Full text data of PPP2R2B
PPP2R2B
[Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform (PP2A subunit B isoform B55-beta; PP2A subunit B isoform PR55-beta; PP2A subunit B isoform R2-beta; PP2A subunit B isoform beta)
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform (PP2A subunit B isoform B55-beta; PP2A subunit B isoform PR55-beta; PP2A subunit B isoform R2-beta; PP2A subunit B isoform beta)
UniProt
Q00005
ID 2ABB_HUMAN Reviewed; 443 AA.
AC Q00005; A6NEJ2; A8K102; B3KPD0; B7Z2F2; B7Z304; D3DQF7; D3DQF8;
read moreAC G3V149;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 22-JAN-2014, entry version 144.
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 PR55-beta;
DE AltName: Full=PP2A subunit B isoform R2-beta;
DE AltName: Full=PP2A subunit B isoform beta;
GN Name=PPP2R2B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=1849734; DOI=10.1021/bi00229a001;
RA Mayer R.E., Hendrix P., Cron P., Matthies R., Stone S.R., Goris J.,
RA Merlevede W., Hofsteenge J., Hemmings B.A.;
RT "Structure of the 55-kDa regulatory subunit of protein phosphatase 2A:
RT evidence for a neuronal-specific isoform.";
RL Biochemistry 30:3589-3597(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-433 (ISOFORM 7).
RC TISSUE=Brain, and Corpus callosum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-131 (ISOFORM 6).
RC TISSUE=Brain, and Hypothalamus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-197 (ISOFORM 2).
RA Strausberg R.L.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INVOLVEMENT IN SCA12.
RX PubMed=10581021; DOI=10.1038/70493;
RA Holmes S.E., O'Hearn E.E., McInnis M.G., Gorelick-Feldman D.A.,
RA Kleiderlein J.J., Callahan C., Kwak N.G., Ingersoll-Ashworth R.G.,
RA Sherr M., Sumner A.J., Sharp A.H., Ananth U., Seltzer W.K., Boss M.A.,
RA Vieria-Saecker A.-M., Epplen J.T., Riess O., Ross C.A., Margolis R.L.;
RT "Expansion of a novel CAG trinucleotide repeat in the 5' region of
RT PPP2R2B is associated with SCA12.";
RL Nat. Genet. 23:391-392(1999).
CC -!- FUNCTION: The B regulatory subunit might modulate substrate
CC selectivity and catalytic activity, and also might direct the
CC localization of the catalytic enzyme to a particular subcellular
CC compartment. Within the PP2A holoenzyme complex, isoform 2 is
CC required to promote proapoptotic activity (By similarity). Isoform
CC 2 regulates neuronal survival through the mitochondrial fission
CC and fusion balance (By similarity).
CC -!- SUBUNIT: PP2A consists of a common heterodimeric core enzyme,
CC composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa
CC constant regulatory subunit (PR65 or subunit A), that associates
CC with a variety of regulatory subunits. Proteins that associate
CC with the core dimer include three families of regulatory subunits
CC B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56
CC families), the 48 kDa variable regulatory subunit, viral proteins,
CC and cell signaling molecules.
CC -!- INTERACTION:
CC O15530:PDPK1; NbExp=8; IntAct=EBI-1052159, EBI-717097;
CC P30153:PPP2R1A; NbExp=5; IntAct=EBI-1052159, EBI-302388;
CC P23443:RPS6KB1; NbExp=2; IntAct=EBI-1052159, EBI-1775921;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm (By similarity).
CC Cytoplasm, cytoskeleton (By similarity). Membrane (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm (By similarity).
CC Mitochondrion (By similarity). Mitochondrion outer membrane (By
CC similarity). Note=Under basal conditions, localizes to both
CC 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
CC required to promote proapoptotic activity (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=Bbeta, Bbeta1;
CC IsoId=Q00005-1; Sequence=Displayed;
CC Note=Conserved additional ATG codons are found 5' of the
CC putative initiator codon in transcripts supporting isoform 1.
CC They may initiate the translation of upstream short open reading
CC frames altering the expression of that isoform as described in
CC PubMed=1849734;
CC Name=2; Synonyms=Bbeta2;
CC IsoId=Q00005-2; Sequence=VSP_037976;
CC Note=Contains a cryptic mitochondrial transit peptide at
CC positions 1-26 (By similarity);
CC Name=3;
CC IsoId=Q00005-3; Sequence=VSP_037977;
CC Name=4;
CC IsoId=Q00005-4; Sequence=VSP_037978;
CC Name=5;
CC IsoId=Q00005-5; Sequence=VSP_037979;
CC Name=6;
CC IsoId=Q00005-6; Sequence=VSP_044923;
CC Name=7;
CC IsoId=Q00005-7; Sequence=VSP_045748;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: The N-terminal 26 residues of isoform 2 constitute a
CC cryptic mitochondrial matrix import signal with critical basic and
CC hydrophobic residues, that is necessary and sufficient for
CC targeting the PP2A holoenzyme to the outer mitochondrial membrane
CC (OMM) and does not affect holoenzyme formation or catalytic
CC activity (By similarity).
CC -!- DOMAIN: The last WD repeat of isoform 2 constitutes a
CC mitochondrial stop-transfer domain that confers resistance to the
CC unfolding step process required for import and therefore prevents
CC PPP2R2B matrix translocation and signal sequence cleavage (By
CC similarity).
CC -!- DISEASE: Spinocerebellar ataxia 12 (SCA12) [MIM:604326]:
CC Spinocerebellar ataxia is a clinically and genetically
CC heterogeneous group of cerebellar disorders. Patients show
CC progressive incoordination of gait and often poor coordination of
CC hands, speech and eye movements, due to degeneration of the
CC cerebellum with variable involvement of the brainstem and spinal
CC cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit B
CC family.
CC -!- SIMILARITY: Contains 7 WD repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH31790.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAG51642.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAG51642.1; Type=Erroneous termination; Positions=116; Note=Translated as Lys;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PPP2R2B";
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DR EMBL; M64930; AAA36493.1; -; mRNA.
DR EMBL; AK056192; BAG51642.1; ALT_SEQ; mRNA.
DR EMBL; AK289717; BAF82406.1; -; mRNA.
DR EMBL; AK294659; BAH11838.1; -; mRNA.
DR EMBL; AK295347; BAH12040.1; -; mRNA.
DR EMBL; AC008728; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011357; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW61829.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61831.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61832.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61833.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61834.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61835.1; -; Genomic_DNA.
DR EMBL; BC031790; AAH31790.1; ALT_INIT; mRNA.
DR EMBL; BI490027; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BI669304; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; B38351; B38351.
DR RefSeq; NP_001258828.1; NM_001271899.1.
DR RefSeq; NP_001258829.1; NM_001271900.1.
DR RefSeq; NP_001258877.1; NM_001271948.1.
DR RefSeq; NP_858060.2; NM_181674.2.
DR RefSeq; NP_858061.2; NM_181675.3.
DR RefSeq; NP_858062.1; NM_181676.2.
DR RefSeq; NP_858063.1; NM_181677.2.
DR RefSeq; NP_858064.1; NM_181678.2.
DR UniGene; Hs.627618; -.
DR UniGene; Hs.655213; -.
DR ProteinModelPortal; Q00005; -.
DR SMR; Q00005; 23-442.
DR IntAct; Q00005; 167.
DR MINT; MINT-6631022; -.
DR STRING; 9606.ENSP00000336591; -.
DR PhosphoSite; Q00005; -.
DR DMDM; 231446; -.
DR PaxDb; Q00005; -.
DR PRIDE; Q00005; -.
DR DNASU; 5521; -.
DR Ensembl; ENST00000336640; ENSP00000336591; ENSG00000156475.
DR Ensembl; ENST00000356826; ENSP00000349283; ENSG00000156475.
DR Ensembl; ENST00000394409; ENSP00000377931; ENSG00000156475.
DR Ensembl; ENST00000394410; ENSP00000377932; ENSG00000156475.
DR Ensembl; ENST00000394411; ENSP00000377933; ENSG00000156475.
DR Ensembl; ENST00000394413; ENSP00000377935; ENSG00000156475.
DR Ensembl; ENST00000394414; ENSP00000377936; ENSG00000156475.
DR Ensembl; ENST00000453001; ENSP00000398779; ENSG00000156475.
DR Ensembl; ENST00000504198; ENSP00000421396; ENSG00000156475.
DR Ensembl; ENST00000508545; ENSP00000431320; ENSG00000156475.
DR GeneID; 5521; -.
DR KEGG; hsa:5521; -.
DR UCSC; uc003lok.5; human.
DR CTD; 5521; -.
DR GeneCards; GC05M145969; -.
DR HGNC; HGNC:9305; PPP2R2B.
DR HPA; HPA038118; -.
DR MIM; 604325; gene.
DR MIM; 604326; phenotype.
DR neXtProt; NX_Q00005; -.
DR Orphanet; 98762; Spinocerebellar ataxia type 12.
DR PharmGKB; PA33669; -.
DR eggNOG; COG5170; -.
DR HOVERGEN; HBG000012; -.
DR InParanoid; Q00005; -.
DR KO; K04354; -.
DR OMA; ILHTTWH; -.
DR OrthoDB; EOG7Q5HCZ; -.
DR SignaLink; Q00005; -.
DR ChiTaRS; PPP2R2B; human.
DR GeneWiki; PPP2R2B; -.
DR GenomeRNAi; 5521; -.
DR NextBio; 21356; -.
DR PRO; PR:Q00005; -.
DR ArrayExpress; Q00005; -.
DR Bgee; Q00005; -.
DR CleanEx; HS_PPP2R2B; -.
DR Genevestigator; Q00005; -.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IEA:Ensembl.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:ProtInc.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0033554; P:cellular response to stress; IEA:Ensembl.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IEA:Ensembl.
DR GO; GO:0034047; P:regulation of protein phosphatase type 2A activity; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 3.
DR InterPro; IPR000009; PP2A_PR55.
DR InterPro; IPR018067; PP2A_PR55_CS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR017986; WD40_repeat_dom.
DR PANTHER; PTHR11871; PTHR11871; 1.
DR PIRSF; PIRSF037309; PP2A_PR55; 1.
DR PRINTS; PR00600; PP2APR55.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 3.
DR PROSITE; PS01024; PR55_1; 1.
DR PROSITE; PS01025; PR55_2; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; FALSE_NEG.
DR PROSITE; PS50294; WD_REPEATS_REGION; FALSE_NEG.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Complete proteome; Cytoplasm;
KW Cytoskeleton; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Neurodegeneration; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; Spinocerebellar ataxia; WD repeat.
FT CHAIN 1 443 Serine/threonine-protein phosphatase 2A
FT 55 kDa regulatory subunit B beta isoform.
FT /FTId=PRO_0000071421.
FT REPEAT 22 61 WD 1.
FT REPEAT 87 128 WD 2.
FT REPEAT 171 209 WD 3.
FT REPEAT 220 260 WD 4.
FT REPEAT 279 317 WD 5.
FT REPEAT 334 375 WD 6.
FT REPEAT 410 442 WD 7.
FT MOD_RES 275 275 Phosphoserine (By similarity).
FT MOD_RES 295 295 Phosphotyrosine (By similarity).
FT MOD_RES 298 298 Phosphothreonine (By similarity).
FT VAR_SEQ 1 23 MEEDIDTRKINNSFLRDHSYATE -> MNYPDENTYGNK
FT (in isoform 6).
FT /FTId=VSP_044923.
FT VAR_SEQ 1 21 MEEDIDTRKINNSFLRDHSYA -> MKCFSRYLPYIFRPPN
FT TILSSSCH (in isoform 2).
FT /FTId=VSP_037976.
FT VAR_SEQ 1 21 MEEDIDTRKINNSFLRDHSYA -> MIPGIGTLTQDTLWCF
FT SQVKGTIEIGT (in isoform 3).
FT /FTId=VSP_037977.
FT VAR_SEQ 1 1 M -> MVLQPSERHYRDWNHRRLGPWCSPTGSPAPLSCETG
FT CGEGSWILVCRLLVPTQVSLLSM (in isoform 4).
FT /FTId=VSP_037978.
FT VAR_SEQ 1 1 M -> MLLSLPALHLQTSEHHPFFQLPHRRLGPWCSPTGSP
FT APLSCETGCGEGSWILVCRLLVPTQVSLLSM (in
FT isoform 5).
FT /FTId=VSP_037979.
FT VAR_SEQ 1 1 M -> MHQPPPASCSSSSSSSSSSCECARVGVRVSALAPAA
FT APCPAPRQLPYPRLPEPPSRGTSTLIPARLGPWCSPTGSPA
FT PLSCETGCGEGSWILVCRLLVPTQVSLLSM (in
FT isoform 7).
FT /FTId=VSP_045748.
FT VARIANT 36 36 G -> V (in dbSNP:rs11547494).
FT /FTId=VAR_051738.
FT CONFLICT 22 22 T -> A (in Ref. 2; BAH11838).
FT CONFLICT 62 62 H -> N (in Ref. 5; BI669304).
FT CONFLICT 109 109 S -> F (in Ref. 2; BAH12040).
FT CONFLICT 163 163 T -> S (in Ref. 6; BI490027).
FT CONFLICT 164 164 P -> S (in Ref. 2; BAF82406).
FT CONFLICT 292 292 S -> R (in Ref. 2; BAH12040).
SQ SEQUENCE 443 AA; 51710 MW; C383C834B2852B8F 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
YLTVKVWDLN MENRPIETYQ VHDYLRSKLC SLYENDCIFD KFECVWNGSD SVIMTGSYNN
FFRMFDRNTK RDVTLEASRE NSKPRAILKP RKVCVGGKRR KDEISVDSLD FSKKILHTAW
HPSENIIAVA ATNNLYIFQD KVN
//
ID 2ABB_HUMAN Reviewed; 443 AA.
AC Q00005; A6NEJ2; A8K102; B3KPD0; B7Z2F2; B7Z304; D3DQF7; D3DQF8;
read moreAC G3V149;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 22-JAN-2014, entry version 144.
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 PR55-beta;
DE AltName: Full=PP2A subunit B isoform R2-beta;
DE AltName: Full=PP2A subunit B isoform beta;
GN Name=PPP2R2B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=1849734; DOI=10.1021/bi00229a001;
RA Mayer R.E., Hendrix P., Cron P., Matthies R., Stone S.R., Goris J.,
RA Merlevede W., Hofsteenge J., Hemmings B.A.;
RT "Structure of the 55-kDa regulatory subunit of protein phosphatase 2A:
RT evidence for a neuronal-specific isoform.";
RL Biochemistry 30:3589-3597(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-433 (ISOFORM 7).
RC TISSUE=Brain, and Corpus callosum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-131 (ISOFORM 6).
RC TISSUE=Brain, and Hypothalamus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-197 (ISOFORM 2).
RA Strausberg R.L.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INVOLVEMENT IN SCA12.
RX PubMed=10581021; DOI=10.1038/70493;
RA Holmes S.E., O'Hearn E.E., McInnis M.G., Gorelick-Feldman D.A.,
RA Kleiderlein J.J., Callahan C., Kwak N.G., Ingersoll-Ashworth R.G.,
RA Sherr M., Sumner A.J., Sharp A.H., Ananth U., Seltzer W.K., Boss M.A.,
RA Vieria-Saecker A.-M., Epplen J.T., Riess O., Ross C.A., Margolis R.L.;
RT "Expansion of a novel CAG trinucleotide repeat in the 5' region of
RT PPP2R2B is associated with SCA12.";
RL Nat. Genet. 23:391-392(1999).
CC -!- FUNCTION: The B regulatory subunit might modulate substrate
CC selectivity and catalytic activity, and also might direct the
CC localization of the catalytic enzyme to a particular subcellular
CC compartment. Within the PP2A holoenzyme complex, isoform 2 is
CC required to promote proapoptotic activity (By similarity). Isoform
CC 2 regulates neuronal survival through the mitochondrial fission
CC and fusion balance (By similarity).
CC -!- SUBUNIT: PP2A consists of a common heterodimeric core enzyme,
CC composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa
CC constant regulatory subunit (PR65 or subunit A), that associates
CC with a variety of regulatory subunits. Proteins that associate
CC with the core dimer include three families of regulatory subunits
CC B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56
CC families), the 48 kDa variable regulatory subunit, viral proteins,
CC and cell signaling molecules.
CC -!- INTERACTION:
CC O15530:PDPK1; NbExp=8; IntAct=EBI-1052159, EBI-717097;
CC P30153:PPP2R1A; NbExp=5; IntAct=EBI-1052159, EBI-302388;
CC P23443:RPS6KB1; NbExp=2; IntAct=EBI-1052159, EBI-1775921;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm (By similarity).
CC Cytoplasm, cytoskeleton (By similarity). Membrane (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm (By similarity).
CC Mitochondrion (By similarity). Mitochondrion outer membrane (By
CC similarity). Note=Under basal conditions, localizes to both
CC 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
CC required to promote proapoptotic activity (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=Bbeta, Bbeta1;
CC IsoId=Q00005-1; Sequence=Displayed;
CC Note=Conserved additional ATG codons are found 5' of the
CC putative initiator codon in transcripts supporting isoform 1.
