PPP2R5D explained

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform is an enzyme that in humans is encoded by the PPP2R5D gene.^{[1] [2]} Mutations in PPP2R5D cause Jordan's syndrome.

Function

The product of this gene belongs to the phosphatase 2A regulatory subunit B family. 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. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a delta isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified.^[2]

Interactions

PPP2R5D has been shown to interact with:

• HAND2,^[3]
• PPP2CA,^[4]
• PPP2R1B,^[5] and
• liprin-alpha-1.^[6]

Further reading

• Le Rouzic E, Benichou S . The Vpr protein from HIV-1: distinct roles along the viral life cycle. . Retrovirology . 2 . 11 . 2006 . 15725353 . 554975 . 10.1186/1742-4690-2-11 . free .
• Zhao RY, Elder RT . Viral infections and cell cycle G2/M regulation. . Cell Res. . 15 . 3 . 143–9 . 2005 . 15780175 . 10.1038/sj.cr.7290279 . free .
• Zhao RY, Bukrinsky M, Elder RT . HIV-1 viral protein R (Vpr) & host cellular responses. . Indian J. Med. Res. . 121 . 4 . 270–86 . 2005 . 15817944 .
• Tanabe O, Nagase T, Murakami T, Nozaki H, Usui H, Nishito Y, Hayashi H, Kagamiyama H, Takeda M . Molecular cloning of a 74-kDa regulatory subunit (B" or delta) of human protein phosphatase 2A. . FEBS Lett. . 379 . 1 . 107–11 . 1996 . 8566219 . 10.1016/0014-5793(95)01500-0 . 86538311 . free .
• McCright B, Rivers AM, Audlin S, Virshup DM . The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm. . J. Biol. Chem. . 271 . 36 . 22081–9 . 1996 . 8703017 . 10.1074/jbc.271.36.22081 . free .
• McCright B, Brothman AR, Virshup DM . Assignment of human protein phosphatase 2A regulatory subunit genes b56alpha, b56beta, b56gamma, b56delta, and b56epsilon (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2 --> p12. . Genomics . 36 . 1 . 168–70 . 1997 . 8812429 . 10.1006/geno.1996.0438 .
• Tung HY, De Rocquigny H, Zhao LJ, Cayla X, Roques BP, Ozon R . Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr. . FEBS Lett. . 401 . 2–3 . 197–201 . 1997 . 9013886 . 10.1016/S0014-5793(96)01470-6 . 23293768 . free .
• Tanabe O, Gomez GA, Nishito Y, Usui H, Takeda M . Molecular heterogeneity of the cDNA encoding a 74-kDa regulatory subunit (B" or delta) of human protein phosphatase 2A . FEBS Lett. . 408 . 1 . 52–6 . 1997 . 9180267 . 10.1016/S0014-5793(97)00392-X . 83580635 . free .
• Ruediger R, Brewis N, Ohst K, Walter G . Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production . Virology . 238 . 2 . 432–43 . 1998 . 9400615 . 10.1006/viro.1997.8873 . free .
• Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y . 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 . 359–70 . 2001 . 11531413 . 10.1006/viro.2001.1007 . free .
• Hrimech M, Yao XJ, Branton PE, Cohen EA . 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. . 21 . 14 . 3918 . 2002 . 12110603 . 126131 . 10.1093/emboj/cdf420 .
• Firulli BA, Howard MJ, McDaid JR, McIlreavey L, Dionne KM, Centonze VE, Cserjesi P, Virshup DM, Firulli AB . PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation . Mol. Cell . 12 . 5 . 1225–37 . 2004 . 14636580 . 10.1016/S1097-2765(03)00425-8 . free .
• Surpili MJ, Delben TM, Kobarg J . Identification of proteins that interact with the central coiled-coil region of the human protein kinase NEK1 . Biochemistry . 42 . 51 . 15369–76 . 2004 . 14690447 . 10.1021/bi034575v .

Notes and References

1. McCright B, Virshup DM . Identification of a new family of protein phosphatase 2A regulatory subunits . J Biol Chem . 270 . 44 . 26123–8 . Dec 1995 . 7592815 . 10.1074/jbc.270.44.26123 . free .
2. Web site: Entrez Gene: PPP2R5D protein phosphatase 2, regulatory subunit B', delta isoform.
3. Firulli BA, Howard MJ, McDaid JR, McIlreavey L, Dionne KM, Centonze VE, Cserjesi P, Virshup DM, Firulli AB . PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation . Mol. Cell . 12 . 5 . 1225–37 . Nov 2003 . 14636580 . 10.1016/S1097-2765(03)00425-8. free .
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 . 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 . 157–71 . Jan 2009 . 18782753 . 2621004 . 10.1074/mcp.M800266-MCP200 . free .
5. McCright B, Rivers AM, Audlin S, Virshup DM . The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm . J. Biol. Chem. . 271 . 36 . 22081–9 . Sep 1996 . 8703017 . 10.1074/jbc.271.36.22081. free .
6. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .