MOLECULAR-CLONING, EXPRESSION, AND CHARACTERIZATION OF A NOVEL HUMAN SERINE THREONINE PROTEIN PHOSPHATASE, PP7, THAT IS HOMOLOGOUS TO DROSOPHILA RETINAL DEGENERATION C-GENE-PRODUCT (RDGC)/

A novel serine/threonine protein phosphatase (PPase) designated PP7 wa s identified from cDNA produced from human retina RNA. PP7 has a molec ular mass of similar to 75 kDa, and the deduced amino acid sequence of PP7 contains a phosphatase catalytic core domain that possesses all o f the invariant motifs of the PP1, PP2A, PP2B, PP4, PP5, and PP6 gene family. However, PP7 has unique N- and C-terminal regions and shares < 35% identity with the other known PPases. The unique C-terminal region of PP7 contains multiple Ca2+ binding sites (i.e. EF-hand motifs). Th is region of PP7 is similar to the Drosophila retinal degeneration C g ene product (rdgC), and PP7 and rdgC share 42.1% identity. Unlike the other known PPases, the expression of PP7 is not ubiquitous; PP7 was o nly detected in retina and retinal-derived Y-79 retinoblastoma cells. Expression of recombinant human PP7 in baculovirus-infected SF21 insec t cells produces an active soluble enzyme that is capable of utilizing phosphohistone and p-nitrophenyl phosphate as substrates. The activit y of recombinant PP7 is dependent on Mg2+ and is activated by calcium (IC50 congruent to 250 mu M). PP7 is not affected by calmodulin and is insensitive to inhibition by okadaic acid, microcystin-LR, calyculin A, and cantharidin.