Species: Homo sapiens
Subunit composition of
serine/threonine-protein phosphatase 2A = [PPP2R1A][PPP2CA]
serine/threonine-protein phosphatase 2A regulatory subunit = PPP2R1A
serine/threonine-protein phosphatase 2A catalytic subunit = PPP2CA
Protein phosphatase 2A (PP2A) removes the serine- or threonine-bound phosphate group from a wide range of phosphoproteins. The enzyme is very versatile owing to a large number of regulatory subunits and its ability to interact with numerous other proteins. The PP2A holoenzyme is a dimeric or trimeric protein built up from a catalytic subunit (PP2AC) (catalytic subunit of PP2A), a second constant regulatory subunit, and a third variable subunit. Three major classes of third subunits are currently described. Each of the three subunits of PP2A exists in at least two isoforms, thereby leading to a great variety of possible holoenzyme conformations, all with potential different substrate affinities and catalytic activities.
The human enzyme consists of PPP2CA, a 36 kDa catalytic subunit, and PPP2R1A, a 65 kDa constant regulatory subunit. The regulatory subunit exists as two closely related isoforms designated Aα and Aβ [Zhou03a]. The dimer can associate with a variety of additional regulatory subunits.
The catalytic subunit is subject to different types of posttranslational modifications. Tyrosine kinases phosphorylate tyrosine at position 307 [Chen94d], a threonine kinase that is stimulated by autophosphorylation phosphorylates a yet unknown threonine residue [Guo93], and the carboxyl group of the C-terminal leucine amino acid (Leu309) is methylated by a specific methyltransferase [Xie94, Favre94]. This methylation is reversible in vivo due to the presence of a specific methylesterase [Xie94a].
The enzyme plays a role in p38 mitogen-activated protein kinase-mediated regulation of the c-Jun amino-terminal kinase pathway in human neutrophils [Avdi02] and in ceramide-mediated regulation of Bcl2 phosphorylation status and function [Ruvolo02].
A cDNA clone for the catalytic subunit was isolated from human liver and sequenced [Arino88]. The gene encoding the catalytic subunit was located on chromosome bands 5q23-->q31 [Jones93c], and was sequenced [Stone88a]. The structure and transcriptional regulation of the gene have been studied [KhewGoodall91]. The gene encoding regulatory subunit Aβ was located on chromosome band 11q23 [Baysal98].
Instance reactions of [1D-myo-inositol 1,2,3,4,5,6-hexakisphosphate + H2O → a D myo-inositol penta kis phosphate + phosphate] (126.96.36.199):
EC Number: 188.8.131.52
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is physiologically favored in the direction shown.
Synonyms: medium tumor antigen-associated 61 kDa protein
|Gene:||PPP2R1A||Accession Number: HS02763 (MetaCyc)|
Relationship Links: InterPro:IN-FAMILY:IPR000357 , InterPro:IN-FAMILY:IPR011989 , InterPro:IN-FAMILY:IPR016024 , InterPro:IN-FAMILY:IPR021133 , PDB:Structure:1B3U , PDB:Structure:2IE3 , PDB:Structure:2IE4 , PDB:Structure:2NPP , PDB:Structure:2NYL , PDB:Structure:2NYM , PDB:Structure:2PKG , PDB:Structure:3C5W , PDB:Structure:3DW8 , PDB:Structure:3K7V , PDB:Structure:3K7W , PDB:Structure:4I5L , PDB:Structure:4I5N , Pfam:IN-FAMILY:PF02985 , Prosite:IN-FAMILY:PS50077
Synonyms: PP2A-alpha, Replication protein C, RP-C
|Gene:||PPP2CA||Accession Number: HS03696 (MetaCyc)|
Molecular Weight: 35.594 kD (from nucleotide sequence)
Relationship Links: InterPro:IN-FAMILY:IPR004843 , InterPro:IN-FAMILY:IPR006186 , PDB:Structure:2IAE , PDB:Structure:2IE3 , PDB:Structure:2IE4 , PDB:Structure:2NPP , PDB:Structure:2NYL , PDB:Structure:2NYM , PDB:Structure:3C5W , PDB:Structure:3DW8 , PDB:Structure:3FGA , PDB:Structure:3K7V , PDB:Structure:3K7W , PDB:Structure:3P71 , PDB:Structure:4I5L , PDB:Structure:4I5N , PDB:Structure:4IYP , Pfam:IN-FAMILY:PF00149 , Prints:IN-FAMILY:PR00114 , Prosite:IN-FAMILY:PS00125 , Smart:IN-FAMILY:SM00156
Arino88: Arino J, Woon CW, Brautigan DL, Miller TB, Johnson GL (1988). "Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes." Proc Natl Acad Sci U S A 85(12);4252-6. PMID: 2837763
Avdi02: Avdi NJ, Malcolm KC, Nick JA, Worthen GS (2002). "A role for protein phosphatase-2A in p38 mitogen-activated protein kinase-mediated regulation of the c-Jun NH(2)-terminal kinase pathway in human neutrophils." J Biol Chem 277(43);40687-96. PMID: 12186863
Baysal98: Baysal BE, Farr JE, Goss JR, Devlin B, Richard CW (1998). "Genomic organization and precise physical location of protein phosphatase 2A regulatory subunit A beta isoform gene on chromosome band 11q23." Gene 217(1-2);107-16. PMID: 9795170
Chen94d: Chen J, Parsons S, Brautigan DL (1994). "Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts." J Biol Chem 269(11);7957-62. PMID: 7510677
Hemmings90: Hemmings BA, Adams-Pearson C, Maurer F, Muller P, Goris J, Merlevede W, Hofsteenge J, Stone SR (1990). "alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure." Biochemistry 29(13);3166-73. PMID: 2159327
Jones93c: Jones TA, Barker HM, da Cruz e Silva EF, Mayer-Jaekel RE, Hemmings BA, Spurr NK, Sheer D, Cohen PT (1993). "Localization of the genes encoding the catalytic subunits of protein phosphatase 2A to human chromosome bands 5q23-->q31 and 8p12-->p11.2, respectively." Cytogenet Cell Genet 63(1);35-41. PMID: 8383590
KhewGoodall91: Khew-Goodall Y, Mayer RE, Maurer F, Stone SR, Hemmings BA (1991). "Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes." Biochemistry 30(1);89-97. PMID: 1846293
Ruvolo02: Ruvolo PP, Clark W, Mumby M, Gao F, May WS (2002). "A functional role for the B56 alpha-subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function." J Biol Chem 277(25);22847-52. PMID: 11929874
Stone88a: Stone SR, Mayer R, Wernet W, Maurer F, Hofsteenge J, Hemmings BA (1988). "The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A alpha catalytic subunit." Nucleic Acids Res 16(23);11365. PMID: 2849764
Xie94a: Xie H, Clarke S (1994). "An enzymatic activity in bovine brain that catalyzes the reversal of the C-terminal methyl esterification of protein phosphatase 2A." Biochem Biophys Res Commun 203(3);1710-5. PMID: 7945320
Zhou03a: Zhou J, Pham HT, Ruediger R, Walter G (2003). "Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution." Biochem J 369(Pt 2);387-98. PMID: 12370081
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