GCD2/YGR083C Summary Help

Standard Name GCD2 1, 2
Systematic Name YGR083C
Alias GCD12 3 , 4
Feature Type ORF, Verified
Description Delta subunit of the translation initiation factor eIF2B; the guanine-nucleotide exchange factor for eIF2; activity subsequently regulated by phosphorylated eIF2; first identified as a negative regulator of GCN4 expression (5, 6 and see Summary Paragraph)
Name Description General Control Derepressed 1, 7
Chromosomal Location
ChrVII:646815 to 644860 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 54 cM
Gene Ontology Annotations All GCD2 GO evidence and references
  View Computational GO annotations for GCD2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
reduction of function
repressible
Resources
127 total interaction(s) for 53 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 49
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 19
  • Co-fractionation: 3
  • Co-purification: 1
  • PCA: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Rescue: 4
  • Negative Genetic: 31
  • Phenotypic Suppression: 4
  • Synthetic Lethality: 5
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 651
Molecular Weight (Da) 70,852
Isoelectric Point (pI) 10.22
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:646815 to 644860 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 54 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1956 646815..644860 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 SGDIDS000003315
SUMMARY PARAGRAPH for GCD2

Gcd2p is the delta subunit of the heteropentameric eukaryotic initiation factor 2B (eIF2B), which is required for translation initiation and its regulation in all eukaryotes (8, 9). Deletion of GCD2 is lethal, and mutations in GCD2 lead to slow growth and derepressed, or otherwise altered, translation. (3, 10, 11, 4, 1, 12).

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 (8, 9, 13). 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 (5, 14). Gcd2p, Gcd7p, and Gcn3p together mediate this inhibition of eIF2B activity by phosphorylated eIF2 (14).

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 (5). All five yeast subunits of eIF2B share extensive sequence similarity with their mammalian counterparts (5). 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) (15, 13).

Last updated: 2006-11-15 Contact SGD

References cited on this page View Complete Literature Guide for GCD2
1) Niederberger P, et al.  (1986) Identification and characterization of four new GCD genes in Saccharomyces cerevisiae. Curr Genet 10(9):657-64
2) Paddon, C.J.  (1989) Personal Communication, Mortimer Map Edition 10
3) Paddon CJ and Hinnebusch AG  (1989) gcd12 mutations are gcn3-dependent alleles of GCD2, a negative regulator of GCN4 in the general amino acid control of Saccharomyces cerevisiae. Genetics 122(3):543-50
4) Harashima S and Hinnebusch AG  (1986) Multiple GCD genes required for repression of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol 6(11):3990-8
5) 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
6) 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
7) Lucchini G, et al.  (1984) Positive regulatory interactions of the HIS4 gene of Saccharomyces cerevisiae. Mol Cell Biol 4(7):1326-33
8) 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
9) 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
10) Paddon CJ, et al.  (1989) Amino acid sequence similarity between GCN3 and GCD2, positive and negative translational regulators of GCN4: evidence for antagonism by competition. Genetics 122(3):551-9
11) Holmberg S and Petersen JG  (1988) Regulation of isoleucine-valine biosynthesis in Saccharomyces cerevisiae. Curr Genet 13(3):207-17
12) Foiani M, et al.  (1991) GCD2, a translational repressor of the GCN4 gene, has a general function in the initiation of protein synthesis in Saccharomyces cerevisiae. Mol Cell Biol 11(6):3203-16
13) 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
14) 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
15) Pavitt GD  (2005) eIF2B, a mediator of general and gene-specific translational control. Biochem Soc Trans 33(Pt 6):1487-92