HMG2/YLR450W Summary Help

Standard Name HMG2
Systematic Name YLR450W
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 the nuclear periphery upon DNA replication stress; HMG2 has a paralog, HMG1, that arose from the whole genome duplication (1, 2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description 3-Hydroxy-3-MethylGlutaryl-coenzyme a reductase 2
Chromosomal Location
ChrXII:1032627 to 1035764 | ORF Map | GBrowse
Gbrowse
Genetic position: 343 cM
Gene Ontology Annotations All HMG2 GO evidence and references
  View Computational GO annotations for HMG2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Pathways
Mutant phenotypes All HMG2 Phenotype evidence and references
Classical genetics
null
overexpression
Large-scale survey
null
Resources
interactions All HMG2 Interaction evidence and references
86 total interaction(s) for 60 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 11
  • Biochemical Activity: 3
  • 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: 31
  • Positive Genetic: 16
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 2
Resources
Expression Summary
histogram
Resources
Protein Information All HMG2 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:1032627 to 1035764 | ORF Map | GBrowse
SGD ORF map
Genetic position: 343 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..3138 1032627..1035764 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000004442
SUMMARY PARAGRAPH for HMG2

HMG2 encodes one of two isozymes of hydroxymethylglutaryl-CoA (HMG-CoA) reductase in yeast (2). 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 (7); in yeast ergosterol is the end product of the sterol biosynthetic pathway (8, 1).

Deletion of HMG2 or of the other HMG-CoA reductase gene, HMG1, has little effect on cell growth; the hmg1 hmg2 double null mutant is auxotrophic for mevalonate (9). The hmg1 hmg2 mutant also shows MATa-specific sterility, because the mating pheromone a-factor is not farnesylated (10). Unlike Hmg1p, Hmg2p is unstable; its stability is regulated by flux through the mevalonate pathway (11, 12). Hmg2p is degraded by the ubiquitin pathway (13). When present at endogenous levels, Hmg2p is found in the nuclear envelope; upon overproduction, Hmg2p becomes concentrated in peripheral ER membranes (4).

HMG-CoA reductases are found in many species; the human and hamster enzymes can complement the yeast hmg1 hmg2 mutant (14, 7). Lovastatin and related drugs used to treat hypercholesterolemia act by inhibiting HMG-CoA reductase (7).

Last updated: 2000-08-22

References cited on this page View Complete Literature Guide for HMG2
1) Parks LW, et al.  (1995) Biochemical and physiological effects of sterol alterations in yeast--a review. Lipids 30(3):227-30
2) 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
3) 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
4) 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
5) 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
6) 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
7) Stryer L  (1995) Biochemistry (4th ed.). New York: W. H. Freeman and Company
8) 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
9) 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
10) Schafer WR, et al.  (1989) Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans. Science 245(4916):379-85
11) 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
12) Gardner R, et al.  (1998) Sequence determinants for regulated degradation of yeast 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol Biol Cell 9(9):2611-26
13) Hampton RY and Bhakta H  (1997) Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase. Proc Natl Acad Sci U S A 94(24):12944-8
14) 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