2A5B_HUMAN
ID 2A5B_HUMAN Reviewed; 497 AA.
AC Q15173; Q13853;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform;
DE AltName: Full=PP2A B subunit isoform B'-beta;
DE AltName: Full=PP2A B subunit isoform B56-beta;
DE AltName: Full=PP2A B subunit isoform PR61-beta;
DE AltName: Full=PP2A B subunit isoform R5-beta;
GN Name=PPP2R5B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1).
RC TISSUE=Fetal brain;
RX PubMed=7592815; DOI=10.1074/jbc.270.44.26123;
RA McCright B., Virshup D.M.;
RT "Identification of a new family of protein phosphatase 2A regulatory
RT subunits.";
RL J. Biol. Chem. 270:26123-26128(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Brain;
RX PubMed=8694763; DOI=10.1042/bj3170187;
RA Zolnierowicz S., van Hoof C., Andjelkovic N., Cron P., Stevens I.,
RA Merlevede W., Goris J., Hemmings B.A.;
RT "The variable subunit associated with protein phosphatase 2A0 defines a
RT novel multimember family of regulatory subunits.";
RL Biochem. J. 317:187-194(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-1).
RC TISSUE=Brain;
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 [4]
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=8703017; DOI=10.1074/jbc.271.36.22081;
RA McCright B., Rivers A.M., Audlin S., Virshup D.M.;
RT "The B56 family of protein phosphatase 2A (PP2A) regulatory subunits
RT encodes differentiation-induced phosphoproteins that target PP2A to both
RT nucleus and cytoplasm.";
RL J. Biol. Chem. 271:22081-22089(1996).
RN [5]
RP INTERACTION WITH SGO1.
RX PubMed=16541025; DOI=10.1038/nature04663;
RA Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T.,
RA Kawashima S.A., Watanabe Y.;
RT "Shugoshin collaborates with protein phosphatase 2A to protect cohesin.";
RL Nature 441:46-52(2006).
RN [6]
RP FUNCTION, PHOSPHORYLATION AT SER-32; SER-35; SER-44; SER-46; SER-47 AND
RP SER-48, AND INTERACTION WITH AKT1.
RX PubMed=21329884; DOI=10.1016/j.molcel.2011.02.007;
RA Rodgers J.T., Vogel R.O., Puigserver P.;
RT "Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A
RT phosphatase holoenzyme complex on Akt.";
RL Mol. Cell 41:471-479(2011).
RN [7]
RP INTERACTION WITH CUL3 AND KLHL15, IDENTIFICATION IN PP2A COMPLEX,
RP UBIQUITINATION, AND MUTAGENESIS OF TYR-52; 103-LYS-ARG-104 AND
RP 232-ARG-LYS-233.
RX PubMed=23135275; DOI=10.1074/jbc.m112.420281;
RA Oberg E.A., Nifoussi S.K., Gingras A.C., Strack S.;
RT "Selective proteasomal degradation of the B'beta subunit of protein
RT phosphatase 2A by the E3 ubiquitin ligase adaptor Kelch-like 15.";
RL J. Biol. Chem. 287:43378-43389(2012).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: As the regulatory component of the serine/threonine-protein
CC phosphatase 2A (PP2A) holoenzyme, modulates substrate specificity,
CC subcellular localization, and responsiveness to phosphorylation. The
CC phosphorylated form mediates the interaction between PP2A and AKT1,
CC leading to AKT1 dephosphorylation. {ECO:0000269|PubMed:21329884}.
CC -!- SUBUNIT: Component of the serine/threonine-protein phosphatase 2A
CC complex (PP2A). This complex consists of a common heterodimeric core
CC enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa
CC constant scaffold subunit (PR65 or subunit A), that associates with a
CC variety of regulatory subunits. Proteins that associate with the core
CC dimer include three families of regulatory subunits B (the
CC R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48
CC kDa variable regulatory subunit, viral proteins, and cell signaling
CC molecules (PubMed:23135275). Interacts with SGO1 (PubMed:16541025).
CC Interacts with AKT1 (PubMed:21329884). Interacts with CUL3 and KLHL15;
CC this interaction leads to proteasomal degradation (PubMed:23135275).
CC {ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:21329884,
CC ECO:0000269|PubMed:23135275}.
