Full text data of PPP2R1A
PPP2R1A
[Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (Medium tumor antigen-associated 61 kDa protein; PP2A subunit A isoform PR65-alpha; PP2A subunit A isoform R1-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (Medium tumor antigen-associated 61 kDa protein; PP2A subunit A isoform PR65-alpha; PP2A subunit A isoform R1-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30153
ID 2AAA_HUMAN Reviewed; 589 AA.
AC P30153; Q13773; Q6ICQ3; Q96DH3;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-APR-2007, sequence version 4.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform;
DE AltName: Full=Medium tumor antigen-associated 61 kDa protein;
DE AltName: Full=PP2A subunit A isoform PR65-alpha;
DE AltName: Full=PP2A subunit A isoform R1-alpha;
GN Name=PPP2R1A;
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], AND PROTEIN SEQUENCE OF 242-255.
RC TISSUE=Placenta;
RX PubMed=2554323; DOI=10.1073/pnas.86.22.8669;
RA Walter G., Ferre F., Espiritu O., Carbone-Wiley A.;
RT "Molecular cloning and sequence of cDNA encoding polyoma medium tumor
RT antigen-associated 61-kDa protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8669-8672(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP PROTEIN SEQUENCE OF 34-46, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 204-214; 261-272 AND 521-527.
RX PubMed=8694763;
RA Zolnierowicz S., van Hoof C., Andjelkovic N., Cron P., Stevens I.,
RA Merlevede W., Goris J., Hemmings B.A.;
RT "The variable subunit associated with protein phosphatase 2A0 defines
RT a novel multimember family of regulatory subunits.";
RL Biochem. J. 317:187-194(1996).
RN [7]
RP BINDING DOMAINS.
RX PubMed=8254721;
RA Ruediger R., Hentz M., Fait J., Mumby M., Walter G.;
RT "Molecular model of the A subunit of protein phosphatase 2A:
RT interaction with other subunits and tumor antigens.";
RL J. Virol. 68:123-129(1994).
RN [8]
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH SGOL1.
RX PubMed=16580887; DOI=10.1016/j.devcel.2006.03.010;
RA Tang Z., Shu H., Qi W., Mahmood N.A., Mumby M.C., Yu H.;
RT "PP2A is required for centromeric localization of Sgo1 and proper
RT chromosome segregation.";
RL Dev. Cell 10:575-585(2006).
RN [10]
RP INTERACTION WITH TP53.
RX PubMed=17245430; DOI=10.1038/sj.emboj.7601519;
RA Li H.H., Cai X., Shouse G.P., Piluso L.G., Liu X.;
RT "A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-
RT induced dephosphorylation of p53 at Thr55.";
RL EMBO J. 26:402-411(2007).
RN [11]
RP INTERACTION WITH PLA2G16.
RX PubMed=17374643; DOI=10.1242/jcs.000018;
RA Nazarenko I., Schafer R., Sers C.;
RT "Mechanisms of the HRSL3 tumor suppressor function in ovarian
RT carcinoma cells.";
RL J. Cell Sci. 120:1393-1404(2007).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP INTERACTION WITH CTTNBP2NL.
RX PubMed=18782753; DOI=10.1074/mcp.M800266-MCP200;
RA Goudreault M., D'Ambrosio L.M., Kean M.J., Mullin M.J., Larsen B.G.,
RA Sanchez A., Chaudhry S., Chen G.I., Sicheri F., Nesvizhskii A.I.,
RA Aebersold R., Raught B., Gingras A.C.;
RT "A PP2A phosphatase high density interaction network identifies a
RT novel striatin-interacting phosphatase and kinase complex linked to
RT the cerebral cavernous malformation 3 (CCM3) protein.";
RL Mol. Cell. Proteomics 8:157-171(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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 [17]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=9989501; DOI=10.1016/S0092-8674(00)80963-0;
RA Groves M.R., Hanlon N., Turowski P., Hemmings B.A., Barford D.;
RT "The structure of the protein phosphatase 2A PR65/A subunit reveals
RT the conformation of its 15 tandemly repeated HEAT motifs.";
RL Cell 96:99-110(1999).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 9-589 IN COMPLEX WITH WITH
RP PPP2CA AND PPME1.
RX PubMed=18394995; DOI=10.1016/j.cell.2008.02.041;
RA Xing Y., Li Z., Chen Y., Stock J.B., Jeffrey P.D., Shi Y.;
RT "Structural mechanism of demethylation and inactivation of protein
RT phosphatase 2A.";
RL Cell 133:154-163(2008).
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. Required for proper
CC chromosome segregation and for centromeric localization of SGOL1
CC in mitosis.
CC -!- SUBUNIT: Found in a complex with at least ARL2, PPP2CB, PPP2R1A,
CC PPP2R2A, PPP2R5E and TBCD. Interacts with FOXO1; the interaction
CC dephosphorylates FOXO1 on AKT-mediated phosphoylation sites (By
CC similarity). PP2A consists of a common heterodimeric core enzyme,
CC composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and
CC PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A),
CC that associates with a variety of regulatory subunits. Proteins
CC that associate with the core dimer include three families of
CC regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59
CC and R5/B'/B56 families), the 48 kDa variable regulatory subunit,
CC viral proteins, and cell signaling molecules. Interacts with IPO9.
CC Interacts with TP53 and SGOL1. Interacts with PLA2G16; this
CC interaction might decrease PP2A activity. Interacts with
CC CTTNBP2NL.
