Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

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Reviewed, UniProtKB/Swiss-Prot P67775 (PP2AA_HUMAN)

Last modified February 9, 2010. Version 63. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
      Short name=PP2A-alpha
    EC=3.1.3.16
Alternative name(s):
    Replication protein C
      Short name=RP-C

Gene names

Name:

PPP2CA

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I By similarity. Can dephosphorylate SV40 large T antigen and p53/TP53. Dephosphorylates SV40 large T antigen, preferentially on serine residues 120, 123, 677, and perhaps 679. The C subunit was most active, followed by the AC form, which was more active than the ABC form, and activity of all three forms was strongly stimulated by manganese, and to a lesser extent by magnesium. Dephosphorylation by the AC form, but not C or ABC form is inhibited by small T antigen.
Catalytic activity	A phosphoprotein + H₂O = a protein + phosphate.
Cofactor	Binds 1 iron ion per subunit By similarity. Binds 1 manganese ion per subunit By similarity.
Subunit structure	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 NXN; the interaction is direct By similarity. Interacts with TP53, SGOL1 and SGOL2. Ref.11
Subcellular location	Cytoplasm. Nucleus. Centromere. Cytoplasm › cytoskeleton › spindle pole. Note: In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles. Centromeric localization requires the presence of SGOL2 By similarity. Ref.11
Post-translational modification	Reversibly methyl esterified on Leu-309. Carboxyl methylation may play a role in holoenzyme assembly. It varies during the cell cycle. Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.
Sequence similarities	Belongs to the PPP phosphatase family. PP-1 subfamily.

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Ontologies

Keywords
Biological process	Meiosis
Cellular component	Centromere Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	RNA splicing Non-traceable author statement. Source: UniProtKB ceramide metabolic process Non-traceable author statement. Source: UniProtKB inactivation of MAPK activity Non-traceable author statement. Source: UniProtKB induction of apoptosis Traceable author statement. Source: UniProtKB negative regulation of cell growth Non-traceable author statement. Source: UniProtKB negative regulation of tyrosine phosphorylation of Stat3 protein Non-traceable author statement. Source: UniProtKB protein amino acid dephosphorylation Ref.1 Traceable author statement. Source: UniProtKB regulation of DNA replication Non-traceable author statement. Source: UniProtKB regulation of Wnt receptor signaling pathway Non-traceable author statement. Source: UniProtKB regulation of cell adhesion Non-traceable author statement. Source: UniProtKB regulation of cell differentiation Non-traceable author statement. Source: UniProtKB regulation of transcription Non-traceable author statement. Source: UniProtKB response to organic substance Non-traceable author statement. Source: UniProtKB second-messenger-mediated signaling Non-traceable author statement. Source: UniProtKB
Cellular component	chromosome, centromeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: UniProtKB mitochondrion Non-traceable author statement. Source: UniProtKB nucleus Non-traceable author statement. Source: UniProtKB protein phosphatase type 2A complex Traceable author statement. Source: UniProtKB soluble fraction Non-traceable author statement. Source: UniProtKB spindle pole Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoprotein phosphatase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
IGBP1	P78318	2	EBI-712311,EBI-1055954
PPP2R1A	P30153	2	EBI-712311,EBI-302388
PPP2R1B	P30154	2	EBI-712311,EBI-357094
SGOL1	Q5FBB7	1	EBI-712311,EBI-989069
SGOL2	Q562F6	1	EBI-712311,EBI-989213
STRN	O43815	1	EBI-712311,EBI-1046642
TRIP13	Q15645	2	EBI-712311,EBI-358993

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 309

309

Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

PRO_0000058839

Sites

Active site

118

Proton donor By similarity

Metal binding

Iron By similarity

Metal binding

Iron By similarity

Metal binding

Iron By similarity

Metal binding

Manganese By similarity

Metal binding

117

Manganese By similarity

Metal binding

167

Manganese By similarity

Metal binding

241

Manganese By similarity

Amino acid modifications

Modified residue

N6-acetyllysine Ref.15

Modified residue

307

Phosphotyrosine Ref.8

Modified residue

309

Leucine methyl ester Ref.6

Natural variations

Natural variant

V → A: dbSNP rs11552681.

VAR_051735

Experimental info

Mutagenesis

309

L → A: Loss of binding to PP2A B-alpha regulatory subunit. Ref.7

Secondary structure

309

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P67775-1 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: C602291F78F34555
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FASTA

309

35,594

        10         20         30         40         50         60 
MDEKVFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG 

        70         80         90        100        110        120 
QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYRER ITILRGNHES 

       130        140        150        160        170        180 
RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI 

       190        200        210        220        230        240 
RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA 

       250        260        270        280        290        300 
HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV 


