eukaryotic initiation factor 5


Summary: A eukaryotic initiation factor that interacts with the 40S initiation complex and promotes the hydrolysis of the bound GTP. The hydrolysis of GTP causes the release of EUKARYOTIC INITIATION FACTOR-2 and EUKARYOTIC INITIATION FACTOR-3 from the 40S subunit and the subsequent joining of the 60S ribosomal subunit to the 40S complex to form the functional 80S initiation complex

Top Publications

  1. Chakrabarti A, Maitra U. Function of eukaryotic initiation factor 5 in the formation of an 80 S ribosomal polypeptide chain initiation complex. J Biol Chem. 1991;266:14039-45 pubmed
    b>Eukaryotic initiation factor 5 (eIF-5), isolated from rabbit reticulocyte lysates, is a monomeric protein of 58-62 kDa...
  2. Lee C, Um P, Park M. Structure-function studies of human deoxyhypusine synthase: identification of amino acid residues critical for the binding of spermidine and NAD. Biochem J. 2001;355:841-9 pubmed
    ..These findings permit the positive identification of amino acid residues critical for binding of spermidine and NAD, and provide a new insight into the complex molecular interactions involved in the deoxyhypusine synthase reaction. ..
  3. Searfoss A, Dever T, Wickner R. Linking the 3' poly(A) tail to the subunit joining step of translation initiation: relations of Pab1p, eukaryotic translation initiation factor 5b (Fun12p), and Ski2p-Slh1p. Mol Cell Biol. 2001;21:4900-8 pubmed
    ..This suggests that Ski2p and Slh1p block translation of non-poly(A) mRNA by an effect on Fun12p, possibly by affecting 60S subunit joining. ..
  4. Roll Mecak A, Shin B, Dever T, Burley S. Engaging the ribosome: universal IFs of translation. Trends Biochem Sci. 2001;26:705-9 pubmed
    ..These processes yield a translationally competent ribosome with Met-tRNA in the ribosomal peptidyl-tRNA site (P site), base-paired to the AUG start codon of a mRNA. ..
  5. Majumdar R, Maitra U. Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation. EMBO J. 2005;24:3737-46 pubmed
    ..These results, taken together, demonstrate the biochemical requirements for regulation of GTP hydrolysis and its coupling to the AUG selection process during translation initiation. ..
  6. López Ribera I, Ruiz Avila L, Puigdomenech P. The eukaryotic translation initiation factor 5, eIF-5, a protein from Zea mays, containing a zinc-finger structure, binds nucleic acids in a zinc-dependent manner. Biochem Biophys Res Commun. 1997;236:510-6 pubmed
    ..These results suggest that the zinc-finger structure is involved in the binding of the eIF-5 protein to RNA. ..
  7. Roll Mecak A, Cao C, Dever T, Burley S. X-Ray structures of the universal translation initiation factor IF2/eIF5B: conformational changes on GDP and GTP binding. Cell. 2000;103:781-92 pubmed
    ..Mechanisms of GTPase function and ribosome binding are discussed...
  8. Marintchev A, Kolupaeva V, Pestova T, Wagner G. Mapping the binding interface between human eukaryotic initiation factors 1A and 5B: a new interaction between old partners. Proc Natl Acad Sci U S A. 2003;100:1535-40 pubmed
    ..The binding between the C termini of eIF1A and eIF5B has implications for eukaryote-specific mechanisms of recruitment and release of translation IFs from the ribosome. ..
  9. Phan L, Zhang X, Asano K, Anderson J, Vornlocher H, Greenberg J, et al. Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5. Mol Cell Biol. 1998;18:4935-46 pubmed
    ..Thus, eIF5 and Sui1p may be recruited to the 40S ribosomes through physical interactions with the Nip1p subunit of eIF3. ..

More Information


  1. Gao G, Raikar S, Davenport B, Mutapcic L, Montgomery R, Kuzmin E, et al. Cross-species RNAi: selected Ascaris suum dsRNAs can sterilize Caenorhabditis elegans. Mol Biochem Parasitol. 2006;146:124-8 pubmed
  2. Conte M, Kelly G, Babon J, Proud C. Resonance assignment for the N-terminal region of the eukaryotic initiation factor 5 (eIF5). J Biomol NMR. 2006;36 Suppl 1:42 pubmed
  3. Reibarkh M, Yamamoto Y, Singh C, del Rio F, Fahmy A, Lee B, et al. Eukaryotic initiation factor (eIF) 1 carries two distinct eIF5-binding faces important for multifactor assembly and AUG selection. J Biol Chem. 2008;283:1094-103 pubmed
    ..Thus, eIF5 is an excellent candidate for the direct partner of eIF1-KH that mediates the critical link. The direct interaction at eIF1-KH also places eIF5 near the decoding site of the 40 S subunit. ..
  4. VALASEK L, Mathew A, Shin B, Nielsen K, Szamecz B, Hinnebusch A. The yeast eIF3 subunits TIF32/a, NIP1/c, and eIF5 make critical connections with the 40S ribosome in vivo. Genes Dev. 2003;17:786-99 pubmed
  5. Conte M, Kelly G, Babon J, Sanfelice D, Youell J, Smerdon S, et al. Structure of the eukaryotic initiation factor (eIF) 5 reveals a fold common to several translation factors. Biochemistry. 2006;45:4550-8 pubmed
    b>Eukaryotic initiation factor 5 (eIF5) plays multiple roles in translation initiation...
  6. Chan K, New D, Ghandhi S, Wong F, Lam C, Wong J. Transcript levels of the eukaryotic translation initiation factor 5A gene peak at early G(1) phase of the cell cycle in the dinoflagellate Crypthecodinium cohnii. Appl Environ Microbiol. 2002;68:2278-84 pubmed
    ..The possible links of polyamines and saxitoxin synthesis to the arginine cycle are also discussed. ..
  7. Bylund G, Lövgren J, Wikström P. Characterization of mutations in the metY-nusA-infB operon that suppress the slow growth of a DeltarimM mutant. J Bacteriol. 2001;183:6095-106 pubmed
    ..The nusA gene has previously been shown to be essential at 42 degrees C and below 32 degrees C. Here, we show that nusA is also essential at 37 degrees C. ..
  8. Thompson G, Pacheco E, Melo E, Castilho B. Conserved sequences in the beta subunit of archaeal and eukaryal translation initiation factor 2 (eIF2), absent from eIF5, mediate interaction with eIF2gamma. Biochem J. 2000;347 Pt 3:703-9 pubmed
    ..eIF5 does not interact with eIF2gamma, despite its similarity with eIF2beta, probably because of a gap in homology in this region. These observations have implications for the evolution of the mechanism of translation initiation. ..
  9. Chamot D, Kuhlemeier C. Differential expression of genes encoding the hypusine-containing translation initiation factor, eIF-5A, in tobacco. Nucleic Acids Res. 1992;20:665-9 pubmed
    ..coli. NeIF-5A1 antiserum crossreacts with an 18 kDa polypeptide doublet in all tobacco tissues examined. At least one polypeptide of ca. 18 kDa from a diversity of higher and lower plants crossreacts with NeIF-5A1 antiserum. ..
  10. Larigauderie G, Laalami S, Nyengaard N, Grunberg Manago M, Cenatiempo Y, Mortensen K, et al. Mutation of Thr445 and Ile500 of initiation factor 2 G-domain affects Escherichia coli growth rate at low temperature. Biochimie. 2000;82:1091-8 pubmed
    ..The mutant proteins were overexpressed and purified. As observed in vivo, a reduced activity at low temperature was measured when carrying out in vitro ribosome dependent GTPase and stimulation of ribosomal fMet-tRNAfMet binding. ..
  11. Yaksi E, Wilson R. Electrical coupling between olfactory glomeruli. Neuron. 2010;67:1034-47 pubmed publisher
    ..We propose that when stimuli are weak, lateral excitation promotes sensitivity, whereas when stimuli are strong, lateral excitation helps recruit inhibitory gain control. ..
  12. Chakravarti D, Maitra U. Eukaryotic translation initiation factor 5 from Saccharomyces cerevisiae. Cloning, characterization, and expression of the gene encoding the 45,346-Da protein. J Biol Chem. 1993;268:10524-33 pubmed
    ..Second, the predicted amino acid sequence of eIF-5 contains sequence motifs characteristic of proteins of the GTPase superfamily. ..
  13. López Ribera I, Puigdomenech P. Structure, organization and expression of the eukaryotic translation initiation factor 5, eIF-5, gene in Zea mays. Gene. 1999;240:355-9 pubmed
    ..The observed distribution of mRNA may correlate with the function of the protein, as it appears to be highly abundant in tissues where the proportion of cells actively dividing is very high, such as meristematic regions. ..
