GCD6/YDR211W Summary Help

Standard Name GCD6 1
Systematic Name YDR211W
Feature Type ORF, Verified
Description Catalytic epsilon subunit of the translation initiation factor eIF2B; eIF2B is the guanine-nucleotide exchange factor for eIF2; activity subsequently regulated by phosphorylated eIF2; first identified as a negative regulator of GCN4 expression; forms cytoplasmic foci upon DNA replication stress (2, 3, 4 and see Summary Paragraph)
Name Description General Control Derepressed 5
Chromosomal Location
ChrIV:884727 to 886865 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All GCD6 GO evidence and references
  View Computational GO annotations for GCD6
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Classical genetics
reduction of function
Large-scale survey
null
reduction of function
unspecified
Resources
143 total interaction(s) for 47 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 76
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 32
  • Co-fractionation: 4
  • Co-purification: 4
  • Reconstituted Complex: 5
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 3
  • Negative Genetic: 6
  • Synthetic Lethality: 4
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 712
Molecular Weight (Da) 81,160
Isoelectric Point (pI) 4.48
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:884727 to 886865 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2139 884727..886865 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 SGDIDS000002619
SUMMARY PARAGRAPH for GCD6

Gcd6p is the epsilon subunit of the heteropentameric eukaryotic initiation factor 2B (eIF2B), which is required for translation initiation and its regulation in all eukaryotes (6, 7, 8). 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, 9). Gcd6p possesses the actual guanine nucleotide exchange activity, and formation of the catalytic subcomplex with gamma subunit Gcd1p serves to stabilize the interaction of Gcd6p with eIF2, thereby enhancing its nucleotide-exchange activity (2). The C terminus of Gcd6p (residues 518 to 712) is required both for catalytic activity and interaction with eIF2, and the N-terminal region of Gcd6p is an activation domain that responds to eIF2B complex formation (10, 11). Mutations in GCD6 lead to derepressed translation and slow growth (1, 6), and deletion of GCD6 is lethal (6).

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 (2). All five yeast subunits of eIF2B share extensive sequence similarity with their mammalian counterparts (2). 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) (12, 9).

Last updated: 2006-11-15 Contact SGD

References cited on this page View Complete Literature Guide for GCD6
1) Niederberger P, et al.  (1986) Identification and characterization of four new GCD genes in Saccharomyces cerevisiae. Curr Genet 10(9):657-64
2) 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
3) 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
4) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
5) Lucchini G, et al.  (1984) Positive regulatory interactions of the HIS4 gene of Saccharomyces cerevisiae. Mol Cell Biol 4(7):1326-33
6) Bushman JL, et al.  (1993) Evidence that GCD6 and GCD7, translational regulators of GCN4, are subunits of the guanine nucleotide exchange factor for eIF-2 in Saccharomyces cerevisiae. Mol Cell Biol 13(3):1920-32
7) 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
8) 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
9) 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
10) Gomez E and Pavitt GD  (2000) Identification of domains and residues within the epsilon subunit of eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation. Mol Cell Biol 20(11):3965-76
11) Gomez E, et al.  (2002) Characterization of the minimal catalytic domain within eIF2B: the guanine-nucleotide exchange factor for translation initiation. EMBO J 21(19):5292-301
12) Pavitt GD  (2005) eIF2B, a mediator of general and gene-specific translational control. Biochem Soc Trans 33(Pt 6):1487-92