GCN4/YEL009C Summary Help

Standard Name GCN4 1
Systematic Name YEL009C
Alias AAS3 2 , ARG9 2 , AAS101 3
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 (4, 5 and see Summary Paragraph)
Name Description General Control Nonderepressible 1
Chromosomal Location
ChrV:139763 to 138918 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -3 cM
Gene Ontology Annotations All GCN4 GO evidence and references
  View Computational GO annotations for GCN4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 413 genes
Regulators 2 genes
Classical genetics
reduction of function
Large-scale survey
173 total interaction(s) for 101 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 7
  • Affinity Capture-Western: 53
  • Biochemical Activity: 5
  • Co-crystal Structure: 5
  • Co-localization: 2
  • Far Western: 1
  • FRET: 1
  • PCA: 12
  • Protein-peptide: 1
  • Reconstituted Complex: 20
  • Two-hybrid: 10

Genetic Interactions
  • Dosage Lethality: 5
  • Dosage Rescue: 6
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 18
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 1
  • Synthetic Rescue: 12

Expression Summary
Length (a.a.) 281
Molecular Weight (Da) 31,310
Isoelectric Point (pI) 4.93
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrV:139763 to 138918 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -3 cM
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..846 139763..138918 1996-07-31 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 SGDIDS000000735

GCN4 ("General Control Nondepressible") encodes a transcriptional activator (2). GCN4 was originally characterized as a positive regulator of genes expressed during amino acid starvation (4). Microarray analysis of strains of yeast in which GCN4 has been deleted and strains of yeast in which Gcn4p is constitutively active has identified additional pathways in which Gcn4p may act as a transcriptional activator (6). In addition to the derepression of genes involved in 19 out of 20 amino acid biosynthetic pathways, Gcn4p may directly or indirectly regulate the expression of genes involved in purine biosynthesis, organelle biosynthesis, autophagy, glycogen homeostasis, and multiple stress responses (6).

The level of Gcn4p is tightly regulated. Gcn4p is rapidly degraded by the ubiquitin pathway during conditions of non-starvation, but its half-life dramatically increases during amino acid starvation (7, 8). Translational regulation also contributes to the level of Gcn4p in the cell. Four small upstream ORFs (uORF1-4) in the 5' leader region of the GCN4 mRNA act as negative regulators of translation (9). The ribosome initiates translation at uORF1 and becomes re-activated for translation at subsequent uORFs. Under environmental stresses, such as amino acid starvation, purine limitation, or nitrogen limitation, the translation of GCN4 is induced in a GCN2-dependent pathway (10); the scanning ribosome is not re-activated until it bypasses the uORFs and initiates translation at the GCN4 ORF (10).

Gcn4p is a member of the basic leucine-zipper (bZIP) family and binds DNA as a homodimer (11). The carboxy terminus DNA binding domain of each Gcn4p monomer forms a continuous alpha helix that interacts with DNA in the major groove (12). Gcn4p has been shown to bind the consensus sequence TGACTC, located upstream of many genes induced during amino acid starvation (13, 14, 15).

Last updated: 2002-04-17 Contact SGD

References cited on this page View Complete Literature Guide for GCN4
1) Lucchini G, et al.  (1984) Positive regulatory interactions of the HIS4 gene of Saccharomyces cerevisiae. Mol Cell Biol 4(7):1326-33
2) Hinnebusch AG and Fink GR  (1983) Positive regulation in the general amino acid control of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 80(17):5374-8
3) Thireos G, et al.  (1984) 5' untranslated sequences are required for the translational control of a yeast regulatory gene. Proc Natl Acad Sci U S A 81(16):5096-100
4) Hinnebusch A  (1992) "General and Pathway-specific Regulatory Mechanisms Controlling the Synthesis of Amino Acid Biosynthetic Enzymes in Saccharomyces cerevisiae". Pp. 319-414 in The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression, edited by Jones EW, Pringle JR and Broach JR. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
5) Hinnebusch AG and Natarajan K  (2002) Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress. Eukaryot Cell 1(1):22-32
6) 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
7) Kornitzer D, et al.  (1994) Regulated degradation of the transcription factor Gcn4. EMBO J 13(24):6021-30
8) Meimoun A, et al.  (2000) Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex. Mol Biol Cell 11(3):915-27
9) Hinnebusch AG  (1984) Evidence for translational regulation of the activator of general amino acid control in yeast. Proc Natl Acad Sci U S A 81(20):6442-6
10) Hinnebusch AG  (1997) Translational regulation of yeast GCN4. A window on factors that control initiator-trna binding to the ribosome. J Biol Chem 272(35):21661-4
11) Hope IA and Struhl K  (1987) GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA. EMBO J 6(9):2781-4
12) Ellenberger TE, et al.  (1992) The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex. Cell 71(7):1223-37
13) Hill DE, et al.  (1986) Saturation mutagenesis of the yeast his3 regulatory site: requirements for transcriptional induction and for binding by GCN4 activator protein. Science 234(4775):451-7
14) Arndt K and Fink GR  (1986) GCN4 protein, a positive transcription factor in yeast, binds general control promoters at all 5' TGACTC 3' sequences. Proc Natl Acad Sci U S A 83(22):8516-20
15) Oliphant AR, et al.  (1989) Defining the sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: analysis of yeast GCN4 protein. Mol Cell Biol 9(7):2944-9
16) Matys V, et al.  (2003) TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31(1):374-8
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