[1]
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NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Fibroblast;
DOI=10.1093/nar/16.23.11365; PubMed=2849764 [NCBI, ExPASy, EBI, Israel, Japan]
Stone S.R.,
Mayer R.,
Wernet W.,
Maurer F.,
Hofsteenge J.,
Hemmings B.A.;
"The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A alpha catalytic subunit.";
Nucleic Acids Res. 16:11365-11365(1988).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
DOI=10.1073/pnas.85.12.4252; PubMed=2837763 [NCBI, ExPASy, EBI, Israel, Japan]
Arino J.,
Woon C.W.,
Brautigan D.L.,
Miller T.B. Jr.,
Johnson G.L.;
"Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes.";
Proc. Natl. Acad. Sci. U.S.A. 85:4252-4256(1988).
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[3]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1021/bi00215a014; PubMed=1846293 [NCBI, ExPASy, EBI, Israel, Japan]
Khew-Goodall Y.,
Mayer R.E.,
Maurer F.,
Stone S.R.,
Hemmings B.A.;
"Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes.";
Biochemistry 30:89-97(1991).
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[4]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung, Placenta, and Uterus;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[5]
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DEPHOSPHORYLATION OF SV40 LARGE-T ANTIGEN AND P53 PROTEIN.
PubMed=1848668 [NCBI, ExPASy, EBI, Israel, Japan]
Scheidtmann K.H.,
Mumby M.C.,
Rundell K.,
Walter G.;
"Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen.";
Mol. Cell. Biol. 11:1996-2003(1991).
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[6]
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METHYLATION AT LEU-309.
PubMed=8206937 [NCBI, ExPASy, EBI, Israel, Japan]
Favre B.,
Zolnierowicz S.,
Turowski P.,
Hemmings B.A.;
"The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo.";
J. Biol. Chem. 269:16311-16317(1994).
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[7]
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MUTAGENESIS OF LEU-309.
DOI=10.1042/0264-6021:3390241; PubMed=10191253 [NCBI, ExPASy, EBI, Israel, Japan]
Bryant J.C.,
Westphal R.S.,
Wadzinski B.E.;
"Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit.";
Biochem. J. 339:241-246(1999).
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[8]
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SITES OF DEPHOSPHORYLATION AT SV40 LARGE-T ANTIGEN.
PubMed=1848320 [NCBI, ExPASy, EBI, Israel, Japan]
Scheidtmann K.H.,
Virshup D.M.,
Kelly T.J.;
"Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity.";
J. Virol. 65:2098-2101(1991).
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[9]
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PARTIAL PROTEIN SEQUENCE, AND ACTIVATION OF SV40 REPLICATION.
PubMed=2555176 [NCBI, ExPASy, EBI, Israel, Japan]
Virshup D.M.,
Kauffman M.G.,
Kelly T.J.;
"Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A.";
EMBO J. 8:3891-3898(1989).
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[10]
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SUBCELLULAR LOCATION, AND INTERACTION WITH SGOL1.
DOI=10.1038/nature04663; PubMed=16541025 [NCBI, ExPASy, EBI, Israel, Japan]
Kitajima T.S.,
Sakuno T.,
Ishiguro K.,
Iemura S.,
Natsume T.,
Kawashima S.A.,
Watanabe Y.;
"Shugoshin collaborates with protein phosphatase 2A to protect cohesin.";
Nature 441:46-52(2006).
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[11]
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IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J.,
Superti-Furga G.,
Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
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- FUNCTION: PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Can dephosphorylate SV40 large T antigen and p53. 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).
- COFACTOR: Binds 1 manganese ion per subunit (By similarity).
- SUBUNIT: PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and 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). May indirectly interact with SGOL1, most probably through regulatory B56 subunits.
- INTERACTION:
P78318:IGBP1; NbExp=2; IntAct=EBI-712311, EBI-1055954;
P30153:PPP2R1A; NbExp=1; IntAct=EBI-712311, EBI-302388;
P30154:PPP2R1B; NbExp=1; IntAct=EBI-712311, EBI-357094;
Q5FBB7:SGOL1; NbExp=1; IntAct=EBI-712311, EBI-989069;
Q562F6:SGOL2; NbExp=1; IntAct=EBI-712311, EBI-989213;
- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Centromere. Spindle. Note=In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles.
- PTM: Reversibly methyl esterified on Leu-309. Carboxyl methylation may play a role in holoenzyme assembly. It varies during the cell cycle.
- PTM: 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.
- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
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