CC They may initiate the translation of upstream short open reading
CC frames altering the expression of that isoform as described in
CC PubMed=1849734;
CC Name=2; Synonyms=Bbeta2;
CC IsoId=Q00005-2; Sequence=VSP_037976;
CC Note=Contains a cryptic mitochondrial transit peptide at
CC positions 1-26 (By similarity);
CC Name=3;
CC IsoId=Q00005-3; Sequence=VSP_037977;
CC Name=4;
CC IsoId=Q00005-4; Sequence=VSP_037978;
CC Name=5;
CC IsoId=Q00005-5; Sequence=VSP_037979;
CC Name=6;
CC IsoId=Q00005-6; Sequence=VSP_044923;
CC Name=7;
CC IsoId=Q00005-7; Sequence=VSP_045748;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: The N-terminal 26 residues of isoform 2 constitute a
CC cryptic mitochondrial matrix import signal with critical basic and
CC hydrophobic residues, that is necessary and sufficient for
CC targeting the PP2A holoenzyme to the outer mitochondrial membrane
CC (OMM) and does not affect holoenzyme formation or catalytic
CC activity (By similarity).
CC -!- DOMAIN: The last WD repeat of isoform 2 constitutes a
CC mitochondrial stop-transfer domain that confers resistance to the
CC unfolding step process required for import and therefore prevents
CC PPP2R2B matrix translocation and signal sequence cleavage (By
CC similarity).
CC -!- DISEASE: Spinocerebellar ataxia 12 (SCA12) [MIM:604326]:
CC Spinocerebellar ataxia is a clinically and genetically
CC heterogeneous group of cerebellar disorders. Patients show
CC progressive incoordination of gait and often poor coordination of
CC hands, speech and eye movements, due to degeneration of the
CC cerebellum with variable involvement of the brainstem and spinal
CC cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit B
CC family.
CC -!- SIMILARITY: Contains 7 WD repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH31790.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAG51642.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAG51642.1; Type=Erroneous termination; Positions=116; Note=Translated as Lys;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PPP2R2B";
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DR EMBL; M64930; AAA36493.1; -; mRNA.
DR EMBL; AK056192; BAG51642.1; ALT_SEQ; mRNA.
DR EMBL; AK289717; BAF82406.1; -; mRNA.
DR EMBL; AK294659; BAH11838.1; -; mRNA.
DR EMBL; AK295347; BAH12040.1; -; mRNA.
DR EMBL; AC008728; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011357; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW61829.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61831.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61832.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61833.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61834.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61835.1; -; Genomic_DNA.
DR EMBL; BC031790; AAH31790.1; ALT_INIT; mRNA.
DR EMBL; BI490027; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BI669304; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; B38351; B38351.
DR RefSeq; NP_001258828.1; NM_001271899.1.
DR RefSeq; NP_001258829.1; NM_001271900.1.
DR RefSeq; NP_001258877.1; NM_001271948.1.
DR RefSeq; NP_858060.2; NM_181674.2.
DR RefSeq; NP_858061.2; NM_181675.3.
DR RefSeq; NP_858062.1; NM_181676.2.
DR RefSeq; NP_858063.1; NM_181677.2.
DR RefSeq; NP_858064.1; NM_181678.2.
DR UniGene; Hs.627618; -.
DR UniGene; Hs.655213; -.
DR ProteinModelPortal; Q00005; -.
DR SMR; Q00005; 23-442.
DR IntAct; Q00005; 167.
DR MINT; MINT-6631022; -.
DR STRING; 9606.ENSP00000336591; -.
DR PhosphoSite; Q00005; -.
DR DMDM; 231446; -.
DR PaxDb; Q00005; -.
DR PRIDE; Q00005; -.
DR DNASU; 5521; -.
DR Ensembl; ENST00000336640; ENSP00000336591; ENSG00000156475.
DR Ensembl; ENST00000356826; ENSP00000349283; ENSG00000156475.
DR Ensembl; ENST00000394409; ENSP00000377931; ENSG00000156475.
DR Ensembl; ENST00000394410; ENSP00000377932; ENSG00000156475.
DR Ensembl; ENST00000394411; ENSP00000377933; ENSG00000156475.
DR Ensembl; ENST00000394413; ENSP00000377935; ENSG00000156475.
DR Ensembl; ENST00000394414; ENSP00000377936; ENSG00000156475.
DR Ensembl; ENST00000453001; ENSP00000398779; ENSG00000156475.
DR Ensembl; ENST00000504198; ENSP00000421396; ENSG00000156475.
DR Ensembl; ENST00000508545; ENSP00000431320; ENSG00000156475.
DR GeneID; 5521; -.
DR KEGG; hsa:5521; -.
DR UCSC; uc003lok.5; human.
DR CTD; 5521; -.
DR GeneCards; GC05M145969; -.
DR HGNC; HGNC:9305; PPP2R2B.
DR HPA; HPA038118; -.
DR MIM; 604325; gene.
DR MIM; 604326; phenotype.
DR neXtProt; NX_Q00005; -.
DR Orphanet; 98762; Spinocerebellar ataxia type 12.
DR PharmGKB; PA33669; -.
DR eggNOG; COG5170; -.
DR HOVERGEN; HBG000012; -.
DR InParanoid; Q00005; -.
DR KO; K04354; -.
DR OMA; ILHTTWH; -.
DR OrthoDB; EOG7Q5HCZ; -.
DR SignaLink; Q00005; -.
DR ChiTaRS; PPP2R2B; human.
DR GeneWiki; PPP2R2B; -.
DR GenomeRNAi; 5521; -.
DR NextBio; 21356; -.
DR PRO; PR:Q00005; -.
DR ArrayExpress; Q00005; -.
DR Bgee; Q00005; -.
DR CleanEx; HS_PPP2R2B; -.
DR Genevestigator; Q00005; -.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IEA:Ensembl.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:ProtInc.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0033554; P:cellular response to stress; IEA:Ensembl.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IEA:Ensembl.
DR GO; GO:0034047; P:regulation of protein phosphatase type 2A activity; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 3.
DR InterPro; IPR000009; PP2A_PR55.
DR InterPro; IPR018067; PP2A_PR55_CS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR017986; WD40_repeat_dom.
DR PANTHER; PTHR11871; PTHR11871; 1.
DR PIRSF; PIRSF037309; PP2A_PR55; 1.
DR PRINTS; PR00600; PP2APR55.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 3.
DR PROSITE; PS01024; PR55_1; 1.
DR PROSITE; PS01025; PR55_2; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; FALSE_NEG.
DR PROSITE; PS50294; WD_REPEATS_REGION; FALSE_NEG.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Complete proteome; Cytoplasm;
KW Cytoskeleton; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Neurodegeneration; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; Spinocerebellar ataxia; WD repeat.
FT CHAIN 1 443 Serine/threonine-protein phosphatase 2A
FT 55 kDa regulatory subunit B beta isoform.
FT /FTId=PRO_0000071421.
FT REPEAT 22 61 WD 1.
FT REPEAT 87 128 WD 2.
FT REPEAT 171 209 WD 3.
FT REPEAT 220 260 WD 4.
FT REPEAT 279 317 WD 5.
FT REPEAT 334 375 WD 6.
FT REPEAT 410 442 WD 7.
FT MOD_RES 275 275 Phosphoserine (By similarity).
FT MOD_RES 295 295 Phosphotyrosine (By similarity).
FT MOD_RES 298 298 Phosphothreonine (By similarity).
FT VAR_SEQ 1 23 MEEDIDTRKINNSFLRDHSYATE -> MNYPDENTYGNK
FT (in isoform 6).
FT /FTId=VSP_044923.
FT VAR_SEQ 1 21 MEEDIDTRKINNSFLRDHSYA -> MKCFSRYLPYIFRPPN
FT TILSSSCH (in isoform 2).
FT /FTId=VSP_037976.
FT VAR_SEQ 1 21 MEEDIDTRKINNSFLRDHSYA -> MIPGIGTLTQDTLWCF
FT SQVKGTIEIGT (in isoform 3).
FT /FTId=VSP_037977.
FT VAR_SEQ 1 1 M -> MVLQPSERHYRDWNHRRLGPWCSPTGSPAPLSCETG
FT CGEGSWILVCRLLVPTQVSLLSM (in isoform 4).
FT /FTId=VSP_037978.
FT VAR_SEQ 1 1 M -> MLLSLPALHLQTSEHHPFFQLPHRRLGPWCSPTGSP
FT APLSCETGCGEGSWILVCRLLVPTQVSLLSM (in
FT isoform 5).
FT /FTId=VSP_037979.
FT VAR_SEQ 1 1 M -> MHQPPPASCSSSSSSSSSSCECARVGVRVSALAPAA
FT APCPAPRQLPYPRLPEPPSRGTSTLIPARLGPWCSPTGSPA
FT PLSCETGCGEGSWILVCRLLVPTQVSLLSM (in
FT isoform 7).
FT /FTId=VSP_045748.
FT VARIANT 36 36 G -> V (in dbSNP:rs11547494).
FT /FTId=VAR_051738.
FT CONFLICT 22 22 T -> A (in Ref. 2; BAH11838).
