PPP2R1A

Protein phosphatase 2, regulatory subunit A, alpha
PDB rendering based on 1b3u.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1B3U​, 2IE3​, 2IE4​, 2NPP​, 2NYL​, 2NYM​, 2PKG​, 3C5W​, 3DW8​, 3K7V​, 3K7W​, 4I5L​, 4I5N​, 4LAC​
Identifiers
Symbols	PPP2R1A ; MRD36; PP2A-Aalpha; PP2AAALPHA; PR65A
External IDs	OMIM: 605983 MGI: 1926334 HomoloGene: 68559 GeneCards: PPP2R1A Gene
EC number	3.1.3.16
Gene ontology Molecular function • antigen binding • protein serine/threonine phosphatase activity • protein binding • protein phosphatase type 2A regulator activity • protein heterodimerization activity Cellular component • protein phosphatase type 2A complex • chromosome, centromeric region • nucleus • mitochondrion • cytosol • microtubule cytoskeleton • membrane • extracellular exosome Biological process • G2/M transition of mitotic cell cycle • nuclear-transcribed mRNA catabolic process, nonsense-mediated decay • inactivation of MAPK activity • mitotic cell cycle • regulation of DNA replication • regulation of transcription, DNA-templated • protein complex assembly • protein dephosphorylation • ceramide metabolic process • apoptotic process • organelle organization • chromosome segregation • mitotic nuclear envelope reassembly • female meiotic division • RNA splicing • fibroblast growth factor receptor signaling pathway • response to organic substance • gene expression • second-messenger-mediated signaling • regulation of Wnt signaling pathway • regulation of cell adhesion • negative regulation of cell growth • regulation of protein phosphatase type 2A activity • regulation of growth • negative regulation of tyrosine phosphorylation of Stat3 protein • regulation of cell differentiation • meiotic spindle elongation • mitotic sister chromatid separation • meiotic sister chromatid cohesion, centromeric • peptidyl-serine dephosphorylation • regulation of meiotic cell cycle process involved in oocyte maturation • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5518	51792
Ensembl	ENSG00000105568	ENSMUSG00000007564
UniProt	P30153	Q76MZ3
RefSeq (mRNA)	NM_014225	NM_016891
RefSeq (protein)	NP_055040	NP_058587
Location (UCSC)	Chr 19: 52.19 – 52.23 Mb	Chr 17: 20.95 – 20.97 Mb
PubMed search

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]

Interactions

PPP2R1A has been shown to interact with:

• CTTNBP2NL,^[4]
• FAM40A,^[4]
• PPP2CB,^[4][5] PPP2CA,^[4][5] PPP4C,^[6]
• PPP2R2A,^[4][5]
• PPP2R3B,^[4][5]
• PPP2R5A.^[4][5]
• STK24,^[4][7]
• STRN,^[4] and
• STRN3.^[4]

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. Everett AD, Xue C, Stoops T (August 1999). "Developmental expression of protein phosphatase 2A in the kidney". J. Am. Soc. Nephrol. 10 (8): 1737–45. PMID 10446941.
2. 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". Eur. J. Biochem. 260 (1): 127–136. doi:10.1046/j.1432-1327.1999.00154.x. PMID 10091592.
3. "Entrez Gene: PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform".
4. 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 (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". Mol. Cell Proteomics 8 (1): 157–171. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
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". Biochem. J. 369 (Pt 2): 387–98. doi:10.1042/BJ20021244. PMC 1223084. PMID 12370081.
6. 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". J. Biol. Chem. 283 (43): 29273–29284. doi:10.1074/jbc.M803443200. PMC 2662017. PMID 18715871.
7. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. 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.
• Walter G, Ruediger R, Slaughter C, Mumby M (1990). "Association of protein phosphatase 2A with polyoma virus medium tumor antigen". Proc. Natl. Acad. Sci. U.S.A. 87 (7): 2521–2525. doi:10.1073/pnas.87.7.2521. PMC 53721. PMID 2157202.
• Hemmings BA, Adams-Pearson C, Maurer F, et al. (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". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8669–8672. 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". J. Biol. Chem. 270 (44): 26123–26128. doi:10.1074/jbc.270.44.26123. PMID 7592815.
• Ruediger R, Hentz M, Fait J, et al. (1994). "Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens". J. Virol. 68 (1): 123–9. PMC 236271. PMID 8254721.
• Zolnierowicz S, Van Hoof C, Andjelković N, et al. (1996). "The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits". Biochem. J. 317 (1): 187–94. PMC 1217462. PMID 8694763.
• Tung HY, De Rocquigny H, Zhao LJ, et al. (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.
• 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". J. Virol. 73 (1): 839–42. PMC 103900. PMID 9847399.
• Groves MR, Hanlon N, Turowski P, et al. (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.
• Hong Y, Sarge KD (1999). "Regulation of protein phosphatase 2A activity by heat shock transcription factor 2". J. Biol. Chem. 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". Mol. Cell. Biol. 20 (3): 1021–1029. doi:10.1128/MCB.20.3.1021-1029.2000. PMC 85219. PMID 10629059.
• Husi H, Ward MA, Choudhary JS, et al. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–669. doi:10.1038/76615. PMID 10862698.
• Hrimech M, Yao XJ, Branton PE, Cohen EA (2000). "Human immunodeficiency virus type 1 Vpr-mediated G(2) cell cycle arrest: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A". EMBO J. 19 (15): 3956–3967. doi:10.1093/emboj/19.15.3956. PMC 306605. PMID 10921877. (Retracted. If this is intentional, please replace {{Retracted}} with {{Retracted|intentional=yes}}.)
• 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". J. Biol. Chem. 276 (42): 38582–38587. doi:10.1074/jbc.M106906200. PMID 11504734.
• Elder RT, Yu M, Chen M, et al. (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". Eur. J. Biochem. 269 (2): 546–552. doi:10.1046/j.0014-2956.2001.02680.x. PMID 11856313.