CC -!- INTERACTION:
CC Q15173; O96017: CHEK2; NbExp=2; IntAct=EBI-1369497, EBI-1180783;
CC Q15173; P46695: IER3; NbExp=4; IntAct=EBI-1369497, EBI-1748945;
CC Q15173; P67775: PPP2CA; NbExp=6; IntAct=EBI-1369497, EBI-712311;
CC Q15173; P30153: PPP2R1A; NbExp=4; IntAct=EBI-1369497, EBI-302388;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8703017}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Beta-1;
CC IsoId=Q15173-1; Sequence=Displayed;
CC Name=Beta-2;
CC IsoId=Q15173-2; Sequence=VSP_005109;
CC -!- TISSUE SPECIFICITY: Highest expression in brain.
CC -!- INDUCTION: By retinoic acid; in neuroblastoma cell lines.
CC -!- PTM: Ubiquitinated by E3 CUL3-KLHL15 complex; this modification leads
CC to proteasomal degradation. {ECO:0000269|PubMed:23135275}.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit B56
CC family. {ECO:0000305}.
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DR EMBL; L42374; AAC37602.1; -; mRNA.
DR EMBL; Z69028; CAA93152.1; -; mRNA.
DR EMBL; BC045619; AAH45619.1; -; mRNA.
DR CCDS; CCDS8085.1; -. [Q15173-1]
DR PIR; I70147; I70147.
DR RefSeq; NP_006235.1; NM_006244.3. [Q15173-1]
DR AlphaFoldDB; Q15173; -.
DR SMR; Q15173; -.
DR BioGRID; 111518; 43.
DR ELM; Q15173; -.
DR IntAct; Q15173; 11.
DR MINT; Q15173; -.
DR STRING; 9606.ENSP00000164133; -.
DR iPTMnet; Q15173; -.
DR PhosphoSitePlus; Q15173; -.
DR BioMuta; PPP2R5B; -.
DR DMDM; 7387497; -.
DR EPD; Q15173; -.
DR jPOST; Q15173; -.
DR MassIVE; Q15173; -.
DR MaxQB; Q15173; -.
DR PaxDb; Q15173; -.
DR PeptideAtlas; Q15173; -.
DR PRIDE; Q15173; -.
DR ProteomicsDB; 60483; -.
DR ProteomicsDB; 60484; -. [Q15173-2]
DR TopDownProteomics; Q15173-1; -. [Q15173-1]
DR Antibodypedia; 29566; 105 antibodies from 29 providers.
DR DNASU; 5526; -.
DR Ensembl; ENST00000164133.7; ENSP00000164133.2; ENSG00000068971.14. [Q15173-1]
DR GeneID; 5526; -.
DR KEGG; hsa:5526; -.
DR MANE-Select; ENST00000164133.7; ENSP00000164133.2; NM_006244.4; NP_006235.1.
DR UCSC; uc001oby.4; human. [Q15173-1]
DR CTD; 5526; -.
DR DisGeNET; 5526; -.
DR GeneCards; PPP2R5B; -.
DR HGNC; HGNC:9310; PPP2R5B.
DR HPA; ENSG00000068971; Low tissue specificity.
DR MIM; 601644; gene.
DR neXtProt; NX_Q15173; -.
DR OpenTargets; ENSG00000068971; -.
DR PharmGKB; PA33673; -.
DR VEuPathDB; HostDB:ENSG00000068971; -.
DR eggNOG; KOG2085; Eukaryota.
DR GeneTree; ENSGT01030000234620; -.
DR HOGENOM; CLU_012437_4_0_1; -.
DR InParanoid; Q15173; -.
DR OMA; QDRRMQM; -.
DR PhylomeDB; Q15173; -.
DR TreeFam; TF105556; -.
DR PathwayCommons; Q15173; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-HSA-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling.
DR Reactome; R-HSA-432142; Platelet sensitization by LDL.
DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-HSA-5339716; Signaling by GSK3beta mutants.
DR Reactome; R-HSA-5358747; CTNNB1 S33 mutants aren't phosphorylated.
DR Reactome; R-HSA-5358749; CTNNB1 S37 mutants aren't phosphorylated.
DR Reactome; R-HSA-5358751; CTNNB1 S45 mutants aren't phosphorylated.
DR Reactome; R-HSA-5358752; CTNNB1 T41 mutants aren't phosphorylated.
DR Reactome; R-HSA-5467337; APC truncation mutants have impaired AXIN binding.
DR Reactome; R-HSA-5467340; AXIN missense mutants destabilize the destruction complex.
DR Reactome; R-HSA-5467348; Truncations of AMER1 destabilize the destruction complex.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q15173; -.
DR SIGNOR; Q15173; -.
