LEU3/YLR451W Summary 
LEU3 BASIC INFORMATION
| Standard Name | LEU3 |
|---|---|
| Systematic Name | YLR451W |
| Feature Type | ORF, Verified |
| Description | Zinc-finger transcription factor that regulates genes involved in branched chain amino acid biosynthesis and ammonia assimilation; positively regulated by alpha-isopropylmalate, an intermediate in leucine biosynthesis (1, 2 and see Summary Paragraph) 
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| Name Description | LEUcine biosynthesis 3 |
| GO Annotations | All LEU3 GO evidence and references |
|---|---|
| View Computational GO annotations for LEU3 | |
| Molecular Function | |
| Manually curated | |
| High-throughput | |
| Biological Process | |
| Manually curated | |
| Cellular Component | |
| Manually curated |
| Regulatory Role | |
|---|---|
| Binding motifs | LEU3 Transcription Factor Binding Sites and References |
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| Mutant Phenotype | All LEU3 Phenotype details and references |
|---|---|
| Large-scale survey | |
| null | |
| overexpression |
| Interactions | LEU3 All interactions details and references |
|---|---|
| 11 total interaction(s) for 10 unique genes/features. | |
| Physical Interactions |
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| Genetic Interactions |
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| External Links | All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB |
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| Primary SGDID | S000004443 |
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LEU3 RESOURCES
| SGD ORF map | GBrowse |
|---|---|
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Click on histogram for expression summary
Expression Summary
ADDITIONAL INFORMATION for LEU3
SUMMARY PARAGRAPH for LEU3
LEU3 encodes a transcription factor that regulates the transcription of genes encoding enzymes involved in branched-chain amino acid synthesis (1). It is a member of the zinc cluster protein family, containing six conserved cysteines that bind two zinc ions in a binuclear cluster (2), Zn(II)2Cys6 genes reviewed in (4).
The Leu3 protein consists of the following five domains:
- zinc cluster DNA binding domain from amino acids 37-67, which is similar to the Gal4 DNA binding domain (5).
- linker region that specifies binding to the everted repeat (rather than a palindrome or direct repeat) target site (6, 7).
- alpha-helix/heptad repeat domain from amino acids 85-102 involved in dimerization (5).
- middle region that is involved in the regulation of Leu3p by alpha-IPM (see below) (8, 7, 5).
- acidic activation domain from amino acids 856-886 (5, 7).
The Leu3p target site is an everted repeat, not a palindrome or direct repeat (9); Leu3p binds this CCG-N4-CGG sequence as a homodimer (10). The four basepair spacing is necessary for recognition by Leu3p; altering the spacing to three or five abolishes binding (9). The activity of Leu3p is positively regulated by alpha-isopropylmalate (IPM), the product of the first step in leucine biosynthesis (11). The absence of IPM promotes intramolecular Leu3p interactions between the Leu3p activation domain and the middle region. This results in the masking of the Leu3p activation domain (7, 5). This regulation does not affect Leu3p nuclear localization or DNA binding, as Leu3p is constitutively bound to its target sites (12). The degree of activation by Leu3p is Leu3p concentration dependent, and it has been shown that LEU3 gene expression is regulated by general amino acid control, which is mediated by the Gcn4 transcription factor (2, 5).
Several genes whose expression is regulated by Leu3p have been identified, including LEU1(1), LEU2(1, 9), LEU4(1), ILV2(1), ILV5(1), GDH1(13), and BAP2(14).
Last updated: 2002-05-20
REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for LEU3]
| 1) | Friden P and Schimmel P (1988) LEU3 of Saccharomyces cerevisiae activates multiple genes for branched-chain amino acid biosynthesis by binding to a common decanucleotide core sequence. Mol Cell Biol 8(7):2690-7 |
| 2) | Zhou K, et al. (1987) Structure of yeast regulatory gene LEU3 and evidence that LEU3 itself is under general amino acid control. Nucleic Acids Res 15(13):5261-73 |
| 3) | Beltzer JP, et al. (1988) Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase. J Biol Chem 263(1):368-74 |
| 4) | Todd RB and Andrianopoulos A (1997) Evolution of a fungal regulatory gene family: the Zn(II)2Cys6 binuclear cluster DNA binding motif. Fungal Genet Biol 21(3):388-405 |
| 5) | Wang D, et al. (1999) Yeast transcriptional regulator Leu3p. Self-masking, specificity of masking, and evidence for regulation by the intracellular level of Leu3p. J Biol Chem 274(27):19017-24 |
| 6) | Mamane Y, et al. (1998) A linker region of the yeast zinc cluster protein leu3p specifies binding to everted repeat DNA. J Biol Chem 273(29):18556-61 |
| 7) | Zhou KM, et al. (1990) Yeast regulatory protein LEU3: a structure-function analysis. Nucleic Acids Res 18(2):291-8 |
| 8) | Friden P, et al. (1989) A large internal deletion converts yeast LEU3 to a constitutive transcriptional activator. Mol Cell Biol 9(9):4056-60 |
| 9) | Hellauer K, et al. (1996) A novel DNA binding motif for yeast zinc cluster proteins: the Leu3p and Pdr3p transcriptional activators recognize everted repeats. Mol Cell Biol 16(11):6096-102 |
| 10) | Remboutsika E and Kohlhaw GB (1994) Molecular architecture of a Leu3p-DNA complex in solution: a biochemical approach. Mol Cell Biol 14(8):5547-57 |
| 11) | Sze JY, et al. (1992) In vitro transcriptional activation by a metabolic intermediate: activation by Leu3 depends on alpha-isopropylmalate. Science 258(5085):1143-5 |
| 12) | Kirkpatrick CR and Schimmel P (1995) Detection of leucine-independent DNA site occupancy of the yeast Leu3p transcriptional activator in vivo. Mol Cell Biol 15(8):4021-30 |
| 13) | Hu Y, et al. (1995) The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation. Mol Cell Biol 15(1):52-7 |
| 14) | Nielsen PS, et al. (2001) Transcriptional regulation of the Saccharomyces cerevisiae amino acid permease gene BAP2. Mol Gen Genet 264(5):613-22 |
