FYVE-DSP1, a dual-specificity protein phosphatase containing an FYVE domain

Dual-specificity protein phosphatases (DSPs) dephosphorylate proteins at Se r/Thr and Tyr. FYVE domain is a double zinc finger motif which specifically binds phosphatidylinositol(3)-phosphate. Here, we report a novel dual spec ificity phosphatase that contains a FYVE domain at the C-terminus. We desig nate the protein FYVE-DSP1. Molecular cloning yielded three isoforms of the enzyme presumably derived from alternate RNA splicing. Sequence alignment revealed that the catalytic phosphatase domain of FYVE-DSP1 closely resembl ed that of myotubularin, while its FYVE domain has all the conserved amino acid residues found in other proteins of the same family. Recombinant FYVE- DSP1 is partitioned in both cytosolic and membrane fractions. it dephosphor ylates proteins phosphorylated on Ser, Thr, and Tyr residues and low molecu lar weight phosphatase substrate para-nitrophenylphosphate. It shows typica l characteristics of other DSPs and protein tyrosine phosphatases (PTPs). T hese include inhibition by sodium vanadate and pervanadate, pH dependency, and inactivation by mutation of the hey cysteinyl residue at the phosphatas e signature motif. Finally, PCR analyses demonstrated that FYVE-DSP1 is wid ely distributed in human tissues but different spliced forms expressed diff erently, (C) 2000 Academic Press.