CC -!- INTERACTION:
CC P03081:- (xeno); NbExp=3; IntAct=EBI-302388, EBI-1266256;
CC P31749:AKT1; NbExp=2; IntAct=EBI-302388, EBI-296087;
CC P13569:CFTR; NbExp=3; IntAct=EBI-302388, EBI-349854;
CC P03129:E7 (xeno); NbExp=3; IntAct=EBI-302388, EBI-866453;
CC P04020:E7 (xeno); NbExp=2; IntAct=EBI-302388, EBI-7005254;
CC Q8TCG1:KIAA1524; NbExp=4; IntAct=EBI-302388, EBI-1379376;
CC P97346:Nxn (xeno); NbExp=2; IntAct=EBI-302388, EBI-309684;
CC P53816:PLA2G16; NbExp=7; IntAct=EBI-302388, EBI-746318;
CC P67775:PPP2CA; NbExp=14; IntAct=EBI-302388, EBI-712311;
CC P63151:PPP2R2A; NbExp=8; IntAct=EBI-302388, EBI-1048931;
CC Q00005:PPP2R2B; NbExp=5; IntAct=EBI-302388, EBI-1052159;
CC Q15172:PPP2R5A; NbExp=3; IntAct=EBI-302388, EBI-641666;
CC Q13362:PPP2R5C; NbExp=6; IntAct=EBI-302388, EBI-1266156;
CC Q13362-1:PPP2R5C; NbExp=5; IntAct=EBI-302388, EBI-1266170;
CC Q13362-2:PPP2R5C; NbExp=2; IntAct=EBI-302388, EBI-1266173;
CC Q60996-3:Ppp2r5c (xeno); NbExp=2; IntAct=EBI-302388, EBI-1369292;
CC Q14738:PPP2R5D; NbExp=4; IntAct=EBI-302388, EBI-396563;
CC Q16537:PPP2R5E; NbExp=3; IntAct=EBI-302388, EBI-968374;
CC P60510:PPP4C; NbExp=3; IntAct=EBI-302388, EBI-1046072;
CC P53041:PPP5C; NbExp=3; IntAct=EBI-302388, EBI-716663;
CC Q04206:RELA; NbExp=2; IntAct=EBI-302388, EBI-73886;
CC O43815:STRN; NbExp=4; IntAct=EBI-302388, EBI-1046642;
CC P04637:TP53; NbExp=2; IntAct=EBI-302388, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Chromosome,
CC centromere. Note=Centromeric localization requires the presence of
CC BUB1.
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.
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DR EMBL; M31786; AAA35531.1; -; mRNA.
DR EMBL; J02902; AAA36399.1; -; mRNA.
DR EMBL; CR450340; CAG29336.1; -; mRNA.
DR EMBL; BC001537; AAH01537.1; -; mRNA.
DR PIR; A34541; A34541.
DR RefSeq; NP_055040.2; NM_014225.5.
DR UniGene; Hs.467192; -.
DR PDB; 1B3U; X-ray; 2.30 A; A/B=2-589.
DR PDB; 2IE3; X-ray; 2.80 A; A=1-589.
DR PDB; 2IE4; X-ray; 2.60 A; A=1-589.
DR PDB; 2NPP; X-ray; 3.30 A; A/D=1-589.
DR PDB; 2NYL; X-ray; 3.80 A; A/D=8-589.
DR PDB; 2NYM; X-ray; 3.60 A; A/D=8-589.
DR PDB; 2PKG; X-ray; 3.30 A; A/B=10-589.
DR PDB; 3C5W; X-ray; 2.80 A; A=9-589.
DR PDB; 3DW8; X-ray; 2.85 A; A/D=9-589.
DR PDB; 3K7V; X-ray; 2.85 A; A=1-589.
DR PDB; 3K7W; X-ray; 2.96 A; A=1-589.
DR PDB; 4I5L; X-ray; 2.43 A; A/D=9-589.
DR PDB; 4I5N; X-ray; 2.80 A; A/D=9-589.
DR PDB; 4LAC; X-ray; 2.82 A; A=404-589.
DR PDBsum; 1B3U; -.
DR PDBsum; 2IE3; -.
DR PDBsum; 2IE4; -.
DR PDBsum; 2NPP; -.
DR PDBsum; 2NYL; -.
DR PDBsum; 2NYM; -.
DR PDBsum; 2PKG; -.
DR PDBsum; 3C5W; -.
DR PDBsum; 3DW8; -.
DR PDBsum; 3K7V; -.
DR PDBsum; 3K7W; -.
DR PDBsum; 4I5L; -.
DR PDBsum; 4I5N; -.
DR PDBsum; 4LAC; -.
DR ProteinModelPortal; P30153; -.
DR SMR; P30153; 2-589.
DR DIP; DIP-29394N; -.
DR IntAct; P30153; 116.
DR MINT; MINT-1141071; -.
DR STRING; 9606.ENSP00000324804; -.
DR PhosphoSite; P30153; -.
DR DMDM; 143811355; -.
DR OGP; P30153; -.
DR REPRODUCTION-2DPAGE; IPI00554737; -.
DR PaxDb; P30153; -.
DR PRIDE; P30153; -.
DR DNASU; 5518; -.
DR Ensembl; ENST00000322088; ENSP00000324804; ENSG00000105568.
DR GeneID; 5518; -.
DR KEGG; hsa:5518; -.
DR UCSC; uc002pyp.3; human.
DR CTD; 5518; -.
DR GeneCards; GC19P052693; -.
DR HGNC; HGNC:9302; PPP2R1A.
DR HPA; CAB018599; -.
DR MIM; 605983; gene.
DR neXtProt; NX_P30153; -.
DR PharmGKB; PA33666; -.
DR eggNOG; NOG247268; -.
DR HOGENOM; HOG000078539; -.
DR HOVERGEN; HBG000011; -.
DR InParanoid; P30153; -.
DR KO; K03456; -.
DR OMA; FPEVRLH; -.
DR OrthoDB; EOG764722; -.
DR PhylomeDB; P30153; -.
