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

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	589 AA.
Sequence status	Complete.
Protein existence	Evidence 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.12
Subcellular location	Cytoplasm By similarity. Chromosome › centromere. 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 process	Chromosome partition
Cellular component	Centromere Chromosome Cytoplasm
Domain	Repeat
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome RNA splicing Non-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 inactivation of MAPK activity Non-traceable author statement PubMed 11007961. Source: UniProtKB induction of apoptosis Traceable author statement PubMed 11007961. Source: UniProtKB 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: Compara protein complex assembly Traceable author statement Ref.15. 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 receptor 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 transcription, DNA-dependent Non-traceable author statement PubMed 11007961. Source: UniProtKB second-messenger-mediated signaling Non-traceable author statement PubMed 11007961. Source: UniProtKB
Cellular_component	chromosome, 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_function	antigen binding 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: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KIAA1524	Q8TCG1	4	EBI-302388,EBI-1379376
PLA2G16	P53816	7	EBI-302388,EBI-746318
PPP2CA	P67775	14	EBI-302388,EBI-712311
PPP2R2B	Q00005	5	EBI-302388,EBI-1052159
PPP2R5C	Q13362-1	3	EBI-302388,EBI-1266170
PPP2R5C	Q13362-2	2	EBI-302388,EBI-1266173
Ppp2r5c	Q60996-3	2	EBI-302388,EBI-1369292	From a different organism.
PPP2R5D	Q14738	4	EBI-302388,EBI-396563
PPP2R5E	Q16537	3	EBI-302388,EBI-968374
PPP4C	P60510	3	EBI-302388,EBI-1046072
STRN	O43815	4	EBI-302388,EBI-1046642

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 589

589

Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform

PRO_0000071400

Regions

Repeat

8 – 46

39

HEAT 1

Repeat

47 – 84

38

HEAT 2

Repeat

85 – 123

39

HEAT 3

Repeat

124 – 161

38

HEAT 4

Repeat

162 – 200

39

HEAT 5

Repeat

201 – 239

39

HEAT 6

Repeat

240 – 278

39

HEAT 7

Repeat

279 – 321

43

HEAT 8

Repeat

322 – 360

39

HEAT 9

Repeat

361 – 399

39

HEAT 10

Repeat

400 – 438

39

HEAT 11

Repeat

439 – 477

39

HEAT 12

Repeat

478 – 516

39

HEAT 13

Repeat

517 – 555

39

HEAT 14

Repeat

556 – 589

34

HEAT 15

Region

8 – 399

392

PP2A subunit B binding

Region

47 – 321

275

Polyoma small and medium T antigens Binding

Region

85 – 239

155

SV40 small T antigen binding

Region

400 – 589

190

PP2A subunit C binding

Amino acid modifications

Modified residue

280

1

N6-acetyllysine Ref.13

Experimental info

Sequence conflict

130

1

P → A in AAA35531. Ref.1

Sequence conflict

258

1

R → A in AAA36399. Ref.2

Sequence conflict

272

1

K → R AA sequence Ref.6

Sequence conflict

551

1

L → P in CAG29336. Ref.3

Secondary structure

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589

Helix Strand Turn

Details...