  14. Singh C, He H, Ii M, Yamamoto Y, Asano K. Efficient incorporation of eukaryotic initiation factor 1 into the multifactor complex is critical for formation of functional ribosomal preinitiation complexes in vivo. J Biol Chem. 2004;279:31910-20 pubmed
    ..We propose that the coordinated recruitment of eIF1 to the 40 S ribosome in the MFC is critical for the production of functional 40 S preinitiation complex. ..
  15. Olsen D, Savner E, Mathew A, Zhang F, Krishnamoorthy T, Phan L, et al. Domains of eIF1A that mediate binding to eIF2, eIF3 and eIF5B and promote ternary complex recruitment in vivo. EMBO J. 2003;22:193-204 pubmed
    ..We propose a modular organization for eIF1A wherein a core ribosome-binding domain is flanked by flexible segments that mediate interactions with other factors involved in recruitment of TC and release of eIF1A at subunit joining. ..
  16. Fletcher C, Pestova T, Hellen C, Wagner G. Structure and interactions of the translation initiation factor eIF1. EMBO J. 1999;18:2631-7 pubmed
    ..This interaction explains how eIF1 is recruited to the 40S ribosomal subunit. ..
  17. Phan L, Schoenfeld L, VALASEK L, Nielsen K, Hinnebusch A. A subcomplex of three eIF3 subunits binds eIF1 and eIF5 and stimulates ribosome binding of mRNA and tRNA(i)Met. EMBO J. 2001;20:2954-65 pubmed
    ..Thus, several key functions of eIF3 can be carried out by the PRT1-TIF32-NIP1 subcomplex. ..
  18. Das S, Maitra U. 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. Mol Cell Biol. 2000;20:3942-50 pubmed
    ..These findings suggest that eIF5-eIF2beta interaction plays an essential role in eIF5 function in eukaryotic cells. ..
  19. Homma M, Homma Y. Cell cycle and activation of CK2. Mol Cell Biochem. 2008;316:49-55 pubmed publisher
  20. Devineni A, Heberlein U. Preferential ethanol consumption in Drosophila models features of addiction. Curr Biol. 2009;19:2126-32 pubmed publisher
    ..Third, flies rapidly return to high levels of ethanol consumption after a period of imposed abstinence. Thus, ethanol preference in Drosophila provides a new model for studying aspects of addiction. ..
  21. Bieniossek C, Schütz P, Bumann M, Limacher A, Uson I, Baumann U. The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5. J Mol Biol. 2006;360:457-65 pubmed
    The carboxy-terminal domain (CTD) of eukaryotic initiation factor 5 (eIF5) plays a central role in the formation of the multifactor complex (MFC), an important intermediate for the 43 S pre-initiation complex assembly...
  22. Chakravarti D, Maiti T, Maitra U. Isolation and immunochemical characterization of eukaryotic translation initiation factor 5 from Saccharomyces cerevisiae. J Biol Chem. 1993;268:5754-62 pubmed
    ..No precursor forms of molecular weight higher than 56,000 were detected in any preparations. These results suggest that yeast eIF-5 is a monomeric protein of apparent M(r) = 50,000-56,000. ..
  23. La Teana A, Gualerzi C, Dahlberg A. Initiation factor IF 2 binds to the alpha-sarcin loop and helix 89 of Escherichia coli 23S ribosomal RNA. RNA. 2001;7:1173-9 pubmed
    ..This result, confirmed by sucrose density gradient analysis, seems to be a universally conserved property of IF2. ..
  24. Si K, Das K, Maitra U. Characterization of multiple mRNAs that encode mammalian translation initiation factor 5 (eIF-5). J Biol Chem. 1996;271:16934-8 pubmed
    ..Additionally, we demonstrate tissue-specific variations in eIF-5 mRNA expression as well as preference for polyadenylation sites. These results should lead to increased understanding of the regulation of eIF-5 gene expression. ..
  25. Algire M, Maag D, Lorsch J. Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation. Mol Cell. 2005;20:251-62 pubmed
    ..Release of P(i), which makes GTP hydrolysis irreversible, appears to be controlled by the AUG-dependent dissociation of eIF1 from the preinitiation complex. ..
  26. Lee J, Godon C, Lagniel G, Spector D, Garin J, Labarre J, et al. Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem. 1999;274:16040-6 pubmed
    ..Such a specialization may explain, at least in part, the dissociated function of Yap1 and Skn7 in H2O2 and cadmium resistance. ..
  27. Majumdar R, Bandyopadhyay A, Deng H, Maitra U. Phosphorylation of mammalian translation initiation factor 5 (eIF5) in vitro and in vivo. Nucleic Acids Res. 2002;30:1154-62 pubmed
    ..The same mutations also abolish phosphorylation of eIF5 when transfected into mammalian cells suggesting that CK II phosphorylates eIF5 at these two serine residues in vivo as well. ..
  28. Huang J, Zhang W, Qiao W, Hu A, Wang Z. Functional connectivity and selective odor responses of excitatory local interneurons in Drosophila antennal lobe. Neuron. 2010;67:1021-33 pubmed publisher
  29. Maiti T, Maitra U. Characterization of translation initiation factor 5 (eIF5) from Saccharomyces cerevisiae. Functional homology with mammalian eIF5 and the effect of depletion of eIF5 on protein synthesis in vivo and in vitro. J Biol Chem. 1997;272:18333-40 pubmed
    ..Additionally, we show that rat eIF5 can functionally substitute yeast eIF5 in translation of mRNAs in vitro as well as in complementing in vivo a genetic disruption in the chromosomal copy of TIF5. ..
  30. Asano K, Clayton J, Shalev A, Hinnebusch A. A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo. Genes Dev. 2000;14:2534-46 pubmed
    ..We propose that the multifactor complex is an important intermediate in translation initiation in vivo. ..
  31. Painter J, Merritt E. Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr D Biol Crystallogr. 2006;62:439-50 pubmed
    ..The models generated by TLSMD analysis can significantly improve the standard crystallographic residuals R and R(free) and can reveal intrinsic dynamic properties of the protein. ..
  32. Raychaudhuri P, Chevesich J, Ghosh S, Maitra U. Characterization of eukaryotic initiation factor 5 from rabbit reticulocytes. Evidence that the initiation factor is a monomeric protein of Mr of about 58,000-62,000. J Biol Chem. 1987;262:14222-7 pubmed
    b>Eukaryotic initiation factor 5 (eIF-5) has been purified from the ribosomal salt-wash proteins of rabbit reticulocyte lysates...
  33. Asano K, Krishnamoorthy T, Phan L, Pavitt G, Hinnebusch A. Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2. EMBO J. 1999;18:1673-88 pubmed
    ..Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S pre-initiation complex through interaction with eIF3 in addition to binding of its substrate eIF2. ..
  34. Lee C, Park M. Human deoxyhypusine synthase: interrelationship between binding of NAD and substrates. Biochem J. 2000;352 Pt 3:851-7 pubmed
  35. Asano K, Shalev A, Phan L, Nielsen K, Clayton J, VALASEK L, et al. Multiple roles for the C-terminal domain of eIF5 in translation initiation complex assembly and GTPase activation. EMBO J. 2001;20:2326-37 pubmed
  36. Pestova T, Lomakin I, Lee J, Choi S, Dever T, Hellen C. The joining of ribosomal subunits in eukaryotes requires eIF5B. Nature. 2000;403:332-5 pubmed
    ..It is a homologue of the prokaryotic initiation factor IF2 (re and, like it, mediates joining of subunits and has a ribosome-dependent GTPase activity that is essential for its function. ..
  37. Maiti T, Das S, Maitra U. Isolation and functional characterization of a temperature-sensitive mutant of the yeast Saccharomyces cerevisiae in translation initiation factor eIF5: an eIF5-dependent cell-free translation system. Gene. 2000;244:109-18 pubmed
  38. Nika J, Rippel S, Hannig E. Biochemical analysis of the eIF2beta gamma complex reveals a structural function for eIF2alpha in catalyzed nucleotide exchange. J Biol Chem. 2001;276:1051-6 pubmed
    ..We suggest that this function contributes to the ability of the alpha-subunit to control the rate of nucleotide exchange through reversible phosphorylation. ..
  39. Homma M, Wada I, Suzuki T, Yamaki J, Krebs E, Homma Y. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression. Proc Natl Acad Sci U S A. 2005;102:15688-93 pubmed
    ..These results suggest that CK2 may be involved in the regulation of cell cycle progression by associating with and phosphorylating a key molecule for translation initiation. ..
  40. Das S, Ghosh R, Maitra U. Eukaryotic translation initiation factor 5 functions as a GTPase-activating protein. J Biol Chem. 2001;276:6720-6 pubmed
    ..The implications of these results in relation to other well characterized GAPs are discussed and provide additional evidence that eIF5 functions as a GTPase-activating protein. ..
