MetaCyc Enzyme: serine/threonine-protein phosphatase 2A

Superclasses: a phosphatase-2A

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 [Zhou03]. 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 [Chen94a], 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 [Jones93a], and was sequenced [Stone88]. 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].

Gene-Reaction Schematic

Gene-Reaction Schematic

Instance reactions of [phytate + H2O → a D myo-inositol penta kis phosphate + phosphate] (
i1: phytate + H2O → D-myo-inositol (1,2,3,4,5)-pentakisphosphate + phosphate (

i2: phytate + H2O → 1D-myo-inositol (1,2,3,4,6)-pentakisphosphate + phosphate (

i3: phytate + H2O → D-myo-inositol (1,2,4,5,6)-pentakisphosphate + phosphate (

i4: phytate + H2O → D-myo-inositol (1,2,4,5,6)-pentakisphosphate + phosphate (

i5: phytate + H2O → D-myo-inositol (1,2,3,5,6) pentakisphosphate + phosphate (

i6: phytate + H2O → D-myo-inositol (1,2,3,5,6) pentakisphosphate + phosphate (

i7: phytate + H2O → D-myo-inositol 1,3,4,5,6-pentakisphosphate + phosphate (

Created 10-Apr-2011 by Caspi R, SRI International

Enzymatic reaction of: phosphoprotein phosphatase (serine/threonine-protein phosphatase 2A)

EC Number:

a [protein] (L-serine/L-threonine) phosphate + H2O → a [protein]-(L-serine/L-threonine) + phosphate

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Cofactors or Prosthetic Groups: Mn2+, Fe2+

Inhibitors (Unknown Mechanism): glutathione disulfide [Rao02]

Subunit of serine/threonine-protein phosphatase 2A: serine/threonine-protein phosphatase 2A regulatory subunit

Synonyms: medium tumor antigen-associated 61 kDa protein

Gene: PPP2R1A Accession Number: HS02763 (MetaCyc)

Unification Links: DIP:DIP-29394N, Mint:MINT-1141071, PhosphoSite:P30153, PhylomeDB:P30153, Pride:P30153, Protein Model Portal:P30153, SMR:P30153, UniProt:P30153

Relationship Links: InterPro:IN-FAMILY:IPR000357, InterPro:IN-FAMILY:IPR011989, InterPro:IN-FAMILY:IPR016024, InterPro:IN-FAMILY:IPR021133, InterPro:IN-FAMILY:IPR031090, Panther:IN-FAMILY:PTHR10648:SF9, 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, PDB:Structure:4LAC, Pfam:IN-FAMILY:PF02985, Prosite:IN-FAMILY:PS50077

Citations: [Hemmings90]

Subunit of serine/threonine-protein phosphatase 2A: serine/threonine-protein phosphatase 2A catalytic subunit

Synonyms: PP2A-alpha, Replication protein C, RP-C

Gene: PPP2CA Accession Number: HS03696 (MetaCyc)

Molecular Weight: 35.594 kD (from nucleotide sequence)

Unification Links: DIP:DIP-29395N, Mint:MINT-215645, PhosphoSite:P67775, PhylomeDB:P67775, Pride:P67775, Protein Model Portal:P67775, SMR:P67775, UniProt:P67775

Relationship Links: InterPro:IN-FAMILY:IPR004843, InterPro:IN-FAMILY:IPR006186, InterPro:IN-FAMILY:IPR029052, 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, PDB:Structure:4LAC, 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

Chen94a: 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

Favre94: Favre B, Zolnierowicz S, Turowski P, Hemmings BA (1994). "The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo." J Biol Chem 269(23);16311-7. PMID: 8206937

Guo93: Guo H, Damuni Z (1993). "Autophosphorylation-activated protein kinase phosphorylates and inactivates protein phosphatase 2A." Proc Natl Acad Sci U S A 90(6);2500-4. PMID: 7681598

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

Jones93a: 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

Rao02: Rao RK, Clayton LW (2002). "Regulation of protein phosphatase 2A by hydrogen peroxide and glutathionylation." Biochem Biophys Res Commun 293(1);610-6. PMID: 12054646

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

Stone88: 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

Xie94: Xie H, Clarke S (1994). "Protein phosphatase 2A is reversibly modified by methyl esterification at its C-terminal leucine residue in bovine brain." J Biol Chem 269(3);1981-4. PMID: 8294450

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

Zhou03: 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

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.5 on Sat Nov 28, 2015, BIOCYC11A.