Multiple inositol polyphosphate phosphatase: Evolution as a distinct groupwithin the histidine phosphatase family and chromosomal localization of the human and mouse genes to chromosomes 10q23 and 19

Multiple inositol polyphosphate phosphatase is the only enzyme known to hyd rolyze the abundant metabolites inositol pentakisphosphate and inositol hex akisphosphate, We have previously demonstrated that the chick homolog of mu ltiple inositol polyphosphate phosphatase, designated HiPER1, has a role in growth plate chondrocyte differentiation. The relationship of these enzyme s to intracellular signaling is obscure, and as part of our investigation w e have examined the murine ((MMU)Minpp1) and human ((HSA)MINPP1) homologs, Northern blot analysis demonstrated expression of ((MMU)Minpp1 in a variety of mouse tissues, comparable to the expression of other mammalian homologs , but less restricted than the expression of HiPER1 in chick. a purified (M MU)Minpp1 fusion protein cleaved phosphate from inositol (1,3,4,5)-tetrakis phosphate and para-nitrophenyl phosphate, When the presumptive active site histidine was altered to alanine by site-directed mutagenesis, enzyme activ ity was abolished, confirming the classification of (MMU)Minpp1 as a histid ine phosphatase, The amino acid sequences of the murine and human MINPP pro teins share >80% identity with the rat enzyme and >56% identity with HiPER1 , with conservation of the C-terminal consensus sequence that retains prote ins in the endoplasmic reticulum, The intron/exon structure of the mammalia n (MMU)Minpp1 and (HSA)MINPP1 genes is also conserved compared to the chick HiPER1 gene. Sequence analysis of plant and fruit fly MINPP homologs suppo rts the hypothesis that the MINPP enzymes constitute a distinct evolutionar y group within the histidine phosphatase family. We have mapped (HSA)MINPP1 to human chromosome 10q23 by fluorescence in situ hybridization, YAC scree ning, and radiation hybrid mapping. This assignment places (HSA)MINPP1 in a region of chromosome 10 that is frequently mutated in human cancers and pl aces (MSA)MINPP1 proximal to the tumor suppressor PTEN, which maps to 10q23 ,3, Using a radiation hybrid panel, we localized (MMU)Minpp1 to a region of mouse chromosome 19 that includes the murine homolog of Pten, The evolutio nary conservation of this novel enzyme within the inositol polyphosphate pa thway suggests a significant role for multiple inositol polyphosphate phosp hatase throughout higher eukaryotes. (C) 1999 Academic Press.