FYVE-DSP2, a FYVE domain-containing dual specificity protein phosphatase that dephosphorylates phosphotidylinositol 3-phosphate

We have recently isolated FYVE-DSP1, a FYVE domain-containing dual specific ity protein phosphatase (R., Zhao, Y. Qi, and Z. J. Zhao, Biochem. Biophys. Res. Commun. 270, 222-229 (2000)). Here, we report a novel isozyme that we designated FYVE-DSP2. FYVE-2 contains a single FYVE domain at the C-termin us, and it shares similar to 47% overall sequence identity with FYBE-DSP1. Genomic sequence analyses revealed that the FYVE-DSP1 and FYVE-DSP2 genes s hare similar intron/exon organization, They are localized on human chromoso me 22q12 and chromosome 17, respectively, Like FYVE-DBSP1, recombinant FYVE -DSP2 dephosphorylated low-molecular-weight phosphatase substrate para-nitr ophenylphosphate, and its activity was inhibited by sodium vanadate. More i mportantly, our study also revealed that both FYVE-DSP1 and FYVE-DSP2 effic iently and specifically dephosphorylated phosphotidylinositol 3-phosphate. Subcellular fractionation demonstrated partition of FYVE-DSP1 and FYVE-DSP2 in membrane fractions, and. immunofluorescent cell staining showed perinuc lear localization of the enzymes. FYVE-DSP2 is expressed in many human tiss ues with an alternatively spliced isoform expressed in the kidney. Together with two homologous hypothetical proteins found in Caenorhabditis elegans and Drosophila, FYVE-DSP1 and FYVE-DSP2 form a subfamily of phosphatases th at may have an important role in cellular processes. (C) 2001 Academic Pres s.