DR BioGRID-ORCS; 5526; 30 hits in 1080 CRISPR screens.
DR ChiTaRS; PPP2R5B; human.
DR GeneWiki; PPP2R5B; -.
DR GenomeRNAi; 5526; -.
DR Pharos; Q15173; Tbio.
DR PRO; PR:Q15173; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q15173; protein.
DR Bgee; ENSG00000068971; Expressed in right hemisphere of cerebellum and 181 other tissues.
DR ExpressionAtlas; Q15173; baseline and differential.
DR Genevisible; Q15173; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IBA:GO_Central.
DR GO; GO:0072542; F:protein phosphatase activator activity; IBA:GO_Central.
DR GO; GO:0019888; F:protein phosphatase regulator activity; TAS:ProtInc.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0070317; P:negative regulation of G0 to G1 transition; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0051388; P:positive regulation of neurotrophin TRK receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0031952; P:regulation of protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0010469; P:regulation of signaling receptor activity; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR002554; PP2A_B56.
DR PANTHER; PTHR10257; PTHR10257; 1.
DR Pfam; PF01603; B56; 1.
DR PIRSF; PIRSF028043; PP2A_B56; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..497
FT /note="Serine/threonine-protein phosphatase 2A 56 kDa
FT regulatory subunit beta isoform"
FT /id="PRO_0000071450"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 475..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..24
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 32
FT /note="Phosphoserine; by CLK2"
FT /evidence="ECO:0000305|PubMed:21329884"
FT MOD_RES 35
FT /note="Phosphoserine; by CLK2"
FT /evidence="ECO:0000305|PubMed:21329884"
FT MOD_RES 44
FT /note="Phosphoserine; by CLK2"
FT /evidence="ECO:0000305|PubMed:21329884"
FT MOD_RES 46
FT /note="Phosphoserine; by CLK2"
FT /evidence="ECO:0000305|PubMed:21329884"
FT MOD_RES 47
FT /note="Phosphoserine; by CLK2"
FT /evidence="ECO:0000305|PubMed:21329884"
FT MOD_RES 48
FT /note="Phosphoserine; by CLK2"
FT /evidence="ECO:0000305|PubMed:21329884"
FT VAR_SEQ 1..19
FT /note="METKLPPASTPTSPSSPGL -> MITVNPPLPQDTVNLF (in isoform
FT Beta-2)"
FT /evidence="ECO:0000303|PubMed:8694763"
FT /id="VSP_005109"
FT MUTAGEN 52
FT /note="Y->S: Loss of KLHL15-binding and enhanced
FT stability."
FT /evidence="ECO:0000269|PubMed:23135275"
FT MUTAGEN 103..104
FT /note="KR->DE: Impaired trimer formation with PP2A subunits
FT A/C, no effect on KLHL15-binding."
FT /evidence="ECO:0000269|PubMed:23135275"
FT MUTAGEN 232..233
FT /note="RK->ED: Impaired trimer formation with PP2A subunits
FT A/C, no effect on KLHL15-binding."
FT /evidence="ECO:0000269|PubMed:23135275"
FT CONFLICT 57..58
FT /note="QE -> IF (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 177..178
FT /note="ES -> GA (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="F -> M (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="S -> M (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="W -> E (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 497 AA; 57393 MW; 8BEF84F20A77982D CRC64;
METKLPPAST PTSPSSPGLS PVPPPDKVDG FSRRSLRRAR PRRSHSSSQF RYQSNQQELT
PLPLLKDVPA SELHELLSRK LAQCGVMFDF LDCVADLKGK EVKRAALNEL VECVGSTRGV
LIEPVYPDII RMISVNIFRT LPPSENPEFD PEEDEPNLEP SWPHLQLVYE FFLRFLESPD
FQPSVAKRYV DQKFVLMLLE LFDSEDPRER EYLKTILHRV YGKFLGLRAY IRKQCNHIFL
RFIYEFEHFN GVAELLEILG SIINGFALPL KTEHKQFLVR VLIPLHSVKS LSVFHAQLAY
CVVQFLEKDA TLTEHVIRGL LKYWPKTCTQ KEVMFLGEME EILDVIEPSQ FVKIQEPLFK
QVARCVSSPH FQVAERALYF WNNEYILSLI EDNCHTVLPA VFGTLYQVSK EHWNQTIVSL
IYNVLKTFME MNGKLFDELT ASYKLEKQQE QQKAQERQEL WQGLEELRLR RLQGTQGAKE
APLQRLTPQV AASGGQS
