LEU2/YCL018W Summary Help

Standard Name LEU2 1
Systematic Name YCL018W
Feature Type ORF, Verified
Description Beta-isopropylmalate dehydrogenase (IMDH); catalyzes the third step in the leucine biosynthesis pathway; can additionally catalyze the conversion of β-ethylmalate into α-ketovalerate (2, 3 and see Summary Paragraph)
Name Description LEUcine biosynthesis 2
Chromosomal Location
ChrIII:91324 to 92418 | ORF Map | GBrowse
Genetic position: -5 cM
Gene Ontology Annotations All LEU2 GO evidence and references
  View Computational GO annotations for LEU2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Classical genetics
18 total interaction(s) for 17 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 5
  • Affinity Capture-RNA: 1
  • Biochemical Activity: 1

Genetic Interactions
  • Dosage Rescue: 4
  • Phenotypic Suppression: 2
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 3

Expression Summary
Length (a.a.) 364
Molecular Weight (Da) 38,952
Isoelectric Point (pI) 5.55
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIII:91324 to 92418 | ORF Map | GBrowse
This feature contains embedded feature(s): YCLX10C
Genetic position: -5 cM
Last Update Coordinates: 2006-01-12 | Sequence: 2000-09-13
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1095 91324..92418 2006-01-12 2000-09-13
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) | UniProtKB
Primary SGDIDS000000523

LEU2 encodes beta-isopropylmalate dehydrogenase, the enzyme that catalyzes the third step in leucine biosynthesis (shown here), the conversion of beta-isopropylmalate into alpha-ketoisocaproate (4). In contrast to most of the enzymes involved in the superpathway of branched-chain amino acid (valine, leucine, isoleucine) biosynthesis, which are mitochondrial, Leu2p localizes to the cytoplasm (5). Like the other genes in the leucine biosynthesis pathway, LEU2 is transcriptionally repressed in the presence of leucine (6, 7). However, the major regulatory mechanism of LEU2 expression is mediated by the dual regulator Leu3p and its co-activator alpha-isopropylmalate, an upstream intermediate in leucine biosynthesis (8). Leu3p binds to an upstream activation signal in the LEU2 promoter irrespective of the presence or absence of alpha-isopropylmalate, but in its presence Leu3p upregulates LEU2 transcription while in its absence Leu3p represses transcription (8). In cells lacking Leu3p, the transcriptional activator Gcn4p is required for basal levels of LEU2 expression (8). Additionally, LEU2 transcription is upregulated in a dose-dependent manner by the transcription factor Mot3p, which also mediates repression of pheromone-induced gene expression (9).

Although leu2 null mutants are viable, leu2 is synthetically lethal in combination with the amino acid sensor and transport genes ssy1, ptr3, and bap2 (10). Leu2p is very sensitive to low temperatures and dilution when removed from the cellular environment but intact yeast cells can be stored frozen for months without loss of dehydrogenase activity (11).

Last updated: 2005-10-14 Contact SGD

References cited on this page View Complete Literature Guide for LEU2
1) Toh-e A, et al.  (1980) A stable plasmid carrying the yeast Leu2 gene and containing only yeast deoxyribonucleic acid. J Bacteriol 141(1):413-6
2) Andreadis A, et al.  (1984) Yeast LEU2. Repression of mRNA levels by leucine and primary structure of the gene product. J Biol Chem 259(13):8059-62
3) Branduardi P, et al.  (2013) A novel pathway to produce butanol and isobutanol in Saccharomyces cerevisiae. Biotechnol Biofuels 6(1):68
4) Kohlhaw GB  (1988) Beta-isopropylmalate dehydrogenase from yeast. Methods Enzymol 166:429-35
5) Ryan ED, et al.  (1973) Subcellular localization of the leucine biosynthetic enzymes in yeast. J Bacteriol 116(1):222-5
6) Satyanarayana T, et al.  (1968) Biosynthesis of branched-chain amino acids in yeast: regulation of leucine biosynthesis in prototrophic and leucine auxotrophic strains. J Bacteriol 96(6):2018-24
7) Brown HD, et al.  (1975) Biosynthesis of branched-chain amino acids in yeast: effect of carbon source on leucine biosynthetic enzymes. J Bacteriol 121(3):959-69
8) Brisco PR and Kohlhaw GB  (1990) Regulation of yeast LEU2. Total deletion of regulatory gene LEU3 unmasks GCN4-dependent basal level expression of LEU2. J Biol Chem 265(20):11667-75
9) Grishin AV, et al.  (1998) Mot3, a Zn finger transcription factor that modulates gene expression and attenuates mating pheromone signaling in Saccharomyces cerevisiae. Genetics 149(2):879-92
10) Nigavekar SS and Cannon JF  (2002) Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae. Yeast 19(2):115-22
11) Kohlhaw GB, et al.  (1980) Transposed LEU2 gene of Saccharomyces cerevisiae is regulated normally. J Bacteriol 144(2):852-5