LEU3/YLR451W Summary Help

Standard Name LEU3 1
Systematic Name YLR451W
Feature Type ORF, Verified
Description Zinc-knuckle transcription factor, repressor and activator; regulates genes involved in branched chain amino acid biosynthesis and ammonia assimilation; acts as a repressor in leucine-replete conditions and as an activator in the presence of alpha-isopropylmalate, an intermediate in leucine biosynthesis that accumulates during leucine starvation (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description LEUcine biosynthesis 7
Chromosomal Location
ChrXII:1036093 to 1038753 | ORF Map | GBrowse
Genetic position: 346 cM
Gene Ontology Annotations All LEU3 GO evidence and references
  View Computational GO annotations for LEU3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 136 genes
Regulators 2 genes
Classical genetics
reduction of function
Large-scale survey
53 total interaction(s) for 47 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Biochemical Activity: 4
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Growth Defect: 1
  • Negative Genetic: 36
  • Phenotypic Enhancement: 1
  • Positive Genetic: 5
  • Synthetic Growth Defect: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 886
Molecular Weight (Da) 100,152
Isoelectric Point (pI) 5.99
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:1036093 to 1038753 | ORF Map | GBrowse
Genetic position: 346 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2661 1036093..1038753 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004443

LEU3 encodes a transcription factor that regulates the transcription of genes encoding enzymes involved in branched-chain amino acid synthesis (2). It is a member of the zinc cluster protein family, containing six conserved cysteines that bind two zinc ions in a binuclear cluster (3), Zn(II)2Cys6 genes reviewed in (8).

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 (9).
  • linker region that specifies binding to the everted repeat (rather than a palindrome or direct repeat) target site (10, 4).
  • alpha-helix/heptad repeat domain from amino acids 85-102 involved in dimerization (9).
  • middle region that is involved in the regulation of Leu3p by alpha-IPM (see below) (11, 4, 9).
  • acidic activation domain from amino acids 856-886 (9, 4).

The Leu3p target site is an everted repeat, not a palindrome or direct repeat (12); Leu3p binds this CCG-N4-CGG sequence as a homodimer (13). The four basepair spacing is necessary for recognition by Leu3p; altering the spacing to three or five abolishes binding (12). The activity of Leu3p is positively regulated by alpha-isopropylmalate (IPM), the product of the first step in leucine biosynthesis (6). 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 (4, 9). This regulation does not affect Leu3p nuclear localization or DNA binding, as Leu3p is constitutively bound to its target sites (14). 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 (3, 9).
Several genes whose expression is regulated by Leu3p have been identified, including LEU1(2), LEU2(2, 12), LEU4(2), ILV2(2), ILV5(2), GDH1(15), and BAP2(16).

Last updated: 2002-05-20 Contact SGD

References cited on this page View Complete Literature Guide for LEU3
1) Baichwal VR, 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):369-77
2) 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
3) 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
4) Zhou KM, et al.  (1990) Yeast regulatory protein LEU3: a structure-function analysis. Nucleic Acids Res 18(2):291-8
5) 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
6) 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
7) Beltzer JP, et al.  (1988) Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase. J Biol Chem 263(1):368-74
8) 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
9) 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
10) 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
11) Friden P, et al.  (1989) A large internal deletion converts yeast LEU3 to a constitutive transcriptional activator. Mol Cell Biol 9(9):4056-60
12) 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
13) 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
14) 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
15) 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
16) Nielsen PS, et al.  (2001) Transcriptional regulation of the Saccharomyces cerevisiae amino acid permease gene BAP2. Mol Gen Genet 264(5):613-22
17) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66
18) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
19) Zhu J and Zhang MQ  (1999) SCPD: a promoter database of the yeast Saccharomyces cerevisiae. Bioinformatics 15(7-8):607-11
20) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87