Full text data of PPP2R1B
PPP2R1B
[Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform (PP2A subunit A isoform PR65-beta; PP2A subunit A isoform R1-beta)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform (PP2A subunit A isoform PR65-beta; PP2A subunit A isoform R1-beta)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30154
ID 2AAB_HUMAN Reviewed; 601 AA.
AC P30154; A8MY67; B0YJ69; B4DGQ6; B4DK91; B4DWW5; F8W8G1; O75620;
read moreAC Q8NHV8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform;
DE AltName: Full=PP2A subunit A isoform PR65-beta;
DE AltName: Full=PP2A subunit A isoform R1-beta;
GN Name=PPP2R1B;
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 [GENOMIC DNA].
RX PubMed=9795170; DOI=10.1016/S0378-1119(98)00350-3;
RA Baysal B.E., Farr J.E., Goss J.R., Devlin B., Richard C.W. III;
RT "Genomic organization and precise physical location of protein
RT phosphatase 2A regulatory subunit A beta isoform gene on chromosome
RT band 11q23.";
RL Gene 217:107-116(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-8; SER-65;
RP ASP-90; PRO-101; GLU-343; ALA-448; GLY-504 AND ALA-545.
RX PubMed=9765152; DOI=10.1126/science.282.5387.284;
RA Wang S.S., Esplin E.D., Li J.L., Huang L., Gazdar A., Minna J.,
RA Evans G.A.;
RT "Alterations of the PPP2R1B gene in human lung and colon cancer.";
RL Science 282:284-287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11313745; DOI=10.1038/sj/ejhg/5200585;
RA Baysal B.E., Willett-Brozick J.E., Taschner P.E.M., Dauwerse J.G.,
RA Devilee P., Devlin B.;
RT "A high-resolution integrated map spanning the SDHD gene at 11q23: a
RT 1.1-Mb BAC contig, a partial transcript map and 15 new repeat
RT polymorphisms in a tumour-suppressor region.";
RL Eur. J. Hum. Genet. 9:121-129(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5).
RC TISSUE=Brain, Testis, and Thalamus;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-601 (ISOFORM 1).
RX PubMed=2159327; DOI=10.1021/bi00465a002;
RA Hemmings B.A., Adams-Pearson C., Maurer F., Mueller P., Goris J.,
RA Merlevede W., Hofsteenge J., Stone S.R.;
RT "Alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A
RT have a similar 39 amino acid repeating structure.";
RL Biochemistry 29:3166-3173(1990).
RN [10]
RP INTERACTION WITH RAF1.
RX PubMed=10801873; DOI=10.1074/jbc.M003259200;
RA Abraham D., Podar K., Pacher M., Kubicek M., Welzel N., Hemmings B.A.,
RA Dilworth S.M., Mischak H., Kolch W., Baccarini M.;
RT "Raf-1-associated protein phosphatase 2A as a positive regulator of
RT kinase activation.";
RL J. Biol. Chem. 275:22300-22304(2000).
RN [11]
RP INTERACTION WITH IPO9.
RX PubMed=12670497; DOI=10.1016/S0006-291X(03)00434-0;
RA Lubert E.J., Sarge K.D.;
RT "Interaction between protein phosphatase 2A and members of the
RT importin beta superfamily.";
RL Biochem. Biophys. Res. Commun. 303:908-913(2003).
RN [12]
RP INTERACTION WITH SGOL1.
RX PubMed=16541025; DOI=10.1038/nature04663;
RA Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T.,
RA Kawashima S.A., Watanabe Y.;
RT "Shugoshin collaborates with protein phosphatase 2A to protect
RT cohesin.";
RL Nature 441:46-52(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP VARIANT ASP-90.
RX PubMed=10597236; DOI=10.1038/sj.onc.1203070;
RA Campbell I.G., Manolitsas T.;
RT "Absence of PPP2R1B gene alterations in primary ovarian cancers.";
RL Oncogene 18:6367-6369(1999).
RN [16]
RP VARIANTS ALA-15; PRO-365; GLU-498; ILE-499 AND GLY-500.
RX PubMed=10896920; DOI=10.1136/gut.47.2.268;
RA Takagi Y., Futamura M., Yamaguchi K., Aoki S., Takahashi T., Saji S.;
RT "Alterations of the PPP2R1B gene located at 11q23 in human colorectal
RT cancers.";
RL Gut 47:268-271(2000).
RN [17]
RP VARIANT ASP-90.
RX PubMed=11996789; DOI=10.1016/S0165-4608(01)00597-0;
RA Hemmer S., Wasenius V.M., Haglund C., Zhu Y., Knuutila S.,
RA Franssila K., Joensuu H.;
RT "Alterations in the suppressor gene PPP2R1B in parathyroid
RT hyperplasias and adenomas.";
RL Cancer Genet. Cytogenet. 134:13-17(2002).
CC -!- FUNCTION: The PR65 subunit of protein phosphatase 2A serves as a
CC scaffolding molecule to coordinate the assembly of the catalytic
CC subunit and a variable regulatory B subunit.
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. Interacts with IPO9. Interacts with
CC SGOL1. Interacts with RAF1.
