PPP2CA

PPP2CA
Identifiers
Aliases	PPP2CA, PP2Ac, PP2CA, PP2Calpha, RP-C, protein phosphatase 2 catalytic subunit alpha, NEDLBA
External IDs	OMIM: 176915; MGI: 1321159; GeneCards: 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
Enzyme activity
Gene location (Human)
Chr.	Chromosome 5 (human)
End	134,226,073 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	52,018,605 bp
RNA expression pattern
	Top expressed in
	lateral nuclear group of thalamus; ; ventricular zone; ; ganglionic eminence; ; stromal cell of endometrium; ; Skeletal muscle tissue of rectus abdominis; ; postcentral gyrus; ; prefrontal cortex; ; pars compacta; ; pons; ; right ventricle;
	Top expressed in
	medial ganglionic eminence; ; molar; ; nucleus accumbens; ; substantia nigra; ; endocardial cushion; ; barrel cortex; ; atrioventricular valve; ; dorsal striatum; ; abdominal wall; ; human fetus;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	phosphoprotein phosphatase activity; GABA receptor binding; metal ion binding; protein C-terminus binding; protein binding; hydrolase activity; protein heterodimerization activity; protein serine/threonine phosphatase activity; tau protein binding;
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; membrane raft; synapse;
Biological process	apoptotic process; regulation of transcription, DNA-templated; ceramide metabolic process; regulation of DNA replication; protein dephosphorylation; response to organic substance; positive regulation of protein serine/threonine kinase activity; regulation of Wnt signaling pathway; regulation of cell adhesion; meiosis; negative regulation of cell growth; RNA splicing; regulation of cell differentiation; regulation of growth; mitotic nuclear membrane 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 STAT protein; regulation of protein phosphorylation; response to lead ion; peptidyl-threonine dephosphorylation; peptidyl-serine dephosphorylation; regulation of microtubule binding; positive regulation of microtubule binding;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	5515
	19052
	ENSG00000113575
	ENSMUSG00000020349
	P67775
	P63330
	NM_002715; NM_001355019
	NM_019411
	NP_002706; NP_001341948
	NP_062284
	Wikidata
View/Edit Human	View/Edit Mouse

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

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.

Role in human pathology

Genetic ablation of the PP2A catalytic subunit PPP2CA or depletion of the regulatory subunit PP2A-B56α induced senescence in Medulloblastoma models.

PPP2CA may serve as an immunotherapy target. Coculture experiments demonstrate PPP2CA deficiency in glioma cells promotes dendritic cell presentation. This may benefit immunologically cold tumors. In vivo experiments have show PPP2CA depletion can sensitize tumors and potentially allow for immune checkpoint inhibitors and radiotherapy to become more effective.

Interactions

PPP2CA has been shown to interact with:

