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 to chromosome 1p13-1q22-23 and present a genomic map indicating that the gene spans more than 8.4 kb in the human genome. Furthermore, we show that message levels and enzyme activity of rat liver phosphomevalonate kinase are regulated in response to dietary sterol levels and that this regulation is coordinate with 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol biosynthesis. In addition, we demonstrate that phosphomevalonate kinase is a peroxisomal protein which requires the C-terminal peroxisomal targeting signal, Ser-Arg-Leu, for localization to the organelle.
Olivier
L M
LM
Department of Biology, San Diego State University, San Diego, CA 92182, USA.
Chambliss
K L
KL
Gibson
K M
KM
Krisans
S K
SK
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018390:Gene Targeting; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000201:enzymology; D008969:Molecular Sequence Data; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D013261:Sterols / Q000008:administration & dosage
D021382:Protein Sorting Signals; D012333:RNA, Messenger; D013261:Sterols; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase