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Gene Review

EIF5  -  eukaryotic translation initiation factor 5

Homo sapiens

Synonyms: EIF-5, EIF-5A, Eukaryotic translation initiation factor 5, eIF-5
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Disease relevance of EIF5

  • Binding analysis with human eIF2beta deletion mutants expressed in Escherichia coli identified a 22-amino acid domain, between amino acids 68 and 89, as the primary eIF5-binding region of eIF2beta [1].

High impact information on EIF5

  • Here we show that hydrolysis of eIF2-bound GTP induced by eIF5 in 48S complexes is necessary but not sufficient for the subunits to join [2].
  • In the absence of eIF1, eIF5-stimulated hydrolysis of eIF2-bound GTP occurred at the same rate in 43S pre-initiation and 48S initiation complexes [3].
  • Interestingly, the 131,133 CTT mutation enhances initiation at UUG codons (Sui(-) phenotype) and decreases leaky scanning at AUG, while the NTT mutation 17-21 suppresses the Sui(-) phenotypes of eIF5 and eIF2beta mutations and increases leaky scanning [4].
  • An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during translation initiation [5].
  • CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression [6].

Biological context of EIF5

  • This interaction is essential for eIF5-promoted hydrolysis of GTP bound to the 40 S initiation complex [7].
  • Additionally, alanine substitution mutagenesis of eIF5 defined Lys-33 and Lys-55 as also critical for eIF5 function in vitro and in vivo [7].
  • Using MS, we show that Ser-389 and -390 of eIF5 are major sites of phosphorylation by CK2 [6].
  • Expression of these mutants reveals that they have a dominant-negative effect on phosphorylation of endogenous eIF5, and that they perturb synchronous progression of cells through S to M phase, resulting in a significant reduction in growth rate [6].
  • Additionally, we demonstrate tissue-specific variations in eIF-5 mRNA expression as well as preference for polyadenylation sites [8].

Anatomical context of EIF5

  • Joining of 48S complexes to 60S subunits to form 80S ribosomes requires eIF5B, which has an essential ribosome-dependent GTPase activity and hydrolysis of eIF2-bound GTP induced by eIF5 [9].
  • These findings suggest that eIF5-eIF2beta interaction plays an essential role in eIF5 function in eukaryotic cells [10].
  • We isolated a protein kinase from rabbit reticulocyte lysates on the basis of its ability to phosphorylate purified bacterially expressed recombinant rat eIF5 [11].

Associations of EIF5 with chemical compounds

  • Mutation of this arginine residue to alanine or even to conservative lysine caused a severe defect in the ability of eIF5 to promote GTP hydrolysis from the 40 S initiation complex, although the ability of these mutant proteins to bind to eIF2 beta remained unchanged [7].
  • Alanine substitution mutagenesis at sites within this region defined several conserved glutamic acid residues in a bipartite motif as critical for eIF5 function [10].
  • Thus, rather than allosterically regulating eIF2gamma-G domain function via eIF2beta, our data support a model in which the GTPase-activating factor eIF5 and the guanine-nucleotide exchange factor eIF2B modulate eIF2 function through direct interactions with the eIF2gamma-G domain [12].
  • Direct Binding of Translation Initiation Factor eIF2{gamma}-G Domain to Its GTPase-activating and GDP-GTP Exchange Factors eIF5 and eIF2B{epsilon} [12].
  • These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation [11].

Other interactions of EIF5

  • We have determined the crystal structure of residues 544-704 from yeast eIF2Bepsilon at 2.3-A resolution, and this fragment is an all-helical protein built around the conserved aromatic acidic (AA) boxes also found in eIF4G and eIF5 [13].
  • Here, we report the quantitative characterization of energetic interactions between eIF1A, eIF5 and the AUG codon in an in vitro reconstituted yeast translation initiation system [14].

Analytical, diagnostic and therapeutic context of EIF5


  1. Specific interaction of eukaryotic translation initiation factor 5 (eIF5) with the beta-subunit of eIF2. Das, S., Maiti, T., Das, K., Maitra, U. J. Biol. Chem. (1997) [Pubmed]
  2. The joining of ribosomal subunits in eukaryotes requires eIF5B. Pestova, T.V., Lomakin, I.B., Lee, J.H., Choi, S.K., Dever, T.E., Hellen, C.U. Nature (2000) [Pubmed]
  3. Release of initiation factors from 48S complexes during ribosomal subunit joining and the link between establishment of codon-anticodon base-pairing and hydrolysis of eIF2-bound GTP. Unbehaun, A., Borukhov, S.I., Hellen, C.U., Pestova, T.V. Genes Dev. (2004) [Pubmed]
  4. N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selection. Fekete, C.A., Mitchell, S.F., Cherkasova, V.A., Applefield, D., Algire, M.A., Maag, D., Saini, A.K., Lorsch, J.R., Hinnebusch, A.G. EMBO J. (2007) [Pubmed]
  5. An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during translation initiation. Singh, C.R., Lee, B., Udagawa, T., Mohammad-Qureshi, S.S., Yamamoto, Y., Pavitt, G.D., Asano, K. EMBO J. (2006) [Pubmed]
  6. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression. Homma, M.K., Wada, I., Suzuki, T., Yamaki, J., Krebs, E.G., Homma, Y. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Eukaryotic translation initiation factor 5 functions as a GTPase-activating protein. Das, S., Ghosh, R., Maitra, U. J. Biol. Chem. (2001) [Pubmed]
  8. Characterization of multiple mRNAs that encode mammalian translation initiation factor 5 (eIF-5). Si, K., Das, K., Maitra, U. J. Biol. Chem. (1996) [Pubmed]
  9. Molecular mechanisms of translation initiation in eukaryotes. Pestova, T.V., Kolupaeva, V.G., Lomakin, I.B., Pilipenko, E.V., Shatsky, I.N., Agol, V.I., Hellen, C.U. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. Mutational analysis of mammalian translation initiation factor 5 (eIF5): role of interaction between the beta subunit of eIF2 and eIF5 in eIF5 function in vitro and in vivo. Das, S., Maitra, U. Mol. Cell. Biol. (2000) [Pubmed]
  11. Phosphorylation of mammalian translation initiation factor 5 (eIF5) in vitro and in vivo. Majumdar, R., Bandyopadhyay, A., Deng, H., Maitra, U. Nucleic Acids Res. (2002) [Pubmed]
  12. Direct Binding of Translation Initiation Factor eIF2{gamma}-G Domain to Its GTPase-activating and GDP-GTP Exchange Factors eIF5 and eIF2B{epsilon}. Alone, P.V., Dever, T.E. J. Biol. Chem. (2006) [Pubmed]
  13. Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue. Boesen, T., Mohammad, S.S., Pavitt, G.D., Andersen, G.R. J. Biol. Chem. (2004) [Pubmed]
  14. Communication between eukaryotic translation initiation factors 5 and 1A within the ribosomal pre-initiation complex plays a role in start site selection. Maag, D., Algire, M.A., Lorsch, J.R. J. Mol. Biol. (2006) [Pubmed]
  15. Structure, organization and expression of the eukaryotic translation initiation factor 5, eIF-5, gene in Zea mays. López Ribera, I., Puigdomènech, P. Gene (1999) [Pubmed]
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