FT CONFLICT 62 62 H -> N (in Ref. 5; BI669304).
FT CONFLICT 109 109 S -> F (in Ref. 2; BAH12040).
FT CONFLICT 163 163 T -> S (in Ref. 6; BI490027).
FT CONFLICT 164 164 P -> S (in Ref. 2; BAF82406).
FT CONFLICT 292 292 S -> R (in Ref. 2; BAH12040).
SQ SEQUENCE 443 AA; 51710 MW; C383C834B2852B8F 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
YLTVKVWDLN MENRPIETYQ VHDYLRSKLC SLYENDCIFD KFECVWNGSD SVIMTGSYNN
FFRMFDRNTK RDVTLEASRE NSKPRAILKP RKVCVGGKRR KDEISVDSLD FSKKILHTAW
HPSENIIAVA ATNNLYIFQD KVN
//
MIM
604325
*RECORD*
*FIELD* NO
604325
*FIELD* TI
*604325 PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B, BETA; PPP2R2B
;;PP2APR55-BETA;;
read morePP2AB55-BETA;;
PP2AB-BETA;;
PR55-BETA;;
B55-BETA
*FIELD* TX
DESCRIPTION
The PPP2R2B gene encodes a brain-specific regulatory subunit B of
protein phosphatase 2. Protein phosphatase 2A (PP2A), a heterotrimeric
serine/threonine phosphatase, has been implicated in a variety of
regulatory processes, including cell growth and division, muscle
contraction, and gene transcription. PP2A is composed of a 36-kD
catalytic subunit (176915), a highly homologous 65-kD structural subunit
(176915), and any of several different regulatory subunits that control
its specificity, including PPP2R2B (Mayer et al., 1991).
CLONING
By screening lung fibroblast and fetal brain cDNA libraries using 2
overlapping oligonucleotides corresponding to a tryptic peptide derived
from the 55-kD subunit of rabbit PP2A (PR55), Mayer et al. (1991)
isolated human cDNAs encoding PPP2R2A (604941) and PPP2R2B, which they
termed PR55-alpha and PR55-beta, respectively. Sequence analysis
indicated that the PPP2R2B gene encodes a deduced 443-amino acid protein
of approximately 52 kD. The nucleotide sequence of PPP2R2B is 75%
identical to PPP2R2A in the coding region. Northern blot analysis
detected strong expression of an approximately 2.5-kb PPP2R2A transcript
in a neuroblastoma cell line but weak or no expression in other
neuroblastoma and tumor cell lines.
GENE FUNCTION
Using deletion/site-directed mutagenesis, cDNA overexpression assays,
DNA pull-down and chromatin immunoprecipation assays, and in silico
analysis, Lin et al. (2010) found that CREB1 (123810) and SP1 (189906)
upregulate PPP2R2B expression by binding to conserved sequences upstream
of the polymorphic CAG repeat site, whereas TFAP4 (600743) binds
downstream of the CAG repeats to downregulate PPP2R2B expression. The
CAG repeats themselves also function as a cis element to upregulate
PPP2R2B expression.
MOLECULAR GENETICS
Schols et al. (1997) identified a novel form of autosomal dominant
spinocerebellar ataxia (SCA), termed SCA12 (604326), in a large
pedigree, 'R,' of German descent. The phenotype was variable, but the
prototypic phenotype was that of a classic spinocerebellar ataxia, and
the disease resembled the spinocerebellar ataxias more closely than any
other form of neurodegenerative disorder. Holmes et al. (1999) used
repeat expansion detection (RED), as described by Schalling et al.
(1993), to identify an expanded CAG repeat (604325.0001) in the proband
and other affected family members with SCA12. From the proband, they
cloned a 2.5-kb genomic clone that contained a repeat of 93
uninterrupted CAGs. The CAG tract lies 133 nucleotides upstream of the
reported transcription start site of the PPP2R2B gene, encoding a
brain-specific regulatory subunit of the protein phosphatase PP2A. The
PPP2R2B gene had been mapped to 5q31-q33 between markers D5S436 and
D5S470. The region surrounding the CAG tract showed no homology with any
additional genes in the EST database. Although the possibility that the
CAG tract may lie within an unidentified gene overlapping or adjacent to
PPP2R2B could not be excluded, an antibody probe did not detect
polyglutamine expansions in protein derived from lymphoblastoid cell
lines of affected family members. The correlation between repeat
expansion and disease in pedigree R, the lack of expansions in controls,
and the known capacity of expansion mutations outside of protein-coding
regions to cause disease indicated that the expansion was causative.
Although the precise role of the subunit encoded by PPP2R2B remained to
be determined, the trimeric holoenzyme PP2A had been implicated in a
number of cellular functions (Millward et al., 1999), including
modulation of cell cycle progression (Mayer-Jaekel et al., 1993), tau
phosphorylation (Sontag et al., 1999), and apoptosis (Deng et al., 1998;
Santoro et al., 1998).
*FIELD* AV
.0001
SPINOCEREBELLAR ATAXIA 12
PPP2R2B, (CAG)n EXPANSION
In a large pedigree, 'R,' of German descent with SCA12 (604326)
described by Schols et al. (1997), Holmes et al. (1999) used repeat
expansion detection (RED) to identify an expanded CAG repeat in the
5-prime region of the PPP2R2B gene in the proband and other affected
family members. From the proband, they cloned a 2.5-kb genomic clone
that contained a repeat of 93 uninterrupted CAGs. All 10 affected family
members still living had a repeat expansion. They also tested 8
unaffected offspring of affected family members, 5 older than age 60
years and 3 aged 42 to 49 years. Seven lacked an expansion and a
49-year-old, with no signs or symptoms of SCA12, had an expansion. There
was no apparent correlation between repeat size and age of onset,
although the range of expanded alleles was relatively narrow (66 to 78
repeats) and the precise age of onset of tremor, typically the first
symptom, was difficult to define in this disorder.
In a screening of 145 families with autosomal dominant cerebellar
ataxia, Fujigasaki et al. (2001) identified a family from India with the
CAG repeat expansion in the PPP2R2B gene.
Among 20 families from northern India with SCA12, Bahl et al. (2005)
identified expanded CAG repeats ranging from 51 to 69 triplets.
Unaffected individuals had repeats ranging from 8 to 23 triplets. Of
note, 1 asymptomatic individual was homozygous for an expanded repeat
(52 and 59 triplets). Haplotype analysis identified 1 haplotype that was
associated with the disease alleles, indicating a common founder. Bahl
et al. (2005) estimated that SCA12 accounts for about 16% of all ADCA
cases in northern India.
In in vitro studies, Lin et al. (2010) demonstrated that expanded CAG
repeats in the 5-prime region of the PPP2R2B gene caused increased gene
expression.
*FIELD* RF
1. Bahl, S.; Virdi, K.; Mittal, U.; Sachdeva, M. P.; Kalla, A. K.;
Holmes, S. E.; O'Hearn, E.; Margolis, R. L.; Jain, S.; Srivastava,
A. K.; Mukerji, M.: Evidence of a common founder for SCA12 in the
Indian population. Ann. Hum. Genet. 69: 528-534, 2005.
2. Deng, X.; Ito, T.; Carr, B.; Mumby, M.; May, W. S., Jr.: Reversible
phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is
mediated by direct interaction with protein phosphatase 2A. J. Biol.
Chem. 273: 34157-34163, 1998.
3. Fujigasaki, H.; Verma, I. C.; Camuzat, A.; Margolis, R. L.; Zander,
C.; Lebre, A.-S.; Jamot, L.; Saxena, R.; Anand, I.; Holmes, S. E.;
Ross, C. A.; Durr, A.; Brice, A.: SCA12 is a rare locus for autosomal
dominant cerebellar ataxia: a study of an Indian family. Ann. Neurol. 49:
117-121, 2001.
4. Holmes, S. E.; O'Hearn, E. E.; McInnis, M. G.; Gorelick-Feldman,
D. A.; Kleiderlein, J. J.; Callahan, C.; Kwak, N. G.; Ingersoll-Ashworth,
R. G.; Sherr, M.; Sumner, A. J.; Sharp, A. H.; Ananth, U.; Seltzer,
W. K.; Boss, M. A.; Vieria-Saecker, A.-M.; Epplen, J. T.; Riess, O.;
Ross, C. A.; Margolis, R. L.: Expansion of a novel CAG trinucleotide
repeat in the 5-prime region of PPP2R2B is associated with SCA12.
(Letter) Nature Genet. 23: 391-392, 1999.
5. Lin, C.-H.; Chen, C.-M.; Hou, Y.-T.; Wu, Y.-R.; Hsieh-Li, H.-M.;
Su, M.-T.; Lee-Chen, G.-J.: The CAG repeat in SCA12 functions as
a cis element to up-regulate PPP2R2B expression. Hum. Genet. 128:
205-212, 2010.
