tyr307 and Leu309 in the protein phosphatase 2A catalytic
RT   subunit favors association with the alpha 4 subunit which promotes
RT   dephosphorylation of elongation factor-2.";
RL   Biochemistry 38:10371-10376(1999).
RN   [8]
RP   INTERACTION WITH NXN.
RX   PubMed=16764867; DOI=10.1016/j.febslet.2006.04.101;
RA   Lechward K., Sugajska E., de Baere I., Goris J., Hemmings B.A.,
RA   Zolnierowicz S.;
RT   "Interaction of nucleoredoxin with protein phosphatase 2A.";
RL   FEBS Lett. 580:3631-3637(2006).
RN   [9]
RP   INTERACTION WITH ADCY8.
RX   PubMed=16258073; DOI=10.1124/mol.105.018275;
RA   Crossthwaite A.J., Ciruela A., Rayner T.F., Cooper D.M.;
RT   "A direct interaction between the N terminus of adenylyl cyclase AC8 and
RT   the catalytic subunit of protein phosphatase 2A.";
RL   Mol. Pharmacol. 69:608-617(2006).
RN   [10]
RP   INTERACTION WITH BTBD10.
RX   PubMed=18160256; DOI=10.1016/j.cellsig.2007.11.004;
RA   Nawa M., Kanekura K., Hashimoto Y., Aiso S., Matsuoka M.;
RT   "A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits
RT   familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal
RT   death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB.";
RL   Cell. Signal. 20:493-505(2008).
RN   [11]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=18084284; DOI=10.1038/ncb1667;
RA   Lee J., Kitajima T.S., Tanno Y., Yoshida K., Morita T., Miyano T.,
RA   Miyake M., Watanabe Y.;
RT   "Unified mode of centromeric protection by shugoshin in mammalian oocytes
RT   and somatic cells.";
RL   Nat. Cell Biol. 10:42-52(2008).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [13]
RP   INTERACTION WITH KCTD20.
RX   PubMed=24156551; DOI=10.1186/1471-2091-14-27;
RA   Nawa M., Matsuoka M.;
RT   "KCTD20, a relative of BTBD10, is a positive regulator of Akt.";
RL   BMC Biochem. 14:27-27(2013).
RN   [14]
RP   MONUBIQUITINATION BY NOSIP.
RX   PubMed=25546391; DOI=10.1371/journal.pone.0116150;
RA   Hoffmeister M., Prelle C., Kuechler P., Kovacevic I., Moser M.,
RA   Mueller-Esterl W., Oess S.;
RT   "The ubiquitin E3 ligase NOSIP modulates protein phosphatase 2A activity in
RT   craniofacial development.";
RL   PLoS ONE 9:E116150-E116150(2014).
RN   [15]
RP   FUNCTION, AND INTERACTION WITH AMBRA1.
RX   PubMed=25438055; DOI=10.1038/ncb3072;
RA   Cianfanelli V., Fuoco C., Lorente M., Salazar M., Quondamatteo F.,
RA   Gherardini P.F., De Zio D., Nazio F., Antonioli M., D'Orazio M., Skobo T.,
RA   Bordi M., Rohde M., Dalla Valle L., Helmer-Citterich M., Gretzmeier C.,
RA   Dengjel J., Fimia G.M., Piacentini M., Di Bartolomeo S., Velasco G.,
RA   Cecconi F.;
RT   "AMBRA1 links autophagy to cell proliferation and tumorigenesis by
RT   promoting c-Myc dephosphorylation and degradation.";
RL   Nat. Cell Biol. 17:20-30(2015).
RN   [16]
RP   FUNCTION.
RX   PubMed=26974206; DOI=10.1038/ni.3390;
RA   Apostolidis S.A., Rodriguez-Rodriguez N., Suarez-Fueyo A., Dioufa N.,
RA   Ozcan E., Crispin J.C., Tsokos M.G., Tsokos G.C.;
RT   "Phosphatase PP2A is requisite for the function of regulatory T cells.";
RL   Nat. Immunol. 17:556-564(2016).
