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P30153 (2AAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Alternative name(s):
Medium tumor antigen-associated 61 kDa protein
PP2A subunit A isoform PR65-alpha
PP2A subunit A isoform R1-alpha
Gene names
Name:PPP2R1A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length589 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis. Ref.9

Subunit structure

Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphoylation sites By similarity. PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with IPO9. Interacts with TP53 and SGOL1. Interacts with PLA2G16; this interaction might decrease PP2A activity. Interacts with CTTNBP2NL. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

Subcellular location

Cytoplasm By similarity. Chromosomecentromere. Note: Centromeric localization requires the presence of BUB1. Ref.9

Domain

Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure. Ref.7

Sequence similarities

Belongs to the phosphatase 2A regulatory subunit A family.

Contains 15 HEAT repeats.

Ontologies

Keywords
   Biological processChromosome partition
   Cellular componentCentromere
Chromosome
Cytoplasm
   DomainRepeat
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

RNA metabolic process

Traceable author statement. Source: Reactome

RNA splicing

Non-traceable author statement PubMed 11007961. Source: UniProtKB

apoptotic process

Traceable author statement PubMed 11007961. Source: UniProtKB

ceramide metabolic process

Non-traceable author statement PubMed 11007961. Source: UniProtKB

chromosome segregation

Inferred from direct assay Ref.9. Source: UniProtKB

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

inactivation of MAPK activity

Non-traceable author statement PubMed 11007961. Source: UniProtKB

mRNA metabolic process

Traceable author statement. Source: Reactome

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic nuclear envelope reassembly

Traceable author statement. Source: Reactome

negative regulation of cell growth

Non-traceable author statement PubMed 11007961. Source: UniProtKB

negative regulation of tyrosine phosphorylation of Stat3 protein

Non-traceable author statement PubMed 11007961. Source: UniProtKB

nuclear-transcribed mRNA catabolic process, nonsense-mediated decay

Traceable author statement. Source: Reactome

peptidyl-serine dephosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

protein complex assembly

Traceable author statement Ref.18. Source: UniProtKB

protein dephosphorylation

Traceable author statement PubMed 11007961. Source: UniProtKB

regulation of DNA replication

Non-traceable author statement PubMed 11007961. Source: UniProtKB

regulation of Wnt signaling pathway

Non-traceable author statement PubMed 11007961. Source: UniProtKB

regulation of cell adhesion

Non-traceable author statement PubMed 11007961. Source: UniProtKB

regulation of cell differentiation

Non-traceable author statement PubMed 11360189. Source: UniProtKB

regulation of growth

Non-traceable author statement PubMed 11360189. Source: UniProtKB

regulation of transcription, DNA-templated

Non-traceable author statement PubMed 11007961. Source: UniProtKB

response to organic substance

Non-traceable author statement PubMed 11007961. Source: UniProtKB

second-messenger-mediated signaling

Non-traceable author statement PubMed 11007961. Source: UniProtKB

   Cellular_componentchromosome, centromeric region

Inferred from direct assay Ref.9. Source: UniProtKB

cytosol

Traceable author statement PubMed 11007961. Source: UniProtKB

membrane

Non-traceable author statement PubMed 11007961. Source: UniProtKB

microtubule cytoskeleton

Non-traceable author statement PubMed 11007961. Source: UniProtKB

mitochondrion

Non-traceable author statement PubMed 11007961. Source: UniProtKB

nucleus

Non-traceable author statement PubMed 11007961. Source: UniProtKB

protein phosphatase type 2A complex

Inferred from direct assay PubMed 17055435PubMed 17174897. Source: UniProtKB

   Molecular_functionantigen binding

Inferred from physical interaction PubMed 9847399. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 9847399. Source: UniProtKB

protein phosphatase type 2A regulator activity

Traceable author statement PubMed 11007961. Source: UniProtKB

protein serine/threonine phosphatase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.12
Chain2 – 589588Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
PRO_0000071400

