HMG1 / YML075C Overview
- Standard Name
- HMG1 1
- Systematic Name
- YML075C
- SGD ID
- SGD:S000004540
- Feature Type
- ORF , Verified
- Description
- HMG-CoA reductase; catalyzes conversion of HMG-CoA to mevalonate, which is a rate-limiting step in sterol biosynthesis; one of two isozymes; localizes to nuclear envelope; overproduction induces formation of karmellae; forms foci at nuclear periphery upon DNA replication stress; expressed almost exclusively on the peri-nuclear side of the ER; human homolog HMGCR can complement yeast hmg1 mutant 1 2 3 4 5 6 7 8 9
- Name Description
- 3-Hydroxy-3-MethylGlutaryl-coenzyme a reductase 1
- Paralog
- HMG2
- Comparative Info
-
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
- HMG1 has a paralog, HMG2, that arose from the whole genome duplication
Analyze Sequence
S288C only
BLASTN | BLASTP | Design Primers | Restriction Fragment Map | Restriction Fragment Sizes | Six-Frame Translation
S288C vs. other species
BLASTN vs. fungi | BLASTP at NCBI | BLASTP vs. fungi
S288C vs. other strains
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.)
- 1054
- Mol. Weight (Da)
- 115631.8
- Isoelectric Point
- 8.09
- Median Abundance (molecules/cell)
- 4026 +/- 1095
- Half-life (hr)
- 14.4
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.
View all HMG1 alleles in SGD search
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 and the biosynthesis of isopentenyl disphosphate; localizes to membranes of both the nucleus and the endoplasmic reticulum
View computational annotations
Molecular Function
- Manually Curated
Biological Process
- Manually Curated
- involved in ergosterol biosynthetic process (IDA, IMP)
Cellular Component
- Manually Curated
- is active in endoplasmic reticulum (IDA)
- located in endoplasmic reticulum membrane (IDA)
- located in nuclear envelope (IDA)
- located in nuclear periphery (HDA)
Pathways
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 displays decreased resistance to statins including mevastatin, atorvastatin and fluvastatin, has an increased chronological lifespan and decreased starvation resistance; overexpression results in increased synthesis of squalene and decreased synthesis of ergosterol, a decreased rate of vegetative growth and results in the formation of karmellae, nuclear-associated, paired membranes
Classical Genetics
- overexpression
- null
- null
- overexpression
- reduction of function
Large-scale Survey
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 hmg1 null mutant is viable; the null mutant of paralog hmg2 is viable; the hmg1 hmg2 double mutant is inviable or displays a growth defect.
339 total interactions for 250 unique genes
Physical Interactions
- Affinity Capture-MS: 64
- Affinity Capture-RNA: 4
- Biochemical Activity: 1
- PCA: 16
- Proximity Label-MS: 1
- Reconstituted Complex: 3
- Two-hybrid: 1
Genetic Interactions
- Dosage Lethality: 3
- Negative Genetic: 186
- Phenotypic Enhancement: 24
- Phenotypic Suppression: 6
- Positive Genetic: 26
- Synthetic Growth Defect: 1
- Synthetic Lethality: 3
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
- HMG1 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 ergosterol, 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. Hmg1p is the primary HMGR during aerobic growth. Such conditions stimulate synthesis of heme, which activates HMG1 transcription via the transcription factor Hap1p. On the other hand, transcription of HMG2 is repressed during aerobic growth by an unknown mechanism. The activity of Hmg1p is also controlled by a negative feedback mechanism at the level of translation. Depletion of mevalonate leads to accumulation of Hmg1p and an increased HMGR activity without an increase in HMG1 transcription. This effect depends on 5'-untranslated region of HMG1 mRNA, but the exact mechanisms remain unknown. 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
- 7
- Targets
- 0
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
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.