PPP2CA

PPP2CA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2IAE, 2IE3, 2IE4, 2NPP, 2NYL, 2NYM, 3C5W, 3DW8, 3FGA, 3K7V, 3K7W, 3P71, 4I5L, 4I5N, 4IYP, 4LAC
Identifiers
Aliases	PPP2CA, PP2Ac, PP2CA, PP2Calpha, RP-C, protein phosphatase 2 catalytic subunit alpha
External IDs	MGI: 1321159 HomoloGene: 37660 GeneCards: PPP2CA
Gene ontology Molecular function • phosphoprotein phosphatase activity • GABA receptor binding • metal ion binding • protein C-terminus binding • protein binding • hydrolase activity Cellular component • cytoplasm • cytosol • spindle pole • membrane • microtubule cytoskeleton • plasma membrane • protein phosphatase type 2A complex • chromosome • mitochondrion • chromosome, centromeric region • cytoskeleton • extracellular exosome • nucleus Biological process • apoptotic process • regulation of transcription, DNA-templated • ceramide metabolic process • regulation of DNA replication • inactivation of MAPK activity • protein dephosphorylation • response to organic substance • positive regulation of protein serine/threonine kinase activity • regulation of Wnt signaling pathway • regulation of cell adhesion • meiotic cell cycle • negative regulation of cell growth • RNA splicing • regulation of cell differentiation • regulation of growth • mitotic nuclear envelope reassembly • nuclear-transcribed mRNA catabolic process, nonsense-mediated decay • mesoderm development • second-messenger-mediated signaling • negative regulation of epithelial to mesenchymal transition • negative regulation of tyrosine phosphorylation of Stat3 protein Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5515	19052
Ensembl	ENSG00000113575	ENSMUSG00000020349
UniProt	P67775	P63330
RefSeq (mRNA)	NM_002715	NM_019411
RefSeq (protein)	NP_002706.1	NP_062284.1
Location (UCSC)	Chr 5: 134.19 – 134.23 Mb	Chr 11: 52.1 – 52.13 Mb
PubMed search	[1]	[2]
Wikidata

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Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is an enzyme that (in humans) is encoded by the PPP2CA gene.^[3]

Function

This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes an alpha isoform of the catalytic subunit.^[4]

Interactions

PPP2CA has been shown to interact with:

• Bcl-2,^[5]
• Bestrophin 1,^[6]
• CCNG2,^[7]
• CTTNBP2NL,^[8]
• CTTNBP2,^[8]
• Cyclin-dependent kinase 2,^[9]
• Cyclin-dependent kinase 6,^[9]
• FAM40A,^[8]
• IGBP1,^{[8][10][11][12]}
• MOBKL3,^[8]
• PPP2R1A,^[8][13]
• PPP2R1B,^[8][13]
• PPP2R2A,^[8][14]
• PPP2R3B,^[8][15]
• PPP2R5A,^[8][16]
• PPP2R5B,^[8][16]
• PPP2R5C,^[8][16][17]
• PPP2R5D,^[8][16]
• PPP2R5E,^[8][16]
• STRN3,^[8]
• STRN,^[8] and
• TLX1.^[18]

