PPP2R1A
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform is an enzyme that in humans is encoded by the PPP2R1A gene. In the plant Arabidopsis thaliana a similar enzyme is encoded by the RCN1 gene (At1g25490).
Function
This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 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. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A.
Role in human pathology
Mutations of the PPP2R1A gene cause Houge-Janssens syndrome-2, an intellectual developmental disorder.
PPP2R1A encodes the scaffolding subunit of PP2A, a protein complex with tumor-suppressive functions that regulates cell growth and survival. Mutations in PPP2R1A can disrupt PP2A activity and contribute to the development and progression of certain cancers.
Interactions
PPP2R1A has been shown to interact with:
PPP2R1A has also been shown to bind to sphingosine, a bioactive sphingolipid that activates PP2A. Given PP2A's tumor-suppressive functions, sphingosine-mediated PP2A activation may have potential anticancer implications.
Arabidopsis RCN1
RCN1 At1g25490 is one of three genes in Arabidopsis encoding Phosphoprotein Phosphatase 2A Regulatory Subunit A (PP2Aa). The association of different b subunits with a PP2Aa-PP2ac dimer is believed to determine substrate specificity.
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000105568 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000007564 – 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.
- ↑ Everett AD, Xue C, Stoops T (August 1999). "Developmental expression of protein phosphatase 2A in the kidney". Journal of the American Society of Nephrology. 10 (8): 1737–1745. doi:10.1681/ASN.V1081737. PMID 10446941.
- ↑ Haynes JG, Hartung AJ, Hendershot JD, Passingham RS, Rundle SJ (February 1999). "Molecular characterization of the B' regulatory subunit gene family of Arabidopsis protein phosphatase 2A". European Journal of Biochemistry. 260 (1): 127–136. doi:10.1046/j.1432-1327.1999.00154.x. PMID 10091592.
- ↑ "Entrez Gene: PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform".
- 1 2 Jayashankar V, Kubiniok P, McCracken AN, Gentry RG, Eckenstein KH, Sernissi L, et al. (August 2025). "Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A". The EMBO Journal. 44 (16): 4473–4498. doi:10.1038/s44318-025-00490-5. PMC 12361511. PMID 40588551.
- 1 2 3 4 5 6 7 8 9 10 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 3 4 5 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.
- ↑ Chen GI, Tisayakorn S, Jorgensen C, D'Ambrosio LM, Goudreault M, Gingras AC (October 2008). "PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4". The Journal of Biological Chemistry. 283 (43): 29273–29284. doi:10.1074/jbc.M803443200. PMC 2662017. PMID 18715871.
- ↑ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1) 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
Further reading
- 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.
- Walter G, Ruediger R, Slaughter C, Mumby M (1990). "Association of protein phosphatase 2A with polyoma virus medium tumor antigen". Proceedings of the National Academy of Sciences of the United States of America. 87 (7): 2521–2525. Bibcode:1990PNAS...87.2521W. doi:10.1073/pnas.87.7.2521. PMC 53721. PMID 2157202.
- Hemmings BA, Adams-Pearson C, Maurer F, Müller P, Goris J, Merlevede W, et al. (April 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): 3166–3173. doi:10.1021/bi00465a002. PMID 2159327.
- Walter G, Ferre F, Espiritu O, Carbone-Wiley A (1989). "Molecular cloning and sequence of cDNA encoding polyoma medium tumor antigen-associated 61-kDa protein". Proceedings of the National Academy of Sciences of the United States of America. 86 (22): 8669–8672. Bibcode:1989PNAS...86.8669W. doi:10.1073/pnas.86.22.8669. PMC 298349. PMID 2554323.
- McCright B, Virshup DM (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.
- Ruediger R, Hentz M, Fait J, Mumby M, Walter G (January 1994). "Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens". Journal of Virology. 68 (1): 123–129. doi:10.1128/JVI.68.1.123-129.1994. PMC 236271. PMID 8254721.
- Zolnierowicz S, Van Hoof C, Andjelković N, Cron P, Stevens I, Merlevede W, et al. (July 1996). "The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits". The Biochemical Journal. 317 (Pt 1): 187–194. doi:10.1042/bj3170187. PMC 1217462. PMID 8694763.
- Tung HY, De Rocquigny H, Zhao LJ, Cayla X, Roques BP, Ozon R (January 1997). "Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr". FEBS Letters. 401 (2–3): 197–201. Bibcode:1997FEBSL.401..197T. doi:10.1016/S0014-5793(96)01470-6. PMID 9013886. S2CID 23293768.
- Ruediger R, Brewis N, Ohst K, Walter G (1998). "Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production". Virology. 238 (2): 432–443. doi:10.1006/viro.1997.8873. PMID 9400615.
- Ruediger R, Fields K, Walter G (1999). "Binding specificity of protein phosphatase 2A core enzyme for regulatory B subunits and T antigens". Journal of Virology. 73 (1): 839–842. doi:10.1128/JVI.73.1.839-842.1999. PMC 103900. PMID 9847399.
- Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D (January 1999). "The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs". Cell. 96 (1): 99–110. doi:10.1016/S0092-8674(00)80963-0. PMID 9989501. S2CID 14465060.
- Hong Y, Sarge KD (1999). "Regulation of protein phosphatase 2A activity by heat shock transcription factor 2". The Journal of Biological Chemistry. 274 (19): 12967–12970. doi:10.1074/jbc.274.19.12967. PMID 10224043.
- Yan Z, Fedorov SA, Mumby MC, Williams RS (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.
- Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (July 2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nature Neuroscience. 3 (7): 661–669. doi:10.1038/76615. hdl:1842/742. PMID 10862698. S2CID 14392630.
- Ruteshouser EC, Ashworth LK, Huff V (2001). "Absence of PPP2R1A mutations in Wilms tumor". Oncogene. 20 (16): 2050–2054. doi:10.1038/sj.onc.1204301. PMID 11360189.
- Lubert EJ, Hong Y, Sarge KD (2001). "Interaction between protein phosphatase 5 and the A subunit of protein phosphatase 2A: evidence for a heterotrimeric form of protein phosphatase 5". The Journal of Biological Chemistry. 276 (42): 38582–38587. doi:10.1074/jbc.M106906200. PMID 11504734.
- Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y (September 2001). "HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25". Virology. 287 (2): 359–370. doi:10.1006/viro.2001.1007. PMID 11531413.
- Li X, Virshup DM (2002). "Two conserved domains in regulatory B subunits mediate binding to the A subunit of protein phosphatase 2A". European Journal of Biochemistry. 269 (2): 546–552. doi:10.1046/j.0014-2956.2001.02680.x. PMID 11856313.
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