Regions

Repeat8 – 4639HEAT 1
Repeat47 – 8438HEAT 2
Repeat85 – 12339HEAT 3
Repeat124 – 16138HEAT 4
Repeat162 – 20039HEAT 5
Repeat201 – 23939HEAT 6
Repeat240 – 27839HEAT 7
Repeat279 – 32143HEAT 8
Repeat322 – 36039HEAT 9
Repeat361 – 39939HEAT 10
Repeat400 – 43839HEAT 11
Repeat439 – 47739HEAT 12
Repeat478 – 51639HEAT 13
Repeat517 – 55539HEAT 14
Repeat556 – 58934HEAT 15
Region8 – 399392PP2A subunit B binding
Region47 – 321275Polyoma small and medium T antigens Binding
Region85 – 239155SV40 small T antigen binding
Region400 – 589190PP2A subunit C binding

Amino acid modifications

Modified residue21N-acetylalanine Ref.12 Ref.16 Ref.17
Modified residue2801N6-acetyllysine Ref.14

Experimental info

Sequence conflict1301P → A in AAA35531. Ref.1
Sequence conflict2581R → A in AAA36399. Ref.2
Sequence conflict2721K → R AA sequence Ref.6
Sequence conflict5511L → P in CAG29336. Ref.3

Secondary structure

.......................................................................................................... 589
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P30153 [UniParc].

Last modified April 3, 2007. Version 4.
Checksum: 5174EBE94D537836

FASTA58965,309
        10         20         30         40         50         60 
MAAADGDDSL YPIAVLIDEL RNEDVQLRLN SIKKLSTIAL ALGVERTRSE LLPFLTDTIY 

        70         80         90        100        110        120 
DEDEVLLALA EQLGTFTTLV GGPEYVHCLL PPLESLATVE ETVVRDKAVE SLRAISHEHS 

       130        140        150        160        170        180 
PSDLEAHFVP LVKRLAGGDW FTSRTSACGL FSVCYPRVSS AVKAELRQYF RNLCSDDTPM 

       190        200        210        220        230        240 
VRRAAASKLG EFAKVLELDN VKSEIIPMFS NLASDEQDSV RLLAVEACVN IAQLLPQEDL 

       250        260        270        280        290        300 
EALVMPTLRQ AAEDKSWRVR YMVADKFTEL QKAVGPEITK TDLVPAFQNL MKDCEAEVRA 

       310        320        330        340        350        360 
AASHKVKEFC ENLSADCREN VIMSQILPCI KELVSDANQH VKSALASVIM GLSPILGKDN 

       370        380        390        400        410        420 
TIEHLLPLFL AQLKDECPEV RLNIISNLDC VNEVIGIRQL SQSLLPAIVE LAEDAKWRVR 

       430        440        450        460        470        480 
LAIIEYMPLL AGQLGVEFFD EKLNSLCMAW LVDHVYAIRE AATSNLKKLV EKFGKEWAHA 

       490        500        510        520        530        540 
TIIPKVLAMS GDPNYLHRMT TLFCINVLSE VCGQDITTKH MLPTVLRMAG DPVANVRFNV 

