LEU1/YGL009C Summary

Standard Name	LEU1
Systematic Name	YGL009C
Feature Type	ORF, Verified
Description	Isopropylmalate isomerase, catalyzes the second step in the leucine biosynthesis pathway (1, 2 and see Summary Paragraph)
Name Description	LEUcine biosynthesis 1

Chromosomal Location	ChrVII:478652 to 476313 \| ORF Map \| GBrowse
	Note: this feature is encoded on the Crick strand.

	Genetic position: -5 cM

Gene Ontology Annotations All LEU1 GO evidence and references

	View Computational GO annotations for LEU1
Molecular Function
Manually curated	3-isopropylmalate dehydratase activity (IMP)
Biological Process
Manually curated	leucine biosynthetic process (IMP)
Cellular Component
Manually curated	cytosol (IDA)

Pathways	leucine biosynthesis superpathway of leucine, isoleucine, and valine biosynthesis

Mutant phenotypes All LEU1 Phenotype evidence and references

Classical genetics
unspecified	auxotrophy
Large-scale survey
null	competitive fitness: decreased metal resistance: decreased starvation resistance: decreased vacuolar morphology: abnormal viable
overexpression	vegetative growth: decreased
Resources	PROPHECY \| SCMD \| ScreenTroll \| Yeast Fitness Database

interactions All LEU1 Interaction evidence and references

	63 total interaction(s) for 52 unique genes/features.
Physical Interactions	Affinity Capture-MS: 18 Affinity Capture-RNA: 3 PCA: 2
Genetic Interactions	Negative Genetic: 32 Phenotypic Suppression: 2 Positive Genetic: 6
Resources	BioGRID \| BOND \| BioPIXIE \| CYC2008 (complexes) \| Complexome \| DIP \| DRYGIN \| GeneMANIA \| InterologFinder

Expression Summary


Resources	Expression Summary \| Cell cycle and metabolic oscillation \| Cell cycle transcript profile \| Cyclebase \| Genevestigator \| GermOnline \| SPELL \| YMGV \| YeastFunc

Protein Information All LEU1 Protein evidence and references

Localization	YeastRC \| Organelle DB (UMich) \| YPL+ \| YeastGFP
Phosphorylation	PhosphoGRID \| PhosphoPep Database
Structure	GPMDB \| SCOP \| YeastRC
Homologs	Ashbya (AGD) \| AspGD Homologs \| CGD Homologs \| CandidaDB Homologs \| Fungal Orthogroups Repository \| P-POD \| PDB Homologs \| PhylomeDB \| YGOB \| YOGY

sequence information

ChrVII:478652 to 476313 | |

Note: this feature is encoded on the Crick strand.

: -5 cM

Last Update

Coordinates: 2011-02-03 | Sequence: 1996-07-31

Subfeature details

	Relative Coordinates	Chromosomal Coordinates	Most Recent Updates
	Relative Coordinates	Chromosomal Coordinates	Coordinates	Sequence
CDS	1..2340	478652..476313	2011-02-03	1996-07-31

Retrieve sequences

Analyze Sequence

S288C only	BLASTP \| ATCC/WashU Clones \| BLASTN \| Design Primers \| Restriction Fragment Map \| Restriction Fragment Sizes \| Six-Frame Translation
S288C vs. other species	Fungal Alignment \| BLASTN vs. fungi \| BLASTP at NCBI \| BLASTP vs. fungi \| Synteny Viewer
S288C vs. other strains	Strain Alignment

Resources

External Links	All Associated Seq \| E.C. \| Entrez Gene \| Entrez RefSeq Protein \| MIPS \| Search all NCBI (Entrez) \| UniProtKB

Primary SGDID	S000002977

SUMMARY PARAGRAPH for LEU1

LEU1 encodes isopropylmalate isomerase (isopropylmalate dehydratase), which catalyzes the conversion of alpha-isopropylmalate into beta-isopropylmalate in the second step of leucine biosynthesis (see pathway diagram) (3 and reviewed in 4). Leu1p is an iron-sulfur (Fe-S) protein that is very sensitive to degradation when removed from intact cells but can be stabilized by high glycerol or high ionic concentrations, conditions which also inactivate the enzyme (5). In contrast to most of the enzymes involved in the superpathway of branched-chain amino acid (valine, leucine, isoleucine) biosynthesis, which are mitochondrial, Leu1p localizes to the cytoplasm (6).

Like the other genes in the leucine biosynthesis pathway, LEU1 is transcriptionally repressed in the presence of leucine (7, 1). LEU1 expression is induced by the transcriptional regulator Leu3p bound to the leucine precursor alpha-isopropylmalate, which recognizes an upstream activation signal in the LEU1 promoter (8, 9). LEU1 transcription has also been shown to be upregulated by the transcriptional activator Gcn4p (10).

leu1 null mutations result in leucine auxotrophy (1), as do mutations affecting gene products that contribute to the incorporation or stability of the Leu1p Fe-S cluster, such as Atm1p and Sod1p (11 and reviewed in 4).

Last updated: 2006-08-08

References cited on this page View Complete Literature Guide for LEU1

1)	Hsu YP and Schimmel P (1984) Yeast LEU1. Repression of mRNA levels by leucine and relationship of 5'-noncoding region to that of LEU2. J Biol Chem 259(6):3714-9
2)	Skala J, et al. (1991) Complete sequence of the Saccharomyces cerevisiae LEU1 gene encoding isopropylmalate isomerase. Yeast 7(3):281-5
3)	Kohlhaw GB (1988) Isopropylmalate dehydratase from yeast. Methods Enzymol 166:423-9
4)	Kohlhaw GB (2003) Leucine biosynthesis in fungi: entering metabolism through the back door. Microbiol Mol Biol Rev 67(1):1-15, table of contents
5)	Bigelis R and Umbarger HE (1976) Yeast alpha-isopropylmalate isomerase. Factors affecting stability and enzyme activity. J Biol Chem 251(12):3545-52
6)	Ryan ED, et al. (1973) Subcellular localization of the leucine biosynthetic enzymes in yeast. J Bacteriol 116(1):222-5
7)	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
8)	Friden P and Schimmel P (1987) LEU3 of Saccharomyces cerevisiae encodes a factor for control of RNA levels of a group of leucine-specific genes. Mol Cell Biol 7(8):2708-17
9)	Baichwal V, et al. (1983) Leucine biosynthesis in yeast. Identification of two genes (LEU4, LEU5) that affect alpha-Isopropylmalate synthase activity and evidence that LEU1 and LEU2 gene expression is controlled by alpha-Isopropylmalate and the product of a regulatory gene. Curr Genet 7(5):369-377
10)	Natarajan K, et al. (2001) Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. Mol Cell Biol 21(13):4347-68
11)	Wallace MA, et al. (2004) Superoxide inhibits 4Fe-4S cluster enzymes involved in amino acid biosynthesis. Cross-compartment protection by CuZn-superoxide dismutase. J Biol Chem 279(31):32055-62