GCN3/YKR026C Summary Help

Standard Name GCN3 1
Systematic Name YKR026C
Alias AAS2 2
Feature Type ORF, Verified
Description Alpha subunit of the translation initiation factor eIF2B, the guanine-nucleotide exchange factor for eIF2; activity subsequently regulated by phosphorylated eIF2; first identified as a positive regulator of GCN4 expression (3, 4 and see Summary Paragraph)
Name Description General Control Nonderepressible 5
Chromosomal Location
ChrXI:489655 to 488738 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 7 cM
Gene Ontology Annotations All GCN3 GO evidence and references
  View Computational GO annotations for GCN3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant phenotypes All GCN3 Phenotype evidence and references
Classical genetics
null
reduction of function
Large-scale survey
null
overexpression
Resources
interactions All GCN3 Interaction evidence and references
186 total interaction(s) for 92 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 70
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 13
  • Co-fractionation: 3
  • Co-purification: 1
  • PCA: 2
  • Two-hybrid: 14
Genetic Interactions
  • Dosage Rescue: 6
  • Negative Genetic: 41
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 10
  • Positive Genetic: 7
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 5
  • Synthetic Rescue: 7
Resources
Expression Summary
histogram
Resources
Protein Information All GCN3 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXI:489655 to 488738 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 7 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..918 489655..488738 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001734
SUMMARY PARAGRAPH for GCN3

Gcn3p is the alpha subunit of the heteropentameric eukaryotic initiation factor 2B (eIF2B), which is required for translation initiation and its regulation in all eukaryotes (6, 7). Deletion of GCN3 is lethal, and mutations in GCN3 lead to derepressed, or otherwise altered, translation (1, 8, 9, 10, 11).

eIF2B comprises a regulatory subcomplex composed of Gcd2p, Gcd7p, and Gcn3p, and a catalytic subcomplex containing Gcd1p and Gcd6p. As the guanine nucleotide exchange factor for translation initiation factor eIF2, eIF2B recycles eIF2 from a GDP- to a GTP-bound form that is competent for translation initiation, a key control point for translation (6, 7, 12). The trimeric regulatory subcomplex does not possess guanine-nucleotide exchange activity, but interacts stably with eIF2 with a binding preference for phosphorylated eIF2 which, in its GDP-bound form, is an inhibitor of eIF2B (3, 13). Gcd2p, Gcd7p, and Gcn3p together mediate this inhibition of eIF2B activity by phosphorylated eIF2 (13).

eIF2B is found in a specific cytoplasmic focus in yeast, with eIF2 shuttling back and forth, implicating this cytoplasmic focus as a site of guanine nucleotide exchange. eIF2B activity is inhibited in response to starvation or stress by phosphorylation of the alpha subunit of eIF2 (3). All five yeast subunits of eIF2B share extensive sequence similarity with their mammalian counterparts (3). Mutations in any of the five human subunits cause a fatal disease called CACH (childhood ataxia with central nervous system hypomyelination) or VWM (vanishing white matter disease) (14, 12).

Last updated: 2006-11-15

References cited on this page View Complete Literature Guide for GCN3
1) Hannig EM and Hinnebusch AG  (1988) Molecular analysis of GCN3, a translational activator of GCN4: evidence for posttranslational control of GCN3 regulatory function. Mol Cell Biol 8(11):4808-20
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) Pavitt GD, et al.  (1998) eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange. Genes Dev 12(4):514-26
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) Lucchini G, et al.  (1984) Positive regulatory interactions of the HIS4 gene of Saccharomyces cerevisiae. Mol Cell Biol 4(7):1326-33
6) Cigan AM, et al.  (1993) A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast. Proc Natl Acad Sci U S A 90(11):5350-4
7) Bushman JL, et al.  (1993) Guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 in Saccharomyces cerevisiae: interactions between the essential subunits GCD2, GCD6, and GCD7 and the regulatory subunit GCN3. Mol Cell Biol 13(8):4618-31
8) Harashima S, et al.  (1987) Interactions between positive and negative regulators of GCN4 controlling gene expression and entry into the yeast cell cycle. Genetics 117(3):409-19
9) Williams NP, et al.  (1989) Mutations in the structural genes for eukaryotic initiation factors 2 alpha and 2 beta of Saccharomyces cerevisiae disrupt translational control of GCN4 mRNA. Proc Natl Acad Sci U S A 86(19):7515-9
10) Pavitt GD, et al.  (1997) Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2. Mol Cell Biol 17(3):1298-313
11) Hannig EM, et al.  (1990) The translational activator GCN3 functions downstream from GCN1 and GCN2 in the regulatory pathway that couples GCN4 expression to amino acid availability in Saccharomyces cerevisiae. Genetics 126(3):549-62
12) Campbell SG and Ashe MP  (2006) Localization of the translational guanine nucleotide exchange factor eIF2B: a common theme for GEFs? Cell Cycle 5(7):678-80
13) Yang W and Hinnebusch AG  (1996) Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2. Mol Cell Biol 16(11):6603-16
14) Pavitt GD  (2005) eIF2B, a mediator of general and gene-specific translational control. Biochem Soc Trans 33(Pt 6):1487-92