  41. Yamamoto Y, Singh C, Marintchev A, Hall N, Hannig E, Wagner G, et al. The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G. Proc Natl Acad Sci U S A. 2005;102:16164-9 pubmed
    ..These results indicate that the eIF5 HEAT domain is a critical nucleation core for preinitiation complex assembly and function. ..
  42. Maag D, Algire M, Lorsch J. Communication between eukaryotic translation initiation factors 5 and 1A within the ribosomal pre-initiation complex plays a role in start site selection. J Mol Biol. 2006;356:724-37 pubmed
    ..These data suggest strongly that the interaction between eIF1A and eIF5 is involved in maintaining the fidelity of start codon recognition in vivo. ..
  43. Das S, Maitra U. Functional significance and mechanism of eIF5-promoted GTP hydrolysis in eukaryotic translation initiation. Prog Nucleic Acid Res Mol Biol. 2001;70:207-31 pubmed
    ..This invariant arginine residue is presumably involved in the stabilization of the transition state of the GTP hydrolysis reaction catalyzed by initiation factor eIF2. ..
  44. Inoue Y, Matsuda T, Sugiyama K, Izawa S, Kimura A. Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae. J Biol Chem. 1999;274:27002-9 pubmed
    ..Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Delta mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase. ..
  45. Singh C, Udagawa T, Lee B, Wassink S, He H, Yamamoto Y, et al. Change in nutritional status modulates the abundance of critical pre-initiation intermediate complexes during translation initiation in vivo. J Mol Biol. 2007;370:315-30 pubmed
    ..Interestingly, the TC increase is suppressed by eIF5 overexpression and Gcn2p expression. Thus, eIF2B-catalyzed TC formation appears to be fine-tuned by eIF2 phosphorylation and the novel eIF2/eIF5 complex lacking tRNA(i)(Met). ..
  46. Kapp L, Kolitz S, Lorsch J. Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation. RNA. 2006;12:751-64 pubmed
  47. Choi S, Olsen D, Roll Mecak A, Martung A, Remo K, Burley S, et al. Physical and functional interaction between the eukaryotic orthologs of prokaryotic translation initiation factors IF1 and IF2. Mol Cell Biol. 2000;20:7183-91 pubmed
  48. Ghosh S, Chevesich J, Maitra U. Further characterization of eukaryotic initiation factor 5 from rabbit reticulocytes. Immunochemical characterization and phosphorylation by casein kinase II. J Biol Chem. 1989;264:5134-40 pubmed
    ..Based on its specific activity, we demonstrate that 1 pmol of rabbit reticulocyte eIF-5 mediates the formation of approximately 180 pmol of 80 S initiation complex under the conditions of in vitro initiation reactions. ..
  49. Wei Z, Xue Y, Xu H, Gong W. Crystal structure of the C-terminal domain of S.cerevisiae eIF5. J Mol Biol. 2006;359:1-9 pubmed
    ..The structure of eIF5-CTD provides useful information in understanding the mechanism of the MFC assembly. ..
  50. Huang H, Yoon H, Hannig E, Donahue T. GTP hydrolysis controls stringent selection of the AUG start codon during translation initiation in Saccharomyces cerevisiae. Genes Dev. 1997;11:2396-413 pubmed
  51. Sørensen H, Hedegaard J, Sperling Petersen H, Mortensen K. Remarkable conservation of translation initiation factors: IF1/eIF1A and IF2/eIF5B are universally distributed phylogenetic markers. IUBMB Life. 2001;51:321-7 pubmed
    ..Because of these two application levels, IF1/eIF1A-IF2/eIF5B is a phylogenetic "dual level" marker. ..
  52. Singh C, Yamamoto Y, Asano K. Physical association of eukaryotic initiation factor (eIF) 5 carboxyl-terminal domain with the lysine-rich eIF2beta segment strongly enhances its binding to eIF3. J Biol Chem. 2004;279:49644-55 pubmed
    ..We propose that the primary function of eIF5-CTD is to serve as an assembly guide by rapidly promoting stoichiometric MFC assembly with the aid of eIF2 while excluding formation of nonfunctional complexes. ..
  53. Ober D, Gibas L, Witte L, Hartmann T. Evidence for general occurrence of homospermidine in plants and its supposed origin as by-product of deoxyhypusine synthase. Phytochemistry. 2003;62:339-44 pubmed
    ..The synthesis of homospermidine as an enzymatic by-product of an essential enzyme is discussed in respect to the evolutionary origin of homospermidine synthase and the biosynthetic pathway of pyrrolizidine alkaloids. ..