ERG12 / YMR208W Overview


Standard Name
ERG12 1
Systematic Name
YMR208W
SGD ID
SGD:S000004821
Aliases
RAR1 8
Feature Type
ORF , Verified
Description
Mevalonate kinase; acts in the biosynthesis of isoprenoids and sterols, including ergosterol, from mevalonate; human MVK functionally complements the lethality of the erg12 null mutation 2 3 4
Name Description
ERGosterol biosynthesis 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Length (a.a.)
443
Mol. Weight (Da)
48447.9
Isoelectric Point
5.28
Median Abundance (molecules/cell)
5083 +/- 2395
Half-life (hr)
14.7

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results. Click "YeastMine" to view all alleles in YeastMine.


View all ERG12 alleles in SGD search | YeastMine

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Mevalonate kinase involved in the mevalonate pathway including biosynthesis of farnesyl and isopentenyl diphosphate; contributes to ergosterol biosynthesis; localizes to nucleus, cytoplasm and cytosol in high-throughput studies

View computational annotations

Molecular Function

Manually Curated

Cellular Component

Manually Curated

Pathways


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Summary
Essential gene; mutants require ergosterol; in large-scale studies, repression confers increased competitive fitness and abnormal mitochondrial morphology; heterozygous null mutant is sensitive to zaragozic acid C
Disease Details

Disease

Disease Annotations consist of three mandatory components: a gene product, a term from the Disease Ontology (DO) controlled vocabulary and an evidence code. SGD provides manually curated DO Annotations derived from the literature. Click "Disease Details" to view all Disease information and evidence for this locus as well as diseases it shares with other genes.


Summary
Yeast ERG12 is homologous to human MVK, and has been used to study cancer and mevalonate kinase deficiency (MKD), a peroxisomal disease characterized by cortical atrophy, microcephaly, dysmorphic facies, muscular hypotonia and intellectual disability

Manually Curated

Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


104 total interactions for 100 unique genes

Physical Interactions

  • Affinity Capture-MS: 6
  • Affinity Capture-RNA: 3
  • Co-localization: 1
  • Co-purification: 1
  • Reconstituted Complex: 2

Genetic Interactions

  • Negative Genetic: 81
  • Positive Genetic: 8
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 1
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Summary
ERG12 encodes a mevalonate kinase that phosphorylates mevalonate to mevalonate-5-phosphate, an intermediate in the mevalonate biosynthesis pathway, which produces essential isoprenoids and also provides a precursor for ergosterol biosynthesis. Ergosterol, the major sterol in fungi and the equivalent of cholesterol in mammalian cells, is an essential component of the plasma membrane, necessary for membrane integrity, fluidity, and proper function of membrane proteins. The entire sterol biosynthetic pathway occurs primarily in the endoplasmic reticulum (ER) and requires almost 30 enzymes. Activities of these enzymes have to be tightly controlled to ensure sufficient supply but also to prevent an excess accumulation of free sterols, which leads to toxicity. This regulation involves multiple mechanisms at transcriptional, translational and post-translational levels. The first major metabolic checkpoint in sterol biosynthesis occurs at the third step of mevalonate pathway, reduction of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonate. This step is catalyzed by the HMG-CoA reductases Hmg1p and Hmg2p, which are under feedback inhibition by sterols. Since sterol biosynthesis requires oxygen, under low-oxygen conditions sterol levels become low, which triggers relocation of two transcription factors, Upc2p and Ecm22p, to the nucleus. The two proteins then recognize and bind sterol regulatory elements (SRE) in the promoters of sterol biosynthesis genes and activate their transcription. Independently, oxygen levels affect transcription of sterol biosynthesis genes through a heme-dependent transcription factor Hap1p and a transcriptional repressor Rox1p. Despite some similarities, there are significant differences in sterol biosynthesis and its regulation between fungal and mammalian cells, which has made ergosterol biosynthesis an attractive target for antifungal drugs. Widely used azole drugs target lanosterol 14-alpha demethylase (Erg11p), whereas Erg1p is a target for terbinafine. Mutations in these genes are a major cause of antifungal drug resistance.
Regulators
5
Targets
0
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2000-08-22

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
15
Additional
80
Reviews
34

Resources