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Protein

Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform

Gene

Ppp2r2b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity. Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance.2 Publications

GO - Molecular functioni

  • protein complex binding Source: RGD
  • protein phosphatase type 2A regulator activity Source: InterPro

GO - Biological processi

  • brain development Source: RGD
  • mitochondrial fission Source: RGD
  • mitochondrial fragmentation involved in apoptotic process Source: RGD
  • neuron differentiation Source: RGD
  • positive regulation of neuron apoptotic process Source: UniProtKB
  • protein targeting to mitochondrion Source: RGD
  • regulation of protein phosphatase type 2A activity Source: UniProtKB
  • spermatid development Source: RGD
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform
Alternative name(s):
PP2A subunit B isoform B55-beta
PP2A subunit B isoform BRB
PP2A subunit B isoform PR55-beta
PP2A subunit B isoform R2-beta
PP2A subunit B isoform beta
Gene namesi
Name:Ppp2r2b
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi631441. Ppp2r2b.

Subcellular locationi

Isoform 1 :
Isoform 2 :
  • Cytoplasm
  • Mitochondrion
  • Mitochondrion outer membrane

  • Note: Under basal conditions, localizes to both cytosolic and mitochondrial compartments. Relocalizes from the cytosolic to the mitochondrial compartment during apoptosis. Its targeting to the outer mitochondrial membrane (OMM) involves an association with import receptors of the TOM complex and is required to promote proapoptotic activity.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: RGD
  • membrane Source: RGD
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • protein phosphatase type 2A complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi165 – 1662RR → EE: Inhibits incorporation into the PP2A holoenzyme complex and proapoptotic activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 443443Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoformPRO_0000071427Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei275 – 2751PhosphoserineCombined sources
Modified residuei295 – 2951PhosphotyrosineCombined sources
Modified residuei298 – 2981PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP36877.

PTM databases

iPTMnetiP36877.
PhosphoSiteiP36877.

Expressioni

Tissue specificityi

Expressed in the brain. Isoform 1 and isoform 2 are expressed in the forbrain. Isoform 1 is more strongly expressed than isoform 2 in the olfactory bulb. Isoform 1 and isoform 2 are weakly expressed in the cerebellum. Isoform 1 is expressed in the testis. Isoform 2 expression is undetectable at birth rising to adult level at day 14.2 Publications

Inductioni

Up-regulated postnatally and in response to neuronal differentiation.1 Publication

Gene expression databases

ExpressionAtlasiP36877. baseline and differential.
GenevisibleiP36877. RN.

Interactioni

Subunit structurei

PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and 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 TOMM22.1 Publication

GO - Molecular functioni

  • protein complex binding Source: RGD

Protein-protein interaction databases

IntActiP36877. 1 interaction.
MINTiMINT-8198660.

Structurei

3D structure databases

ProteinModelPortaliP36877.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati22 – 6140WD 1Add
BLAST
Repeati87 – 12842WD 2Add
BLAST
Repeati171 – 20939WD 3Add
BLAST
Repeati220 – 26041WD 4Add
BLAST
Repeati279 – 31739WD 5Add
BLAST
Repeati334 – 37542WD 6Add
BLAST
Repeati410 – 44233WD 7Add
BLAST

Domaini

The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal with critical basic and hydrophobic residues, that is necessary and sufficient for targeting the PP2A holoenzyme to the outer mitochondrial membrane (OMM) and does not affect holoenzyme formation or catalytic activity.
The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that confers resistance to the unfolding step process required for import and therefore prevents PPP2R2B matrix translocation and signal sequence cleavage.

Sequence similaritiesi

Contains 7 WD repeats.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

GeneTreeiENSGT00390000006311.
HOGENOMiHOG000089745.
HOVERGENiHBG000012.
InParanoidiP36877.
KOiK04354.
OrthoDBiEOG7Q5HCZ.
TreeFamiTF105553.

Family and domain databases

Gene3Di2.130.10.10. 3 hits.
InterProiIPR000009. PP2A_PR55.
IPR018067. PP2A_PR55_CS.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR11871. PTHR11871. 1 hit.
PIRSFiPIRSF037309. PP2A_PR55. 1 hit.
PRINTSiPR00600. PP2APR55.
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 3 hits.
PROSITEiPS01024. PR55_1. 1 hit.
PS01025. PR55_2. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P36877-1) [UniParc]FASTAAdd to basket

Also known as: Bbeta, Bbeta1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEEDIDTRKI NNSFLRDHSY ATEADIISTV EFNHTGELLA TGDKGGRVVI
60 70 80 90 100
FQREQESKNQ VHRRGEYNVY STFQSHEPEF DYLKSLEIEE KINKIRWLPQ
110 120 130 140 150
QNAAYFLLST NDKTVKLWKV SERDKRPEGY NLKDEEGRLR DPATITTLRV
160 170 180 190 200
PVLRPMDLMV EATPRRVFAN AHTYHINSIS VNSDYETYMS ADDLRINLWN
210 220 230 240 250
FEITNQSFNI VDIKPANMEE LTEVITAAEF HPHHCNTFVY SSSKGTIRLC
260 270 280 290 300
DMRASALCDR HTKFFEEPED PSNRSFFSEI ISSISDVKFS HSGRYIMTRD
310 320 330 340 350
YLTAKVWDLN MENRPVETYQ VHDYLRSKLC SLYENDCIFD KFECVWNGSD
360 370 380 390 400
SVIMTGSYNN FFRMFDRNTK RDVTLEASRE NSKPRAILKP RKVCVGGKRR
410 420 430 440
KDEISVDSLD FSKKILHTAW HPSENIIAVA ATNNLYIFQD KVN
Length:443
Mass (Da):51,668
Last modified:November 1, 1997 - v2
Checksum:i0089EF6E8ED53082
GO
Isoform 2 (identifier: P36877-2) [UniParc]FASTAAdd to basket

