Disease relevance of ERG12

• A synthetic operon coding for yeast 5-diphosphomevalonate decarboxylase, human 5-phosphomevalonate kinase, yeast mevalonate kinase and E. coli isopentenyl diphosphate isomerase was incorporated in the chromosome of this bacterium [1].

High impact information on ERG12

• 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 [2].
• 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 [2].
• 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 [2].
• A hem3 mutant was isolated which was also blocked between 2,3-oxidosqualene and lanosterol (erg12) [3].
• As part of a map-based cloning strategy designed to isolate Rar1, five barley yeast artificial chromosomes (YACs) have been identified, ranging in size from 300 to 1100 kb [4].

Biological context of ERG12

• The nucleotide sequence of the ERG12 gene, encoding mevalonate kinase, from Saccharomyces cerevisiae is presented [5].
• The RAR1 gene is linked to rna1 on chromosome XIII [6].
• The analysis of the nucleotide sequence reveals a complete identity with the yeast gene RAR1, isolated elsewhere by complementation of a rar1 mutation involved in the stability of plasmids with weak ARS [5].
• Silencing the barley gene Sgt1 reveals its role in R gene-triggered, Rar1-dependent disease resistance [7].
• RAR1 is an early convergence point in a signaling pathway engaged by multiple R genes [7].

Anatomical context of ERG12

• It was previously demonstrated that brain HK anchors to mitochondria porins, also designated as voltage dependent-anion channels (VDAC) via the MK sequence [8].

Associations of ERG12 with chemical compounds

• 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 [2].
• In addition, we show that mevalonate kinase is not a rate-limiting enzyme; however its sensitivity to FFP could be a key regulatory mechanism in the sterol pathway of yeast [5].
• No mevalonate kinase was detected in crude extracts of Saccharomyces cerevisiae strains, however, because of background interference measured in the absence of mevalonate [9].

Analytical, diagnostic and therapeutic context of ERG12

• Molecular cloning of mevalonate kinase and regulation of its mRNA levels in rat liver [2].

References