CC -!- INTERACTION:
CC O08785:Clock (xeno); NbExp=2; IntAct=EBI-357094, EBI-79859;
CC P67775:PPP2CA; NbExp=7; IntAct=EBI-357094, EBI-712311;
CC P63151:PPP2R2A; NbExp=2; IntAct=EBI-357094, EBI-1048931;
CC Q15172:PPP2R5A; NbExp=2; IntAct=EBI-357094, EBI-641666;
CC Q13362:PPP2R5C; NbExp=2; IntAct=EBI-357094, EBI-1266156;
CC Q14738:PPP2R5D; NbExp=2; IntAct=EBI-357094, EBI-396563;
CC Q16537:PPP2R5E; NbExp=3; IntAct=EBI-357094, EBI-968374;
CC P11233:RALA; NbExp=6; IntAct=EBI-357094, EBI-1036803;
CC O08722:Unc5b (xeno); NbExp=4; IntAct=EBI-357094, EBI-4404185;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P30154-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30154-2; Sequence=VSP_036460;
CC Name=3;
CC IsoId=P30154-3; Sequence=VSP_043379, VSP_036460;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=P30154-4; Sequence=VSP_045275;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=P30154-5; Sequence=VSP_046684;
CC -!- DOMAIN: Each HEAT repeat appears to consist of two alpha helices
CC joined by a hydrophilic region, the intrarepeat loop. The repeat
CC units may be arranged laterally to form a rod-like structure.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit A
CC family.
CC -!- SIMILARITY: Contains 15 HEAT repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA59983.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part;
CC Sequence=BAG59103.1; Type=Frameshift; Positions=540;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF083439; AAC63525.1; -; Genomic_DNA.
DR EMBL; AF083425; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083426; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083427; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083428; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083429; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083430; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083431; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083432; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083433; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083434; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083435; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083436; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083437; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083438; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF087438; AAC69624.1; -; mRNA.
DR EMBL; AF163473; AAG39644.1; -; mRNA.
DR EMBL; AK294716; BAG57867.1; -; mRNA.
DR EMBL; AK296455; BAG59103.1; ALT_FRAME; mRNA.
DR EMBL; AK301705; BAG63177.1; -; mRNA.
DR EMBL; EF445011; ACA06046.1; -; Genomic_DNA.
DR EMBL; EF445011; ACA06047.1; -; Genomic_DNA.
DR EMBL; AP000925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67150.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67151.1; -; Genomic_DNA.
DR EMBL; BC027596; AAH27596.1; -; mRNA.
DR EMBL; M65254; AAA59983.1; ALT_SEQ; mRNA.
DR PIR; B34541; B34541.
DR RefSeq; NP_001171033.1; NM_001177562.1.
DR RefSeq; NP_001171034.1; NM_001177563.1.
DR RefSeq; NP_002707.3; NM_002716.4.
DR RefSeq; NP_859050.1; NM_181699.2.
DR RefSeq; NP_859051.1; NM_181700.1.
DR UniGene; Hs.584790; -.
DR ProteinModelPortal; P30154; -.
DR SMR; P30154; 19-601.
DR IntAct; P30154; 63.
DR MINT; MINT-1150161; -.
DR STRING; 9606.ENSP00000311344; -.
DR PhosphoSite; P30154; -.
DR DMDM; 116241236; -.
DR PaxDb; P30154; -.
DR PRIDE; P30154; -.
DR DNASU; 5519; -.
DR Ensembl; ENST00000311129; ENSP00000311344; ENSG00000137713.
DR Ensembl; ENST00000341980; ENSP00000343317; ENSG00000137713.
DR Ensembl; ENST00000393055; ENSP00000376775; ENSG00000137713.
DR Ensembl; ENST00000426998; ENSP00000410671; ENSG00000137713.
DR Ensembl; ENST00000527614; ENSP00000437193; ENSG00000137713.
DR Ensembl; ENST00000571902; ENSP00000459644; ENSG00000262764.
DR Ensembl; ENST00000571959; ENSP00000459838; ENSG00000262764.
DR Ensembl; ENST00000573946; ENSP00000459456; ENSG00000262764.
DR Ensembl; ENST00000575443; ENSP00000459827; ENSG00000262764.
DR Ensembl; ENST00000576276; ENSP00000461254; ENSG00000262764.
DR GeneID; 5519; -.
DR KEGG; hsa:5519; -.
DR UCSC; uc010rwl.1; human.
DR CTD; 5519; -.
DR GeneCards; GC11M111642; -.
DR HGNC; HGNC:9303; PPP2R1B.
DR HPA; CAB004034; -.
DR HPA; HPA018908; -.
DR MIM; 603113; gene.
DR neXtProt; NX_P30154; -.
DR PharmGKB; PA33667; -.
DR eggNOG; NOG247268; -.
DR HOGENOM; HOG000078539; -.
DR HOVERGEN; HBG000011; -.
DR KO; K03456; -.
DR OMA; PQEDLET; -.
DR OrthoDB; EOG764722; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; PPP2R1B; human.
DR GeneWiki; PPP2R1B; -.
DR GenomeRNAi; 5519; -.
DR NextBio; 21346; -.
DR PRO; PR:P30154; -.
DR ArrayExpress; P30154; -.
DR Bgee; P30154; -.
DR CleanEx; HS_PPP2R1B; -.
DR Genevestigator; P30154; -.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000357; HEAT.
DR InterPro; IPR021133; HEAT_type_2.
DR Pfam; PF02985; HEAT; 2.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 12.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Polymorphism;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 601 Serine/threonine-protein phosphatase 2A
FT 65 kDa regulatory subunit A beta isoform.
FT /FTId=PRO_0000071403.
FT REPEAT 20 58 HEAT 1.
FT REPEAT 59 96 HEAT 2.
FT REPEAT 97 135 HEAT 3.
FT REPEAT 136 173 HEAT 4.
FT REPEAT 174 212 HEAT 5.
FT REPEAT 213 251 HEAT 6.
FT REPEAT 252 290 HEAT 7.
FT REPEAT 291 333 HEAT 8.
FT REPEAT 334 372 HEAT 9.
FT REPEAT 373 411 HEAT 10.
FT REPEAT 412 450 HEAT 11.
FT REPEAT 451 489 HEAT 12.
FT REPEAT 490 528 HEAT 13.
FT REPEAT 529 567 HEAT 14.
FT REPEAT 568 601 HEAT 15.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 39 102 Missing (in isoform 3).
