GCN4 / YEL009C Overview


Standard Name
GCN4 1
Systematic Name
YEL009C
SGD ID
SGD:S000000735
Aliases
AAS3 4 , ARG9 4 , AAS101 16
Feature Type
ORF , Verified
Description
bZIP transcriptional activator of amino acid biosynthetic genes; activator responds to amino acid starvation; expression is tightly regulated at both the transcriptional and translational levels; contains four upstream open reading frames (uORFs) in 5' untranslated region which regulate translation; participates in sulfur starvation-induced autophagy along with Met4p, but is dispensable 2 3
Name Description
General Control Nonderepressible 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Summary
GCN4 is on the left arm of chromosome V between tRNA-Arg and uncharacterized gene YEL008W; gene structure includes coding sequence of 846 nucleotides with 4 uORFs and 4 SNPs, 3 of which cause amino acid polymorphisms
Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Summary
Gcn4p is 281 amino acids long, of low abundance, contains basic-leucine zipper domain, phosphorylated on 7 residues, sumoylated on 2 lysines
Length (a.a.)
281
Mol. Weight (Da)
31300.4
Isoelectric Point
4.83
Median Abundance (molecules/cell)
1648 +/- 1209

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.


View all GCN4 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Transcription factor with a role in positive regulation of the assembly of RNA polymerase II transcriptional preinitiation complex and the negative regulation of transcription from RNA polymerase II promoter; localizes to the nucleus

View computational annotations

Cellular Component

Manually Curated
Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Summary
Non-essential gene; null mutants grow slowly, have decreased ethanol tolerance, abnormal vacuolar morphology, and cannot utilize galactose; null also has increased lifespan, decreased competitive fitness and biofilm formation, G1 checkpoint deficiency, and is sensitive to a wide variety of different chemicals; overexpression stunts growth
Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


Summary
Gcn4p interacts physically with proteins involved in transcription; GCN4 interacts genetically with genes involved in transcription

392 total interactions for 294 unique genes

Physical Interactions

  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 11
  • Affinity Capture-Western: 53
  • Biochemical Activity: 6
  • Co-crystal Structure: 7
  • Co-localization: 2
  • Co-purification: 2
  • Far Western: 1
  • FRET: 1
  • PCA: 12
  • Protein-peptide: 3
  • Reconstituted Complex: 34
  • Two-hybrid: 11

Genetic Interactions

  • Dosage Lethality: 6
  • Dosage Rescue: 12
  • Negative Genetic: 103
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 28
  • Positive Genetic: 74
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 1
  • Synthetic Rescue: 13
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Summary
GCN4 encodes a conserved eukaryotic basic zipper protein that functions as a global transcription factor of the general amino acid control (GAAC) network required for increased biosynthesis of translation precursors such as ribosomal proteins, amino acids and purines. The GAAC regulatory network is induced not only by amino acid starvation but also by other environmental insults such as glucose limitation, UV radiation, or high salinity stress. GCN4 targets include amino-acid biosynthesis genes and stress response factors, including components of the unfolded protein response, as well as the developmental cell-surface flocculin gene FLO11. Gcn4p activates target genes by direct binding as a homodimer to specific Gcn4-response elements (GCREs) in their promoters (consensus sequence, TGACTCA). GCN4 is regulated at the translational level by a mechanism involving a series of small regulatory upstream open reading frames (uORFs) in its 5' UTR. Under normal growth conditions, GCN4 is expressed at a low basal level. Translation is activated in response to starvation for any single amino acid or a defective aminoacyl tRNA synthetase, when most mRNAs experience reduced translation. Initiation at the GCN4 uORFs inhibits translation of the main GCN4 ORF since a strong termination signal promotes dissociation of the ribosome, and the short distance between the proximal uORF and the GCN4 ORF precludes re-initiation. Amino-acid or carbohydrate limitation both lead to reduced translation initiation, allowing the small ribosomal subunit to scan past the uORFs before associating with the large subunit and initiation factors, leading to increased translation of the main GCN4 ORF. Gcn4p is also subject to a self-controlled feedback circuit between its transcriptional activity and its stability, which depends on the Gcn4p-controlled cyclin PCL5. Increased Gcn4p transcriptional activity increases expression of PCL5, which increases degradation of Gcn4p, resulting in rapid turnover. This buffer system to restrict transcriptional activity results in a reciprocal correlation between Gcn4p transcriptional activity and protein stability.
Regulators
10
Targets
1257
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2002-04-17

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
360
Additional
527
Reviews
134

Resources