A NOVEL HUMAN PROTEIN SERINE THREONINE PHOSPHATASE, WHICH POSSESSES 4TETRATRICOPEPTIDE REPEAT MOTIFS AND LOCALIZES TO THE NUCLEUS/

A novel human protein serine/threonine phosphatase, PP5, and a structu rally related phosphatase in Saccharomyces cerevisiae, PPT1, have been identified from their cDNA and gene respectively. Their predicted mol ecular mass is 58 kDa and they comprise a C-terminal phosphatase catal ytic domain and an N-terminal domain, which has four repeats of 34 ami no acids, three of which are tandemly arranged. The phosphatase domain possesses all the invariant moths of the PP1/PP2A/PP2B gene family, b ut is not closely related to any other known member (less than or equa l to 40% identity). Thus PP5 and PPT1 comprise a new subfamily: The re peats in the N-terminal domain are similar to the tetratricopeptide re peat (TPR) motifs which have been found in several proteins that are r equired for mitosis, transcription and RNA splicing. Bacterially expre ssed PP5 is able to dephosphorylate serine residues in proteins and is more sensitive than PP1 to the tumour promoter okadaic acid. A 2.3 kb mRNA encoding PP5 is present in ah human tissues examined. Investigat ion of the intracellular distribution of PP5 by immunofluorescence, us ing two different antibodies raised against the TPR and phosphatase do mains, localizes PP5 predominantly to the nucleus. This suggests that, like other nuclear TPR-containing proteins, it may play a role in the regulation of RNA biogenesis and/or mitosis.