InterPro domain: IPR011236

These eukaryotic serine/threonine phosphoprotein phosphatases, first described from human (PP5) and Saccharomyces cerevisiae (PPT1), are distinguished from related protein phosphatases by an N-terminal region of about 200 residues that contains three tandem tetratricopeptide repeats (TPR) [ 1 ]. Structurally, TPR repeats form a helical scaffold of antiparallel alpha-helices with an amphipathic groove that mediates protein-protein interactions [ 2 ]. The TPR domains contribute to regulation of PP5 activity, which is normally low but stimulated by interaction with lipid [ 3 ], and to interaction with other proteins [ 4 ].

PPT1 specifically binds to and dephosphorylates Hsp90 and this dephosphorylation positively regulates the Hsp90 chaperone machinery [ 5 ]. PPP5 is involved in a wide range of processes including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response hormones, calcium, fatty acids, TGF-beta and also oxidative and genotoxic stresses [ 6 , 7 , 8 ].

1. A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus. EMBO J. 13, 4278-90
2. The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions. EMBO J. 17, 1192-9
3. Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation. Biochemistry 40, 10485-90
4. 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, 38582-7
5. The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90. EMBO J. 25, 367-76
6. Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest. J. Biol. Chem. 282, 14690-4
7. Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor-? (PPAR?). J. Biol. Chem. 286, 42911-22
8. Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells. Diabetologia 55, 2005-15