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000113575 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020349 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Jones TA, Barker HM, da Cruz e Silva EF, Mayer-Jaekel RE, Hemmings BA, Spurr NK, et al. (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.
↑ "Entrez Gene: PPP2CA protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform".
↑ Ho WS, Mondal I, Liu J, Sun R, Huo J, Gao C, et al. (July 2026). "Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models". The Journal of Clinical Investigation. 136 (13) e196753. doi:10.1172/JCI196753. PMC 13318113. PMID 42085538.
↑ Mondal I, Das O, Sun R, Gao J, Yu B, Diaz A, et al. (August 2023). "PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma". Cancer Research. 83 (15): 2527–2542. doi:10.1158/0008-5472.CAN-22-3382. PMC 10525036. PMID 37219874.
↑ Deng X, Ito T, Carr B, Mumby M, May WS (December 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): 34157–34163. doi:10.1074/jbc.273.51.34157. PMID 9852076.
↑ Marmorstein LY, McLaughlin PJ, Stanton JB, Yan L, Crabb JW, Marmorstein AD (August 2002). "Bestrophin interacts physically and functionally with protein phosphatase 2A". The Journal of Biological Chemistry. 277 (34): 30591–30597. doi:10.1074/jbc.M204269200. PMID 12058047.
↑ Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, et al. (July 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): 27449–27467. doi:10.1074/jbc.M111693200. PMID 11956189.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, et al. (January 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): 157–171. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
1 2 Cheng A, Kaldis P, Solomon MJ (November 2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms". The Journal of Biological Chemistry. 275 (44): 34744–34749. doi:10.1074/jbc.M006210200. PMID 10934208.
↑ Gingras AC, Caballero M, Zarske M, Sanchez A, Hazbun TR, Fields S, et al. (November 2005). "A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity". Molecular & Cellular Proteomics. 4 (11): 1725–1740. doi:10.1074/mcp.M500231-MCP200. PMID 16085932.
↑ Chen J, Peterson RT, Schreiber SL (June 1998). "Alpha 4 associates with protein phosphatases 2A, 4, and 6". Biochemical and Biophysical Research Communications. 247 (3): 827–832. doi:10.1006/bbrc.1998.8792. PMID 9647778.
↑ Chung H, Nairn AC, Murata K, Brautigan DL (August 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): 10371–10376. doi:10.1021/bi990902g. PMID 10441131.
1 2 Zhou J, Pham HT, Ruediger R, Walter G (January 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): 387–398. doi:10.1042/BJ20021244. PMC 1223084. PMID 12370081.
↑ Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC (October 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): 21864–21872. doi:10.1016/S0021-9258(19)36692-X. PMID 1328247.
↑ Yan Z, Fedorov SA, Mumby MC, Williams RS (February 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): 1021–1029. doi:10.1128/mcb.20.3.1021-1029.2000. PMC 85219. PMID 10629059.
1 2 3 4 5 McCright B, Rivers AM, Audlin S, Virshup DM (September 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): 22081–22089. doi:10.1074/jbc.271.36.22081. PMID 8703017.
↑ Ito A, Kataoka TR, Watanabe M, Nishiyama K, Mazaki Y, Sabe H, et al. (February 2000). "A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation". The EMBO Journal. 19 (4): 562–571. doi:10.1093/emboj/19.4.562. PMC 305594. PMID 10675325.
↑ Kawabe T, Muslin AJ, Korsmeyer SJ (January 1997). "HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint". Nature. 385 (6615): 454–458. Bibcode:1997Natur.385..454K. doi:10.1038/385454a0. PMID 9009195. S2CID 608633.

Cohen P, Cohen PT (December 1989). "Protein phosphatases come of age". The Journal of Biological Chemistry. 264 (36): 21435–21438. doi:10.1016/S0021-9258(20)88197-6. PMID 2557326.
Zolnierowicz S (October 2000). "Type 2A protein phosphatase, the complex regulator of numerous signaling pathways". Biochemical Pharmacology. 60 (8): 1225–1235. doi:10.1016/S0006-2952(00)00424-X. PMID 11007961.
Goedert M, Cohen ES, Jakes R, Cohen P (November 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): 95–99. doi:10.1016/0014-5793(92)81418-L. PMID 1330687. S2CID 34940651.
Khew-Goodall Y, Mayer RE, Maurer F, Stone SR, Hemmings BA (January 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 (April 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): 2098–2101. doi:10.1128/JVI.65.4.2098-2101.1991. PMC 240073. PMID 1848320.
Scheidtmann KH, Mumby MC, Rundell K, Walter G (April 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 (December 1989). "Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A". The EMBO Journal. 8 (12): 3891–3898. doi:10.1002/j.1460-2075.1989.tb08568.x. PMC 402079. PMID 2555176.
Arino J, Woon CW, Brautigan DL, Miller TB, Johnson GL (June 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): 4252–4256. Bibcode:1988PNAS...85.4252A. doi:10.1073/pnas.85.12.4252. PMC 280405. PMID 2837763.
Stone SR, Mayer R, Wernet W, Maurer F, Hofsteenge J, Hemmings BA (December 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 (December 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): 3735–3742. doi:10.1002/j.1460-2075.1985.tb04142.x. PMC 554725. PMID 4092695.
McCright B, Virshup DM (November 1995). "Identification of a new family of protein phosphatase 2A regulatory subunits". The Journal of Biological Chemistry. 270 (44): 26123–26128. doi:10.1074/jbc.270.44.26123. PMID 7592815.
Favre B, Zolnierowicz S, Turowski P, Hemmings BA (June 1994). "The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo". The Journal of Biological Chemistry. 269 (23): 16311–16317. doi:10.1016/S0021-9258(17)34009-7. PMID 8206937.
Redpath NT, Price NT, Severinov KV, Proud CG (April 1993). "Regulation of elongation factor-2 by multisite phosphorylation". European Journal of Biochemistry. 213 (2): 689–699. doi:10.1111/j.1432-1033.1993.tb17809.x. PMID 8386634.
Muramatsu T, Kincaid RL (July 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 (BBA) - Molecular Cell Research. 1178 (1): 117–120. doi:10.1016/0167-4889(93)90117-8. PMID 8392375.
Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, et al. (December 1995). "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex". Nature. 378 (6557): 641–644. Bibcode:1995Natur.378..641K. doi:10.1038/378641a0. PMID 8524402. S2CID 4337105.
Ohguro H, Rudnicka-Nawrot M, Buczyłko J, Zhao X, Taylor JA, Walsh KA, et al. (March 1996). "Structural and enzymatic aspects of rhodopsin phosphorylation". The Journal of Biological Chemistry. 271 (9): 5215–5224. doi:10.1074/jbc.271.9.5215. PMID 8617805.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000113575 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020349 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Jones_1993-5] Jones TA, Barker HM, da Cruz e Silva EF, Mayer-Jaekel RE, Hemmings BA, Spurr NK, et al. (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.