DR BioCyc; MetaCyc:ENSG00000105568-MONOMER; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_21257; Metabolism of RNA.
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 Reactome; REACT_71; Gene Expression.
DR SignaLink; P30153; -.
DR EvolutionaryTrace; P30153; -.
DR GeneWiki; PPP2R1A; -.
DR GenomeRNAi; 5518; -.
DR NextBio; 21342; -.
DR PMAP-CutDB; P30153; -.
DR PRO; PR:P30153; -.
DR ArrayExpress; P30153; -.
DR Bgee; P30153; -.
DR CleanEx; HS_PPP2R1A; -.
DR Genevestigator; P30153; -.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; NAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; NAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IDA:UniProtKB.
DR GO; GO:0003823; F:antigen binding; IPI:UniProtKB.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; NAS:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IDA:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0000188; P:inactivation of MAPK activity; NAS:UniProtKB.
DR GO; GO:0007084; P:mitotic nuclear envelope reassembly; TAS:Reactome.
DR GO; GO:0030308; P:negative regulation of cell growth; NAS:UniProtKB.
DR GO; GO:0042518; P:negative regulation of tyrosine phosphorylation of Stat3 protein; NAS:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IEA:Ensembl.
DR GO; GO:0006461; P:protein complex assembly; TAS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030155; P:regulation of cell adhesion; NAS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; NAS:UniProtKB.
DR GO; GO:0006275; P:regulation of DNA replication; NAS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; NAS:UniProtKB.
DR GO; GO:0019932; P:second-messenger-mediated signaling; NAS: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; 11.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Centromere; Chromosome;
KW Chromosome partition; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 589 Serine/threonine-protein phosphatase 2A
FT 65 kDa regulatory subunit A alpha
FT isoform.
FT /FTId=PRO_0000071400.
FT REPEAT 8 46 HEAT 1.
FT REPEAT 47 84 HEAT 2.
FT REPEAT 85 123 HEAT 3.
FT REPEAT 124 161 HEAT 4.
FT REPEAT 162 200 HEAT 5.
FT REPEAT 201 239 HEAT 6.
FT REPEAT 240 278 HEAT 7.
FT REPEAT 279 321 HEAT 8.
FT REPEAT 322 360 HEAT 9.
FT REPEAT 361 399 HEAT 10.
FT REPEAT 400 438 HEAT 11.
FT REPEAT 439 477 HEAT 12.
FT REPEAT 478 516 HEAT 13.
FT REPEAT 517 555 HEAT 14.
FT REPEAT 556 589 HEAT 15.
FT REGION 8 399 PP2A subunit B binding.
FT REGION 47 321 Polyoma small and medium T antigens
FT Binding.
FT REGION 85 239 SV40 small T antigen binding.
FT REGION 400 589 PP2A subunit C binding.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 280 280 N6-acetyllysine.
FT CONFLICT 130 130 P -> A (in Ref. 1; AAA35531).
FT CONFLICT 258 258 R -> A (in Ref. 2; AAA36399).
FT CONFLICT 272 272 K -> R (in Ref. 6; AA sequence).
FT CONFLICT 551 551 L -> P (in Ref. 3; CAG29336).
FT TURN 6 8
FT HELIX 11 19
FT HELIX 25 33
FT HELIX 35 41
FT HELIX 44 49
FT HELIX 51 57
FT HELIX 63 73
FT HELIX 78 80
FT HELIX 83 89
FT HELIX 90 96
FT STRAND 99 101
FT HELIX 102 116
FT HELIX 121 126
FT HELIX 128 136
FT STRAND 138 140
FT HELIX 141 147
FT HELIX 148 150
FT HELIX 151 154
FT TURN 155 157
FT HELIX 160 174
FT HELIX 179 194
FT HELIX 198 203
FT HELIX 205 213
FT HELIX 218 221
FT HELIX 224 234
FT HELIX 237 239
FT HELIX 240 243
FT HELIX 245 252
FT HELIX 257 265
FT HELIX 267 274
FT HELIX 276 281
FT HELIX 283 291
FT HELIX 296 311
FT TURN 315 317
FT HELIX 318 324
FT HELIX 326 334
FT HELIX 339 346
FT HELIX 349 352
FT HELIX 353 356
FT HELIX 358 364
FT HELIX 366 373
FT HELIX 378 385
FT HELIX 389 394
FT HELIX 397 412
FT HELIX 417 434
FT HELIX 436 438
FT HELIX 441 449
FT HELIX 450 452
FT HELIX 456 473
FT HELIX 475 481
FT HELIX 483 488
FT TURN 489 491
FT HELIX 495 520
FT HELIX 522 527
FT HELIX 528 530
FT HELIX 534 547
FT HELIX 548 550
FT HELIX 553 567
FT HELIX 573 585
SQ SEQUENCE 589 AA; 65309 MW; 5174EBE94D537836 CRC64;
MAAADGDDSL YPIAVLIDEL RNEDVQLRLN SIKKLSTIAL ALGVERTRSE LLPFLTDTIY
DEDEVLLALA EQLGTFTTLV GGPEYVHCLL PPLESLATVE ETVVRDKAVE SLRAISHEHS
PSDLEAHFVP LVKRLAGGDW FTSRTSACGL FSVCYPRVSS AVKAELRQYF RNLCSDDTPM
VRRAAASKLG EFAKVLELDN VKSEIIPMFS NLASDEQDSV RLLAVEACVN IAQLLPQEDL
EALVMPTLRQ AAEDKSWRVR YMVADKFTEL QKAVGPEITK TDLVPAFQNL MKDCEAEVRA
AASHKVKEFC ENLSADCREN VIMSQILPCI KELVSDANQH VKSALASVIM GLSPILGKDN
TIEHLLPLFL AQLKDECPEV RLNIISNLDC VNEVIGIRQL SQSLLPAIVE LAEDAKWRVR
LAIIEYMPLL AGQLGVEFFD EKLNSLCMAW LVDHVYAIRE AATSNLKKLV EKFGKEWAHA
TIIPKVLAMS GDPNYLHRMT TLFCINVLSE VCGQDITTKH MLPTVLRMAG DPVANVRFNV
AKSLQKIGPI LDNSTLQSEV KPILEKLTQD QDVDVKYFAQ EALTVLSLA
//
ID 2AAA_HUMAN Reviewed; 589 AA.
AC P30153; Q13773; Q6ICQ3; Q96DH3;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-APR-2007, sequence version 4.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform;
DE AltName: Full=Medium tumor antigen-associated 61 kDa protein;
DE AltName: Full=PP2A subunit A isoform PR65-alpha;
DE AltName: Full=PP2A subunit A isoform R1-alpha;
GN Name=PPP2R1A;
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], AND PROTEIN SEQUENCE OF 242-255.
RC TISSUE=Placenta;
RX PubMed=2554323; DOI=10.1073/pnas.86.22.8669;
RA Walter G., Ferre F., Espiritu O., Carbone-Wiley A.;
RT "Molecular cloning and sequence of cDNA encoding polyoma medium tumor
RT antigen-associated 61-kDa protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8669-8672(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [5]
RP PROTEIN SEQUENCE OF 34-46, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 204-214; 261-272 AND 521-527.
RX PubMed=8694763;
RA Zolnierowicz S., van Hoof C., Andjelkovic N., Cron P., Stevens I.,
RA Merlevede W., Goris J., Hemmings B.A.;
RT "The variable subunit associated with protein phosphatase 2A0 defines
RT a novel multimember family of regulatory subunits.";
RL Biochem. J. 317:187-194(1996).
RN [7]
RP BINDING DOMAINS.
RX PubMed=8254721;
RA Ruediger R., Hentz M., Fait J., Mumby M., Walter G.;
RT "Molecular model of the A subunit of protein phosphatase 2A:
RT interaction with other subunits and tumor antigens.";
RL J. Virol. 68:123-129(1994).
RN [8]
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH SGOL1.
RX PubMed=16580887; DOI=10.1016/j.devcel.2006.03.010;
RA Tang Z., Shu H., Qi W., Mahmood N.A., Mumby M.C., Yu H.;
RT "PP2A is required for centromeric localization of Sgo1 and proper
RT chromosome segregation.";
RL Dev. Cell 10:575-585(2006).
RN [10]
RP INTERACTION WITH TP53.
RX PubMed=17245430; DOI=10.1038/sj.emboj.7601519;
RA Li H.H., Cai X., Shouse G.P., Piluso L.G., Liu X.;
RT "A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-
RT induced dephosphorylation of p53 at Thr55.";
RL EMBO J. 26:402-411(2007).
RN [11]
RP INTERACTION WITH PLA2G16.
RX PubMed=17374643; DOI=10.1242/jcs.000018;
RA Nazarenko I., Schafer R., Sers C.;
RT "Mechanisms of the HRSL3 tumor suppressor function in ovarian
RT carcinoma cells.";
RL J. Cell Sci. 120:1393-1404(2007).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP INTERACTION WITH CTTNBP2NL.
RX PubMed=18782753; DOI=10.1074/mcp.M800266-MCP200;
RA Goudreault M., D'Ambrosio L.M., Kean M.J., Mullin M.J., Larsen B.G.,
RA Sanchez A., Chaudhry S., Chen G.I., Sicheri F., Nesvizhskii A.I.,
RA Aebersold R., Raught B., Gingras A.C.;
RT "A PP2A phosphatase high density interaction network identifies a
RT novel striatin-interacting phosphatase and kinase complex linked to
RT the cerebral cavernous malformation 3 (CCM3) protein.";
RL Mol. Cell. Proteomics 8:157-171(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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 [17]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=9989501; DOI=10.1016/S0092-8674(00)80963-0;
RA Groves M.R., Hanlon N., Turowski P., Hemmings B.A., Barford D.;
RT "The structure of the protein phosphatase 2A PR65/A subunit reveals
RT the conformation of its 15 tandemly repeated HEAT motifs.";
RL Cell 96:99-110(1999).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 9-589 IN COMPLEX WITH WITH
RP PPP2CA AND PPME1.
RX PubMed=18394995; DOI=10.1016/j.cell.2008.02.041;
RA Xing Y., Li Z., Chen Y., Stock J.B., Jeffrey P.D., Shi Y.;
RT "Structural mechanism of demethylation and inactivation of protein
RT phosphatase 2A.";
RL Cell 133:154-163(2008).
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. Required for proper
CC chromosome segregation and for centromeric localization of SGOL1
CC in mitosis.
CC -!- SUBUNIT: Found in a complex with at least ARL2, PPP2CB, PPP2R1A,
CC PPP2R2A, PPP2R5E and TBCD. Interacts with FOXO1; the interaction
CC dephosphorylates FOXO1 on AKT-mediated phosphoylation sites (By
CC similarity). PP2A consists of a common heterodimeric core enzyme,
CC composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and
CC PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A),
CC that associates with a variety of regulatory subunits. Proteins
CC that associate with the core dimer include three families of
CC regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59
CC and R5/B'/B56 families), the 48 kDa variable regulatory subunit,
CC viral proteins, and cell signaling molecules. Interacts with IPO9.
CC Interacts with TP53 and SGOL1. Interacts with PLA2G16; this
CC interaction might decrease PP2A activity. Interacts with
CC CTTNBP2NL.
