2ABB_RAT
ID 2ABB_RAT Reviewed; 443 AA.
AC P36877; Q80W84;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform;
DE AltName: Full=PP2A subunit B isoform B55-beta;
DE AltName: Full=PP2A subunit B isoform BRB;
DE AltName: Full=PP2A subunit B isoform PR55-beta;
DE AltName: Full=PP2A subunit B isoform R2-beta;
DE AltName: Full=PP2A subunit B isoform beta;
GN Name=Ppp2r2b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7607250; DOI=10.1111/j.1432-1033.1995.tb20619.x;
RA Akiyama N., Shima H., Hatano Y., Osawa Y., Sugimura T., Nagao M.;
RT "cDNA cloning of BR gamma, a novel brain-specific isoform of the B
RT regulatory subunit of type-2A protein phosphatase.";
RL Eur. J. Biochem. 230:766-772(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INDUCTION, MUTAGENESIS OF
RP 165-ARG-ARG-166, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=12716901; DOI=10.1074/jbc.m302832200;
RA Dagda R.K., Zaucha J.A., Wadzinski B.E., Strack S.;
RT "A developmentally regulated, neuron-specific splice variant of the
RT variable subunit Bbeta targets protein phosphatase 2A to mitochondria and
RT modulates apoptosis.";
RL J. Biol. Chem. 278:24976-24985(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 8-177 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=8389301; DOI=10.1016/0014-5793(93)81535-8;
RA Hatano Y., Shima H., Haneji T., Miura A.B., Sugimura T., Nagao M.;
RT "Expression of PP2A B regulatory subunit beta isotype in rat testis.";
RL FEBS Lett. 324:71-75(1993).
RN [5]
RP INTERACTION WITH TOMM22, MUTAGENESIS OF ISOFORM 2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15923182; DOI=10.1074/jbc.m503693200;
RA Dagda R.K., Barwacz C.A., Cribbs J.T., Strack S.;
RT "Unfolding-resistant translocase targeting: a novel mechanism for outer
RT mitochondrial membrane localization exemplified by the Bbeta2 regulatory
RT subunit of protein phosphatase 2A.";
RL J. Biol. Chem. 280:27375-27382(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; TYR-295 AND THR-298, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18940801; DOI=10.1074/jbc.m800989200;
RA Dagda R.K., Merrill R.A., Cribbs J.T., Chen Y., Hell J.W., Usachev Y.M.,
RA Strack S.;
RT "The spinocerebellar ataxia 12 gene product and protein phosphatase 2A
RT regulatory subunit Bbeta2 antagonizes neuronal survival by promoting
RT mitochondrial fission.";
RL J. Biol. Chem. 283:36241-36248(2008).
CC -!- FUNCTION: The B regulatory subunit might modulate substrate selectivity
CC and catalytic activity, and also might direct the localization of the
CC catalytic enzyme to a particular subcellular compartment. Within the
CC PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic
CC activity. Isoform 2 regulates neuronal survival through the
CC mitochondrial fission and fusion balance. {ECO:0000269|PubMed:12716901,
CC ECO:0000269|PubMed:18940801}.
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 or 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 (By
CC similarity). Interacts with IER5 (via N- and C-terminal regions) (By
CC similarity). Interacts with TOMM22 (PubMed:15923182). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q00005, ECO:0000269|PubMed:15923182}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Membrane {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Mitochondrion.
CC Mitochondrion outer membrane. Note=Under basal conditions, localizes to
CC both cytosolic and mitochondrial compartments. Relocalizes from the
CC cytosolic to the mitochondrial compartment during apoptosis. Its
CC targeting to the outer mitochondrial membrane (OMM) involves an
CC association with import receptors of the TOM complex and is required to
CC promote proapoptotic activity.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Bbeta, Bbeta1;
CC IsoId=P36877-1; Sequence=Displayed;
CC Name=2; Synonyms=Bbeta2;
CC IsoId=P36877-2; Sequence=VSP_037984;
CC -!- TISSUE SPECIFICITY: Expressed in the brain. Isoform 1 and isoform 2 are
CC expressed in the forbrain. Isoform 1 is more strongly expressed than
CC isoform 2 in the olfactory bulb. Isoform 1 and isoform 2 are weakly
CC expressed in the cerebellum. Isoform 1 is expressed in the testis.
CC Isoform 2 expression is undetectable at birth rising to adult level at
CC day 14. {ECO:0000269|PubMed:12716901, ECO:0000269|PubMed:8389301}.
CC -!- INDUCTION: Up-regulated postnatally and in response to neuronal
CC differentiation. {ECO:0000269|PubMed:12716901}.
CC -!- DOMAIN: The N-terminal 26 residues of isoform 2 constitute a cryptic
CC mitochondrial matrix import signal with critical basic and hydrophobic
CC residues, that is necessary and sufficient for targeting the PP2A
CC holoenzyme to the outer mitochondrial membrane (OMM) and does not
CC affect holoenzyme formation or catalytic activity.
CC -!- DOMAIN: The last WD repeat of isoform 2 constitutes a mitochondrial
CC stop-transfer domain that confers resistance to the unfolding step
CC process required for import and therefore prevents PPP2R2B matrix
CC translocation and signal sequence cleavage.
CC -!- MISCELLANEOUS: [Isoform 2]: Contains a cryptic mitochondrial transit
CC peptide at positions 1-23. Mutagenesis of Lys-2 to Ala greatly reduces
CC interaction with TOMM22, the outer mitochondrial membrane (OMM)
CC localization and proapoptotic activity. Mutagenesis of Arg-6 to Ala
CC greatly reduces outer mitochondrial membrane (OMM) localization and
CC proapoptotic activity. Combined mutagenesis of Thy-7 and Leu-8 to Ala
CC or Thy-10 and Ile-11 and Phe-12 to Ala or Ile-18 and Leu-19 to Ala
CC strongly impaired mitochondrial localization and proapoptotic activity.
CC Mutagenesis of Arg-13 to Ala does not inhibit OMM localization and
CC proapoptotic activity. Mutagenesis of Cys-3 to Ala or Ser does not
CC inhibit OMM localization and proapoptotic activity. Mutagenesis of Phe-
CC 4 to Ala or Thy-7 to Ala or Leu-8 to Ala or Tyr-10 to Ala or Ile-11 to
CC Ala or Phe-12 to Ala weakly impaired mitochondrial localization and
CC proapoptotic activity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit B family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D38260; BAA07412.1; -; mRNA.
DR EMBL; AY251277; AAP33142.1; -; mRNA.
DR EMBL; BC078834; AAH78834.1; -; mRNA.
DR EMBL; D14421; BAA03313.1; -; mRNA.
DR PIR; S33257; S33257.
DR RefSeq; NP_071545.2; NM_022209.3. [P36877-2]
DR RefSeq; XP_017456514.1; XM_017601025.1. [P36877-1]
DR AlphaFoldDB; P36877; -.
DR SMR; P36877; -.
DR IntAct; P36877; 1.
DR MINT; P36877; -.
DR STRING; 10116.ENSRNOP00000041264; -.
DR iPTMnet; P36877; -.
DR PhosphoSitePlus; P36877; -.
DR jPOST; P36877; -.
DR PaxDb; P36877; -.
DR PRIDE; P36877; -.
DR Ensembl; ENSRNOT00000079585; ENSRNOP00000071824; ENSRNOG00000018851. [P36877-1]
DR Ensembl; ENSRNOT00000107651; ENSRNOP00000077436; ENSRNOG00000018851. [P36877-2]
DR GeneID; 60660; -.
DR KEGG; rno:60660; -.
DR UCSC; RGD:631441; rat. [P36877-1]
DR CTD; 5521; -.
DR RGD; 631441; Ppp2r2b.
DR eggNOG; KOG1354; Eukaryota.
DR GeneTree; ENSGT00950000182864; -.
DR InParanoid; P36877; -.
DR OrthoDB; 810409at2759; -.
DR TreeFam; TF105553; -.
DR PRO; PR:P36877; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000018851; Expressed in frontal cortex and 18 other tissues.
DR ExpressionAtlas; P36877; baseline and differential.
DR Genevisible; P36877; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IDA:UniProtKB.
DR GO; GO:0019888; F:protein phosphatase regulator activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0000266; P:mitochondrial fission; IDA:RGD.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IMP:RGD.
DR GO; GO:0030182; P:neuron differentiation; IEP:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IMP:RGD.
DR GO; GO:0043666; P:regulation of phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0007286; P:spermatid development; IEP:RGD.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR000009; PP2A_PR55.
DR InterPro; IPR018067; PP2A_PR55_CS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR11871; PTHR11871; 1.
DR PIRSF; PIRSF037309; PP2A_PR55; 1.
DR PRINTS; PR00600; PP2APR55.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS01024; PR55_1; 1.
DR PROSITE; PS01025; PR55_2; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cytoplasm; Cytoskeleton; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..443
FT /note="Serine/threonine-protein phosphatase 2A 55 kDa
FT regulatory subunit B beta isoform"
FT /id="PRO_0000071427"
FT REPEAT 22..61
FT /note="WD 1"
FT REPEAT 87..128
FT /note="WD 2"
FT REPEAT 171..209
FT /note="WD 3"
FT REPEAT 220..260
FT /note="WD 4"
FT REPEAT 279..317
FT /note="WD 5"
FT REPEAT 334..375
FT /note="WD 6"
FT REPEAT 410..442
FT /note="WD 7"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 295
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 298
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT VAR_SEQ 1..21
FT /note="MEEDIDTRKINNSFLRDHSYA -> MKCFSRYLPYIFRPPNTILSSSCH
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12716901"
FT /id="VSP_037984"
FT MUTAGEN 165..166
FT /note="RR->EE: Inhibits incorporation into the PP2A
FT holoenzyme complex and proapoptotic activity."
FT /evidence="ECO:0000269|PubMed:12716901"
SQ SEQUENCE 443 AA; 51668 MW; 0089EF6E8ED53082 CRC64;
MEEDIDTRKI NNSFLRDHSY ATEADIISTV EFNHTGELLA TGDKGGRVVI FQREQESKNQ
VHRRGEYNVY STFQSHEPEF DYLKSLEIEE KINKIRWLPQ QNAAYFLLST NDKTVKLWKV
SERDKRPEGY NLKDEEGRLR DPATITTLRV PVLRPMDLMV EATPRRVFAN AHTYHINSIS
VNSDYETYMS ADDLRINLWN FEITNQSFNI VDIKPANMEE LTEVITAAEF HPHHCNTFVY
SSSKGTIRLC DMRASALCDR HTKFFEEPED PSNRSFFSEI ISSISDVKFS HSGRYIMTRD
YLTAKVWDLN MENRPVETYQ VHDYLRSKLC SLYENDCIFD KFECVWNGSD SVIMTGSYNN
FFRMFDRNTK RDVTLEASRE NSKPRAILKP RKVCVGGKRR KDEISVDSLD FSKKILHTAW
HPSENIIAVA ATNNLYIFQD KVN
