HMG2 / YLR450W Overview


Standard Name
HMG2 1
Systematic Name
YLR450W
SGD ID
SGD:S000004442
Feature Type
ORF , Verified
Description
HMG-CoA reductase; converts HMG-CoA to mevalonate, a rate-limiting step in sterol biosynthesis; one of two isozymes; overproduction induces assembly of peripheral ER membrane arrays and short nuclear-associated membrane stacks; forms foci at nuclear periphery upon DNA replication stress; primarily expressed on the peri-membrane side of the ER; human homolog HMGCR can complement yeast hmg2 mutant 1 2 3 4 5 6 7 8
Name Description
3-Hydroxy-3-MethylGlutaryl-coenzyme a reductase 1
Paralog
HMG1
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.


Summary
HMG2 has a paralog, HMG1, that arose from the whole genome duplication
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.)
1045
Mol. Weight (Da)
115694.0
Isoelectric Point
7.62
Median Abundance (molecules/cell)
3501 +/- 1509
Half-life (hr)
12.9

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 HMG2 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
HMG-CoA reductase that catalyzes the conversion of (R)-mevalonate and coenzyme A into (S)-3-hydroxy-3-methylglutaryl-coenzyme A; involved in the biosynthesis of ergosterol; localizes to membranes of both the nucleus and the endoplasmic reticulum

View computational annotations

Molecular Function

Manually Curated

Biological Process

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
Non-essential gene; null mutant is sensitive to hypoxia-inducing compounds cobalt chloride hexahydrate and ferrozine; null mutant diploid shows decreased sporulation; overexpression causes abnormal ER morphology
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.


Summary
The hmg2 null mutant is viable; the null mutant of paralog hmg1 is viable; the hmg2 hmg1 double mutant is inviable or displays a growth defect.

233 total interactions for 167 unique genes

Physical Interactions

  • Affinity Capture-MS: 48
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 21
  • Biochemical Activity: 5
  • Co-purification: 1
  • PCA: 4
  • Reconstituted Complex: 3
  • Two-hybrid: 1

Genetic Interactions

  • Dosage Growth Defect: 3
  • Dosage Lethality: 1
  • Dosage Rescue: 1
  • Negative Genetic: 96
  • Phenotypic Suppression: 5
  • Positive Genetic: 24
  • Synthetic Growth Defect: 10
  • Synthetic Lethality: 5
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
HMG2 encodes an HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (HMGR), an endoplasmic reticulum membrane-bound enzyme that catalyzes the reduction of HMG-CoA to mevalonate. This is a rate-limiting step in biosynthesis of all isoprene-containing compounds, including sterols, ubiquinone, dolichol and isopentenyl adenosine derivatives, that have key roles in maintaining membrane structure, electron transport, protein farnesylation, biosynthesis of glycoproteins, translation and DNA replication. Yeast cells have two HMGRs encoded by a pair of paralogous genes HMG1 and HMG2. Even though they can substitute for each other in supplying sufficient HMGR activity when the other gene is deleted, there are significant differences in their regulation. Hmg1p is a stable protein controlled at the transcriptional and translational levels, whereas Hmg2p is controlled posttranslationally. During aerobic growth, transcription of HMG2 is repressed by an unknown mechanism and Hmg1p takes over as the primary source of HMGR activity. Under anaerobic conditions, Hmg2p is controlled by the endoplasmic reticulum-associated degradation (ERAD) system. High levels of HMGR activity lead to accumulation of downstream intermediates geranylgeranyl pyrophosphate (GGPP) and sterols, particularly oxysterol. GGPP stimulates ubiquitination of Hmg2p, possibly by altering its conformation and making it accessible to ubiquitinating enzymes. Oxysterol enhances the action of GGPP. Ubiquitination of Hmg2p is catalyzed by a multisubunit HMGR degradation (HRD) complex composed of Cdc48p, Cue1p, Hrd1p, Hrd3p, Npl4p, Ubc1p, Ubc7p, Ubx2p, Ufd1p and Usa1p. Ubiquitinated Hmg2p is subsequently removed from the membrane and degraded by proteasome. Under low-oxygen conditions, this turnover of Hmg2p is reduced by Nsg1p, a homolog of mammalian cholesterol biosynthesis regulator Insig, which binds Hmg2p and decreases its accessibility to the HRD complex. HMGRs are highly conserved and the human homolog HMGCR can complement both hmg1 and hmg2 mutations in yeast. In humans, the HMGR activity catalyzes a rate-limiting step in biosynthesis of cholesterol, an equivalent of ergosterol in yeast, and is a target of cholesterol-lowering drugs (statins).
Regulators
2
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
53
Additional
85
Reviews
37

Resources