FT /FTId=VSP_043379.
FT VAR_SEQ 103 229 Missing (in isoform 5).
FT /FTId=VSP_046684.
FT VAR_SEQ 344 388 Missing (in isoform 4).
FT /FTId=VSP_045275.
FT VAR_SEQ 598 601 LALA -> VAQRLRKLEFPVKDSGEPSVPRADKNHFPRPTV
FT PGEDMGKGPVYQLRGDTRDTLAQLGIAELVHFSQSTD (in
FT isoform 2 and isoform 3).
FT /FTId=VSP_036460.
FT VARIANT 8 8 G -> R (in a lung cancer patient;
FT dbSNP:rs142771326).
FT /FTId=VAR_022895.
FT VARIANT 15 15 G -> A (in a colorectal cancer patient).
FT /FTId=VAR_022896.
FT VARIANT 65 65 P -> S (in a lung cancer patient).
FT /FTId=VAR_022897.
FT VARIANT 90 90 G -> D (in a lung cancer patient;
FT dbSNP:rs1805076).
FT /FTId=VAR_006384.
FT VARIANT 101 101 L -> P (in a colon adenocarcinoma).
FT /FTId=VAR_022898.
FT VARIANT 343 343 K -> E (in a lung cancer patient).
FT /FTId=VAR_022899.
FT VARIANT 365 365 S -> P (in a colorectal cancer patient).
FT /FTId=VAR_022900.
FT VARIANT 448 448 V -> A (in a colon adenocarcinoma).
FT /FTId=VAR_022901.
FT VARIANT 498 498 V -> E (in a colorectal cancer patient).
FT /FTId=VAR_022902.
FT VARIANT 499 499 L -> I (in a colorectal cancer patient).
FT /FTId=VAR_022903.
FT VARIANT 500 500 V -> G (in a colorectal cancer patient).
FT /FTId=VAR_022904.
FT VARIANT 504 504 D -> G (in a lung cancer patient).
FT /FTId=VAR_022905.
FT VARIANT 545 545 V -> A (in a colon adenocarcinoma).
FT /FTId=VAR_022906.
FT CONFLICT 74 74 E -> V (in Ref. 9; AAA59983).
FT CONFLICT 178 178 I -> T (in Ref. 1; AAC63525, 3; AAG39644
FT and 9; AAA59983).
FT CONFLICT 211 211 D -> G (in Ref. 4; BAG57867).
FT CONFLICT 411 411 Q -> R (in Ref. 9; AAA59983).
FT CONFLICT 503 503 N -> S (in Ref. 4; BAG57867).
SQ SEQUENCE 601 AA; 66214 MW; 86AB20D7505210B0 CRC64;
MAGASELGTG PGAAGGDGDD SLYPIAVLID ELRNEDVQLR LNSIKKLSTI ALALGVERTR
SELLPFLTDT IYDEDEVLLA LAEQLGNFTG LVGGPDFAHC LLPPLENLAT VEETVVRDKA
VESLRQISQE HTPVALEAYF VPLVKRLASG DWFTSRTSAC GLFSVCYPRA SNAVKAEIRQ
QFRSLCSDDT PMVRRAAASK LGEFAKVLEL DSVKSEIVPL FTSLASDEQD SVRLLAVEAC
VSIAQLLSQD DLETLVMPTL RQAAEDKSWR VRYMVADRFS ELQKAMGPKI TLNDLIPAFQ
NLLKDCEAEV RAAAAHKVKE LGENLPIEDR ETIIMNQILP YIKELVSDTN QHVKSALASV
IMGLSTILGK ENTIEHLLPL FLAQLKDECP DVRLNIISNL DCVNEVIGIR QLSQSLLPAI
VELAEDAKWR VRLAIIEYMP LLAGQLGVEF FDEKLNSLCM AWLVDHVYAI REAATNNLMK
LVQKFGTEWA QNTIVPKVLV MANDPNYLHR MTTLFCINAL SEACGQEITT KQMLPIVLKM
AGDQVANVRF NVAKSLQKIG PILDTNALQG EVKPVLQKLG QDEDMDVKYF AQEAISVLAL
A
//
ID 2AAB_HUMAN Reviewed; 601 AA.
AC P30154; A8MY67; B0YJ69; B4DGQ6; B4DK91; B4DWW5; F8W8G1; O75620;
read moreAC Q8NHV8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform;
DE AltName: Full=PP2A subunit A isoform PR65-beta;
DE AltName: Full=PP2A subunit A isoform R1-beta;
GN Name=PPP2R1B;
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 [GENOMIC DNA].
RX PubMed=9795170; DOI=10.1016/S0378-1119(98)00350-3;
RA Baysal B.E., Farr J.E., Goss J.R., Devlin B., Richard C.W. III;
RT "Genomic organization and precise physical location of protein
RT phosphatase 2A regulatory subunit A beta isoform gene on chromosome
RT band 11q23.";
RL Gene 217:107-116(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-8; SER-65;
RP ASP-90; PRO-101; GLU-343; ALA-448; GLY-504 AND ALA-545.
RX PubMed=9765152; DOI=10.1126/science.282.5387.284;
RA Wang S.S., Esplin E.D., Li J.L., Huang L., Gazdar A., Minna J.,
RA Evans G.A.;
RT "Alterations of the PPP2R1B gene in human lung and colon cancer.";
RL Science 282:284-287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11313745; DOI=10.1038/sj/ejhg/5200585;
RA Baysal B.E., Willett-Brozick J.E., Taschner P.E.M., Dauwerse J.G.,
RA Devilee P., Devlin B.;
RT "A high-resolution integrated map spanning the SDHD gene at 11q23: a
RT 1.1-Mb BAC contig, a partial transcript map and 15 new repeat
RT polymorphisms in a tumour-suppressor region.";
RL Eur. J. Hum. Genet. 9:121-129(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5).
RC TISSUE=Brain, Testis, and Thalamus;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-601 (ISOFORM 1).
RX PubMed=2159327; DOI=10.1021/bi00465a002;
RA Hemmings B.A., Adams-Pearson C., Maurer F., Mueller P., Goris J.,
RA Merlevede W., Hofsteenge J., Stone S.R.;
RT "Alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A
RT have a similar 39 amino acid repeating structure.";
RL Biochemistry 29:3166-3173(1990).
RN [10]
RP INTERACTION WITH RAF1.
RX PubMed=10801873; DOI=10.1074/jbc.M003259200;
RA Abraham D., Podar K., Pacher M., Kubicek M., Welzel N., Hemmings B.A.,
RA Dilworth S.M., Mischak H., Kolch W., Baccarini M.;
RT "Raf-1-associated protein phosphatase 2A as a positive regulator of
RT kinase activation.";
RL J. Biol. Chem. 275:22300-22304(2000).
RN [11]
RP INTERACTION WITH IPO9.
RX PubMed=12670497; DOI=10.1016/S0006-291X(03)00434-0;
RA Lubert E.J., Sarge K.D.;
RT "Interaction between protein phosphatase 2A and members of the
RT importin beta superfamily.";
RL Biochem. Biophys. Res. Commun. 303:908-913(2003).
RN [12]
RP INTERACTION WITH SGOL1.
RX PubMed=16541025; DOI=10.1038/nature04663;
RA Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T.,
RA Kawashima S.A., Watanabe Y.;
RT "Shugoshin collaborates with protein phosphatase 2A to protect
RT cohesin.";
RL Nature 441:46-52(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP VARIANT ASP-90.
RX PubMed=10597236; DOI=10.1038/sj.onc.1203070;
RA Campbell I.G., Manolitsas T.;
RT "Absence of PPP2R1B gene alterations in primary ovarian cancers.";
RL Oncogene 18:6367-6369(1999).
RN [16]
RP VARIANTS ALA-15; PRO-365; GLU-498; ILE-499 AND GLY-500.
RX PubMed=10896920; DOI=10.1136/gut.47.2.268;
RA Takagi Y., Futamura M., Yamaguchi K., Aoki S., Takahashi T., Saji S.;
RT "Alterations of the PPP2R1B gene located at 11q23 in human colorectal
RT cancers.";
RL Gut 47:268-271(2000).
RN [17]
RP VARIANT ASP-90.
RX PubMed=11996789; DOI=10.1016/S0165-4608(01)00597-0;
RA Hemmer S., Wasenius V.M., Haglund C., Zhu Y., Knuutila S.,
RA Franssila K., Joensuu H.;
RT "Alterations in the suppressor gene PPP2R1B in parathyroid
RT hyperplasias and adenomas.";
RL Cancer Genet. Cytogenet. 134:13-17(2002).
CC -!- FUNCTION: The PR65 subunit of protein phosphatase 2A serves as a
CC scaffolding molecule to coordinate the assembly of the catalytic
CC subunit and a variable regulatory B subunit.
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. Interacts with IPO9. Interacts with
CC SGOL1. Interacts with RAF1.
CC -!- INTERACTION:
CC O08785:Clock (xeno); NbExp=2; IntAct=EBI-357094, EBI-79859;
CC P67775:PPP2CA; NbExp=7; IntAct=EBI-357094, EBI-712311;
CC P63151:PPP2R2A; NbExp=2; IntAct=EBI-357094, EBI-1048931;
CC Q15172:PPP2R5A; NbExp=2; IntAct=EBI-357094, EBI-641666;
CC Q13362:PPP2R5C; NbExp=2; IntAct=EBI-357094, EBI-1266156;
CC Q14738:PPP2R5D; NbExp=2; IntAct=EBI-357094, EBI-396563;
CC Q16537:PPP2R5E; NbExp=3; IntAct=EBI-357094, EBI-968374;
CC P11233:RALA; NbExp=6; IntAct=EBI-357094, EBI-1036803;
CC O08722:Unc5b (xeno); NbExp=4; IntAct=EBI-357094, EBI-4404185;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P30154-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30154-2; Sequence=VSP_036460;
CC Name=3;
CC IsoId=P30154-3; Sequence=VSP_043379, VSP_036460;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=P30154-4; Sequence=VSP_045275;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=P30154-5; Sequence=VSP_046684;
CC -!- DOMAIN: Each HEAT repeat appears to consist of two alpha helices
CC joined by a hydrophilic region, the intrarepeat loop. The repeat
CC units may be arranged laterally to form a rod-like structure.
CC -!- SIMILARITY: Belongs to the phosphatase 2A regulatory subunit A
CC family.
CC -!- SIMILARITY: Contains 15 HEAT repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA59983.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part;
CC Sequence=BAG59103.1; Type=Frameshift; Positions=540;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF083439; AAC63525.1; -; Genomic_DNA.
DR EMBL; AF083425; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083426; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083427; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083428; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083429; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083430; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083431; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083432; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083433; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083434; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083435; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083436; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083437; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF083438; AAC63525.1; JOINED; Genomic_DNA.
DR EMBL; AF087438; AAC69624.1; -; mRNA.
DR EMBL; AF163473; AAG39644.1; -; mRNA.
DR EMBL; AK294716; BAG57867.1; -; mRNA.
DR EMBL; AK296455; BAG59103.1; ALT_FRAME; mRNA.
DR EMBL; AK301705; BAG63177.1; -; mRNA.
DR EMBL; EF445011; ACA06046.1; -; Genomic_DNA.
DR EMBL; EF445011; ACA06047.1; -; Genomic_DNA.
DR EMBL; AP000925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67150.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67151.1; -; Genomic_DNA.
DR EMBL; BC027596; AAH27596.1; -; mRNA.
DR EMBL; M65254; AAA59983.1; ALT_SEQ; mRNA.
DR PIR; B34541; B34541.
DR RefSeq; NP_001171033.1; NM_001177562.1.
DR RefSeq; NP_001171034.1; NM_001177563.1.
DR RefSeq; NP_002707.3; NM_002716.4.
DR RefSeq; NP_859050.1; NM_181699.2.
DR RefSeq; NP_859051.1; NM_181700.1.
DR UniGene; Hs.584790; -.
DR ProteinModelPortal; P30154; -.
DR SMR; P30154; 19-601.
DR IntAct; P30154; 63.
DR MINT; MINT-1150161; -.
DR STRING; 9606.ENSP00000311344; -.
DR PhosphoSite; P30154; -.
DR DMDM; 116241236; -.
DR PaxDb; P30154; -.
DR PRIDE; P30154; -.
DR DNASU; 5519; -.
DR Ensembl; ENST00000311129; ENSP00000311344; ENSG00000137713.
DR Ensembl; ENST00000341980; ENSP00000343317; ENSG00000137713.
DR Ensembl; ENST00000393055; ENSP00000376775; ENSG00000137713.
DR Ensembl; ENST00000426998; ENSP00000410671; ENSG00000137713.
DR Ensembl; ENST00000527614; ENSP00000437193; ENSG00000137713.
DR Ensembl; ENST00000571902; ENSP00000459644; ENSG00000262764.
DR Ensembl; ENST00000571959; ENSP00000459838; ENSG00000262764.
DR Ensembl; ENST00000573946; ENSP00000459456; ENSG00000262764.
DR Ensembl; ENST00000575443; ENSP00000459827; ENSG00000262764.
DR Ensembl; ENST00000576276; ENSP00000461254; ENSG00000262764.
DR GeneID; 5519; -.
DR KEGG; hsa:5519; -.
DR UCSC; uc010rwl.1; human.
DR CTD; 5519; -.
DR GeneCards; GC11M111642; -.
DR HGNC; HGNC:9303; PPP2R1B.
DR HPA; CAB004034; -.
DR HPA; HPA018908; -.
DR MIM; 603113; gene.
DR neXtProt; NX_P30154; -.
DR PharmGKB; PA33667; -.
DR eggNOG; NOG247268; -.
DR HOGENOM; HOG000078539; -.
DR HOVERGEN; HBG000011; -.
DR KO; K03456; -.
DR OMA; PQEDLET; -.
DR OrthoDB; EOG764722; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; PPP2R1B; human.
DR GeneWiki; PPP2R1B; -.
DR GenomeRNAi; 5519; -.
DR NextBio; 21346; -.
DR PRO; PR:P30154; -.
DR ArrayExpress; P30154; -.
DR Bgee; P30154; -.
DR CleanEx; HS_PPP2R1B; -.
DR Genevestigator; P30154; -.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000357; HEAT.
DR InterPro; IPR021133; HEAT_type_2.
DR Pfam; PF02985; HEAT; 2.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 12.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Polymorphism;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 601 Serine/threonine-protein phosphatase 2A
FT 65 kDa regulatory subunit A beta isoform.
FT /FTId=PRO_0000071403.
FT REPEAT 20 58 HEAT 1.
FT REPEAT 59 96 HEAT 2.
FT REPEAT 97 135 HEAT 3.
FT REPEAT 136 173 HEAT 4.
FT REPEAT 174 212 HEAT 5.
FT REPEAT 213 251 HEAT 6.
FT REPEAT 252 290 HEAT 7.
FT REPEAT 291 333 HEAT 8.
FT REPEAT 334 372 HEAT 9.
FT REPEAT 373 411 HEAT 10.
FT REPEAT 412 450 HEAT 11.
FT REPEAT 451 489 HEAT 12.
FT REPEAT 490 528 HEAT 13.
FT REPEAT 529 567 HEAT 14.
FT REPEAT 568 601 HEAT 15.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 39 102 Missing (in isoform 3).
FT /FTId=VSP_043379.
FT VAR_SEQ 103 229 Missing (in isoform 5).
FT /FTId=VSP_046684.
FT VAR_SEQ 344 388 Missing (in isoform 4).
FT /FTId=VSP_045275.
FT VAR_SEQ 598 601 LALA -> VAQRLRKLEFPVKDSGEPSVPRADKNHFPRPTV
FT PGEDMGKGPVYQLRGDTRDTLAQLGIAELVHFSQSTD (in
FT isoform 2 and isoform 3).
FT /FTId=VSP_036460.
FT VARIANT 8 8 G -> R (in a lung cancer patient;
FT dbSNP:rs142771326).
FT /FTId=VAR_022895.
FT VARIANT 15 15 G -> A (in a colorectal cancer patient).
FT /FTId=VAR_022896.
FT VARIANT 65 65 P -> S (in a lung cancer patient).
FT /FTId=VAR_022897.
FT VARIANT 90 90 G -> D (in a lung cancer patient;
FT dbSNP:rs1805076).
FT /FTId=VAR_006384.
FT VARIANT 101 101 L -> P (in a colon adenocarcinoma).
FT /FTId=VAR_022898.
FT VARIANT 343 343 K -> E (in a lung cancer patient).
FT /FTId=VAR_022899.
FT VARIANT 365 365 S -> P (in a colorectal cancer patient).
FT /FTId=VAR_022900.
FT VARIANT 448 448 V -> A (in a colon adenocarcinoma).
FT /FTId=VAR_022901.
FT VARIANT 498 498 V -> E (in a colorectal cancer patient).
FT /FTId=VAR_022902.
FT VARIANT 499 499 L -> I (in a colorectal cancer patient).
FT /FTId=VAR_022903.
FT VARIANT 500 500 V -> G (in a colorectal cancer patient).
FT /FTId=VAR_022904.
FT VARIANT 504 504 D -> G (in a lung cancer patient).
FT /FTId=VAR_022905.
FT VARIANT 545 545 V -> A (in a colon adenocarcinoma).
FT /FTId=VAR_022906.
FT CONFLICT 74 74 E -> V (in Ref. 9; AAA59983).
FT CONFLICT 178 178 I -> T (in Ref. 1; AAC63525, 3; AAG39644
FT and 9; AAA59983).
FT CONFLICT 211 211 D -> G (in Ref. 4; BAG57867).
FT CONFLICT 411 411 Q -> R (in Ref. 9; AAA59983).
FT CONFLICT 503 503 N -> S (in Ref. 4; BAG57867).
SQ SEQUENCE 601 AA; 66214 MW; 86AB20D7505210B0 CRC64;
MAGASELGTG PGAAGGDGDD SLYPIAVLID ELRNEDVQLR LNSIKKLSTI ALALGVERTR
SELLPFLTDT IYDEDEVLLA LAEQLGNFTG LVGGPDFAHC LLPPLENLAT VEETVVRDKA
VESLRQISQE HTPVALEAYF VPLVKRLASG DWFTSRTSAC GLFSVCYPRA SNAVKAEIRQ
QFRSLCSDDT PMVRRAAASK LGEFAKVLEL DSVKSEIVPL FTSLASDEQD SVRLLAVEAC
VSIAQLLSQD DLETLVMPTL RQAAEDKSWR VRYMVADRFS ELQKAMGPKI TLNDLIPAFQ
NLLKDCEAEV RAAAAHKVKE LGENLPIEDR ETIIMNQILP YIKELVSDTN QHVKSALASV
IMGLSTILGK ENTIEHLLPL FLAQLKDECP DVRLNIISNL DCVNEVIGIR QLSQSLLPAI
VELAEDAKWR VRLAIIEYMP LLAGQLGVEF FDEKLNSLCM AWLVDHVYAI REAATNNLMK
LVQKFGTEWA QNTIVPKVLV MANDPNYLHR MTTLFCINAL SEACGQEITT KQMLPIVLKM
AGDQVANVRF NVAKSLQKIG PILDTNALQG EVKPVLQKLG QDEDMDVKYF AQEAISVLAL
A
//
MIM
603113
*RECORD*
*FIELD* NO
603113
*FIELD* TI
*603113 PROTEIN PHOSPHATASE 2, STRUCTURAL/REGULATORY SUBUNIT A, BETA; PPP2R1B
;;PP2AA-BETA
read more*FIELD* TX
DESCRIPTION
Serine/threonine protein phosphatase-2A (PP2A) is an important
regulatory enzyme that downregulates the mitogen-activated protein
kinase (MAPK) cascade (see 176948), relays signals for cell
proliferation, and may be linked to carcinogenesis. The PP2A holoenzyme
exists in several trimeric forms consisting of a 36-kD core catalytic
subunit (PP2AC; see 176915), a 65-kD structural/regulatory component
(PP2AA), and a variable regulatory subunit (PP2AB; see 604941) that
confers distinct properties on the holoenzyme. Each subunit exists as
multiple isoforms encoded by different genes, resulting in many forms of
the PP2A trimer that differ in expression pattern and specificity.
PPP2R1B encodes the beta isoform of the structural-regulatory A subunit,
or PP2AA-beta. This subunit is necessary for interaction of the
catalytic PP2AC and variable PP2AB subunits and is critical for
phosphatase activity (Walter and Mumby, 1993; Wang et al., 1998).
CLONING
Loss of heterozygosity (LOH) at chromosome 11q22-q24 has been associated
with lung, colon, breast, cervical, head and neck, and ovarian cancers,
as well as melanoma (Arai et al., 1996). Introduction of a normal
chromosome 11, or a derivative t(X;11) chromosome containing 11pter-q23,
can reverse the tumorigenic potential of several types of cancer cells
and Wilms tumor when introduced into nude mice. These studies suggest
that 1 or more tumor suppressor genes are located centromeric to the
t(X;11) breakpoint at chromosome 11q23. Because of a high frequency of
LOH in lung cancer cells involving D11S1647 and D11S1987, Wang et al.
(1998) systematically surveyed the region between these 2 markers for
candidate tumor suppressor genes. Over 100 candidate genes and ESTs were
identified from a radiation hybrid map of chromosome 11 and from the
NCBI transcript map, including an EST corresponding to PPP2R1B.
GENE STRUCTURE
Baysal et al. (1998) determined that the PPP2R1B gene contains 15 exons
and spans approximately 27 kb.
MAPPING
Wang et al. (1998) determined the precise physical location of the
PPP2R1B gene by colocalizing it within P1-derived artificial chromosome
(PAC) clones containing sequence tagged sites on chromosome 11q22-q23.
They confirmed that the PPP2R1B gene is located in a region showing high
frequency LOH.
GENE FUNCTION
Sablina et al. (2007) found that suppression of PP2A A-beta expression
allowed immortalized human cell lines to achieve a tumorigenic state.
Cancer-associated A-beta mutants failed to reverse this tumorigenic
phenotype, indicating that the mutants functioned as null alleles.
Cancer-derived A-beta mutants failed to form a complex with the small
GTPase RALA (179550), whereas wildtype A-beta-containing complexes
dephosphorylated RALA at ser183 and ser194, inactivating RALA and
abolishing its transforming function. Sablina et al. (2007) concluded
that PP2A A-beta is a tumor suppressor that transforms immortalized
cells by regulating RALA function.
