Protein Phosphatase of Ciona savignyi
• PPP groupThere are 9 phosphatases exist in 7 families
PP1 (2) PP1 enzyme is composed of a catalytic subunit and a regulatory subunit(R subunit). The catalytic domain is conserved among all eukaryotes, and more than 100 regulatory subunits have been found to interact with C domain. Therefore, PP1 is a type of protein phosphatases of functional diversity which regulates a varieties of cellular processes through dephosphorylating different substrates. PP1 can promote the rational use of energy, especially when nutrients are abundant. PP1 plays a key role in the recovery from stress, however promotes apoptosis when cells are damaged beyond repair. In addition, PP1 can regulate the cell cycle (1).
Reference
1. Ceulemans, H. and Bollen, M. (2004) Functional diversity of protein phosphatase-1, a cellular economizer and reset button. Physiol Rev, 84, 1-39. PMID: 14715909 | PP2A (1) PP2A, a family of PPP, is ubiquitously expressed in all eukaryotes. Three subunits compose this phosphatase holoenzyme, among which, subunit A is a 60-65 kDa structural component, B is a regulatory subunit and C is a 36-38 kDa catalytic subunit. The substrate specificity, spatial and temporal functions of PP2A is determined by regulatory subunit B. PP2A is involved in a lot of cellular processes such as cell cycle regulation, cell morphology and development. In addition, PP2A plays a critical role in regulation of specific signal transduction cascades (1).
Reference
1. Basu, S. (2011) PP2A in the regulation of cell motility and invasion. Curr Protein Pept Sci, 12, 3-11. PMID: 21190527 | PP2B (1) PP3, also known as Calcineurin (PP2B), is a Ca(2+)- and calmodulin-dependent Serine/Threonine protein phosphatase. PP2B shares a highly conserved catalytic subunit and heterodimeric quaternary structure from yeast to mammals. PP2B plays a important role in cellular processes and Ca(2+)-dependent signal transduction pathways, such as neurodevelopment, immune response, cardiac hypertrophy, signal transduction and muscle development (1).
Reference
1. Shi, Y. (2009) Serine/threonine phosphatases: mechanism through structure. Cell, 139, 468-484. PMID: 19879837 | PP4 (1) PP4, a family of PPP which is ubiquitously expressed in all eukaryotes, is composed of three subunits, including two regulatory subunits R1 and R2, a catalytic subunit. PP4 is highly conserved among eukaryotes and sequence identity among human, mouse and rabbit is about 99% (1), which suggests that PP4 is an important type of protein phosphatases. PP4 is localized in mitotic centrosomes and plays a critical role in centrosome maturation. In addition, PP4 is also involved in varieties of cellular signaling, such as NF-kB pathway, Jnk pathway and apoptotic signaling. What's more, PP4 has been reported to possess a nuclear function, for example, PP4 is essential for stalled replication forks stabilization and is involved in formation or maintenance of chiasmata (2).
Reference
1. Hu, M.C., Shui, J.W., Mihindukulasuriya, K.A. and Tan, T.H. (2001) Genomic structure of the mouse PP4 gene: a developmentally regulated protein phosphatase. Gene, 278, 89-99. PMID: 11707325 2. Cohen, P.T., Philp, A. and Vazquez-Martin, C. (2005) Protein phosphatase 4--from obscurity to vital functions. FEBS Lett, 579, 3278-3286. PMID: 15913612 | PP5 (1) PP5 is unique member of PPP family. The most characterized feature is the presence of regulatory domain at N-terminus, TPR domain, which mediates protein-protein interactions. The phosphatase catalytic domain of PP5 is suppressed because PP5 is kept autoinhibited by TPR domain and a C-terminal helix αJ. PP5 can get its catalytic activity only if TPR domain is bound or truncated. PP5 plays an essential role in multiple cellular processes including proliferation, migration, differentiation, electrolyte balance, apoptosis, survival, and DNA damage repair (1).
Reference
1. Hinds, T.D., Jr. and Sanchez, E.R. (2008) Protein phosphatase 5. Int J Biochem Cell Biol, 40, 2358-2362. PMID: 17951098
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PP6 (1) PP6, a family of PPP, is highly conserved in evolution. PP6 is composed of a catalytic subunit, a SAPS regulatory subunit and an ankyrin repeat subunit. The three SAPS regulatory subunits are distinct in sequence and function diversity. PP6 plays an important role in signaling pathways such as NFkB signaling pathway and acts as a regulator of cell cycle progression (1). The N terminal domain can restrict G1 to S phase progression (2).
Reference
1. Mi, J., Dziegielewski, J., Bolesta, E., Brautigan, D.L. and Larner, J.M. (2009) Activation of DNA-PK by ionizing radiation is mediated by protein phosphatase 6. PLoS One, 4, e4395. PMID: 19198648 2. Stefansson, B. and Brautigan, D.L. (2007) Protein phosphatase PP6 N terminal domain restricts G1 to S phase progression in human cancer cells. Cell Cycle, 6, 1386-1392. PMID: 17568194 | PPP_Unique (2) Phosphoprotein phosphatase (PPP) is highly conserved among all eukaryotes. Seven phosphatases compose of PPP family in human genome, which are known as PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6 and PP7. PPP family phosphatases share a conserved catalytic domain ~280 amino acids and three signature motifs (-GDXHG-, -GDXVDRG- and -GNHE-) in its domain. The catalytic subunits of several members in PPP family always associate with a number of regulatory subunits, which regulate the substrate recognition and function. For PPP family members, metal ions play an important role during dephosphorylation reaction (1).
Reference
1. Shi, Y. (2009) Serine/threonine phosphatases: mechanism through structure. Cell, 139, 468-484. PMID: 19879837 |
※ Family introduction