CC -!- INTERACTION:
CC P03081:- (xeno); NbExp=3; IntAct=EBI-302388, EBI-1266256;
CC P31749:AKT1; NbExp=2; IntAct=EBI-302388, EBI-296087;
CC P13569:CFTR; NbExp=3; IntAct=EBI-302388, EBI-349854;
CC P03129:E7 (xeno); NbExp=3; IntAct=EBI-302388, EBI-866453;
CC P04020:E7 (xeno); NbExp=2; IntAct=EBI-302388, EBI-7005254;
CC Q8TCG1:KIAA1524; NbExp=4; IntAct=EBI-302388, EBI-1379376;
CC P97346:Nxn (xeno); NbExp=2; IntAct=EBI-302388, EBI-309684;
CC P53816:PLA2G16; NbExp=7; IntAct=EBI-302388, EBI-746318;
CC P67775:PPP2CA; NbExp=14; IntAct=EBI-302388, EBI-712311;
CC P63151:PPP2R2A; NbExp=8; IntAct=EBI-302388, EBI-1048931;
CC Q00005:PPP2R2B; NbExp=5; IntAct=EBI-302388, EBI-1052159;
CC Q15172:PPP2R5A; NbExp=3; IntAct=EBI-302388, EBI-641666;
CC Q13362:PPP2R5C; NbExp=6; IntAct=EBI-302388, EBI-1266156;
CC Q13362-1:PPP2R5C; NbExp=5; IntAct=EBI-302388, EBI-1266170;
CC Q13362-2:PPP2R5C; NbExp=2; IntAct=EBI-302388, EBI-1266173;
CC Q60996-3:Ppp2r5c (xeno); NbExp=2; IntAct=EBI-302388, EBI-1369292;
CC Q14738:PPP2R5D; NbExp=4; IntAct=EBI-302388, EBI-396563;
CC Q16537:PPP2R5E; NbExp=3; IntAct=EBI-302388, EBI-968374;
CC P60510:PPP4C; NbExp=3; IntAct=EBI-302388, EBI-1046072;
CC P53041:PPP5C; NbExp=3; IntAct=EBI-302388, EBI-716663;
CC Q04206:RELA; NbExp=2; IntAct=EBI-302388, EBI-73886;
CC O43815:STRN; NbExp=4; IntAct=EBI-302388, EBI-1046642;
CC P04637:TP53; NbExp=2; IntAct=EBI-302388, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Chromosome,
CC centromere. Note=Centromeric localization requires the presence of
CC BUB1.
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.
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DR EMBL; M31786; AAA35531.1; -; mRNA.
DR EMBL; J02902; AAA36399.1; -; mRNA.
DR EMBL; CR450340; CAG29336.1; -; mRNA.
DR EMBL; BC001537; AAH01537.1; -; mRNA.
DR PIR; A34541; A34541.
DR RefSeq; NP_055040.2; NM_014225.5.
DR UniGene; Hs.467192; -.
DR PDB; 1B3U; X-ray; 2.30 A; A/B=2-589.
DR PDB; 2IE3; X-ray; 2.80 A; A=1-589.
DR PDB; 2IE4; X-ray; 2.60 A; A=1-589.
DR PDB; 2NPP; X-ray; 3.30 A; A/D=1-589.
DR PDB; 2NYL; X-ray; 3.80 A; A/D=8-589.
DR PDB; 2NYM; X-ray; 3.60 A; A/D=8-589.
DR PDB; 2PKG; X-ray; 3.30 A; A/B=10-589.
DR PDB; 3C5W; X-ray; 2.80 A; A=9-589.
DR PDB; 3DW8; X-ray; 2.85 A; A/D=9-589.
DR PDB; 3K7V; X-ray; 2.85 A; A=1-589.
DR PDB; 3K7W; X-ray; 2.96 A; A=1-589.
DR PDB; 4I5L; X-ray; 2.43 A; A/D=9-589.
DR PDB; 4I5N; X-ray; 2.80 A; A/D=9-589.
DR PDB; 4LAC; X-ray; 2.82 A; A=404-589.
DR PDBsum; 1B3U; -.
DR PDBsum; 2IE3; -.
DR PDBsum; 2IE4; -.
DR PDBsum; 2NPP; -.
DR PDBsum; 2NYL; -.
DR PDBsum; 2NYM; -.
DR PDBsum; 2PKG; -.
DR PDBsum; 3C5W; -.
DR PDBsum; 3DW8; -.
DR PDBsum; 3K7V; -.
DR PDBsum; 3K7W; -.
DR PDBsum; 4I5L; -.
DR PDBsum; 4I5N; -.
DR PDBsum; 4LAC; -.
DR ProteinModelPortal; P30153; -.
DR SMR; P30153; 2-589.
DR DIP; DIP-29394N; -.
DR IntAct; P30153; 116.
DR MINT; MINT-1141071; -.
DR STRING; 9606.ENSP00000324804; -.
DR PhosphoSite; P30153; -.
DR DMDM; 143811355; -.
DR OGP; P30153; -.
DR REPRODUCTION-2DPAGE; IPI00554737; -.
DR PaxDb; P30153; -.
DR PRIDE; P30153; -.
DR DNASU; 5518; -.
DR Ensembl; ENST00000322088; ENSP00000324804; ENSG00000105568.
DR GeneID; 5518; -.
DR KEGG; hsa:5518; -.
DR UCSC; uc002pyp.3; human.
DR CTD; 5518; -.
DR GeneCards; GC19P052693; -.
DR HGNC; HGNC:9302; PPP2R1A.
DR HPA; CAB018599; -.
DR MIM; 605983; gene.
DR neXtProt; NX_P30153; -.
DR PharmGKB; PA33666; -.
DR eggNOG; NOG247268; -.
DR HOGENOM; HOG000078539; -.
DR HOVERGEN; HBG000011; -.
DR InParanoid; P30153; -.
DR KO; K03456; -.
DR OMA; FPEVRLH; -.