Turn

6 – 8

3

Helix

11 – 19

9

Helix

25 – 33

9

Helix

35 – 41

7

Helix

44 – 49

6

Helix

51 – 57

7

Helix

63 – 73

11

Helix

78 – 80

3

Helix

83 – 89

7

Helix

90 – 96

7

Beta strand

99 – 101

3

Helix

102 – 116

15

Helix

121 – 126

6

Helix

128 – 136

9

Beta strand

138 – 140

3

Helix

141 – 147

7

Helix

148 – 150

3

Helix

151 – 154

4

Turn

155 – 157

3

Helix

160 – 174

15

Helix

179 – 194

16

Helix

198 – 203

6

Helix

205 – 213

9

Helix

218 – 221

4

Helix

224 – 234

11

Helix

237 – 239

3

Helix

240 – 243

4

Helix

245 – 252

8

Helix

257 – 265

9

Helix

267 – 274

8

Helix

276 – 281

6

Helix

283 – 291

9

Helix

296 – 311

16

Turn

315 – 317

3

Helix

318 – 324

7

Helix

326 – 334

9

Helix

339 – 346

8

Helix

349 – 352

4

Helix

353 – 356

4

Helix

358 – 364

7

Helix

366 – 373

8

Helix

378 – 385

8

Helix

389 – 394

6

Helix

397 – 412

16

Helix

417 – 434

18

Helix

436 – 438

3

Helix

441 – 449

9

Helix

450 – 452

3

Helix

456 – 473

18

Helix

475 – 481

7

Helix

483 – 488

6

Turn

489 – 491

3

Helix

495 – 520

26

Helix

522 – 527

6

Helix

528 – 530

3

Helix

534 – 547

14

Helix

548 – 550

3

Helix

553 – 567

15

Helix

573 – 585

13

Sequences

	Sequence		Length	Mass (Da)
	P30153 [UniParc]. Last modified April 3, 2007. Version 4. Checksum: 5174EBE94D537836	FASTA	589	65,309
	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

References

	« Hide 'large scale' referencesShow '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, 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]	"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.
[13]	"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, MASS SPECTROMETRY.
[14]	"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].
[15]	"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).
[16]	"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.

IPI

IPI00554737.

PIR

A34541.

RefSeq

NP_055040.2. NM_014225.5.

UniGene

Hs.467192.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B3U	X-ray	2.30	A/B	2-589	[»]
2IE3	X-ray	2.80	A	1-589	[»]
2IE4	X-ray	2.60	A	1-589	[»]
2NPP	X-ray	3.30	A/D	1-589	[»]
2NYL	X-ray	3.80	A/D	8-589	[»]
2NYM	X-ray	3.60	A/D	8-589	[»]
2PKG	X-ray	3.30	A/B	10-589	[»]
3C5W	X-ray	2.80	A	9-589	[»]
3DW8	X-ray	2.85	A/D	9-589	[»]
3K7V	X-ray	2.85	A	1-589	[»]
3K7W	X-ray	2.96	A	1-589	[»]

ProteinModelPortal

P30153.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29394N.

IntAct

P30153. 92 interactions.

MINT

MINT-1141071.

STRING

9606.ENSP00000324804.

PTM databases

PhosphoSite

P30153.

Polymorphism databases

DMDM

143811355.

2D gel databases

OGP

P30153.

REPRODUCTION-2DPAGE

IPI00554737.

Proteomic databases

PaxDb

P30153.

PRIDE

P30153.

Protocols and materials databases

DNASU

5518.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000322088; ENSP00000324804; ENSG00000105568.

GeneID

5518.

KEGG

hsa:5518.

UCSC

uc002pyp.3. human.

Organism-specific databases

CTD

5518.

GeneCards

GC19P052693.

HGNC

HGNC:9302. PPP2R1A.

HPA

CAB018599.

MIM

605983. gene.

neXtProt

NX_P30153.

PharmGKB

PA33666.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG247268.

HOGENOM

HOG000078539.

HOVERGEN

HBG000011.

InParanoid

P30153.

KO

K03456.

OMA

TCLFCIN.

OrthoDB

EOG45MN4X.

PhylomeDB

P30153.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000105568-MONOMER.

Reactome

REACT_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.

Gene expression databases

ArrayExpress

P30153.

Bgee

P30153.

CleanEx

HS_PPP2R1A.

Genevestigator

P30153.

GermOnline

ENSG00000105568. Homo sapiens.

Family and domain databases

Gene3D

1.25.10.10. 1 hit.

InterPro

IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000357. HEAT.
IPR021133. HEAT_type_2.
[Graphical view]

Pfam

PF02985. HEAT. 2 hits.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.

PROSITE

PS50077. HEAT_REPEAT. 11 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P30153.

GenomeRNAi

5518.

NextBio

21342.

PMAP-CutDB

P30153.

SOURCE

Search...

Entry information

Entry name

2AAA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 137 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.