6. Mayer, R. E.; Hendrix, P.; Cron, P.; Matthies, R.; Stone, S. R.;
Goris, J.; Merlevede, W.; Hofsteenge, J.; Hemmings, B. A.: Structure
of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence
for a neuronal-specific isoform. Biochemistry 30: 3589-3597, 1991.
7. Mayer-Jaekel, R. E.; Ohkura, H.; Gomes, R.; Sunkel, C. E.; Baumgartner,
S.; Hemmings, B. A.; Glover, D. M.: The 55 kd regulatory subunit
of Drosophila protein phosphatase 2A is required for anaphase. Cell 72:
621-633, 1993.
8. Millward, T. A.; Zolnierowicz, S.; Hemmings, B. A.: Regulation
of protein kinase cascades by protein phosphatase 2A. Trends Biochem.
Sci. 24: 186-191, 1999.
9. Santoro, M. F.; Annand, R. R.; Robertson, M. M.; Peng, Y.-W.; Brady,
M. J.; Mankovich, J. A.; Hackett, M. C.; Ghayur, T.; Walter, G.; Wong,
W. W.; Giegel, D. A.: Regulation of protein phosphatase 2A activity
by caspase-3 during apoptosis. J. Biol. Chem. 273: 13119-13128,
1998.
10. Schalling, M.; Hudson, T. J.; Buetow, K. H.; Housman, D. E.:
Direct detection of novel expanded trinucleotide repeats in the human
genome. Nature Genet. 4: 135-139, 1993.
11. Schols, L.; Amoiridis, G.; Buttner, T.; Przuntek, H.; Epplen,
J. T.; Riess, O.: Autosomal dominant cerebellar ataxia: phenotypic
differences in genetically defined subtypes? Ann. Neurol. 42: 924-932,
1997.
12. Sontag, E.; Nunbhakdi-Craig, V.; Lee, G.; Brandt, R.; Kamibayashi,
C.; Kuret, J.; White, C. L., III; Mumby, M. C.; Bloom, G. S.: Molecular
interactions among protein phosphatase 2A, tau, and microtubules. J.
Biol. Chem. 274: 25490-25498, 1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/6/2011
Cassandra L. Kniffin - updated: 4/6/2010
Victor A. McKusick - updated: 2/22/2002
Paul J. Converse - updated: 5/10/2000
*FIELD* CD
Victor A. McKusick: 11/30/1999
*FIELD* ED
carol: 10/06/2011
ckniffin: 10/6/2011
wwang: 4/6/2010
ckniffin: 3/30/2010
wwang: 4/23/2008
mgross: 12/1/2006
carol: 3/11/2002
cwells: 3/5/2002
terry: 2/22/2002
terry: 12/7/2001
mgross: 5/10/2000
terry: 2/28/2000
alopez: 11/30/1999
*RECORD*
*FIELD* NO
604325
*FIELD* TI
*604325 PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B, BETA; PPP2R2B
;;PP2APR55-BETA;;
read morePP2AB55-BETA;;
PP2AB-BETA;;
PR55-BETA;;
B55-BETA
*FIELD* TX
DESCRIPTION
The PPP2R2B gene encodes a brain-specific regulatory subunit B of
protein phosphatase 2. Protein phosphatase 2A (PP2A), a heterotrimeric
serine/threonine phosphatase, has been implicated in a variety of
regulatory processes, including cell growth and division, muscle
contraction, and gene transcription. PP2A is composed of a 36-kD
catalytic subunit (176915), a highly homologous 65-kD structural subunit
(176915), and any of several different regulatory subunits that control
its specificity, including PPP2R2B (Mayer et al., 1991).
CLONING
By screening lung fibroblast and fetal brain cDNA libraries using 2
overlapping oligonucleotides corresponding to a tryptic peptide derived
from the 55-kD subunit of rabbit PP2A (PR55), Mayer et al. (1991)
isolated human cDNAs encoding PPP2R2A (604941) and PPP2R2B, which they
termed PR55-alpha and PR55-beta, respectively. Sequence analysis
indicated that the PPP2R2B gene encodes a deduced 443-amino acid protein
of approximately 52 kD. The nucleotide sequence of PPP2R2B is 75%
identical to PPP2R2A in the coding region. Northern blot analysis
detected strong expression of an approximately 2.5-kb PPP2R2A transcript
in a neuroblastoma cell line but weak or no expression in other
neuroblastoma and tumor cell lines.
GENE FUNCTION
Using deletion/site-directed mutagenesis, cDNA overexpression assays,
DNA pull-down and chromatin immunoprecipation assays, and in silico
analysis, Lin et al. (2010) found that CREB1 (123810) and SP1 (189906)
upregulate PPP2R2B expression by binding to conserved sequences upstream
of the polymorphic CAG repeat site, whereas TFAP4 (600743) binds
downstream of the CAG repeats to downregulate PPP2R2B expression. The
CAG repeats themselves also function as a cis element to upregulate
PPP2R2B expression.
MOLECULAR GENETICS
Schols et al. (1997) identified a novel form of autosomal dominant
spinocerebellar ataxia (SCA), termed SCA12 (604326), in a large
pedigree, 'R,' of German descent. The phenotype was variable, but the
prototypic phenotype was that of a classic spinocerebellar ataxia, and
the disease resembled the spinocerebellar ataxias more closely than any
other form of neurodegenerative disorder. Holmes et al. (1999) used
repeat expansion detection (RED), as described by Schalling et al.
(1993), to identify an expanded CAG repeat (604325.0001) in the proband
and other affected family members with SCA12. From the proband, they
cloned a 2.5-kb genomic clone that contained a repeat of 93
uninterrupted CAGs. The CAG tract lies 133 nucleotides upstream of the
reported transcription start site of the PPP2R2B gene, encoding a
brain-specific regulatory subunit of the protein phosphatase PP2A. The
PPP2R2B gene had been mapped to 5q31-q33 between markers D5S436 and
D5S470. The region surrounding the CAG tract showed no homology with any
additional genes in the EST database. Although the possibility that the
CAG tract may lie within an unidentified gene overlapping or adjacent to
PPP2R2B could not be excluded, an antibody probe did not detect
polyglutamine expansions in protein derived from lymphoblastoid cell
lines of affected family members. The correlation between repeat
expansion and disease in pedigree R, the lack of expansions in controls,
and the known capacity of expansion mutations outside of protein-coding
regions to cause disease indicated that the expansion was causative.
Although the precise role of the subunit encoded by PPP2R2B remained to
be determined, the trimeric holoenzyme PP2A had been implicated in a
number of cellular functions (Millward et al., 1999), including
modulation of cell cycle progression (Mayer-Jaekel et al., 1993), tau
phosphorylation (Sontag et al., 1999), and apoptosis (Deng et al., 1998;
Santoro et al., 1998).
*FIELD* AV
.0001
SPINOCEREBELLAR ATAXIA 12
PPP2R2B, (CAG)n EXPANSION
In a large pedigree, 'R,' of German descent with SCA12 (604326)
described by Schols et al. (1997), Holmes et al. (1999) used repeat
expansion detection (RED) to identify an expanded CAG repeat in the
5-prime region of the PPP2R2B gene in the proband and other affected
family members. From the proband, they cloned a 2.5-kb genomic clone
that contained a repeat of 93 uninterrupted CAGs. All 10 affected family
members still living had a repeat expansion. They also tested 8
unaffected offspring of affected family members, 5 older than age 60
years and 3 aged 42 to 49 years. Seven lacked an expansion and a
49-year-old, with no signs or symptoms of SCA12, had an expansion. There
was no apparent correlation between repeat size and age of onset,
although the range of expanded alleles was relatively narrow (66 to 78
repeats) and the precise age of onset of tremor, typically the first
symptom, was difficult to define in this disorder.
In a screening of 145 families with autosomal dominant cerebellar
ataxia, Fujigasaki et al. (2001) identified a family from India with the
CAG repeat expansion in the PPP2R2B gene.
Among 20 families from northern India with SCA12, Bahl et al. (2005)
identified expanded CAG repeats ranging from 51 to 69 triplets.
Unaffected individuals had repeats ranging from 8 to 23 triplets. Of
note, 1 asymptomatic individual was homozygous for an expanded repeat
(52 and 59 triplets). Haplotype analysis identified 1 haplotype that was
associated with the disease alleles, indicating a common founder. Bahl
et al. (2005) estimated that SCA12 accounts for about 16% of all ADCA
cases in northern India.
In in vitro studies, Lin et al. (2010) demonstrated that expanded CAG
repeats in the 5-prime region of the PPP2R2B gene caused increased gene
expression.
*FIELD* RF
1. Bahl, S.; Virdi, K.; Mittal, U.; Sachdeva, M. P.; Kalla, A. K.;
Holmes, S. E.; O'Hearn, E.; Margolis, R. L.; Jain, S.; Srivastava,
A. K.; Mukerji, M.: Evidence of a common founder for SCA12 in the
Indian population. Ann. Hum. Genet. 69: 528-534, 2005.
2. Deng, X.; Ito, T.; Carr, B.; Mumby, M.; May, W. S., Jr.: Reversible
phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is
mediated by direct interaction with protein phosphatase 2A. J. Biol.
Chem. 273: 34157-34163, 1998.
3. Fujigasaki, H.; Verma, I. C.; Camuzat, A.; Margolis, R. L.; Zander,
C.; Lebre, A.-S.; Jamot, L.; Saxena, R.; Anand, I.; Holmes, S. E.;
Ross, C. A.; Durr, A.; Brice, A.: SCA12 is a rare locus for autosomal
dominant cerebellar ataxia: a study of an Indian family. Ann. Neurol. 49:
117-121, 2001.
4. Holmes, S. E.; O'Hearn, E. E.; McInnis, M. G.; Gorelick-Feldman,
D. A.; Kleiderlein, J. J.; Callahan, C.; Kwak, N. G.; Ingersoll-Ashworth,
R. G.; Sherr, M.; Sumner, A. J.; Sharp, A. H.; Ananth, U.; Seltzer,
W. K.; Boss, M. A.; Vieria-Saecker, A.-M.; Epplen, J. T.; Riess, O.;
Ross, C. A.; Margolis, R. L.: Expansion of a novel CAG trinucleotide
repeat in the 5-prime region of PPP2R2B is associated with SCA12.
(Letter) Nature Genet. 23: 391-392, 1999.
5. Lin, C.-H.; Chen, C.-M.; Hou, Y.-T.; Wu, Y.-R.; Hsieh-Li, H.-M.;
Su, M.-T.; Lee-Chen, G.-J.: The CAG repeat in SCA12 functions as
a cis element to up-regulate PPP2R2B expression. Hum. Genet. 128:
205-212, 2010.
6. Mayer, R. E.; Hendrix, P.; Cron, P.; Matthies, R.; Stone, S. R.;
Goris, J.; Merlevede, W.; Hofsteenge, J.; Hemmings, B. A.: Structure
of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence
for a neuronal-specific isoform. Biochemistry 30: 3589-3597, 1991.
7. Mayer-Jaekel, R. E.; Ohkura, H.; Gomes, R.; Sunkel, C. E.; Baumgartner,
S.; Hemmings, B. A.; Glover, D. M.: The 55 kd regulatory subunit
of Drosophila protein phosphatase 2A is required for anaphase. Cell 72:
621-633, 1993.
8. Millward, T. A.; Zolnierowicz, S.; Hemmings, B. A.: Regulation
of protein kinase cascades by protein phosphatase 2A. Trends Biochem.
Sci. 24: 186-191, 1999.
9. Santoro, M. F.; Annand, R. R.; Robertson, M. M.; Peng, Y.-W.; Brady,
M. J.; Mankovich, J. A.; Hackett, M. C.; Ghayur, T.; Walter, G.; Wong,
W. W.; Giegel, D. A.: Regulation of protein phosphatase 2A activity
by caspase-3 during apoptosis. J. Biol. Chem. 273: 13119-13128,
1998.
10. Schalling, M.; Hudson, T. J.; Buetow, K. H.; Housman, D. E.:
Direct detection of novel expanded trinucleotide repeats in the human
genome. Nature Genet. 4: 135-139, 1993.
11. Schols, L.; Amoiridis, G.; Buttner, T.; Przuntek, H.; Epplen,
J. T.; Riess, O.: Autosomal dominant cerebellar ataxia: phenotypic
differences in genetically defined subtypes? Ann. Neurol. 42: 924-932,
1997.
12. Sontag, E.; Nunbhakdi-Craig, V.; Lee, G.; Brandt, R.; Kamibayashi,
C.; Kuret, J.; White, C. L., III; Mumby, M. C.; Bloom, G. S.: Molecular
interactions among protein phosphatase 2A, tau, and microtubules. J.
Biol. Chem. 274: 25490-25498, 1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/6/2011
Cassandra L. Kniffin - updated: 4/6/2010
Victor A. McKusick - updated: 2/22/2002
Paul J. Converse - updated: 5/10/2000
*FIELD* CD
Victor A. McKusick: 11/30/1999
*FIELD* ED
carol: 10/06/2011
ckniffin: 10/6/2011
wwang: 4/6/2010
ckniffin: 3/30/2010
wwang: 4/23/2008
mgross: 12/1/2006
carol: 3/11/2002
cwells: 3/5/2002
terry: 2/22/2002
terry: 12/7/2001
mgross: 5/10/2000
terry: 2/28/2000
alopez: 11/30/1999
MIM
604326
*RECORD*
*FIELD* NO
604326
*FIELD* TI
#604326 SPINOCEREBELLAR ATAXIA 12; SCA12
*FIELD* TX
A number sign (#) is used with this entry because an expansion of a CAG
read morerepeat in a brain-specific regulatory subunit of the protein phosphatase
PP2A (PPP2R2B; 604325) is the cause of the disorder.
Normal alleles carry 7 to 32 triplets, whereas disease alleles carry 51
to 78 triplets (Bahl et al., 2005).
For a general discussion of autosomal dominant spinocerebellar ataxia,
see SCA1 (164400).
CLINICAL FEATURES
Holmes et al. (1999) identified a novel form of autosomal dominant
spinocerebellar ataxia (SCA), termed SCA12, in a large pedigree, 'R,' of
German descent. The phenotype was variable, but the prototypic phenotype
was that of a classic spinocerebellar ataxia, and the disease resembled
the spinocerebellar ataxias more closely than any other form of
neurodegenerative disorder. Age of onset ranged from 8 to 55 years. Most
individuals presented in the fourth decade with upper extremity tremor,
progressing over several decades to include head tremor, gait ataxia,
dysmetria, dysdiadokinesis, hyperreflexia, paucity of movement, abnormal
eye movements, and, in the oldest subjects, dementia. MRI or CT scans of
5 cases indicated both cortical and cerebellar atrophy. O'Hearn et al.
(2001) further characterized the phenotype of the 'R' pedigree and found
that action tremor of the head and arms was the most distinguishing
feature in comparison to other dominant SCAs.
Bahl et al. (2005) reported 25 patients from 20 Indian families with
SCA12 who were all members of an endogamous group with origins in the
state of Haryana in northern India. Five of the families had been
previously reported by Srivastava et al. (2001). Age at onset ranged
from 26 to 56 years (mean of 40.2 years), and most presented with upper
extremity tremor. Other features included hyperreflexia, dysarthria, and
mild or no gait ataxia. Two individuals had axial dystonia, and 3 had
facial myokymia. Almost half of patients had a subclinical sensory or
sensorimotor neuropathy. Brain MRI or CT scan showed cerebellar and
cerebral cortical atrophy. Anticipation was not observed.
MOLECULAR GENETICS
Holmes et al. (1999) used repeat expansion detection (RED), as described
by Schalling et al. (1993), to identify an expanded CAG repeat in the
PPP2R2B gene (604325.0001) in the proband and other affected family
members. Using PCR analysis, they demonstrated that the expression was
not 1 of 8 CAG repeats associated with a neurodegenerative disease or 1
of 3 CAG repeats known to undergo nonpathogenic expansion. From the
proband, they cloned a 2.5-kb genomic clone that contained a repeat of
93 uninterrupted CAGs. There was no apparent correlation between repeat
size and age of onset, although the range of expanded alleles was
relatively narrow (66 to 78 repeats) and the precise age of onset of
tremor, typically the first symptom, was difficult to define in this
disorder.
Holmes et al. (1999) assessed the PPP2R2B CAG repeat length in 394
unrelated neurologically normal individuals and 1,099 individuals with
neurologic diseases; no expansion was detected, suggesting that SCA12 is
rare. The CAG tract lies 133 nucleotides upstream of the reported
transcription start site of the PPP2R2B gene (604325), encoding a
brain-specific regulatory subunit of the protein phosphatase PP2A. The
PPP2R2B gene had been mapped to 5q31-q33 between markers D5S436 and
D5S470. Although the possibility that the CAG tract may lie within an
unidentified gene overlapping or adjacent to PPP2R2B, an antibody probe
did not detect polyglutamine expansions in protein derived from
lymphoblastoid cell lines of affected family members. A lod score of
4.61 at theta = 0.0 was obtained for linkage between the expanded repeat
and the disorder. It was possible that the expansion was in linkage
disequilibrium with a second, as-yet-unidentified, causative mutation.
However, the correlation between repeat expansion and disease in
pedigree R, the lack of expansions in controls, and the known capacity
of expansion mutations outside of protein-coding regions to cause
disease indicated that the expansion was causative.