RN   [17]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=28465465; DOI=10.1084/jem.20160933;
RA   Stutz A., Kolbe C.C., Stahl R., Horvath G.L., Franklin B.S., van Ray O.,
RA   Brinkschulte R., Geyer M., Meissner F., Latz E.;
RT   "NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin
RT   domain.";
RL   J. Exp. Med. 214:1725-1736(2017).
RN   [18]
RP   INTERACTION WITH CRTC3.
RX   PubMed=30611118; DOI=10.1016/j.isci.2018.12.012;
RA   Sonntag T., Ostojic J., Vaughan J.M., Moresco J.J., Yoon Y.S.,
RA   Yates J.R. III, Montminy M.;
RT   "Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A
RT   Recruitment.";
RL   IScience 11:134-145(2018).
RN   [19]
RP   FUNCTION.
RX   PubMed=33505023; DOI=10.1038/s41586-021-03231-w;
RA   Chou W.C., Guo Z., Guo H., Chen L., Zhang G., Liang K., Xie L., Tan X.,
RA   Gibson S.A., Rampanelli E., Wang Y., Montgomery S.A., Brickey W.J.,
RA   Deng M., Freeman L., Zhang S., Su M.A., Chen X., Wan Y.Y., Ting J.P.;
RT   "AIM2 in regulatory T cells restrains autoimmune diseases.";
RL   Nature 591:300-305(2021).
CC   -!- FUNCTION: PP2A is the major phosphatase for microtubule-associated
CC       proteins (MAPs) (By similarity). PP2A can modulate the activity of
CC       phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase,
CC       and MAP-2 kinase (By similarity). Cooperates with SGO2 to protect
CC       centromeric cohesin from separase-mediated cleavage in oocytes
CC       specifically during meiosis I (PubMed:18084284). Can dephosphorylate
CC       p53/TP53 (By similarity). Activates RAF1 by dephosphorylating it at
CC       'Ser-259' (By similarity). Mediates dephosphorylation of WEE1,
CC       preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein
CC       levels, and promoting the G2/M checkpoint (By similarity). Mediates
CC       dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis:
CC       interaction with AMBRA1 enhances interaction between PPP2CA and MYC
CC       (PubMed:25438055). Mediates dephosphorylation of FOXO3; promoting its
CC       stabilization: interaction with AMBRA1 enhances interaction between
CC       PPP2CA and FOXO3 (By similarity). Catalyzes dephosphorylation of the
CC       pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome
CC       (PubMed:28465465). Together with RACK1 adapter, mediates
CC       dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and
CC       AKT-mTOR signaling pathway (PubMed:26974206, PubMed:33505023).
CC       Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg)
CC       homeostasis and stability (PubMed:33505023).
CC       {ECO:0000250|UniProtKB:P67775, ECO:0000269|PubMed:18084284,
CC       ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:26974206,
CC       ECO:0000269|PubMed:28465465, ECO:0000269|PubMed:33505023}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC         Evidence={ECO:0000269|PubMed:28465465};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630;
CC         Evidence={ECO:0000269|PubMed:28465465};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC         Evidence={ECO:0000250|UniProtKB:P67775};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC         Evidence={ECO:0000250|UniProtKB:P67775};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:P67775};
CC       Note=Binds 2 manganese ions per subunit.
CC       {ECO:0000250|UniProtKB:P67775};
CC   -!- SUBUNIT: PP2A consists of a common heterodimeric core enzyme, composed
CC       of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa
CC       constant regulatory subunit (PR65 or subunit A), that associates with a
CC       variety of regulatory subunitst (By similarity). Proteins that
CC       associate with the core dimer include three families of regulatory
CC       subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56
CC       families), the 48 kDa variable regulatory subunit, viral proteins, and
CC       cell signaling molecules (By similarity). Interacts with the PP2A A
CC       subunit PPP2R1A (By similarity). Interacts with NXN; the interaction is
CC       direct (By similarity). Interacts with KCTD20 (PubMed:24156551).
CC       Interacts with BTBD10 (PubMed:18160256). Interacts with SGO1 and SGO2
CC       (By similarity). Interacts with TP53 (By similarity). Interacts with
CC       AXIN1; the interaction dephosphorylates AXIN1 (By similarity).
CC       Interacts with PIM3; this interaction promotes dephosphorylation,
CC       ubiquitination and proteasomal degradation of PIM3 (By similarity).
CC       Interacts with RAF1 (By similarity). Interaction with IGBP1 protects
CC       unassembled PPP2CA from degradative ubiquitination (By similarity).
CC       Interacts with GSK3B (via C2 domain) (By similarity). Interacts with
CC       MFHAS1; retains PPP2CA into the cytoplasm and excludes it from the
CC       nucleus (By similarity). Interacts with PABIR1/FAM122A (By similarity).
CC       Interacts with ADCY8; interaction is phosphatase activity-dependent;
CC       antagonizes interaction between ADCY8 and calmodulin (PubMed:16258073).
CC       Interacts with CRTC3 (when phosphorylated at 'Ser-391')
CC       (PubMed:30611118). Interacts with SPRY2; the interaction is inhibited
CC       by TESK1 interaction with SPRY2, possibly by vesicular sequestration of
CC       SPRY2 (By similarity). Interacts with TRAF3IP3 (By similarity).
CC       Interacts with AMBRA1 (via PxP motifs); enhancing interaction between
CC       PPP2CA and MYC or FOXO3 (PubMed:25438055). Forms a complex with AMBRA1
CC       and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC
CC       stability via different pathways (By similarity).
CC       {ECO:0000250|UniProtKB:P67775, ECO:0000269|PubMed:16258073,
CC       ECO:0000269|PubMed:18160256, ECO:0000269|PubMed:24156551,
CC       ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:30611118}.
CC   -!- INTERACTION:
CC       P63330; Q61249: Igbp1; NbExp=2; IntAct=EBI-397144, EBI-7002233;
CC       P63330; Q76MZ3: Ppp2r1a; NbExp=3; IntAct=EBI-397144, EBI-400413;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18084284}. Nucleus
CC       {ECO:0000250|UniProtKB:P67775}. Chromosome, centromere
CC       {ECO:0000269|PubMed:18084284}. Cytoplasm, cytoskeleton, spindle pole
CC       {ECO:0000250|UniProtKB:P67775}. Note=In prometaphase cells, but not in
CC       anaphase cells, localizes at centromeres (By similarity). During
CC       mitosis, also found at spindle poles (By similarity). Centromeric
CC       localization requires the presence of SGO2 (PubMed:18084284).
CC       {ECO:0000250|UniProtKB:P67775, ECO:0000269|PubMed:18084284}.
CC   -!- PTM: Reversibly methyl esterified on Leu-309 by leucine carboxyl
CC       methyltransferase 1 (Lcmt1) and protein phosphatase methylesterase 1
CC       (Ppme1). Carboxyl methylation influences the affinity of the catalytic
CC       subunit for the different regulatory subunits, thereby modulating the
CC       PP2A holoenzyme's substrate specificity, enzyme activity and cellular
CC       localization. {ECO:0000269|PubMed:10441131}.
CC   -!- PTM: Phosphorylation of either threonine (by autophosphorylation-
CC       activated protein kinase) or tyrosine results in inactivation of the
CC       phosphatase. Auto-dephosphorylation has been suggested as a mechanism
CC       for reactivation. {ECO:0000269|PubMed:7510677}.
CC   -!- PTM: Polyubiquitinated, leading to its degradation by the proteasome
CC       (By similarity). May be monoubiquitinated by NOSIP (PubMed:25546391).
CC       {ECO:0000250|UniProtKB:P67775, ECO:0000269|PubMed:25546391}.
CC   -!- MISCELLANEOUS: Double mutation Phe-307 and Gln-309 results in
CC       association of the PP2A C subunit with alpha-4 protein.
CC   -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AF076192; AAD12587.1; -; mRNA.
DR   EMBL; Z67745; CAA91558.1; -; mRNA.
DR   EMBL; AK076110; BAC36190.1; -; mRNA.
DR   EMBL; AK172644; BAE43111.1; -; mRNA.
DR   EMBL; AL935177; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC003856; AAH03856.1; -; mRNA.
DR   EMBL; BC054458; AAH54458.1; -; mRNA.
DR   CCDS; CCDS24666.1; -.
DR   RefSeq; NP_062284.1; NM_019411.4.
DR   AlphaFoldDB; P63330; -.
DR   SMR; P63330; -.
DR   BioGRID; 202341; 115.
DR   CORUM; P63330; -.
DR   IntAct; P63330; 66.
DR   MINT; P63330; -.
DR   STRING; 10090.ENSMUSP00000020608; -.
DR   GlyGen; P63330; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P63330; -.
DR   PhosphoSitePlus; P63330; -.
DR   SwissPalm; P63330; -.
DR   EPD; P63330; -.
DR   jPOST; P63330; -.
DR   MaxQB; P63330; -.
DR   PaxDb; 10090-ENSMUSP00000020608; -.
DR   PeptideAtlas; P63330; -.
DR   ProteomicsDB; 289785; -.
DR   Pumba; P63330; -.
DR   Antibodypedia; 3550; 785 antibodies from 45 providers.
DR   DNASU; 19052; -.
DR   Ensembl; ENSMUST00000020608.3; ENSMUSP00000020608.3; ENSMUSG00000020349.5.
DR   GeneID; 19052; -.
DR   KEGG; mmu:19052; -.
DR   UCSC; uc007ivb.1; mouse.
DR   AGR; MGI:1321159; -.
DR   CTD; 5515; -.
DR   MGI; MGI:1321159; Ppp2ca.
DR   VEuPathDB; HostDB:ENSMUSG00000020349; -.
DR   eggNOG; KOG0371; Eukaryota.
DR   GeneTree; ENSGT00550000074618; -.
DR   HOGENOM; CLU_004962_0_5_1; -.
DR   InParanoid; P63330; -.
DR   OMA; CMKVRYP; -.
DR   OrthoDB; 19833at2759; -.
DR   PhylomeDB; P63330; -.
DR   TreeFam; TF105559; -.
DR   Reactome; R-MMU-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1.
DR   Reactome; R-MMU-1295596; Spry regulation of FGF signaling.
DR   Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR   Reactome; R-MMU-180024; DARPP-32 events.
DR   Reactome; R-MMU-195253; Degradation of beta-catenin by the destruction complex.
DR   Reactome; R-MMU-196299; Beta-catenin phosphorylation cascade.
DR   Reactome; R-MMU-198753; ERK/MAPK targets.
DR   Reactome; R-MMU-202670; ERKs are inactivated.
DR   Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR   Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion.
DR   Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR   Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR   Reactome; R-MMU-432142; Platelet sensitization by LDL.
DR   Reactome; R-MMU-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR   Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR   Reactome; R-MMU-5673000; RAF activation.
DR   Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR   Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-MMU-68877; Mitotic Prometaphase.
DR   Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR   Reactome; R-MMU-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR   Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation.
DR   Reactome; R-MMU-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR   Reactome; R-MMU-9833482; PKR-mediated signaling.
DR   BioGRID-ORCS; 19052; 23 hits in 77 CRISPR screens.
DR   ChiTaRS; Ppp2ca; mouse.
DR   PRO; PR:P63330; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P63330; Protein.
DR   Bgee; ENSMUSG00000020349; Expressed in medial ganglionic eminence and 259 other cell types or tissues.