See also

• PPP2CB

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Jones TA, Barker HM, da Cruz e Silva EF, Mayer-Jaekel RE, Hemmings BA, Spurr NK, Sheer D, Cohen PT (April 1993). "Localization of the genes encoding the catalytic subunits of protein phosphatase 2A to human chromosome bands 5q23-->q31 and 8p12-->p11.2, respectively". Cytogenetics and Cell Genetics. 63 (1): 35–41. doi:10.1159/000133497. PMID 8383590.
4. "Entrez Gene: PPP2CA protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform".
5. Deng X, Ito T, Carr B, Mumby M, May WS (Dec 1998). "Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A". The Journal of Biological Chemistry. 273 (51): 34157–63. doi:10.1074/jbc.273.51.34157. PMID 9852076.
6. Marmorstein LY, McLaughlin PJ, Stanton JB, Yan L, Crabb JW, Marmorstein AD (Aug 2002). "Bestrophin interacts physically and functionally with protein phosphatase 2A". The Journal of Biological Chemistry. 277 (34): 30591–7. doi:10.1074/jbc.M204269200. PMID 12058047.
7. Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, DePaoli-Roach AA, Horne MC (Jul 2002). "Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B' subunits in active complexes and induces nuclear aberrations and a G1/S phase cell cycle arrest". The Journal of Biological Chemistry. 277 (30): 27449–67. doi:10.1074/jbc.M111693200. PMID 11956189.
8. Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC (Jan 2009). "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". Molecular & Cellular Proteomics. 8 (1): 157–71. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
9. Cheng A, Kaldis P, Solomon MJ (Nov 2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms". The Journal of Biological Chemistry. 275 (44): 34744–9. doi:10.1074/jbc.M006210200. PMID 10934208.
10. Gingras AC, Caballero M, Zarske M, Sanchez A, Hazbun TR, Fields S, Sonenberg N, Hafen E, Raught B, Aebersold R (Nov 2005). "A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity". Molecular & Cellular Proteomics. 4 (11): 1725–40. doi:10.1074/mcp.M500231-MCP200. PMID 16085932.
11. Chen J, Peterson RT, Schreiber SL (Jun 1998). "Alpha 4 associates with protein phosphatases 2A, 4, and 6". Biochemical and Biophysical Research Communications. 247 (3): 827–32. doi:10.1006/bbrc.1998.8792. PMID 9647778.
12. Chung H, Nairn AC, Murata K, Brautigan DL (Aug 1999). "Mutation of Tyr307 and Leu309 in the protein phosphatase 2A catalytic subunit favors association with the alpha 4 subunit which promotes dephosphorylation of elongation factor-2". Biochemistry. 38 (32): 10371–6. doi:10.1021/bi990902g. PMID 10441131.
13. Zhou J, Pham HT, Ruediger R, Walter G (Jan 2003). "Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution". The Biochemical Journal. 369 (Pt 2): 387–98. doi:10.1042/BJ20021244. PMC 1223084. PMID 12370081.
14. Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC (Oct 1992). "Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits". The Journal of Biological Chemistry. 267 (30): 21864–72. PMID 1328247.
15. Yan Z, Fedorov SA, Mumby MC, Williams RS (Feb 2000). "PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells". Molecular and Cellular Biology. 20 (3): 1021–9. doi:10.1128/mcb.20.3.1021-1029.2000. PMC 85219. PMID 10629059.
16. McCright B, Rivers AM, Audlin S, Virshup DM (Sep 1996). "The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm". The Journal of Biological Chemistry. 271 (36): 22081–9. doi:10.1074/jbc.271.36.22081. PMID 8703017.
17. Ito A, Kataoka TR, Watanabe M, Nishiyama K, Mazaki Y, Sabe H, Kitamura Y, Nojima H (Feb 2000). "A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation". The EMBO Journal. 19 (4): 562–71. doi:10.1093/emboj/19.4.562. PMC 305594. PMID 10675325.
18. Kawabe T, Muslin AJ, Korsmeyer SJ (Jan 1997). "HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint". Nature. 385 (6615): 454–8. doi:10.1038/385454a0. PMID 9009195.