POPULATION GENETICS
In a study of 145 families with autosomal dominant cerebellar ataxia
(ADCA), Fujigasaki et al. (2001) identified a family from India in which
6 affected and 3 unaffected members had an expanded CAG repeat in the
PPP2R2B gene (604325.0001). They determined the distribution of normal
PPP2R2B repeat length in 157 French and 100 Indian control subjects. In
the French population normal alleles contained 9 to 18 CAG triplets,
most frequently 10. In the Indian population, lengths of up to 45 CAG
triplets were observed, but the most common allele also carried 10
triplets.
Among 293 individuals with ADCA from 77 Indian families, Srivastava et
al. (2001) found an expanded SCA12 repeat in 6 patients and 3
asymptomatic at-risk individuals from 5 families, which accounted for 7%
of the ADCA cases. The expanded allele length ranged from 55 to 69
repeat units. Notable clinical features included age of onset from 26 to
50 years, initial presentation of hand tremor, lack of dementia, and
evidence of a subclinical sensory and motor neuropathy. Of the 77
families, SCA1 (164400) mutation was found in 15.6%, SCA2 (183090) in
24.7%, and SCA3 (109150) and SCA7 (164500) in 2.6% each. SCA6 (186086),
SCA8 (603680), and DRPLA (607462) mutations were not found.
In an ataxia clinic in California, Cholfin et al. (2001) screened 180
kindreds for the SCA12 mutation. The patients were of highly diverse
ethnic origins. None was found to carry the SCA12 expansion. The authors
concluded that the SCA12 mutation is a rare cause of spinocerebellar
degeneration but that it should be considered in patients with an
atypical clinical phenotype, especially when tremor is initially
present.
Among 20 families from northern India with SCA12, Bahl et al. (2005)
identified expanded CAG repeats ranging from 51 to 69 triplets.
Unaffected individuals had repeats ranging from 8 to 23 triplets. Of
note, 1 asymptomatic individual was homozygous for an expanded repeat
(52 and 59 triplets). Haplotype analysis identified 1 haplotype that was
associated with the disease alleles, indicating a common founder. Bahl
et al. (2005) estimated that SCA12 accounts for about 16% of all ADCA
cases in northern India.
*FIELD* RF
1. Bahl, S.; Virdi, K.; Mittal, U.; Sachdeva, M. P.; Kalla, A. K.;
Holmes, S. E.; O'Hearn, E.; Margolis, R. L.; Jain, S.; Srivastava,
A. K.; Mukerji, M.: Evidence of a common founder for SCA12 in the
Indian population. Ann. Hum. Genet. 69: 528-534, 2005.
2. Cholfin, J. A.; Sobrido, M.-J.; Perlman, S.; Pulst, S. M.; Geschwind,
D. H.: The SCA12 mutation as a rare cause of spinocerebellar ataxia. Arch.
Neurol. 58: 1833-1835, 2001.
3. Fujigasaki, H.; Verma, I. C.; Camuzat, A.; Margolis, R. L.; Zander,
C.; Lebre, A.-S.; Jamot, L.; Saxena, R.; Anand, I.; Holmes, S. E.;
Ross, C. A.; Durr, A.; Brice, A.: SCA12 is a rare locus for autosomal
dominant cerebellar ataxia: a study of an Indian family. Ann. Neurol. 49:
117-121, 2001.
4. Holmes, S. E.; O'Hearn, E. E.; McInnis, M. G.; Gorelick-Feldman,
D. A.; Kleiderlein, J. J.; Callahan, C.; Kwak, N. G.; Ingersoll-Ashworth,
R. G.; Sherr, M.; Sumner, A. J.; Sharp, A. H.; Ananth, U.; Seltzer,
W. K.; Boss, M. A.; Vieria-Saecker, A.-M.; Epplen, J. T.; Riess, O.;
Ross, C. A.; Margolis, R. L.: Expansion of a novel CAG trinucleotide
repeat in the 5-prime region of PPP2R2B is associated with SCA12.
(Letter) Nature Genet. 23: 391-392, 1999.
5. O'Hearn, E.; Holmes, S. E.; Calvert, P. C.; Ross, C. A.; Margolis,
R. L.: SCA-12: tremor with cerebellar and cortical atrophy is associated
with a CAG repeat expansion. Neurology 56: 299-303, 2001.
6. Schalling, M.; Hudson, T. J.; Buetow, K. H.; Housman, D. E.: Direct
detection of novel expanded trinucleotide repeats in the human genome. Nature
Genet. 4: 135-139, 1993.
7. Srivastava, A. K.; Choudhry, S.; Gopinath, M. S.; Roy, S.; Tripathi,
M.; Brahmachari, S. K.; Jain, S.: Molecular and clinical correlation
in five Indian families with spinocerebellar ataxia 12. Ann. Neurol. 50:
796-800, 2001.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Face];
Facial myokymia;
[Eyes];
Ocular movement abnormalities
NEUROLOGIC:
[Central nervous system];
Progressive cerebellar ataxia;
Upper extremity action tremor;
Head tremor;
Dysarthria;
Dysmetria;
Dysdiadochokinesis;
Hyperreflexia;
Parkinsonism;
Axial dystonia;
Dementia;
Cortical atrophy;
Cerebellar atrophy;
[Peripheral nervous system];
Subclinical sensory or sensorimotor neuropathy;
[Behavioral/psychiatric manifestations];
Depression;
Anxiety;
Delusions
MISCELLANEOUS:
Age at onset 8 to 55 years (mean 40 years);
Normal CAG repeat length is 7 to 32 triplets;
Pathogenic CAG repeat length is 51 to 78 triplets
MOLECULAR BASIS:
Caused by expanded CAG trinucleotide repeats in the beta subunit of
the protein phosphatase 2 gene (PPP2R2B, 604325.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 3/30/2010
*FIELD* CD
Cassandra L. Kniffin: 8/2/2002
*FIELD* ED
joanna: 04/14/2010
ckniffin: 3/30/2010
ckniffin: 8/14/2002
*FIELD* CN
Cassandra L. Kniffin - updated: 3/30/2010
Cassandra L. Kniffin - updated: 10/28/2002
Victor A. McKusick - updated: 2/22/2002
Victor A. McKusick - updated: 12/21/2001
Kathryn R. Wagner - updated: 8/2/2001
*FIELD* CD
Victor A. McKusick: 11/30/1999
*FIELD* ED
alopez: 09/22/2011
wwang: 8/4/2010
wwang: 4/6/2010
ckniffin: 3/30/2010
wwang: 4/23/2008
carol: 1/24/2003
carol: 11/13/2002
ckniffin: 10/28/2002
ckniffin: 8/7/2002
carol: 3/11/2002
cwells: 3/5/2002
terry: 2/22/2002
cwells: 1/10/2002
cwells: 1/2/2002
terry: 12/21/2001
carol: 8/2/2001
joanna: 1/19/2001
alopez: 12/7/1999
alopez: 12/1/1999
alopez: 11/30/1999
*RECORD*
*FIELD* NO
604326
*FIELD* TI
#604326 SPINOCEREBELLAR ATAXIA 12; SCA12
*FIELD* TX
A number sign (#) is used with this entry because an expansion of a CAG
read morerepeat in a brain-specific regulatory subunit of the protein phosphatase
PP2A (PPP2R2B; 604325) is the cause of the disorder.
Normal alleles carry 7 to 32 triplets, whereas disease alleles carry 51
to 78 triplets (Bahl et al., 2005).
For a general discussion of autosomal dominant spinocerebellar ataxia,
see SCA1 (164400).
CLINICAL FEATURES
Holmes et al. (1999) identified a novel form of autosomal dominant
spinocerebellar ataxia (SCA), termed SCA12, in a large pedigree, 'R,' of
German descent. The phenotype was variable, but the prototypic phenotype
was that of a classic spinocerebellar ataxia, and the disease resembled
the spinocerebellar ataxias more closely than any other form of
neurodegenerative disorder. Age of onset ranged from 8 to 55 years. Most
individuals presented in the fourth decade with upper extremity tremor,
progressing over several decades to include head tremor, gait ataxia,
dysmetria, dysdiadokinesis, hyperreflexia, paucity of movement, abnormal
eye movements, and, in the oldest subjects, dementia. MRI or CT scans of
5 cases indicated both cortical and cerebellar atrophy. O'Hearn et al.
(2001) further characterized the phenotype of the 'R' pedigree and found
that action tremor of the head and arms was the most distinguishing
feature in comparison to other dominant SCAs.
Bahl et al. (2005) reported 25 patients from 20 Indian families with
SCA12 who were all members of an endogamous group with origins in the
state of Haryana in northern India. Five of the families had been
previously reported by Srivastava et al. (2001). Age at onset ranged
from 26 to 56 years (mean of 40.2 years), and most presented with upper
extremity tremor. Other features included hyperreflexia, dysarthria, and
mild or no gait ataxia. Two individuals had axial dystonia, and 3 had
facial myokymia. Almost half of patients had a subclinical sensory or
sensorimotor neuropathy. Brain MRI or CT scan showed cerebellar and
cerebral cortical atrophy. Anticipation was not observed.
MOLECULAR GENETICS
Holmes et al. (1999) used repeat expansion detection (RED), as described
by Schalling et al. (1993), to identify an expanded CAG repeat in the
PPP2R2B gene (604325.0001) in the proband and other affected family
members. Using PCR analysis, they demonstrated that the expression was
not 1 of 8 CAG repeats associated with a neurodegenerative disease or 1
of 3 CAG repeats known to undergo nonpathogenic expansion. From the
proband, they cloned a 2.5-kb genomic clone that contained a repeat of
93 uninterrupted CAGs. There was no apparent correlation between repeat
size and age of onset, although the range of expanded alleles was
relatively narrow (66 to 78 repeats) and the precise age of onset of
tremor, typically the first symptom, was difficult to define in this
disorder.
Holmes et al. (1999) assessed the PPP2R2B CAG repeat length in 394
unrelated neurologically normal individuals and 1,099 individuals with
neurologic diseases; no expansion was detected, suggesting that SCA12 is
rare. The CAG tract lies 133 nucleotides upstream of the reported
transcription start site of the PPP2R2B gene (604325), encoding a
brain-specific regulatory subunit of the protein phosphatase PP2A. The
PPP2R2B gene had been mapped to 5q31-q33 between markers D5S436 and
D5S470. Although the possibility that the CAG tract may lie within an
unidentified gene overlapping or adjacent to PPP2R2B, an antibody probe
did not detect polyglutamine expansions in protein derived from
lymphoblastoid cell lines of affected family members. A lod score of
4.61 at theta = 0.0 was obtained for linkage between the expanded repeat
and the disorder. It was possible that the expansion was in linkage
disequilibrium with a second, as-yet-unidentified, causative mutation.
However, the correlation between repeat expansion and disease in
pedigree R, the lack of expansions in controls, and the known capacity
of expansion mutations outside of protein-coding regions to cause
disease indicated that the expansion was causative.
POPULATION GENETICS
In a study of 145 families with autosomal dominant cerebellar ataxia
(ADCA), Fujigasaki et al. (2001) identified a family from India in which
6 affected and 3 unaffected members had an expanded CAG repeat in the
PPP2R2B gene (604325.0001). They determined the distribution of normal
PPP2R2B repeat length in 157 French and 100 Indian control subjects. In
the French population normal alleles contained 9 to 18 CAG triplets,
most frequently 10. In the Indian population, lengths of up to 45 CAG
triplets were observed, but the most common allele also carried 10
triplets.
Among 293 individuals with ADCA from 77 Indian families, Srivastava et
al. (2001) found an expanded SCA12 repeat in 6 patients and 3
asymptomatic at-risk individuals from 5 families, which accounted for 7%
of the ADCA cases. The expanded allele length ranged from 55 to 69
repeat units. Notable clinical features included age of onset from 26 to
50 years, initial presentation of hand tremor, lack of dementia, and
evidence of a subclinical sensory and motor neuropathy. Of the 77
families, SCA1 (164400) mutation was found in 15.6%, SCA2 (183090) in
24.7%, and SCA3 (109150) and SCA7 (164500) in 2.6% each. SCA6 (186086),
SCA8 (603680), and DRPLA (607462) mutations were not found.
In an ataxia clinic in California, Cholfin et al. (2001) screened 180
kindreds for the SCA12 mutation. The patients were of highly diverse
ethnic origins. None was found to carry the SCA12 expansion. The authors
concluded that the SCA12 mutation is a rare cause of spinocerebellar
degeneration but that it should be considered in patients with an
atypical clinical phenotype, especially when tremor is initially
present.
Among 20 families from northern India with SCA12, Bahl et al. (2005)
identified expanded CAG repeats ranging from 51 to 69 triplets.
Unaffected individuals had repeats ranging from 8 to 23 triplets. Of
note, 1 asymptomatic individual was homozygous for an expanded repeat
(52 and 59 triplets). Haplotype analysis identified 1 haplotype that was
associated with the disease alleles, indicating a common founder. Bahl
et al. (2005) estimated that SCA12 accounts for about 16% of all ADCA
cases in northern India.
*FIELD* RF
1. Bahl, S.; Virdi, K.; Mittal, U.; Sachdeva, M. P.; Kalla, A. K.;
Holmes, S. E.; O'Hearn, E.; Margolis, R. L.; Jain, S.; Srivastava,
A. K.; Mukerji, M.: Evidence of a common founder for SCA12 in the
Indian population. Ann. Hum. Genet. 69: 528-534, 2005.
2. Cholfin, J. A.; Sobrido, M.-J.; Perlman, S.; Pulst, S. M.; Geschwind,
D. H.: The SCA12 mutation as a rare cause of spinocerebellar ataxia. Arch.
Neurol. 58: 1833-1835, 2001.
3. Fujigasaki, H.; Verma, I. C.; Camuzat, A.; Margolis, R. L.; Zander,
C.; Lebre, A.-S.; Jamot, L.; Saxena, R.; Anand, I.; Holmes, S. E.;
Ross, C. A.; Durr, A.; Brice, A.: SCA12 is a rare locus for autosomal
dominant cerebellar ataxia: a study of an Indian family. Ann. Neurol. 49:
117-121, 2001.
4. Holmes, S. E.; O'Hearn, E. E.; McInnis, M. G.; Gorelick-Feldman,
D. A.; Kleiderlein, J. J.; Callahan, C.; Kwak, N. G.; Ingersoll-Ashworth,
R. G.; Sherr, M.; Sumner, A. J.; Sharp, A. H.; Ananth, U.; Seltzer,
W. K.; Boss, M. A.; Vieria-Saecker, A.-M.; Epplen, J. T.; Riess, O.;
Ross, C. A.; Margolis, R. L.: Expansion of a novel CAG trinucleotide
repeat in the 5-prime region of PPP2R2B is associated with SCA12.
(Letter) Nature Genet. 23: 391-392, 1999.
5. O'Hearn, E.; Holmes, S. E.; Calvert, P. C.; Ross, C. A.; Margolis,
R. L.: SCA-12: tremor with cerebellar and cortical atrophy is associated
with a CAG repeat expansion. Neurology 56: 299-303, 2001.
6. Schalling, M.; Hudson, T. J.; Buetow, K. H.; Housman, D. E.: Direct
detection of novel expanded trinucleotide repeats in the human genome. Nature
Genet. 4: 135-139, 1993.
7. Srivastava, A. K.; Choudhry, S.; Gopinath, M. S.; Roy, S.; Tripathi,
M.; Brahmachari, S. K.; Jain, S.: Molecular and clinical correlation
in five Indian families with spinocerebellar ataxia 12. Ann. Neurol. 50:
796-800, 2001.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Face];
Facial myokymia;
[Eyes];
Ocular movement abnormalities
NEUROLOGIC:
[Central nervous system];
Progressive cerebellar ataxia;
Upper extremity action tremor;
Head tremor;
Dysarthria;
Dysmetria;
Dysdiadochokinesis;
Hyperreflexia;
Parkinsonism;
Axial dystonia;
Dementia;
Cortical atrophy;
Cerebellar atrophy;
[Peripheral nervous system];
Subclinical sensory or sensorimotor neuropathy;
[Behavioral/psychiatric manifestations];
Depression;
Anxiety;
Delusions
MISCELLANEOUS:
Age at onset 8 to 55 years (mean 40 years);
Normal CAG repeat length is 7 to 32 triplets;
Pathogenic CAG repeat length is 51 to 78 triplets
MOLECULAR BASIS:
Caused by expanded CAG trinucleotide repeats in the beta subunit of
the protein phosphatase 2 gene (PPP2R2B, 604325.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 3/30/2010
*FIELD* CD
Cassandra L. Kniffin: 8/2/2002
*FIELD* ED
joanna: 04/14/2010
ckniffin: 3/30/2010
ckniffin: 8/14/2002
*FIELD* CN
Cassandra L. Kniffin - updated: 3/30/2010
Cassandra L. Kniffin - updated: 10/28/2002
Victor A. McKusick - updated: 2/22/2002
Victor A. McKusick - updated: 12/21/2001
Kathryn R. Wagner - updated: 8/2/2001
*FIELD* CD
Victor A. McKusick: 11/30/1999
*FIELD* ED
alopez: 09/22/2011
wwang: 8/4/2010
wwang: 4/6/2010
ckniffin: 3/30/2010
wwang: 4/23/2008
carol: 1/24/2003
carol: 11/13/2002
ckniffin: 10/28/2002
ckniffin: 8/7/2002
carol: 3/11/2002
cwells: 3/5/2002
terry: 2/22/2002
cwells: 1/10/2002
cwells: 1/2/2002
terry: 12/21/2001
carol: 8/2/2001
joanna: 1/19/2001
alopez: 12/7/1999
alopez: 12/1/1999
alopez: 11/30/1999