PP2AB_MOUSE
ID PP2AB_MOUSE Reviewed; 309 AA.
AC P62715; P11082;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform;
DE Short=PP2A-beta;
DE EC=3.1.3.16 {ECO:0000250|UniProtKB:P62714};
GN Name=Ppp2cb;
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 [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 62-83.
RX PubMed=8077208; DOI=10.1016/s0021-9258(17)31686-1;
RA Becker W., Kentrup H., Klumpp S., Schultz J.E., Joost H.G.;
RT "Molecular cloning of a protein serine/threonine phosphatase containing a
RT putative regulatory tetratricopeptide repeat domain.";
RL J. Biol. Chem. 269:22586-22592(1994).
RN [4]
RP PROTEIN SEQUENCE OF 284-294, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [5]
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 [6]
RP MUTAGENESIS OF TYR-307 AND 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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, 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 [8]
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).
CC -!- FUNCTION: Catalytic subunit of protein phosphatase 2A (PP2A), a
CC serine/threonine phosphatase involved in the regulation of a wide
CC variety of enzymes, signal transduction pathways, and cellular events.
CC PP2A can modulate the activity of phosphorylase B kinase, casein kinase
CC 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.
CC {ECO:0000250|UniProtKB:P62714}.
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:0000250|UniProtKB:P62714};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630;
CC Evidence={ECO:0000250|UniProtKB:P62714};
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:P62714};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC Evidence={ECO:0000250|UniProtKB:P62714};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: PP2A consists of a common heterodimeric core enzyme (composed
CC of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant
CC regulatory subunit (PR65) (subunit A)) that associates with a variety
CC of regulatory subunits. Proteins that associate with the core dimer
CC include three families of regulatory subunits B (the R2/B/PR55/B55,
CC R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable
CC regulatory subunit, viral proteins, and cell signaling molecules. Binds
CC PPME1. May indirectly interact with SGO1, most probably through
CC regulatory B56 subunits. Found in a complex with at least ARL2, PPP2CB,
CC PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with TBCD. Interacts with
CC CTTNBP2NL. Interacts with PTPA. {ECO:0000250|UniProtKB:P62714,
CC ECO:0000250|UniProtKB:Q0P594}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Chromosome,
CC centromere {ECO:0000250}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250}. Note=In prometaphase cells, but not in anaphase cells,
CC localizes at centromeres. During mitosis, also found at spindle poles
CC (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: May be monoubiquitinated by NOSIP. {ECO:0000269|PubMed:25546391}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
CC {ECO:0000305}.
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DR EMBL; Z67746; CAA91559.1; -; mRNA.
DR EMBL; BC058582; AAH58582.1; -; mRNA.
DR CCDS; CCDS22233.1; -.
DR RefSeq; NP_059070.1; NM_017374.3.
DR AlphaFoldDB; P62715; -.
DR SMR; P62715; -.
DR BioGRID; 202342; 44.
DR IntAct; P62715; 7.
DR MINT; P62715; -.
DR STRING; 10090.ENSMUSP00000009774; -.
DR iPTMnet; P62715; -.
DR PhosphoSitePlus; P62715; -.
DR SwissPalm; P62715; -.
DR EPD; P62715; -.
DR jPOST; P62715; -.
DR MaxQB; P62715; -.
DR PaxDb; P62715; -.
DR PeptideAtlas; P62715; -.
DR PRIDE; P62715; -.
DR ProteomicsDB; 291778; -.
DR Antibodypedia; 4349; 424 antibodies from 33 providers.
DR DNASU; 19053; -.
DR Ensembl; ENSMUST00000009774; ENSMUSP00000009774; ENSMUSG00000009630.
DR GeneID; 19053; -.
DR KEGG; mmu:19053; -.
DR UCSC; uc009lkd.1; mouse.
DR CTD; 5516; -.
DR MGI; MGI:1321161; Ppp2cb.
DR VEuPathDB; HostDB:ENSMUSG00000009630; -.
DR eggNOG; KOG0371; Eukaryota.
DR GeneTree; ENSGT00550000074618; -.
DR HOGENOM; CLU_004962_0_5_1; -.
DR InParanoid; P62715; -.
DR OMA; DHINYAF; -.
DR OrthoDB; 808922at2759; -.
DR PhylomeDB; P62715; -.
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-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 BioGRID-ORCS; 19053; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Ppp2cb; mouse.
DR PRO; PR:P62715; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P62715; protein.
DR Bgee; ENSMUSG00000009630; Expressed in spermatid and 259 other tissues.
DR Genevisible; P62715; MM.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; TAS: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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IMP:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:1904528; P:positive regulation of microtubule binding; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0046677; P:response to antibiotic; IMP:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:MGI.
DR GO; GO:0010288; P:response to lead ion; ISO:MGI.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Centromere; Chromosome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Hydrolase; Manganese; 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 beta isoform"
FT /id="PRO_0000058846"
FT ACT_SITE 118
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 57
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 59
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 85
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 85
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 117
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
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:0000250|UniProtKB:P62714"
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 PP2A B-alpha regulatory
FT subunit."
FT /evidence="ECO:0000269|PubMed:10441131"
FT MUTAGEN 309
FT /note="L->Q: Loss of trimeric subunit ABC assembly."
FT /evidence="ECO:0000269|PubMed:10441131"
SQ SEQUENCE 309 AA; 35575 MW; 51DA9EB0633FC191 CRC64;
MDDKAFTKEL DQWVEQLNEC KQLNENQVRT LCEKAKEILT KESNVQEVRC PVTVCGDVHG
QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYPER ITILRGNHES
RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI
RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA
HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV
TRRTPDYFL
