P36877 (2ABB_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Ppp2r2b

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	443 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.2 Ref.6
Subunit structure	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. Ref.5
Subcellular location	Isoform 1: Cytoplasm. Cytoplasm › cytoskeleton By similarity. Membrane By similarity Ref.2 Ref.5 Ref.6. 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. Ref.2 Ref.5 Ref.6
Tissue specificity	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. Ref.2 Ref.4
Induction	Up-regulated postnatally and in response to neuronal differentiation. Ref.2
Domain	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 similarities	Belongs to the phosphatase 2A regulatory subunit B family. Contains 7 WD repeats.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Cytoskeleton Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat WD repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from expression pattern Ref.2. Source: RGD cellular response to stress Inferred from expression pattern Ref.6. Source: RGD mitochondrial fragmentation involved in apoptotic process Inferred from mutant phenotype Ref.6. Source: RGD neuron differentiation Inferred from expression pattern Ref.2. Source: RGD positive regulation of neuron apoptotic process Inferred from direct assay Ref.6. Source: RGD protein targeting to mitochondrion Inferred from mutant phenotype Ref.2. Source: RGD regulation of protein phosphatase type 2A activity Inferred from direct assay Ref.2. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro spermatid development Inferred from expression pattern Ref.4. Source: RGD
Cellular_component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay PubMed 9514514. Source: RGD membrane Inferred from direct assay PubMed 9514514. Source: RGD mitochondrial outer membrane Inferred from direct assay Ref.5. Source: UniProtKB mitochondrion Inferred from direct assay Ref.6. Source: RGD protein phosphatase type 2A complex Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	protein complex binding Inferred from direct assay Ref.2. Source: RGD protein phosphatase type 2A regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P36877-1)

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.

Isoform 2 (identifier: P36877-2)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 443	443	Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform		PRO_0000071427
Regions
	Repeat	22 – 61	40	WD 1
	Repeat	87 – 128	42	WD 2
	Repeat	171 – 209	39	WD 3
	Repeat	220 – 260	41	WD 4
	Repeat	279 – 317	39	WD 5
	Repeat	334 – 375	42	WD 6
	Repeat	410 – 442	33	WD 7
Natural variations
	Alternative sequence	1 – 21	21	MEEDI…DHSYA → MKCFSRYLPYIFRPPNTILS SSCH in isoform 2.		VSP_037984
Experimental info
	Mutagenesis	165 – 166	2	RR → EE: Inhibits incorporation into the PP2A holoenzyme complex and proapoptotic activity. Ref.2 Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Bbeta) (Bbeta1) [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 0089EF6E8ED53082	FASTA	443	51,668
	10 20 30 40 50 60 MEEDIDTRKI NNSFLRDHSY ATEADIISTV EFNHTGELLA TGDKGGRVVI FQREQESKNQ 70 80 90 100 110 120 VHRRGEYNVY STFQSHEPEF DYLKSLEIEE KINKIRWLPQ QNAAYFLLST NDKTVKLWKV 130 140 150 160 170 180 SERDKRPEGY NLKDEEGRLR DPATITTLRV PVLRPMDLMV EATPRRVFAN AHTYHINSIS 190 200 210 220 230 240 VNSDYETYMS ADDLRINLWN FEITNQSFNI VDIKPANMEE LTEVITAAEF HPHHCNTFVY 250 260 270 280 290 300 SSSKGTIRLC DMRASALCDR HTKFFEEPED PSNRSFFSEI ISSISDVKFS HSGRYIMTRD 310 320 330 340 350 360 YLTAKVWDLN MENRPVETYQ VHDYLRSKLC SLYENDCIFD KFECVWNGSD SVIMTGSYNN 370 380 390 400 410 420 FFRMFDRNTK RDVTLEASRE NSKPRAILKP RKVCVGGKRR KDEISVDSLD FSKKILHTAW 430 440 HPSENIIAVA ATNNLYIFQD KVN
	Isoform 2 (Bbeta2) [UniParc]. Checksum: 16B7FF8B3329D406	FASTA	446	51,975
	10 20 30 40 50 60 MKCFSRYLPY IFRPPNTILS SSCHTEADII STVEFNHTGE LLATGDKGGR VVIFQREQES 70 80 90 100 110 120 KNQVHRRGEY NVYSTFQSHE PEFDYLKSLE IEEKINKIRW LPQQNAAYFL LSTNDKTVKL 130 140 150 160 170 180 WKVSERDKRP EGYNLKDEEG RLRDPATITT LRVPVLRPMD LMVEATPRRV FANAHTYHIN 190 200 210 220 230 240 SISVNSDYET YMSADDLRIN LWNFEITNQS FNIVDIKPAN MEELTEVITA AEFHPHHCNT 250 260 270 280 290 300 FVYSSSKGTI RLCDMRASAL CDRHTKFFEE PEDPSNRSFF SEIISSISDV KFSHSGRYIM 310 320 330 340 350 360 TRDYLTAKVW DLNMENRPVE TYQVHDYLRS KLCSLYENDC IFDKFECVWN GSDSVIMTGS 370 380 390 400 410 420 YNNFFRMFDR NTKRDVTLEA SRENSKPRAI LKPRKVCVGG KRRKDEISVD SLDFSKKILH 430 440 TAWHPSENII AVAATNNLYI FQDKVN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D38260 mRNA. Translation: BAA07412.1. AY251277 mRNA. Translation: AAP33142.1. BC078834 mRNA. Translation: AAH78834.1. D14421 mRNA. Translation: BAA03313.1.
IPI	IPI00206749. IPI00561842.
PIR	S33257.
RefSeq	NP_071545.2. NM_022209.3.
UniGene	Rn.44437.
3D structure databases
ProteinModelPortal	P36877.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000041264.
PTM databases
PhosphoSite	P36877.
Proteomic databases
PaxDb	P36877.
PRIDE	P36877.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	60660.
KEGG	rno:60660.
UCSC	RGD:631441. rat.
Organism-specific databases
CTD	5521.
RGD	631441. Ppp2r2b.
Phylogenomic databases
eggNOG	COG5170.
HOGENOM	HOG000089745.
HOVERGEN	HBG000012.
InParanoid	Q80W84.
KO	K04354.
OMA	NYATEAD.
Gene expression databases
ArrayExpress	P36877.
Genevestigator	P36877.
GermOnline	ENSRNOG00000018851. Rattus norvegicus.
Family and domain databases
Gene3D	2.130.10.10. 3 hits.
InterPro	IPR000009. 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]
PANTHER	PTHR11871. PTHR11871. 1 hit.
PIRSF	PIRSF037309. PP2A_PR55. 1 hit.
PRINTS	PR00600. PP2APR55.
SMART	SM00320. WD40. 6 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS01024. PR55_1. 1 hit. PS01025. PR55_2. 1 hit. PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. False negative. PS50294. WD_REPEATS_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	612355.

Entry information

Entry name

2ABB_RAT

Accession

Primary (citable) accession number: P36877
Secondary accession number(s): Q80W84

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program