DR OrthoDB; EOG764722; -.
DR PhylomeDB; P30153; -.
DR BioCyc; MetaCyc:ENSG00000105568-MONOMER; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_21257; Metabolism of RNA.
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 Reactome; REACT_71; Gene Expression.
DR SignaLink; P30153; -.
DR EvolutionaryTrace; P30153; -.
DR GeneWiki; PPP2R1A; -.
DR GenomeRNAi; 5518; -.
DR NextBio; 21342; -.
DR PMAP-CutDB; P30153; -.
DR PRO; PR:P30153; -.
DR ArrayExpress; P30153; -.
DR Bgee; P30153; -.
DR CleanEx; HS_PPP2R1A; -.
DR Genevestigator; P30153; -.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; NAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; NAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IDA:UniProtKB.
DR GO; GO:0003823; F:antigen binding; IPI:UniProtKB.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; NAS:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IDA:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0000188; P:inactivation of MAPK activity; NAS:UniProtKB.
DR GO; GO:0007084; P:mitotic nuclear envelope reassembly; TAS:Reactome.
DR GO; GO:0030308; P:negative regulation of cell growth; NAS:UniProtKB.
DR GO; GO:0042518; P:negative regulation of tyrosine phosphorylation of Stat3 protein; NAS:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IEA:Ensembl.
DR GO; GO:0006461; P:protein complex assembly; TAS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030155; P:regulation of cell adhesion; NAS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; NAS:UniProtKB.
DR GO; GO:0006275; P:regulation of DNA replication; NAS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; NAS:UniProtKB.
DR GO; GO:0019932; P:second-messenger-mediated signaling; NAS: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; 11.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Centromere; Chromosome;
KW Chromosome partition; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 589 Serine/threonine-protein phosphatase 2A
FT 65 kDa regulatory subunit A alpha
FT isoform.
FT /FTId=PRO_0000071400.
FT REPEAT 8 46 HEAT 1.
FT REPEAT 47 84 HEAT 2.
FT REPEAT 85 123 HEAT 3.
FT REPEAT 124 161 HEAT 4.
FT REPEAT 162 200 HEAT 5.
FT REPEAT 201 239 HEAT 6.
FT REPEAT 240 278 HEAT 7.
FT REPEAT 279 321 HEAT 8.
FT REPEAT 322 360 HEAT 9.
FT REPEAT 361 399 HEAT 10.
FT REPEAT 400 438 HEAT 11.
FT REPEAT 439 477 HEAT 12.
FT REPEAT 478 516 HEAT 13.
FT REPEAT 517 555 HEAT 14.
FT REPEAT 556 589 HEAT 15.
FT REGION 8 399 PP2A subunit B binding.
FT REGION 47 321 Polyoma small and medium T antigens
FT Binding.
FT REGION 85 239 SV40 small T antigen binding.
FT REGION 400 589 PP2A subunit C binding.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 280 280 N6-acetyllysine.
FT CONFLICT 130 130 P -> A (in Ref. 1; AAA35531).
FT CONFLICT 258 258 R -> A (in Ref. 2; AAA36399).
FT CONFLICT 272 272 K -> R (in Ref. 6; AA sequence).
FT CONFLICT 551 551 L -> P (in Ref. 3; CAG29336).
FT TURN 6 8
FT HELIX 11 19
FT HELIX 25 33
FT HELIX 35 41
FT HELIX 44 49
FT HELIX 51 57
FT HELIX 63 73
FT HELIX 78 80
FT HELIX 83 89
FT HELIX 90 96
FT STRAND 99 101
FT HELIX 102 116
FT HELIX 121 126
FT HELIX 128 136
FT STRAND 138 140
FT HELIX 141 147
FT HELIX 148 150
FT HELIX 151 154
FT TURN 155 157
FT HELIX 160 174
FT HELIX 179 194
FT HELIX 198 203
FT HELIX 205 213
FT HELIX 218 221
FT HELIX 224 234
FT HELIX 237 239
FT HELIX 240 243
FT HELIX 245 252
FT HELIX 257 265
FT HELIX 267 274
FT HELIX 276 281
FT HELIX 283 291
FT HELIX 296 311
FT TURN 315 317
FT HELIX 318 324
FT HELIX 326 334
FT HELIX 339 346
FT HELIX 349 352
FT HELIX 353 356
FT HELIX 358 364
FT HELIX 366 373
FT HELIX 378 385
FT HELIX 389 394
FT HELIX 397 412
FT HELIX 417 434
FT HELIX 436 438
FT HELIX 441 449
FT HELIX 450 452
FT HELIX 456 473
FT HELIX 475 481
FT HELIX 483 488
FT TURN 489 491
FT HELIX 495 520
FT HELIX 522 527
FT HELIX 528 530
FT HELIX 534 547
FT HELIX 548 550
FT HELIX 553 567
FT HELIX 573 585
SQ SEQUENCE 589 AA; 65309 MW; 5174EBE94D537836 CRC64;
MAAADGDDSL YPIAVLIDEL RNEDVQLRLN SIKKLSTIAL ALGVERTRSE LLPFLTDTIY
DEDEVLLALA EQLGTFTTLV GGPEYVHCLL PPLESLATVE ETVVRDKAVE SLRAISHEHS
PSDLEAHFVP LVKRLAGGDW FTSRTSACGL FSVCYPRVSS AVKAELRQYF RNLCSDDTPM
VRRAAASKLG EFAKVLELDN VKSEIIPMFS NLASDEQDSV RLLAVEACVN IAQLLPQEDL
EALVMPTLRQ AAEDKSWRVR YMVADKFTEL QKAVGPEITK TDLVPAFQNL MKDCEAEVRA
AASHKVKEFC ENLSADCREN VIMSQILPCI KELVSDANQH VKSALASVIM GLSPILGKDN
TIEHLLPLFL AQLKDECPEV RLNIISNLDC VNEVIGIRQL SQSLLPAIVE LAEDAKWRVR
LAIIEYMPLL AGQLGVEFFD EKLNSLCMAW LVDHVYAIRE AATSNLKKLV EKFGKEWAHA
TIIPKVLAMS GDPNYLHRMT TLFCINVLSE VCGQDITTKH MLPTVLRMAG DPVANVRFNV
AKSLQKIGPI LDNSTLQSEV KPILEKLTQD QDVDVKYFAQ EALTVLSLA
//
MIM
605983
*RECORD*
*FIELD* NO
605983
*FIELD* TI
*605983 PROTEIN PHOSPHATASE 2, STRUCTURAL/REGULATORY SUBUNIT A, ALPHA; PPP2R1A
;;PROTEIN PHOSPHATASE 2, 65-KD REGULATORY SUBUNIT A, ALPHA;;
read morePR65-ALPHA
*FIELD* TX
DESCRIPTION
The PR65/A regulatory subunit of protein phosphatase-2A (PP2A) serves as
a scaffolding molecule that coordinates the assembly of the catalytic
subunit, PPP2CA (176915), and a variable regulatory B subunit to
generate functionally diverse heterotrimers. The PR65/A subunit exists
as 2 isoforms, PPP2R1A and PPP2R1B (603113) (Groves et al., 1999).
CLONING
Hemmings et al. (1990) cloned the cDNA corresponding to the PPP2R1A
gene, encoding the alpha isoform of the 65-kD structural/regulatory
subunit A of the PP2A holoenzyme. The PPP2R1A gene has 86% identity with
the PPP2R1B gene, as demonstrated by Hendrix et al. (1993).
Everett et al. (1999) showed that expression of all 3 subunits of PP2A,
including Ppp2r1a, is regulated in a cell-specific and developmentally
stage-specific manner in rat kidney, with the highest levels of enzyme
activity present in the nephrogenic cortex of fetal kidney.
GENE FUNCTION
To explore the genetic origin of ovarian clear cell carcinoma (167000),
Jones et al. (2010) determined the exomic sequences of 8 tumors after
immunoaffinity purification of cancer cells. Through comparative
analyses of normal cells from the same patients, Jones et al. (2010)
identified 4 genes that were mutated in at least 2 tumors. Two of these
genes, PPP2R1A and ARID1A (603024), which encodes a protein that
participates in chromatin remodeling, were not known to be involved in
ovarian clear cell carcinoma. The other 2 genes, PIK3CA (171834) and
KRAS (190070), had previously been implicated in ovarian clear cell
carcinoma. The nature and pattern of the mutations suggested that
PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene.
In a total of 42 ovarian clear cell carcinomas, 7% had mutations in
PPP2R1A and 57% had mutations in ARID1A. Jones et al. (2010) concluded
that their results suggested that aberrant chromatin remodeling
contributes to the pathogenesis of ovarian clear cell carcinoma.
BIOCHEMICAL FEATURES
Groves et al. (1999) reported that the crystal structure of the PPP2R1A
subunit at 2.3-angstrom resolution revealed the conformation of its 15
tandemly repeated 'heat' sequences, degenerate motifs of 39 amino acids
present in a variety of proteins, including huntingtin (HTT; 613004) and
importin-beta (see 602738). Individual motifs are composed of a pair of
antiparallel alpha-helices that assemble in a mainly linear, repetitive
fashion to form an elongated molecule characterized by a double layer of
alpha-helices. The protein interaction interface is formed from the
intrarepeat turns that are aligned to form a continuous ridge.
GENE STRUCTURE
Ruteshouser et al. (2001) found that the PPP2R1A gene consists of 15
exons, spanning a region 36 kb in length.
MAPPING
The PPP2R1A gene is located on 19q13.4 (Ruteshouser et al., 2001).
*FIELD* RF
1. Everett, A. D.; Xue, C.; Stoops, T.: Developmental expression
of protein phosphatase 2A in the kidney. J. Am. Soc. Nephrol. 10:
1737-1745, 1999.
2. Groves, M. R.; Hanlon, N.; Turowski, P.; Hemmings, B. A.; Barford,
D.: The structure of the protein phosphatase 2A PR65/A subunit reveals
the conformation of its 15 tandemly repeated HEAT motifs. Cell 96:
99-110, 1999.
3. Hemmings, B. A.; Adams-Pearson, C.; Maurer, F.; Muller, P.; Goris,
J.; Merlevede, W.; Hofsteenge, J.; Stone, S. R.: Alpha- and beta-forms
of the 65-kDa subunit of protein phosphatase 2A have a similar 39
amino acid repeating structure. Biochemistry 29: 3166-3173, 1990.
4. Hendrix, P.; Turowski, P.; Mayer-Jaekel, R. E.; Goris, J.; Hofsteenge,
J.; Merlevede, W.; Hemmings, B. A.: Analysis of subunit isoforms
in protein phosphatase 2A holoenzymes from rabbit and Xenopus. J.
Biol. Chem. 268: 7330-7337, 1993.
5. Jones, S.; Wang, T.-L.; Shih, I.-M.; Mao, T.-L.; Nakayama, K.;
Roden, R.; Glas, R.; Slamon, D.; Diaz, L. A., Jr.; Vogelstein, B.;
Kinzler, K. W.; Velculescu, V. E.; Papadopoulos, N.: Frequent mutations
of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330:
228-231, 2010.
6. Ruteshouser, E. C.; Ashworth, L. K.; Huff, V.: Absence of PPP2R1A
mutations in Wilms tumor. Oncogene 20: 2050-2054, 2001.
*FIELD* CN
Ada Hamosh - updated: 11/11/2010
Matthew B. Gross - updated: 3/1/2005
*FIELD* CD
Victor A. McKusick: 5/31/2001
*FIELD* ED
alopez: 11/11/2010
wwang: 9/15/2009
mgross: 3/1/2005
terry: 6/5/2001
cwells: 5/31/2001
alopez: 5/31/2001
*RECORD*
*FIELD* NO
605983
*FIELD* TI
*605983 PROTEIN PHOSPHATASE 2, STRUCTURAL/REGULATORY SUBUNIT A, ALPHA; PPP2R1A
;;PROTEIN PHOSPHATASE 2, 65-KD REGULATORY SUBUNIT A, ALPHA;;
read morePR65-ALPHA
*FIELD* TX
DESCRIPTION
The PR65/A regulatory subunit of protein phosphatase-2A (PP2A) serves as
a scaffolding molecule that coordinates the assembly of the catalytic
subunit, PPP2CA (176915), and a variable regulatory B subunit to
generate functionally diverse heterotrimers. The PR65/A subunit exists
as 2 isoforms, PPP2R1A and PPP2R1B (603113) (Groves et al., 1999).
CLONING
Hemmings et al. (1990) cloned the cDNA corresponding to the PPP2R1A
gene, encoding the alpha isoform of the 65-kD structural/regulatory
subunit A of the PP2A holoenzyme. The PPP2R1A gene has 86% identity with
the PPP2R1B gene, as demonstrated by Hendrix et al. (1993).
Everett et al. (1999) showed that expression of all 3 subunits of PP2A,
including Ppp2r1a, is regulated in a cell-specific and developmentally
stage-specific manner in rat kidney, with the highest levels of enzyme
activity present in the nephrogenic cortex of fetal kidney.
GENE FUNCTION
To explore the genetic origin of ovarian clear cell carcinoma (167000),
Jones et al. (2010) determined the exomic sequences of 8 tumors after
immunoaffinity purification of cancer cells. Through comparative
analyses of normal cells from the same patients, Jones et al. (2010)
identified 4 genes that were mutated in at least 2 tumors. Two of these
genes, PPP2R1A and ARID1A (603024), which encodes a protein that
participates in chromatin remodeling, were not known to be involved in
ovarian clear cell carcinoma. The other 2 genes, PIK3CA (171834) and
KRAS (190070), had previously been implicated in ovarian clear cell
carcinoma. The nature and pattern of the mutations suggested that
PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene.
In a total of 42 ovarian clear cell carcinomas, 7% had mutations in
PPP2R1A and 57% had mutations in ARID1A. Jones et al. (2010) concluded
that their results suggested that aberrant chromatin remodeling
contributes to the pathogenesis of ovarian clear cell carcinoma.
BIOCHEMICAL FEATURES
Groves et al. (1999) reported that the crystal structure of the PPP2R1A
subunit at 2.3-angstrom resolution revealed the conformation of its 15
tandemly repeated 'heat' sequences, degenerate motifs of 39 amino acids
present in a variety of proteins, including huntingtin (HTT; 613004) and
importin-beta (see 602738). Individual motifs are composed of a pair of
antiparallel alpha-helices that assemble in a mainly linear, repetitive
fashion to form an elongated molecule characterized by a double layer of
alpha-helices. The protein interaction interface is formed from the
intrarepeat turns that are aligned to form a continuous ridge.
GENE STRUCTURE
Ruteshouser et al. (2001) found that the PPP2R1A gene consists of 15
exons, spanning a region 36 kb in length.
MAPPING
The PPP2R1A gene is located on 19q13.4 (Ruteshouser et al., 2001).
*FIELD* RF
1. Everett, A. D.; Xue, C.; Stoops, T.: Developmental expression
of protein phosphatase 2A in the kidney. J. Am. Soc. Nephrol. 10:
1737-1745, 1999.
2. Groves, M. R.; Hanlon, N.; Turowski, P.; Hemmings, B. A.; Barford,
D.: The structure of the protein phosphatase 2A PR65/A subunit reveals
the conformation of its 15 tandemly repeated HEAT motifs. Cell 96:
99-110, 1999.
3. Hemmings, B. A.; Adams-Pearson, C.; Maurer, F.; Muller, P.; Goris,
J.; Merlevede, W.; Hofsteenge, J.; Stone, S. R.: Alpha- and beta-forms
of the 65-kDa subunit of protein phosphatase 2A have a similar 39
amino acid repeating structure. Biochemistry 29: 3166-3173, 1990.
4. Hendrix, P.; Turowski, P.; Mayer-Jaekel, R. E.; Goris, J.; Hofsteenge,
J.; Merlevede, W.; Hemmings, B. A.: Analysis of subunit isoforms
in protein phosphatase 2A holoenzymes from rabbit and Xenopus. J.
Biol. Chem. 268: 7330-7337, 1993.
5. Jones, S.; Wang, T.-L.; Shih, I.-M.; Mao, T.-L.; Nakayama, K.;
Roden, R.; Glas, R.; Slamon, D.; Diaz, L. A., Jr.; Vogelstein, B.;
Kinzler, K. W.; Velculescu, V. E.; Papadopoulos, N.: Frequent mutations
of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330:
228-231, 2010.
6. Ruteshouser, E. C.; Ashworth, L. K.; Huff, V.: Absence of PPP2R1A
mutations in Wilms tumor. Oncogene 20: 2050-2054, 2001.
*FIELD* CN
Ada Hamosh - updated: 11/11/2010
Matthew B. Gross - updated: 3/1/2005
*FIELD* CD
Victor A. McKusick: 5/31/2001
*FIELD* ED
alopez: 11/11/2010
wwang: 9/15/2009
mgross: 3/1/2005
terry: 6/5/2001
cwells: 5/31/2001
alopez: 5/31/2001