DR   GO; GO:0000775; C:chromosome, centromeric region; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0000159; C:protein phosphatase type 2A complex; IDA:MGI.
DR   GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR   GO; GO:0031698; F:beta-2 adrenergic receptor binding; ISO:MGI.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR   GO; GO:0050811; F:GABA receptor binding; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:1990405; F:protein antigen binding; ISO:MGI.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR   GO; GO:0043422; F:protein kinase B binding; ISO:MGI.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR   GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; IMP:UniProtKB.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0048156; F:tau protein binding; ISO:MGI.
DR   GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR   GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0007498; P:mesoderm development; IMP:MGI.
DR   GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR   GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:MGI.
DR   GO; GO:1904539; P:negative regulation of glycolytic process through fructose-6-phosphate; IMP:MGI.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB.
DR   GO; GO:1904540; P:positive regulation of glycolytic process through fructose-6-phosphate; ISO:MGI.
DR   GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IMP:UniProtKB.
DR   GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR   GO; GO:0051726; P:regulation of cell cycle; TAS:MGI.
DR   GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR   GO; GO:0031952; P:regulation of protein autophosphorylation; ISO:MGI.
DR   GO; GO:0042176; P:regulation of protein catabolic process; ISO:MGI.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; ISO:MGI.
DR   GO; GO:0043029; P:T cell homeostasis; IMP:UniProtKB.
DR   CDD; cd07415; MPP_PP2A_PP4_PP6; 1.
DR   Gene3D; 3.60.21.10; -; 1.
DR   InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR   InterPro; IPR029052; Metallo-depent_PP-like.
DR   InterPro; IPR047129; PPA2-like.
DR   InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR   PANTHER; PTHR45619; SERINE/THREONINE-PROTEIN PHOSPHATASE PP2A-RELATED; 1.
DR   PANTHER; PTHR45619:SF42; SERINE_THREONINE-PROTEIN PHOSPHATASE 2A CATALYTIC SUBUNIT ALPHA ISOFORM; 1.
DR   Pfam; PF00149; Metallophos; 1.
DR   PRINTS; PR00114; STPHPHTASE.
DR   SMART; SM00156; PP2Ac; 1.
DR   SUPFAM; SSF56300; Metallo-dependent phosphatases; 1.
DR   PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
DR   Genevisible; P63330; MM.
PE   1: Evidence at protein level;
KW   Centromere; Chromosome; Cytoplasm; Cytoskeleton; Hydrolase; Manganese;
KW   Meiosis; Metal-binding; Methylation; Nucleus; Phosphoprotein;
KW   Protein phosphatase; Reference proteome; Ubl conjugation.
FT   CHAIN           1..309
FT                   /note="Serine/threonine-protein phosphatase 2A catalytic
FT                   subunit alpha isoform"
FT                   /id="PRO_0000058840"
FT   ACT_SITE        118
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P36873"
FT   BINDING         57
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         59
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         85
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         85
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         117
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         167
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   BINDING         241
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P67775"
FT   MOD_RES         307
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:7510677"
FT   MOD_RES         309
FT                   /note="Leucine methyl ester"
FT                   /evidence="ECO:0000269|PubMed:10441131"
FT   MUTAGEN         307
FT                   /note="Y->Q: Loss of trimeric subunit ABC assembly."
FT                   /evidence="ECO:0000269|PubMed:10441131"
FT   MUTAGEN         309
FT                   /note="L->A: Loss of binding to PP2AB-alpha regulatory
FT                   subunit."
FT                   /evidence="ECO:0000269|PubMed:10441131"
FT   CONFLICT        31
FT                   /note="L -> P (in Ref. 2; AAD12587)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        73
FT                   /note="G -> V (in Ref. 2; AAD12587)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   309 AA;  35608 MW;  8DC11276E6DF9E33 CRC64;
     MDEKLFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG
     QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYRER ITILRGNHES
     RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI
     RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA
     HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV
     TRRTPDYFL
//