MOLECULAR GENETICS
Wang et al. (1998) identified somatic alterations in the PPP2R1B gene in
15% (5 in 32) of primary lung tumors, 6% (4 in 70) of lung tumor-derived
cell lines, and 15% (2 in 13) of primary colon tumors. One deletion
mutation generated a truncated PP2A-A-beta protein that was unable to
bind to the catalytic subunit of the PP2A holoenzyme. The authors
suggested that the PPP2R1B gene product may suppress tumor development
through its role in cell cycle regulation and cellular growth control.
Deletion of 11q23 is a common alteration in parathyroid adenomas and
hyperplasias. To evaluate the role of the PPP2R1B gene in the
pathogenesis of parathyroid lesions, Hemmer et al. (2002) performed
PCR-based SSCP and direct sequencing on 6 parathyroid hyperplasias and
12 adenomas. The gly90-to-asp mutation (603113.0001) was detected in 1
adenoma; the common gly allele and the variant asp allele were detected
by direct sequencing in the patient's somatic cells. Hemmer et al.
(2002) concluded that mutations of PPP2R1B are not frequent in
parathyroid lesions, and that other genes located at 11q23 may be more
closely associated with the pathogenesis of parathyroid hyperplasia and
adenoma.
*FIELD* AV
.0001
LUNG CANCER
PPP2R1B, GLY90ASP
The alterations observed by Wang et al. (1998) in the PPP2R1B gene in
tumor-derived cell lines and primary tumors included deletions,
frameshifts, and point mutations leading to nonconservative amino acid
substitutions. In a lung cancer cell line 1 allele was found to carry a
G-to-A transition of nucleotide 298, which resulted in a change of the
conserved glycine-90 to aspartic acid (G90D). The G90D alteration was
found in 2 separate tumors and not in surrounding normal tissue, which
suggested that this site may be a hotspot for mutation.
Hemmer et al. (2002) found the G90D mutation in 1 of 12 parathyroid
adenomas. Somatic cells showed the presence of both the gly allele and
the variant asp allele.
*FIELD* RF
1. Arai, Y.; Hosoda, F.; Nakayama, K.; Ohki, M.: A yeast artificial
chromosome contig and NotI restriction map that spans the tumor suppressor
gene(s) locus, 11q.22.2-q23.3. Genomics 35: 196-206, 1996.
2. Baysal, B. E.; Farr, J. E.; Goss, J. R.; Devlin, B.; Richard, C.
W., III: Genomic organization and precise physical location of protein
phosphatase 2A regulatory subunit A beta isoform gene on chromosome
band 11q23. Gene 217: 107-116, 1998.
3. Hemmer, S.; Wasenius, V.-M.; Haglund, C.; Zhu, Y.; Knuutila, S.;
Franssila, K.; Joensuu, H.: Alterations in the suppressor gene PPP2R1B
in parathyroid hyperplasias and adenomas. Cancer Genet. Cytogenet. 134:
13-17, 2002.
4. Sablina, A. A.; Chen, W.; Arroyo, J. D.; Corral, L.; Hector, M.;
Bulmer, S. E.; DeCaprio, J. A.; Hahn, W. C.: The tumor suppressor
PP2A A-beta regulates the RalA GTPase. Cell 129: 969-982, 2007.
5. Walter, G.; Mumby, M.: Protein serine/threonine phosphatases and
cell transformation. Biochim. Biophys. Acta 1155: 207-226, 1993.
6. Wang, S. S.; Esplin, E. D.; Li, J. L.; Huang, L.; Gazdar, A.; Minna,
J.; Evans, G. A.: Alterations of the PPP2R1B gene in human lung and
colon cancer. Science 282: 284-287, 1998.
*FIELD* CN
Paul J. Converse - updated: 3/5/2009
Carol A. Bocchini - updated: 12/11/2002
Victor A. McKusick - updated: 8/9/2002
*FIELD* CD
Victor A. McKusick: 10/9/1998
*FIELD* ED
mgross: 03/06/2009
terry: 3/5/2009
tkritzer: 12/11/2002
carol: 12/11/2002
tkritzer: 8/15/2002
tkritzer: 8/13/2002
terry: 8/9/2002
carol: 8/8/2002
mgross: 4/8/1999
dkim: 10/13/1998
alopez: 10/9/1998
*RECORD*
*FIELD* NO
603113
*FIELD* TI
*603113 PROTEIN PHOSPHATASE 2, STRUCTURAL/REGULATORY SUBUNIT A, BETA; PPP2R1B
;;PP2AA-BETA
read more*FIELD* TX
DESCRIPTION
Serine/threonine protein phosphatase-2A (PP2A) is an important
regulatory enzyme that downregulates the mitogen-activated protein
kinase (MAPK) cascade (see 176948), relays signals for cell
proliferation, and may be linked to carcinogenesis. The PP2A holoenzyme
exists in several trimeric forms consisting of a 36-kD core catalytic
subunit (PP2AC; see 176915), a 65-kD structural/regulatory component
(PP2AA), and a variable regulatory subunit (PP2AB; see 604941) that
confers distinct properties on the holoenzyme. Each subunit exists as
multiple isoforms encoded by different genes, resulting in many forms of
the PP2A trimer that differ in expression pattern and specificity.
PPP2R1B encodes the beta isoform of the structural-regulatory A subunit,
or PP2AA-beta. This subunit is necessary for interaction of the
catalytic PP2AC and variable PP2AB subunits and is critical for
phosphatase activity (Walter and Mumby, 1993; Wang et al., 1998).
CLONING
Loss of heterozygosity (LOH) at chromosome 11q22-q24 has been associated
with lung, colon, breast, cervical, head and neck, and ovarian cancers,
as well as melanoma (Arai et al., 1996). Introduction of a normal
chromosome 11, or a derivative t(X;11) chromosome containing 11pter-q23,
can reverse the tumorigenic potential of several types of cancer cells
and Wilms tumor when introduced into nude mice. These studies suggest
that 1 or more tumor suppressor genes are located centromeric to the
t(X;11) breakpoint at chromosome 11q23. Because of a high frequency of
LOH in lung cancer cells involving D11S1647 and D11S1987, Wang et al.
