Biology:PPP2R1A
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Short description: Enzyme
 Generic protein structure example |
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform is an enzyme that in humans is encoded by the PPP2R1A gene.[1] In the plant Arabidopsis thaliana a similar enzyme is encoded by the RCN1 gene (At1g25490).[2]
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.[3]
Role in human pathology
Mutations of the PPP2R1A gene cause Houge-Janssens syndrome-2, an intellectual developmental disorder.
Interactions
PPP2R1A has been shown to interact with:
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
- ↑ "Developmental expression of protein phosphatase 2A in the kidney". J. Am. Soc. Nephrol. 10 (8): 1737–45. August 1999. doi:10.1681/ASN.V1081737. PMID 10446941.
- ↑ "Molecular characterization of the B' regulatory subunit gene family of Arabidopsis protein phosphatase 2A". Eur. J. Biochem. 260 (1): 127–136. February 1999. doi:10.1046/j.1432-1327.1999.00154.x. PMID 10091592.
- ↑ "Entrez Gene: PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5518.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 "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". Mol. Cell. Proteomics 8 (1): 157–171. January 2009. doi:10.1074/mcp.M800266-MCP200. PMID 18782753.
- ↑ 5.0 5.1 5.2 5.3 5.4 "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. January 2003. doi:10.1042/BJ20021244. PMID 12370081.
- ↑ "PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4". J. Biol. Chem. 283 (43): 29273–29284. October 2008. doi:10.1074/jbc.M803443200. PMID 18715871.
- ↑ "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1). 2007. doi:10.1038/msb4100134. PMID 17353931.
Further reading
- Zolnierowicz S (2000). "Type 2A protein phosphatase, the complex regulator of numerous signaling pathways". Biochem. Pharmacol. 60 (8): 1225–1235. doi:10.1016/S0006-2952(00)00424-X. PMID 11007961.
- "Association of protein phosphatase 2A with polyoma virus medium tumor antigen". Proc. Natl. Acad. Sci. U.S.A. 87 (7): 2521–2525. 1990. doi:10.1073/pnas.87.7.2521. PMID 2157202. Bibcode: 1990PNAS...87.2521W.
- Hemmings BA; Adams-Pearson C; Maurer F; Mueller, Peter; Goris, Jozef; Merlevede, Wilfried; Hofsteenge, Jan; Stone, Stuart R. (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.
- "Molecular cloning and sequence of cDNA encoding polyoma medium tumor antigen-associated 61-kDa protein". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8669–8672. 1989. doi:10.1073/pnas.86.22.8669. PMID 2554323. Bibcode: 1989PNAS...86.8669W.
- "Identification of a new family of protein phosphatase 2A regulatory subunits". J. Biol. Chem. 270 (44): 26123–26128. 1995. doi:10.1074/jbc.270.44.26123. PMID 7592815.
- Ruediger R; Hentz M; Fait J; Mumby, M; Walter, G (1994). "Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens". J. Virol. 68 (1): 123–9. doi:10.1128/JVI.68.1.123-129.1994. PMID 8254721.
- Zolnierowicz S; Van Hoof C; Andjelković N; Cron, P; Stevens, I; Merlevede, W; Goris, J; Hemmings, BA (1996). "The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits". Biochem. J. 317 (1): 187–94. doi:10.1042/bj3170187. PMID 8694763.
- Tung HY; De Rocquigny H; Zhao LJ; Cayla, X; Roques, BP; Ozon, R (1997). "Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr". FEBS Lett. 401 (2–3): 197–201. doi:10.1016/S0014-5793(96)01470-6. PMID 9013886. Bibcode: 1997FEBSL.401..197T.
- "Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production". Virology 238 (2): 432–443. 1998. doi:10.1006/viro.1997.8873. PMID 9400615.
- "Binding specificity of protein phosphatase 2A core enzyme for regulatory B subunits and T antigens". J. Virol. 73 (1): 839–42. 1999. doi:10.1128/JVI.73.1.839-842.1999. PMID 9847399.
- Groves MR; Hanlon N; Turowski P; Hemmings, Brian A.; Barford, David (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.
- "Regulation of protein phosphatase 2A activity by heat shock transcription factor 2". J. Biol. Chem. 274 (19): 12967–12970. 1999. doi:10.1074/jbc.274.19.12967. PMID 10224043.
- "PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells". Mol. Cell. Biol. 20 (3): 1021–1029. 2000. doi:10.1128/MCB.20.3.1021-1029.2000. PMID 10629059.
- Husi H; Ward MA; Choudhary JS; Choudhary, Jyoti S.; Blackstock, Walter P. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–669. doi:10.1038/76615. PMID 10862698.
- "Absence of PPP2R1A mutations in Wilms tumor". Oncogene 20 (16): 2050–2054. 2001. doi:10.1038/sj.onc.1204301. PMID 11360189.
- "Interaction between protein phosphatase 5 and the A subunit of protein phosphatase 2A: evidence for a heterotrimeric form of protein phosphatase 5". J. Biol. Chem. 276 (42): 38582–38587. 2001. doi:10.1074/jbc.M106906200. PMID 11504734.
- Elder RT; Yu M; Chen M; Zhu, X; Yanagida, M; Zhao, Y (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.
- "Two conserved domains in regulatory B subunits mediate binding to the A subunit of protein phosphatase 2A". Eur. J. Biochem. 269 (2): 546–552. 2002. doi:10.1046/j.0014-2956.2001.02680.x. PMID 11856313.
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