Further reading

• Cohen P, Cohen PT (Dec 1989). "Protein phosphatases come of age". The Journal of Biological Chemistry. 264 (36): 21435–8. PMID 2557326.
• Zolnierowicz S (Oct 2000). "Type 2A protein phosphatase, the complex regulator of numerous signaling pathways". Biochemical Pharmacology. 60 (8): 1225–35. doi:10.1016/S0006-2952(00)00424-X. PMID 11007961.
• Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC (Oct 1992). "Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits". The Journal of Biological Chemistry. 267 (30): 21864–72. PMID 1328247.
• Goedert M, Cohen ES, Jakes R, Cohen P (Nov 1992). "p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease [corrected]". FEBS Letters. 312 (1): 95–9. doi:10.1016/0014-5793(92)81418-L. PMID 1330687.
• Khew-Goodall Y, Mayer RE, Maurer F, Stone SR, Hemmings BA (Jan 1991). "Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes". Biochemistry. 30 (1): 89–97. doi:10.1021/bi00215a014. PMID 1846293.
• Scheidtmann KH, Virshup DM, Kelly TJ (Apr 1991). "Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity". Journal of Virology. 65 (4): 2098–101. PMC 240073. PMID 1848320.
• Scheidtmann KH, Mumby MC, Rundell K, Walter G (Apr 1991). "Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen". Molecular and Cellular Biology. 11 (4): 1996–2003. doi:10.1128/mcb.11.4.1996. PMC 359885. PMID 1848668.
• Virshup DM, Kauffman MG, Kelly TJ (Dec 1989). "Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A". The EMBO Journal. 8 (12): 3891–8. PMC 402079. PMID 2555176.
• Arino J, Woon CW, Brautigan DL, Miller TB, Johnson GL (Jun 1988). "Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes". Proceedings of the National Academy of Sciences of the United States of America. 85 (12): 4252–6. doi:10.1073/pnas.85.12.4252. PMC 280405. PMID 2837763.
• Stone SR, Mayer R, Wernet W, Maurer F, Hofsteenge J, Hemmings BA (Dec 1988). "The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A alpha catalytic subunit". Nucleic Acids Research. 16 (23): 11365. doi:10.1093/nar/16.23.11365. PMC 339016. PMID 2849764.
• Carrey EA, Campbell DG, Hardie DG (Dec 1985). "Phosphorylation and activation of hamster carbamyl phosphate synthetase II by cAMP-dependent protein kinase. A novel mechanism for regulation of pyrimidine nucleotide biosynthesis". The EMBO Journal. 4 (13B): 3735–42. PMC 554725. PMID 4092695.
• McCright B, Virshup DM (Nov 1995). "Identification of a new family of protein phosphatase 2A regulatory subunits". The Journal of Biological Chemistry. 270 (44): 26123–8. doi:10.1074/jbc.270.44.26123. PMID 7592815.
• Favre B, Zolnierowicz S, Turowski P, Hemmings BA (Jun 1994). "The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo". The Journal of Biological Chemistry. 269 (23): 16311–7. PMID 8206937.
• Redpath NT, Price NT, Severinov KV, Proud CG (Apr 1993). "Regulation of elongation factor-2 by multisite phosphorylation". European Journal of Biochemistry / FEBS. 213 (2): 689–99. doi:10.1111/j.1432-1033.1993.tb17809.x. PMID 8386634.
• Muramatsu T, Kincaid RL (Jul 1993). "Molecular cloning of a full-length cDNA encoding the catalytic subunit of human calmodulin-dependent protein phosphatase (calcineurin A alpha)". Biochimica et Biophysica Acta. 1178 (1): 117–20. doi:10.1016/0167-4889(93)90117-8. PMID 8392375.
• Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW (Dec 1995). "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex". Nature. 378 (6557): 641–4. doi:10.1038/378641a0. PMID 8524402.
• Ohguro H, Rudnicka-Nawrot M, Buczyłko J, Zhao X, Taylor JA, Walsh KA, Palczewski K (Mar 1996). "Structural and enzymatic aspects of rhodopsin phosphorylation". The Journal of Biological Chemistry. 271 (9): 5215–24. doi:10.1074/jbc.271.9.5215. PMID 8617805.
• McCright B, Rivers AM, Audlin S, Virshup DM (Sep 1996). "The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm". The Journal of Biological Chemistry. 271 (36): 22081–9. doi:10.1074/jbc.271.36.22081. PMID 8703017.