(1998) systematically surveyed the region between these 2 markers for
candidate tumor suppressor genes. Over 100 candidate genes and ESTs were
identified from a radiation hybrid map of chromosome 11 and from the
NCBI transcript map, including an EST corresponding to PPP2R1B.
GENE STRUCTURE
Baysal et al. (1998) determined that the PPP2R1B gene contains 15 exons
and spans approximately 27 kb.
MAPPING
Wang et al. (1998) determined the precise physical location of the
PPP2R1B gene by colocalizing it within P1-derived artificial chromosome
(PAC) clones containing sequence tagged sites on chromosome 11q22-q23.
They confirmed that the PPP2R1B gene is located in a region showing high
frequency LOH.
GENE FUNCTION
Sablina et al. (2007) found that suppression of PP2A A-beta expression
allowed immortalized human cell lines to achieve a tumorigenic state.
Cancer-associated A-beta mutants failed to reverse this tumorigenic
phenotype, indicating that the mutants functioned as null alleles.
Cancer-derived A-beta mutants failed to form a complex with the small
GTPase RALA (179550), whereas wildtype A-beta-containing complexes
dephosphorylated RALA at ser183 and ser194, inactivating RALA and
abolishing its transforming function. Sablina et al. (2007) concluded
that PP2A A-beta is a tumor suppressor that transforms immortalized
cells by regulating RALA function.
MOLECULAR GENETICS
Wang et al. (1998) identified somatic alterations in the PPP2R1B gene in
15% (5 in 32) of primary lung tumors, 6% (4 in 70) of lung tumor-derived
cell lines, and 15% (2 in 13) of primary colon tumors. One deletion
mutation generated a truncated PP2A-A-beta protein that was unable to
bind to the catalytic subunit of the PP2A holoenzyme. The authors
suggested that the PPP2R1B gene product may suppress tumor development
through its role in cell cycle regulation and cellular growth control.
Deletion of 11q23 is a common alteration in parathyroid adenomas and
hyperplasias. To evaluate the role of the PPP2R1B gene in the
pathogenesis of parathyroid lesions, Hemmer et al. (2002) performed
PCR-based SSCP and direct sequencing on 6 parathyroid hyperplasias and
12 adenomas. The gly90-to-asp mutation (603113.0001) was detected in 1
adenoma; the common gly allele and the variant asp allele were detected
by direct sequencing in the patient's somatic cells. Hemmer et al.
(2002) concluded that mutations of PPP2R1B are not frequent in
parathyroid lesions, and that other genes located at 11q23 may be more
closely associated with the pathogenesis of parathyroid hyperplasia and
adenoma.
*FIELD* AV
.0001
LUNG CANCER
PPP2R1B, GLY90ASP
The alterations observed by Wang et al. (1998) in the PPP2R1B gene in
tumor-derived cell lines and primary tumors included deletions,
frameshifts, and point mutations leading to nonconservative amino acid
substitutions. In a lung cancer cell line 1 allele was found to carry a
G-to-A transition of nucleotide 298, which resulted in a change of the
conserved glycine-90 to aspartic acid (G90D). The G90D alteration was
found in 2 separate tumors and not in surrounding normal tissue, which
suggested that this site may be a hotspot for mutation.
Hemmer et al. (2002) found the G90D mutation in 1 of 12 parathyroid
adenomas. Somatic cells showed the presence of both the gly allele and
the variant asp allele.
*FIELD* RF
1. Arai, Y.; Hosoda, F.; Nakayama, K.; Ohki, M.: A yeast artificial
chromosome contig and NotI restriction map that spans the tumor suppressor
gene(s) locus, 11q.22.2-q23.3. Genomics 35: 196-206, 1996.
2. Baysal, B. E.; Farr, J. E.; Goss, J. R.; Devlin, B.; Richard, C.
W., III: Genomic organization and precise physical location of protein
phosphatase 2A regulatory subunit A beta isoform gene on chromosome
band 11q23. Gene 217: 107-116, 1998.
3. Hemmer, S.; Wasenius, V.-M.; Haglund, C.; Zhu, Y.; Knuutila, S.;
Franssila, K.; Joensuu, H.: Alterations in the suppressor gene PPP2R1B
in parathyroid hyperplasias and adenomas. Cancer Genet. Cytogenet. 134:
13-17, 2002.
4. Sablina, A. A.; Chen, W.; Arroyo, J. D.; Corral, L.; Hector, M.;
Bulmer, S. E.; DeCaprio, J. A.; Hahn, W. C.: The tumor suppressor
PP2A A-beta regulates the RalA GTPase. Cell 129: 969-982, 2007.
5. Walter, G.; Mumby, M.: Protein serine/threonine phosphatases and
cell transformation. Biochim. Biophys. Acta 1155: 207-226, 1993.
6. Wang, S. S.; Esplin, E. D.; Li, J. L.; Huang, L.; Gazdar, A.; Minna,
J.; Evans, G. A.: Alterations of the PPP2R1B gene in human lung and
colon cancer. Science 282: 284-287, 1998.
*FIELD* CN
Paul J. Converse - updated: 3/5/2009
Carol A. Bocchini - updated: 12/11/2002
Victor A. McKusick - updated: 8/9/2002
*FIELD* CD
Victor A. McKusick: 10/9/1998
*FIELD* ED
mgross: 03/06/2009
terry: 3/5/2009
tkritzer: 12/11/2002
carol: 12/11/2002
tkritzer: 8/15/2002
tkritzer: 8/13/2002
terry: 8/9/2002
carol: 8/8/2002
mgross: 4/8/1999
dkim: 10/13/1998
alopez: 10/9/1998