Also known as: Bbeta2

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MEEDIDTRKINNSFLRDHSYA → MKCFSRYLPYIFRPPNTILSSSCH

Note: Contains a cryptic mitochondrial transit peptide at positions 1-23. Mutagenesis of Lys-2 to Ala greatly reduces interaction with TOMM22, the outer mitochondrial membrane (OMM) localization and proapoptotic activity. Mutagenesis of Arg-6 to Ala greatly reduces outer mitochondrial membrane (OMM) localization and proapoptotic activity. Combined mutagenesis of Thy-7 and Leu-8 to Ala or Thy-10 and Ile-11 and Phe-12 to Ala or Ile-18 and Leu-19 to Ala strongly impaired mitochondrial localization and proapoptotic activity. Mutagenesis of Arg-13 to Ala does not inhibit OMM localization and proapoptotic activity. Mutagenesis of Cys-3 to Ala or Ser does not inhibit OMM localization and proapoptotic activity. Mutagenesis of Phe-4 to Ala or Thy-7 to Ala or Leu-8 to Ala or Tyr-10 to Ala or Ile-11 to Ala or Phe-12 to Ala weakly impaired mitochondrial localization and proapoptotic activity.
Show »
Length:446
Mass (Da):51,975
Checksum:i16B7FF8B3329D406
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2121MEEDI…DHSYA → MKCFSRYLPYIFRPPNTILS SSCH in isoform 2. 1 PublicationVSP_037984Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38260 mRNA. Translation: BAA07412.1.
AY251277 mRNA. Translation: AAP33142.1.
BC078834 mRNA. Translation: AAH78834.1.
D14421 mRNA. Translation: BAA03313.1.
PIRiS33257.
RefSeqiNP_071545.2. NM_022209.3. [P36877-2]
UniGeneiRn.44437.

Genome annotation databases

EnsembliENSRNOT00000079585; ENSRNOP00000071824; ENSRNOG00000018851. [P36877-1]
GeneIDi60660.
KEGGirno:60660.
UCSCiRGD:631441. rat. [P36877-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38260 mRNA. Translation: BAA07412.1.
AY251277 mRNA. Translation: AAP33142.1.
BC078834 mRNA. Translation: AAH78834.1.
D14421 mRNA. Translation: BAA03313.1.
PIRiS33257.
RefSeqiNP_071545.2. NM_022209.3. [P36877-2]
UniGeneiRn.44437.

3D structure databases

ProteinModelPortaliP36877.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP36877. 1 interaction.
MINTiMINT-8198660.

PTM databases

iPTMnetiP36877.
PhosphoSiteiP36877.

Proteomic databases

PRIDEiP36877.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000079585; ENSRNOP00000071824; ENSRNOG00000018851. [P36877-1]
GeneIDi60660.
KEGGirno:60660.
UCSCiRGD:631441. rat. [P36877-1]

Organism-specific databases

CTDi5521.
RGDi631441. Ppp2r2b.

Phylogenomic databases

GeneTreeiENSGT00390000006311.
HOGENOMiHOG000089745.
HOVERGENiHBG000012.
InParanoidiP36877.
KOiK04354.
OrthoDBiEOG7Q5HCZ.
TreeFamiTF105553.

Miscellaneous databases

PROiP36877.

Gene expression databases

ExpressionAtlasiP36877. baseline and differential.
GenevisibleiP36877. RN.

Family and domain databases

Gene3Di2.130.10.10. 3 hits.
InterProiIPR000009. PP2A_PR55.
IPR018067. PP2A_PR55_CS.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR11871. PTHR11871. 1 hit.
PIRSFiPIRSF037309. PP2A_PR55. 1 hit.
PRINTSiPR00600. PP2APR55.
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 3 hits.
PROSITEiPS01024. PR55_1. 1 hit.
PS01025. PR55_2. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA cloning of BR gamma, a novel brain-specific isoform of the B regulatory subunit of type-2A protein phosphatase."
    Akiyama N., Shima H., Hatano Y., Osawa Y., Sugimura T., Nagao M.
    Eur. J. Biochem. 230:766-772(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "A developmentally regulated, neuron-specific splice variant of the variable subunit Bbeta targets protein phosphatase 2A to mitochondria and modulates apoptosis."
    Dagda R.K., Zaucha J.A., Wadzinski B.E., Strack S.
    J. Biol. Chem. 278:24976-24985(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INDUCTION, MUTAGENESIS OF 165-ARG-ARG-166, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  4. "Expression of PP2A B regulatory subunit beta isotype in rat testis."
    Hatano Y., Shima H., Haneji T., Miura A.B., Sugimura T., Nagao M.
    FEBS Lett. 324:71-75(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-177 (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Testis.
  5. "Unfolding-resistant translocase targeting: a novel mechanism for outer mitochondrial membrane localization exemplified by the Bbeta2 regulatory subunit of protein phosphatase 2A."
    Dagda R.K., Barwacz C.A., Cribbs J.T., Strack S.
    J. Biol. Chem. 280:27375-27382(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TOMM22, MUTAGENESIS OF ISOFORM 2, SUBCELLULAR LOCATION.
  6. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
    Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
    Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; TYR-295 AND THR-298, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission."
    Dagda R.K., Merrill R.A., Cribbs J.T., Chen Y., Hell J.W., Usachev Y.M., Strack S.
    J. Biol. Chem. 283:36241-36248(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry namei2ABB_RAT
AccessioniPrimary (citable) accession number: P36877
Secondary accession number(s): Q80W84
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 1, 1997
Last modified: June 8, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.