GCD1/YOR260W Summary Help

Standard Name GCD1 1
Systematic Name YOR260W
Alias TRA3 2
Feature Type ORF, Verified
Description Gamma 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 (3, 4 and see Summary Paragraph)
Name Description General Control Derepressed 5
Chromosomal Location
ChrXV:813984 to 815720 | ORF Map | GBrowse
Gbrowse
Genetic position: 143 cM
Gene Ontology Annotations All GCD1 GO evidence and references
  View Computational GO annotations for GCD1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Resources
Classical genetics
conditional
null
Large-scale survey
conditional
null
overexpression
reduction of function
Resources
117 total interaction(s) for 31 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 61
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 29
  • Biochemical Activity: 1
  • Co-fractionation: 4
  • Co-purification: 2
  • Reconstituted Complex: 5
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 4
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Synthetic Lethality: 1
  • Synthetic Rescue: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 578
Molecular Weight (Da) 65,699
Isoelectric Point (pI) 4.63
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:813984 to 815720 | ORF Map | GBrowse
SGD ORF map
Genetic position: 143 cM
Last Update Coordinates: 2006-01-05 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1737 813984..815720 2006-01-05 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 SGDIDS000005786
SUMMARY PARAGRAPH for GCD1

Gcd1p is the gamma subunit of the heteropentameric eukaryotic initiation factor 2B (eIF2B), which is required for translation initiation and its regulation in all eukaryotes (6, 7). eIF2B comprises a catalytic subcomplex containing Gcd1p and Gcd6p, and a regulatory subcomplex composed of Gcd2p, Gcd7p, and Gcn3p. 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, 8). The formation of the catalytic Gcd1p-Gcd6p subcomplex serves to stabilize the interaction of Gcd6p, which possesses the actual guanine nucleotide exchange activity, with eIF2, thereby enhancing its nucleotide-exchange activity (3). Mutations in GCD1 lead to derepressed translation (9, 10) or otherwise altered translational control (11, 12), as well as lack of growth at high temperatures because cells cannot proceed beyond START of the cell division cycle (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, 8).

Last updated: 2006-11-15 Contact SGD

References cited on this page View Complete Literature Guide for GCD1
1) Yep, D.  (1973) Ph.D. Thesis, Cornell University, Ithaca, N.Y
2) Wolfner M, et al.  (1975) Integration of amino acid biosynthesis into the cell cycle of Saccharomyces cerevisiae. J Mol Biol 96(2):273-90
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) 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
9) Abastado JP, et al.  (1991) Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control. Mol Cell Biol 11(1):486-96
10) Hinnebusch AG  (1985) A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol 5(9):2349-60
11) 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
12) Tzamarias D, et al.  (1989) Coupling of GCN4 mRNA translational activation with decreased rates of polypeptide chain initiation. Cell 57(6):947-54
13) Hill DE and Struhl K  (1988) Molecular characterization of GCD1, a yeast gene required for general control of amino acid biosynthesis and cell-cycle initiation. Nucleic Acids Res 16(19):9253-65
14) Pavitt GD  (2005) eIF2B, a mediator of general and gene-specific translational control. Biochem Soc Trans 33(Pt 6):1487-92