       550        560        570        580 
AKSLQKIGPI LDNSTLQSEV KPILEKLTQD QDVDVKYFAQ EALTVLSLA 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and sequence of cDNA encoding polyoma medium tumor antigen-associated 61-kDa protein."
Walter G., Ferre F., Espiritu O., Carbone-Wiley A.
Proc. Natl. Acad. Sci. U.S.A. 86:8669-8672(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 242-255.
Tissue: Placenta.
[2]"Alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure."
Hemmings B.A., Adams-Pearson C., Maurer F., Mueller P., Goris J., Merlevede W., Hofsteenge J., Stone S.R.
Biochemistry 29:3166-3173(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[5]Lubec G., Vishwanath V.
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 34-46, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain and Cajal-Retzius cell.
[6]"The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits."
Zolnierowicz S., van Hoof C., Andjelkovic N., Cron P., Stevens I., Merlevede W., Goris J., Hemmings B.A.
Biochem. J. 317:187-194(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 204-214; 261-272 AND 521-527.
[7]"Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens."
Ruediger R., Hentz M., Fait J., Mumby M., Walter G.
J. Virol. 68:123-129(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: BINDING DOMAINS.
[8]"Interaction between protein phosphatase 2A and members of the importin beta superfamily."
Lubert E.J., Sarge K.D.
Biochem. Biophys. Res. Commun. 303:908-913(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IPO9.
[9]"PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation."
Tang Z., Shu H., Qi W., Mahmood N.A., Mumby M.C., Yu H.
Dev. Cell 10:575-585(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SGOL1.
[10]"A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55."
Li H.H., Cai X., Shouse G.P., Piluso L.G., Liu X.
EMBO J. 26:402-411(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TP53.
[11]"Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells."
Nazarenko I., Schafer R., Sers C.
J. Cell Sci. 120:1393-1404(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLA2G16.
[12]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[13]"A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein."
Goudreault M., D'Ambrosio L.M., Kean M.J., Mullin M.J., Larsen B.G., Sanchez A., Chaudhry S., Chen G.I., Sicheri F., Nesvizhskii A.I., Aebersold R., Raught B., Gingras A.C.
Mol. Cell. Proteomics 8:157-171(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTTNBP2NL.
[14]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs."
Groves M.R., Hanlon N., Turowski P., Hemmings B.A., Barford D.
Cell 96:99-110(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[19]"Structural mechanism of demethylation and inactivation of protein phosphatase 2A."
Xing Y., Li Z., Chen Y., Stock J.B., Jeffrey P.D., Shi Y.
Cell 133:154-163(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 9-589 IN COMPLEX WITH WITH PPP2CA AND PPME1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M31786 mRNA. Translation: AAA35531.1.
J02902 mRNA. Translation: AAA36399.1.
CR450340 mRNA. Translation: CAG29336.1.
BC001537 mRNA. Translation: AAH01537.1.
PIRA34541.
RefSeqNP_055040.2. NM_014225.5.
UniGeneHs.467192.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1B3UX-ray2.30A/B2-589[»]
2IE3X-ray2.80A1-589[»]
2IE4X-ray2.60A1-589[»]
2NPPX-ray3.30A/D1-589[»]
2NYLX-ray3.80A/D8-589[»]
2NYMX-ray3.60A/D8-589[»]
2PKGX-ray3.30A/B10-589[»]
3C5WX-ray2.80A9-589[»]
3DW8X-ray2.85A/D9-589[»]
3K7VX-ray2.85A1-589[»]
3K7WX-ray2.96A1-589[»]
4I5LX-ray2.43A/D9-589[»]
4I5NX-ray2.80A/D9-589[»]
4LACX-ray2.82A404-589[»]
ProteinModelPortalP30153.
SMRP30153. Positions 2-589.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111510. 143 interactions.
DIPDIP-29394N.
IntActP30153. 116 interactions.
MINTMINT-1141071.
STRING9606.ENSP00000324804.

PTM databases

PhosphoSiteP30153.

Polymorphism databases

DMDM143811355.

2D gel databases

OGPP30153.
REPRODUCTION-2DPAGEIPI00554737.

Proteomic databases

PaxDbP30153.
PRIDEP30153.

Protocols and materials databases

DNASU5518.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322088; ENSP00000324804; ENSG00000105568.
GeneID5518.
KEGGhsa:5518.
UCSCuc002pyp.3. human.

Organism-specific databases

CTD5518.
GeneCardsGC19P052693.
HGNCHGNC:9302. PPP2R1A.
HPACAB018599.
MIM605983. gene.
neXtProtNX_P30153.
PharmGKBPA33666.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG247268.
HOGENOMHOG000078539.
HOVERGENHBG000011.
InParanoidP30153.
KOK03456.
OMAFPEVRLH.
OrthoDBEOG764722.
PhylomeDBP30153.
TreeFamTF105552.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000105568-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_21257. Metabolism of RNA.
REACT_21300. Mitotic M-M/G1 phases.
REACT_604. Hemostasis.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
REACT_71. Gene Expression.
SignaLinkP30153.

Gene expression databases

ArrayExpressP30153.
BgeeP30153.
CleanExHS_PPP2R1A.
GenevestigatorP30153.

Family and domain databases

Gene3D1.25.10.10. 1 hit.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000357. HEAT.
IPR021133. HEAT_type_2.
[Graphical view]
PfamPF02985. HEAT. 2 hits.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
PROSITEPS50077. HEAT_REPEAT. 11 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP30153.
GeneWikiPPP2R1A.
GenomeRNAi5518.
NextBio21342.
PMAP-CutDBP30153.
PROP30153.
SOURCESearch...

Entry information

Entry name2AAA_HUMAN
AccessionPrimary (citable) accession number: P30153
Secondary accession number(s): Q13773, Q6ICQ3, Q96DH3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 3, 2007
Last modified: April 16, 2014
This is version 147 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM