GSH1/YJL101C Summary Help

Standard Name GSH1 1
Systematic Name YJL101C
Feature Type ORF, Verified
Description Gamma glutamylcysteine synthetase; catalyzes the first step in glutathione (GSH) biosynthesis; expression induced by oxidants, cadmium, and mercury; protein abundance increases in response to DNA replication stress (1, 2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description glutathione (GSH) 1
Chromosomal Location
ChrX:236356 to 234320 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All GSH1 GO evidence and references
  View Computational GO annotations for GSH1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 14 genes
Resources
Pathways
Classical genetics
null
overexpression
Large-scale survey
null
overexpression
Resources
221 total interaction(s) for 167 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 1

Genetic Interactions
  • Dosage Rescue: 2
  • Negative Genetic: 159
  • Phenotypic Enhancement: 6
  • Phenotypic Suppression: 6
  • Positive Genetic: 20
  • Synthetic Growth Defect: 10
  • Synthetic Lethality: 8

Resources
Expression Summary
histogram
Resources
Length (a.a.) 678
Molecular Weight (Da) 78,253
Isoelectric Point (pI) 6.23
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrX:236356 to 234320 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2037 236356..234320 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) | UniProtKB
Primary SGDIDS000003637
SUMMARY PARAGRAPH for GSH1

GSH1 encodes gamma glutamylcysteine synthetase, which catalyzes the first, and rate-limiting, step in the glutathione (GSH) biosynthetic pathway, the conjugation of glutamate and cysteine (3, 7, 1).

Glutathione is an essential antioxidant that protects cells against damage induced by oxidative stress, which is caused by the production of reactive oxygen species (ROS) produced during aerobic metabolism or upon exposure to radical-generating compounds. Glutathione contains a redox-active free sulfhydryl moiety, which can be oxidized to the disulfide form (GSSG) by reaction with free radicals or in reactions mediated by glutathione peroxidases (such as Gpx1p, Gpx2p, and Hyr1p). GSH is regenerated by the action of glutathione reductase Glr1p (reviewed in 8).

Null gsh1 mutants are unable to grow on minimal medium lacking glutathione, and exhibit instability of the mitochondrial genome and increased sensitivity to hydrogen peroxide (9). Mutant cells, like wild type, do show an adaptive response to sublethal doses of hydrogen peroxide (9). Because null mutations in GSH1 prevent synthesis of glutathione, studies with these mutants have been, and continue to be, important in defining the roles of glutathione in the cell (see, for example, 10).

Regulation of GSH1 expression is multifaceted. In the presence of glutathione, expression is repressed (10). In the absense of glutathione, GSH1 expression is induced by Met4p, a transcription activator that also induces expression of genes involved in sulfur assimilation (11, 10). In addition, GSH1 expression is induced by oxidants, such as hydrogen peroxide, and by heat shock, both types of regulation involving the Yap1p transcription factor (4, 12). The GSH1 promoter contains a Yap1p binding site that is required for transcriptional regulation by Yap1p (13). Moreover, the promoter contains two hydrogen peroxide responsive elements that are separate from the Yap1p binding site, suggesting that additional factors may be involved in regulation (14).

GSH1 homologs have been reported in S. pombe, Drosophila, and mammals (15, 16, 17). Mutations in the human homolog GCLC cause the disorder gamma-glutamylcysteine synthetase deficiency which is associated with hemolytic anemia (18).

Last updated: 2007-01-02 Contact SGD

References cited on this page View Complete Literature Guide for GSH1
1) Kistler M, et al.  (1990) Genetic and biochemical analysis of glutathione-deficient mutants of Saccharomyces cerevisiae. Mutagenesis 5(1):39-44
2) Stephen DW, et al.  (1995) The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative stress responses of Saccharomyces cerevisiae. Mol Microbiol 16(3):415-23
3) Ohtake Y and Yabuuchi S  (1991) Molecular cloning of the gamma-glutamylcysteine synthetase gene of Saccharomyces cerevisiae. Yeast 7(9):953-61
4) Stephen DW and Jamieson DJ  (1997) Amino acid-dependent regulation of the Saccharomyces cerevisiae GSH1 gene by hydrogen peroxide. Mol Microbiol 23(2):203-10
5) Westwater J, et al.  (2002) The adaptive response of Saccharomyces cerevisiae to mercury exposure. Yeast 19(3):233-9
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) Grant CM, et al.  (1997) Glutathione synthetase is dispensable for growth under both normal and oxidative stress conditions in the yeast Saccharomyces cerevisiae due to an accumulation of the dipeptide gamma-glutamylcysteine. Mol Biol Cell 8(9):1699-707
8) Grant CM  (2001) Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Mol Microbiol 39(3):533-41
9) Lee JC, et al.  (2001) The essential and ancillary role of glutathione in Saccharomyces cerevisiae analysed using a grande gsh1 disruptant strain. FEMS Yeast Res 1(1):57-65
10) Wheeler GL, et al.  (2002) Glutathione regulates the expression of gamma-glutamylcysteine synthetase via the Met4 transcription factor. Mol Microbiol 46(2):545-56
11) Dormer UH, et al.  (2000) Cadmium-inducible expression of the yeast GSH1 gene requires a functional sulfur-amino acid regulatory network. J Biol Chem 275(42):32611-6
12) Sugiyama K, et al.  (2000) The Yap1p-dependent induction of glutathione synthesis in heat shock response of Saccharomyces cerevisiae. J Biol Chem 275(20):15535-40
13) Wu AL and Moye-Rowley WS  (1994) GSH1, which encodes gamma-glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation. Mol Cell Biol 14(9):5832-9
14) Dormer UH, et al.  (2002) Oxidant regulation of the Saccharomyces cerevisiae GSH1 gene. Biochim Biophys Acta 1576(1-2):23-9
15) Mutoh N, et al.  (1995) Molecular cloning and nucleotide sequencing of the gamma-glutamylcysteine synthetase gene of the fission yeast Schizosaccharomyces pombe. J Biochem 117(2):283-8
16) Saunders RD and McLellan LI  (2000) Molecular cloning of Drosophila gamma-glutamylcysteine synthetase by functional complementation of a yeast mutant. FEBS Lett 467(2-3):337-40
17) Gipp JJ, et al.  (1992) Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase. Biochem Biophys Res Commun 185(1):29-35
18) Beutler E, et al.  (1999) The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency. Blood 94(8):2890-4