TRRTPDYFL

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A alpha catalytic subunit." Stone S.R., Mayer R., Wernet W., Maurer F., Hofsteenge J., Hemmings B.A. Nucleic Acids Res. 16:11365-11365(1988) [PubMed: 2849764] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[2]	"Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes." Arino J., Woon C.W., Brautigan D.L., Miller T.B. Jr., Johnson G.L. Proc. Natl. Acad. Sci. U.S.A. 85:4252-4256(1988) [PubMed: 2837763] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes." Khew-Goodall Y., Mayer R.E., Maurer F., Stone S.R., Hemmings B.A. Biochemistry 30:89-97(1991) [PubMed: 1846293] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung, Placenta and Uterus.
[5]	"Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen." Scheidtmann K.H., Mumby M.C., Rundell K., Walter G. Mol. Cell. Biol. 11:1996-2003(1991) [PubMed: 1848668] [Abstract] Cited for: DEPHOSPHORYLATION OF SV40 LARGE-T ANTIGEN AND P53 PROTEIN.
[6]	"The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo." Favre B., Zolnierowicz S., Turowski P., Hemmings B.A. J. Biol. Chem. 269:16311-16317(1994) [PubMed: 8206937] [Abstract] Cited for: METHYLATION AT LEU-309.
[7]	"Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit." Bryant J.C., Westphal R.S., Wadzinski B.E. Biochem. J. 339:241-246(1999) [PubMed: 10191253] [Abstract] Cited for: MUTAGENESIS OF LEU-309.
[8]	"Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity." Scheidtmann K.H., Virshup D.M., Kelly T.J. J. Virol. 65:2098-2101(1991) [PubMed: 1848320] [Abstract] Cited for: SITES OF DEPHOSPHORYLATION AT SV40 LARGE-T ANTIGEN.
[9]	"Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A." Virshup D.M., Kauffman M.G., Kelly T.J. EMBO J. 8:3891-3898(1989) [PubMed: 2555176] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, ACTIVATION OF SV40 REPLICATION.
[10]	"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: 16580887] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH SGOL1.
[11]	"Shugoshin collaborates with protein phosphatase 2A to protect cohesin." Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T., Kawashima S.A., Watanabe Y. Nature 441:46-52(2006) [PubMed: 16541025] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SGOL1.
[12]	"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: 17245430] [Abstract] Cited for: INTERACTION WITH TP53.
[13]	"Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments." Huang H., Feng J., Famulski J., Rattner J.B., Liu S.T., Kao G.D., Muschel R., Chan G.K., Yen T.J. J. Cell Biol. 177:413-424(2007) [PubMed: 17485487] [Abstract] Cited for: INTERACTION WITH SGOL2.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-4, MASS SPECTROMETRY.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X12646 mRNA. Translation: CAA31176.1.
J03804 mRNA. Translation: AAB38019.1.
M60483 Genomic DNA. Translation: AAA36466.1.
BC000400 mRNA. Translation: AAH00400.1.
BC002657 mRNA. Translation: AAH02657.1.
BC019275 mRNA. Translation: AAH19275.1.
BC031696 mRNA. Translation: AAH31696.1.

IPI

IPI00008380.

PIR

PAHU2A. S01986.

RefSeq

NP_002706.1.

UniGene

Hs.105818

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IAE	X-ray	3.50	C/F	1-309	[»]
2IE3	X-ray	2.80	C	1-309	[»]
2IE4	X-ray	2.60	C	1-309	[»]
2NPP	X-ray	3.30	C/F	1-309	[»]
2NYL	X-ray	3.80	C/F	2-294	[»]
2NYM	X-ray	3.60	C/F	2-294	[»]
3C5W	X-ray	2.80	C	1-309	[»]
3DW8	X-ray	2.85	C/F	1-309	[»]
3FGA	X-ray	2.70	C	1-309	[»]
3K7V	X-ray	2.85	C	1-309	[»]
3K7W	X-ray	2.96	C	1-309	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29395N.

IntAct

P67775. 60 interactions.

STRING

P67775.

PTM databases

PhosphoSite

P67775.

Proteomic databases

PRIDE

P67775.

Genome annotation databases

Ensembl

ENST00000481195; ENSP00000418447; ENSG00000113575; Homo sapiens. [Genome view]

GeneID

5515.

KEGG

hsa:5515.

UCSC

uc003kze.1. human.

Organism-specific databases

CTD

5515.

GeneCards

GC05M133560.

H-InvDB

HIX0005174.

HGNC

HGNC:9299. PPP2CA.

HPA

CAB003848.

MIM

176915. gene.

PharmGKB

PA33663.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17795.

HOGENOM

HBG716770.

HOVERGEN

P67775.

InParanoid

P67775.

OMA

AIMEIDE.

PhylomeDB

P67775.

Enzyme and pathway databases

BRENDA

3.1.3.16. 247.

Pathway_Interaction_DB

tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_11045. Signaling by Wnt.
REACT_11061. Signalling by NGF.
REACT_1505. Integration of energy metabolism.
REACT_152. Cell Cycle, Mitotic.
REACT_15295. Opioid Signalling.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P67775.

Bgee

P67775.

CleanEx

HS_PPP2CA.

Genevestigator

P67775.

GermOnline

ENSG00000113575. Homo sapiens.

Family and domain databases

InterPro

IPR004843. M-pesterase.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]

PANTHER

PTHR11668. T_phtase_apaH. 1 hit.

Pfam

PF00149. Metallophos. 1 hit.
[Graphical view]

PRINTS

PR00114. STPHPHTASE.

SMART

SM00156. PP2Ac. 1 hit.
[Graphical view]

PROSITE

PS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00163. Vitamin E.

NextBio

21330.

SOURCE

Search...

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Entry information

Entry name

PP2AA_HUMAN

Accession

Primary (citable) accession number: P67775
Secondary accession number(s): P05323, P13197

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	February 9, 2010
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents