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Gene Review

SUI2  -  translation initiation factor eIF2 subunit...

Saccharomyces cerevisiae S288c

Synonyms: Eukaryotic translation initiation factor 2 subunit alpha, J1429, TIF211, YJR007W, eIF-2-alpha
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Disease relevance of SUI2


High impact information on SUI2

  • In vivo, phosphorylation of eIF-2 alpha increases in response to amino acid starvation, which is dependent on GCN2 [2].
  • Substitution of Ser-51 with alanine eliminates phosphorylation of eIF-2 alpha by GCN2 in vivo and in vitro and abolishes increased expression of GCN4 and amino acid biosynthetic genes under its control in amino acid-starved cells [2].
  • The latter result indicates that the gamma subunit of eIF-2 participates in recognition of the start site for protein synthesis, a role previously demonstrated in yeast for eIF-2 alpha and eIF-2 beta [3].
  • These mutations may identify a region in eIF-2 alpha that participates directly in a physical interaction with the GCN3 subunit of eIF-2B [4].
  • We have cloned the cDNA of the heme-regulated eIF-2 alpha kinase (HRI) of rabbit reticulocytes [5].

Biological context of SUI2

  • Although substitution of SUI2 genes mutated at these sites for the wild-type gene have no obvious effect on cell growth, one test that we have used appears to demonstrate that the inability to phosphorylate these sites has a physiological consequence on eIF-2 function in S. cerevisiae [6].
  • In mammalian cells, phosphorylation of eIF-2 alpha inhibits the activity of eIF-2B, the GDP-GTP exchange factor for eIF-2 [7].
  • In this report, molecular and biochemical characterizations show that the sui2 suppressor gene encodes the alpha subunit of eIF-2 [8].
  • The amino acid sequence of sui2 is 58% homologous to that encoded by the cDNA of the human eIF-2 alpha [8].
  • Because the mutant tRNA(Val) exacerbated the slow-growth phenotype associated with eIF-2 alpha hyperphosphorylation by an activated GCN2c kinase, we suggest that the GCN2-independent derepression mechanism involves down-regulation of eIF-2 activity [9].

Anatomical context of SUI2


Associations of SUI2 with chemical compounds

  • Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) impairs translation initiation by inhibiting the guanine nucleotide exchange factor for eIF-2, known as eIF-2B [11].
  • Biochemical experiments show that eIF-2 alpha is phosphorylated in response to purine starvation and that this reaction is completely dependent on GCN2 [12].
  • Met-tRNA(iMet) ternary complex is the principal component limiting translation in cells when eIF-2 alpha is phosphorylated on serine 51 [13].
  • Only when cells were starved for a carbon source for 2 h in 1 M sorbitol was eIF-2 alpha isolated in the nonphosphorylated state [14].

Enzymatic interactions of SUI2

  • Here we describe that yeast eIF-2 alpha is a constitutively phosphorylated protein species that is multiply phosphorylated by a GCN2-independent mechanism [6].
  • The protein kinase GCN2 stimulates expression of the yeast transcriptional activator GCN4 at the translational level by phosphorylating the alpha subunit of translation initiation factor 2 (eIF-2 alpha) in amino acid-starved cells [15].

Regulatory relationships of SUI2

  • We isolated mutations in several unlinked genes that suppress the growth-inhibitory effect of eIF-2 alpha phosphorylation catalyzed by mutationally activated forms of GCN2 [11].
  • This double GCD7 mutation also completely suppressed the lethal effect of expressing the mammalian eIF-2 alpha kinase dsRNA-PK in yeast cells, showing that the translational machinery had been rendered completely insensitive to phosphorylated eIF-2 [11].
  • Consistent with eIF-2 functioning in translation as part of a ternary complex composed of eIF-2, GTP, and Met-tRNA(iMet), reduced gene dosage of initiator tRNA(Met) mimicked phosphorylation of eIF-2 alpha and stimulated GCN4 translation [13].

Other interactions of SUI2

  • This finding suggests that mutations in GCD-encoded subunits of the complex derepress GCN4 translation because they mimic eIF-2 alpha phosphorylation in decreasing eIF-2B activity [7].
  • The SUI2 and SUI3 genes of Saccharomyces cerevisiae encode the alpha and beta subunits, respectively, of translation initiation factor eIF-2 (eukaryotic initiation factor 2) [16].
  • 32Pi labeling and isoelectric focusing analysis of a SUI2+ delta gcn2 strain identifies eIF-2 alpha as radiolabeled and a single isoelectric protein species [6].
  • Both sui1 and sui2 are recessive and cause temperature-sensitive growth on enriched medium [17].
  • Protein sequence analysis shows that a sui2 mutant yeast strain allows initiation at a UUG codon in the absence of an AUG codon at HIS4 [8].

Analytical, diagnostic and therapeutic context of SUI2

  • Cell fractionation studies further demonstrated that the synthesised human eIF-2 alpha protein, though present in the cytoplasm, was largely associated with the yeast ribosomes, but could be removed from these by washing with 0.3 M KCl [18].
  • Isoelectric focusing coupled with Western-blot analysis demonstrated that the human eIF-2 alpha subunit synthesized in yeast under a variety of growth conditions was detected as two bands which co-migrated with the phosphorylated and unphosphorylated forms of rabbit eIF-2 alpha, suggesting covalent modification in vivo [18].
  • The phosphorylation state of the alpha subunit of initiation factor 2 (eIF-2 alpha) in Saccharomyces cerevisiae has been determined by two-dimensional gel electrophoresis and autoradiography of lysates from cultures grown under a variety of conditions [14].
  • We now describe the identification of S. mansoni eukaryotic translation initiation factor 2 alpha subunit (eIF2 alpha), through its interaction with SmRK1 in a yeast two-hybrid assay [19].


  1. The highly acidic C-terminal region of the yeast initiation factor subunit 2 alpha (eIF-2 alpha) contains casein kinase phosphorylation sites and is essential for maintaining normal regulation of GCN4. van den Heuvel, J., Lang, V., Richter, G., Price, N., Peacock, L., Proud, C., McCarthy, J.E. Biochim. Biophys. Acta (1995) [Pubmed]
  2. Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Dever, T.E., Feng, L., Wek, R.C., Cigan, A.M., Donahue, T.F., Hinnebusch, A.G. Cell (1992) [Pubmed]
  3. Mutations in GCD11, the structural gene for eIF-2 gamma in yeast, alter translational regulation of GCN4 and the selection of the start site for protein synthesis. Dorris, D.R., Erickson, F.L., Hannig, E.M. EMBO J. (1995) [Pubmed]
  4. Mutations in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) that overcome the inhibitory effect of eIF-2 alpha phosphorylation on translation initiation. Vazquez de Aldana, C.R., Dever, T.E., Hinnebusch, A.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  5. Cloning of the cDNA of the heme-regulated eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase of rabbit reticulocytes: homology to yeast GCN2 protein kinase and human double-stranded-RNA-dependent eIF-2 alpha kinase. Chen, J.J., Throop, M.S., Gehrke, L., Kuo, I., Pal, J.K., Brodsky, M., London, I.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  6. Casein kinase II mediates multiple phosphorylation of Saccharomyces cerevisiae eIF-2 alpha (encoded by SUI2), which is required for optimal eIF-2 function in S. cerevisiae. Feng, L., Yoon, H., Donahue, T.F. Mol. Cell. Biol. (1994) [Pubmed]
  7. A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast. Cigan, A.M., Bushman, J.L., Boal, T.R., Hinnebusch, A.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  8. Yeast translation initiation suppressor sui2 encodes the alpha subunit of eukaryotic initiation factor 2 and shares sequence identity with the human alpha subunit. Cigan, A.M., Pabich, E.K., Feng, L., Donahue, T.F. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  9. Multicopy tRNA genes functionally suppress mutations in yeast eIF-2 alpha kinase GCN2: evidence for separate pathways coupling GCN4 expression to unchanged tRNA. Vazquez de Aldana, C.R., Wek, R.C., Segundo, P.S., Truesdell, A.G., Hinnebusch, A.G. Mol. Cell. Biol. (1994) [Pubmed]
  10. GCD10, a translational repressor of GCN4, is the RNA-binding subunit of eukaryotic translation initiation factor-3. Garcia-Barrio, M.T., Naranda, T., Vazquez de Aldana, C.R., Cuesta, R., Hinnebusch, A.G., Hershey, J.W., Tamame, M. Genes Dev. (1995) [Pubmed]
  11. Mutations in the GCD7 subunit of yeast guanine nucleotide exchange factor eIF-2B overcome the inhibitory effects of phosphorylated eIF-2 on translation initiation. Vazquez de Aldana, C.R., Hinnebusch, A.G. Mol. Cell. Biol. (1994) [Pubmed]
  12. Translation of the yeast transcriptional activator GCN4 is stimulated by purine limitation: implications for activation of the protein kinase GCN2. Rolfes, R.J., Hinnebusch, A.G. Mol. Cell. Biol. (1993) [Pubmed]
  13. Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary complexes. Dever, T.E., Yang, W., Aström, S., Byström, A.S., Hinnebusch, A.G. Mol. Cell. Biol. (1995) [Pubmed]
  14. The alpha subunit of initiation factor 2 is phosphorylated in vivo in the yeast Saccharomyces cerevisiae. Romero, D.P., Dahlberg, A.E. Mol. Cell. Biol. (1986) [Pubmed]
  15. Mutations activating the yeast eIF-2 alpha kinase GCN2: isolation of alleles altering the domain related to histidyl-tRNA synthetases. Ramirez, M., Wek, R.C., Vazquez de Aldana, C.R., Jackson, B.M., Freeman, B., Hinnebusch, A.G. Mol. Cell. Biol. (1992) [Pubmed]
  16. Mutations in the structural genes for eukaryotic initiation factors 2 alpha and 2 beta of Saccharomyces cerevisiae disrupt translational control of GCN4 mRNA. Williams, N.P., Hinnebusch, A.G., Donahue, T.F. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  17. Genetic characterization of the Saccharomyces cerevisiae translational initiation suppressors sui1, sui2 and SUI3 and their effects on HIS4 expression. Castilho-Valavicius, B., Yoon, H., Donahue, T.F. Genetics (1990) [Pubmed]
  18. Synthesis of human initiation factor-2 alpha in Saccharomyces cerevisiae. Green, S.R., Spalding, A., Ashford, T., Proud, C.G., Tuite, M.F. Gene (1991) [Pubmed]
  19. Eukaryotic initiation factor 2 alpha subunit associates with TGF beta receptors and 14-3-3 epsilon and acts as a modulator of the TGF beta response. McGonigle, S., Beall, M.J., Pearce, E.J. Biochemistry (2002) [Pubmed]
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