[6] "Entrez Gene: PPP2CA protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform".

[7] Ho WS, Mondal I, Liu J, Sun R, Huo J, Gao C, et al. (July 2026). "Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models". The Journal of Clinical Investigation. 136 (13) e196753. doi:10.1172/JCI196753. PMC 13318113. PMID 42085538.

[8] Mondal I, Das O, Sun R, Gao J, Yu B, Diaz A, et al. (August 2023). "PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma". Cancer Research. 83 (15): 2527–2542. doi:10.1158/0008-5472.CAN-22-3382. PMC 10525036. PMID 37219874.

[Deng_1998-9] Deng X, Ito T, Carr B, Mumby M, May WS (December 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): 34157–34163. doi:10.1074/jbc.273.51.34157. PMID 9852076.

[Marmorstein_2002-10] Marmorstein LY, McLaughlin PJ, Stanton JB, Yan L, Crabb JW, Marmorstein AD (August 2002). "Bestrophin interacts physically and functionally with protein phosphatase 2A". The Journal of Biological Chemistry. 277 (34): 30591–30597. doi:10.1074/jbc.M204269200. PMID 12058047.

[Bennin_2002-11] Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, et al. (July 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): 27449–27467. doi:10.1074/jbc.M111693200. PMID 11956189.

[Goudreault_2009-12] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, et al. (January 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): 157–171. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.

[Cheng_2000-13] 1 2 Cheng A, Kaldis P, Solomon MJ (November 2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms". The Journal of Biological Chemistry. 275 (44): 34744–34749. doi:10.1074/jbc.M006210200. PMID 10934208.

[Gingras_2005-14] Gingras AC, Caballero M, Zarske M, Sanchez A, Hazbun TR, Fields S, et al. (November 2005). "A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity". Molecular & Cellular Proteomics. 4 (11): 1725–1740. doi:10.1074/mcp.M500231-MCP200. PMID 16085932.

[Chen_1998-15] Chen J, Peterson RT, Schreiber SL (June 1998). "Alpha 4 associates with protein phosphatases 2A, 4, and 6". Biochemical and Biophysical Research Communications. 247 (3): 827–832. doi:10.1006/bbrc.1998.8792. PMID 9647778.

[Chung_1999-16] Chung H, Nairn AC, Murata K, Brautigan DL (August 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): 10371–10376. doi:10.1021/bi990902g. PMID 10441131.

[Zhou_2003-17] 1 2 Zhou J, Pham HT, Ruediger R, Walter G (January 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): 387–398. doi:10.1042/BJ20021244. PMC 1223084. PMID 12370081.

[Kamibayashi_1992-18] Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC (October 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): 21864–21872. doi:10.1016/S0021-9258(19)36692-X. PMID 1328247.

[Yan_2000-19] Yan Z, Fedorov SA, Mumby MC, Williams RS (February 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): 1021–1029. doi:10.1128/mcb.20.3.1021-1029.2000. PMC 85219. PMID 10629059.

[McCright_1996-20] 1 2 3 4 5 McCright B, Rivers AM, Audlin S, Virshup DM (September 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): 22081–22089. doi:10.1074/jbc.271.36.22081. PMID 8703017.

[Ito_2000-21] Ito A, Kataoka TR, Watanabe M, Nishiyama K, Mazaki Y, Sabe H, et al. (February 2000). "A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation". The EMBO Journal. 19 (4): 562–571. doi:10.1093/emboj/19.4.562. PMC 305594. PMID 10675325.

[Kawabe_1997-22] Kawabe T, Muslin AJ, Korsmeyer SJ (January 1997). "HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint". Nature. 385 (6615): 454–458. Bibcode:1997Natur.385..454K. doi:10.1038/385454a0. PMID 9009195. S2CID 608633.

PPP2CA

Function

Role in human pathology

Interactions

See also

References

Further reading