RGD Reference Report - Molecular cloning of mevalonate kinase and regulation of its mRNA levels in rat liver. - Rat Genome Database

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Molecular cloning of mevalonate kinase and regulation of its mRNA levels in rat liver.

Authors: Tanaka, RD  Lee, LY  Schafer, BL  Kratunis, VJ  Mohler, WA  Robinson, GW  Mosley, ST 
Citation: Tanaka RD, etal., Proc Natl Acad Sci U S A 1990 Apr;87(8):2872-6.
RGD ID: 728935
Pubmed: PMID:2158094   (View Abstract at PubMed)
PMCID: PMC53795   (View Article at PubMed Central)

Mevalonate kinase [ATP:(R)-mevalonate 5-phosphotransferase, EC 2.7.1.36] may be a regulatory site in the cholesterol biosynthetic pathway, and a mutation in the gene coding for this enzyme is thought to cause the genetic disease mevalonic aciduria. To characterize this enzyme, a rat liver cDNA library was screened with a monospecific antibody, and a 1.7-kilobase cDNA clone coding for mevalonate kinase was isolated. The complete DNA sequence was determined, and the longest open reading frame coded for a protein containing 395 amino acids with a deduced molecular weight of 41,990. Identification of the cDNA clone was confirmed by expression of enzyme activity in yeast and by protein sequence data obtained from sequencing purified rat mevalonate kinase. The deduced amino acid sequence of mevalonate kinase contained a motif for the ATP-binding site found in protein kinases, and it also showed sequence homology to the yeast RAR1 protein. The size of mevalonate kinase mRNA in rat liver was approximately 2 kilobases. Treatment with diets containing cholesterol-lowering agents caused an increase in both mevalonate kinase activity and mRNA levels, whereas diets containing 5% cholesterol lowered the levels of both enzyme activity and mRNA. These data indicate that long-term regulation of enzyme activity in rat liver is controlled by changes in the levels of mevalonate kinase mRNA.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholesterol biosynthetic process  TAS 728935 RGD 
regulation of cholesterol biosynthetic process  NAS 728935 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mevalonate kinase activity  IDA 728935 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mvk  (mevalonate kinase)


Additional Information