HMG1/YML075C Summary Help

Standard Name HMG1 1
Systematic Name YML075C
Feature Type ORF, Verified
Description HMG-CoA reductase; catalyzes the conversion of HMG-CoA to mevalonate, which is a rate-limiting step in sterol biosynthesis; one of two isozymes; localizes to the nuclear envelope; overproduction induces the formation of karmellae; forms foci at the nuclear periphery upon DNA replication stress; HMG1 has a paralog, HMG2, that arose from the whole genome duplication (1, 2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description 3-Hydroxy-3-MethylGlutaryl-coenzyme a reductase 1
Chromosomal Location
ChrXIII:118898 to 115734 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -50 cM
Gene Ontology Annotations All HMG1 GO evidence and references
  View Computational GO annotations for HMG1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
Large-scale survey
158 total interaction(s) for 113 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 1
  • PCA: 16
  • Reconstituted Complex: 2
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Lethality: 3
  • Negative Genetic: 94
  • Phenotypic Enhancement: 11
  • Phenotypic Suppression: 6
  • Positive Genetic: 17
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 2

Expression Summary
Length (a.a.) 1,054
Molecular Weight (Da) 115,624
Isoelectric Point (pI) 7.96
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXIII:118898 to 115734 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -50 cM
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..3165 118898..115734 1996-07-31 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000004540

HMG1 encodes one of two isozymes of hydroxymethylglutaryl-CoA (HMG-CoA) reductase in yeast (1). HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, which is a rate-limiting step in the biosynthesis of sterols and nonsterol isoprenoids in eukaryotes (8); in yeast ergosterol is the end product of the sterol biosynthetic pathway (9, 2, 2).

Deletion of HMG1 or of the second HMG-CoA reductase gene, HMG2, has little effect on cell growth; the hmg1 hmg2 double null mutant is auxotrophic for mevalonate (10). The hmg1 hmg2 mutant also shows MATa-specific sterility, because the mating pheromone a-factor is not farnesylated (11).

Production of Hmg1p is regulated by a feedback mechanism that acts posttranscriptionally (12); unlike the Hmg2p isozyme, Hmg1p is quite stable (13). Overexpression of a truncated form of Hmg1p in yeast leads to accumulation of squalene, suggesting that HMG-CoA reductase is not the only rate-limiting step in ergosterol biosynthesis (14). Hmg1p is found in the nuclear envelope at endogenous levels and when overproduced (5). Overproduction of Hmg1p induces the formation of stacked membrane structures called karmellae (4, 3). HMG-CoA reductases are found in many species; the human and hamster enzymes can complement the yeast hmg1 hmg2 mutant (15, 8). Lovastatin and related drugs used to treat hypercholesterolemia act by inhibiting HMG-CoA reductase (8).

Last updated: 2000-08-22 Contact SGD

References cited on this page View Complete Literature Guide for HMG1
1) Basson ME, et al.  (1986) Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci U S A 83(15):5563-7
2) Parks LW, et al.  (1995) Biochemical and physiological effects of sterol alterations in yeast--a review. Lipids 30(3):227-30
3) Parrish ML, et al.  (1995) Identification of the sequences in HMG-CoA reductase required for karmellae assembly. Mol Biol Cell 6(11):1535-47
4) Wright R, et al.  (1988) Increased amounts of HMG-CoA reductase induce "karmellae": a proliferation of stacked membrane pairs surrounding the yeast nucleus. J Cell Biol 107(1):101-14
5) Koning AJ, et al.  (1996) Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations. Mol Biol Cell 7(5):769-89
6) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
7) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
8) Stryer L  (1995) Biochemistry (4th ed.). New York: W. H. Freeman and Company
9) Paltauf F, et al.  (1992) "Regulation and compartmentalization of lipid synthesis in yeast." Pp. 415-500 in The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression, edited by Jones EW, Pringle JR and Broach JR. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
10) Basson ME, et al.  (1987) Identifying mutations in duplicated functions in Saccharomyces cerevisiae: recessive mutations in HMG-CoA reductase genes. Genetics 117(4):645-55
11) Schafer WR, et al.  (1989) Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans. Science 245(4916):379-85
12) Dimster-Denk D, et al.  (1994) Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae. Mol Biol Cell 5(6):655-65
13) Hampton RY and Rine J  (1994) Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J Cell Biol 125(2):299-312
14) Polakowski T, et al.  (1998) Overexpression of a cytosolic hydroxymethylglutaryl-CoA reductase leads to squalene accumulation in yeast. Appl Microbiol Biotechnol 49(1):66-71
15) Basson ME, et al.  (1988) Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. Mol Cell Biol 8(9):3797-808