Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting

Phosphomevalonate kinase catalyzes the conversion of mevalonate-5-phosphate to mevalonate-5-diphosphate and was originally believed to be a cytosolic enzyme. In this study we have localized the phosphomevalonate kinase gene t o chromosome 1p13-1q22-23 and present a genomic map indicating that the gen e spans more than 8.4 kb in the human genome, Furthermore, we show that mes sage levels and enzyme activity of rat liver phosphomevalonate kinase are r egulated in response to dietary sterol levels and that this regulation is c oordinate with 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-li miting enzyme of cholesterol biosynthesis. In addition, we demonstrate that phosphomevalonate kinase is a peroxisomal protein which requires the C-ter minal peroxisomal targeting signal, Ser-Arg-Leu, for localization to the or ganelle.