Gene Symbol: TIF5
Description: translation initiation factor eIF5
Alias: SUI5, translation initiation factor eIF5
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. 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. ..
  2. VALASEK L, Phan L, Schoenfeld L, Valášková V, Hinnebusch A. Related eIF3 subunits TIF32 and HCR1 interact with an RNA recognition motif in PRT1 required for eIF3 integrity and ribosome binding. EMBO J. 2001;20:891-904 pubmed
    ..Hence, the PRT1 RRM is crucial for the integrity and ribosome-binding activity of eIF3. ..
  3. 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
  4. Karásková M, Gunišová S, Herrmannová A, Wagner S, Munzarová V, Valášek L. Functional characterization of the role of the N-terminal domain of the c/Nip1 subunit of eukaryotic initiation factor 3 (eIF3) in AUG recognition. J Biol Chem. 2012;287:28420-34 pubmed publisher
    ..Together, our data indicate that binding of eIF1 to the c/Nip1-NTD is equally important for its initial recruitment to PICs and for its proper functioning in selecting the translational start site. ..
  5. Nanda J, Cheung Y, Takacs J, Martin Marcos P, Saini A, Hinnebusch A, et al. eIF1 controls multiple steps in start codon recognition during eukaryotic translation initiation. J Mol Biol. 2009;394:268-85 pubmed publisher
    ..Our data indicate that eIF1 plays multiple roles in start codon recognition and suggest that prior to AUG recognition it prevents eIF5 from binding to a key site in the PIC required for triggering downstream events. ..
  6. 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
    ..The multifactor complex was disrupted by the tif5-7A mutation in the bipartite motif of eIF5...
  7. Singh C, Curtis C, Yamamoto Y, Hall N, Kruse D, He H, et al. Eukaryotic translation initiation factor 5 is critical for integrity of the scanning preinitiation complex and accurate control of GCN4 translation. Mol Cell Biol. 2005;25:5480-91 pubmed
    ..in GCN4 translational control, we isolated mutations leading to temperature sensitivity (Ts- phenotype) targeted at TIF5, the structural gene encoding eIF5 in yeast (Saccharomyces cerevisiae)...
  8. 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. ..
  9. Kouba T, Dányi I, Gunišová S, Munzarová V, Vlčková V, Cuchalová L, et al. Small ribosomal protein RPS0 stimulates translation initiation by mediating 40S-binding of eIF3 via its direct contact with the eIF3a/TIF32 subunit. PLoS ONE. 2012;7:e40464 pubmed publisher
    ..Together we conclude that the interaction between the flexible RPS0A-CTT and the residues 200-400 of the a/TIF32-NTD significantly stimulates attachment of eIF3 and its associated eIFs to small ribosomal subunits in vivo. ..

More Information


  1. 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. ..
  2. Jennings M, Pavitt G. eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature. 2010;465:378-81 pubmed publisher
    ..Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls. ..
  3. Singh C, Lee B, Udagawa T, Mohammad Qureshi S, Yamamoto Y, Pavitt G, et al. An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during translation initiation. EMBO J. 2006;25:4537-46 pubmed
    ..We propose that the eIF2/eIF5 complex represents a cytoplasmic reservoir for eIF2 that antagonizes eIF2B-promoted guanine nucleotide exchange, enabling coordinated regulation of translation initiation. ..
  4. Alone P, Dever T. Direct binding of translation initiation factor eIF2gamma-G domain to its GTPase-activating and GDP-GTP exchange factors eIF5 and eIF2B epsilon. J Biol Chem. 2006;281:12636-44 pubmed
  5. 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. ..
  6. Chiu W, Wagner S, Herrmannová A, Burela L, Zhang F, Saini A, et al. The C-terminal region of eukaryotic translation initiation factor 3a (eIF3a) promotes mRNA recruitment, scanning, and, together with eIF3j and the eIF3b RNA recognition motif, selection of AUG start codons. Mol Cell Biol. 2010;30:4415-34 pubmed publisher
  7. 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
    ..were also defective in overall protein synthesis as well as in their ability to support cell growth of a Delta TIF5 yeast strain...
  8. 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. ..
  9. VALASEK L, Nielsen K, Zhang F, Fekete C, Hinnebusch A. Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection. Mol Cell Biol. 2004;24:9437-55 pubmed
    ..Thus, the NIP1-NTD is required for efficient assembly of preinitiation complexes and also regulates the selection of AUG start codons in vivo. ..
  10. VALASEK L, Nielsen K, Hinnebusch A. Direct eIF2-eIF3 contact in the multifactor complex is important for translation initiation in vivo. EMBO J. 2002;21:5886-98 pubmed
  11. 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
    ..The tif5-7A mutation in eIF5-CTD, which destabilizes the multifactor complex in vivo, reduced the binding of Met-tRNA(i)(Met)..
  12. 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. ..
  13. Fringer J, Acker M, Fekete C, Lorsch J, Dever T. Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joining. Mol Cell Biol. 2007;27:2384-97 pubmed
    ..Following 80S complex formation, GTP hydrolysis by eIF5B enables the release of both eIF5B and eIF1A, and the ribosome enters the elongation phase of protein synthesis. ..
  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. Farley A, Powell D, Weaver C, Jennings J, Link A. Assessing the components of the eIF3 complex and their phosphorylation status. J Proteome Res. 2011;10:1481-94 pubmed publisher
    ..2-D LC-MS/MS analysis of affinity purified eIF3 complexes showed that several other initiation factors (Fun12, Tif5, Sui3, Pab1, Hcr1, and Sui1) and the casein kinase 2 complex (CK2) copurify...
  16. Gilbert R, Gordiyenko Y, von der Haar T, Sonnen A, Hofmann G, Nardelli M, et al. Reconfiguration of yeast 40S ribosomal subunit domains by the translation initiation multifactor complex. Proc Natl Acad Sci U S A. 2007;104:5788-93 pubmed
    ..This is expected to increase the accessibility of the mRNA channel, thus enabling the 40S subunit to convert to a recruitment-competent state. ..
  17. Martin Marcos P, Cheung Y, Hinnebusch A. Functional elements in initiation factors 1, 1A, and 2? discriminate against poor AUG context and non-AUG start codons. Mol Cell Biol. 2011;31:4814-31 pubmed publisher
    ..Although eIF1 autoregulates by discriminating against poor context in yeast and mammals, this mechanism does not prevent eIF1 overproduction in yeast, accounting for the hyperaccuracy phenotype afforded by SUI1 overexpression. ..
  18. Daugeron M, Lenstra T, Frizzarin M, El Yacoubi B, Liu X, Baudin Baillieu A, et al. Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC/KEOPS in the t6A modification of tRNAs. Nucleic Acids Res. 2011;39:6148-60 pubmed publisher
    ..Overall, our data provide a novel twist to understanding the primary function of the EKC/KEOPS and its impact on several essential cellular functions like transcription and telomere homeostasis. ..
  19. Jennings M, Kershaw C, Adomavicius T, Pavitt G. Fail-safe control of translation initiation by dissociation of eIF2? phosphorylated ternary complexes. elife. 2017;6: pubmed publisher
    ..These data uncover competition between eIF2B and eIF5 for TC and identify that phosphorylated eIF2-GTP translation initiation intermediate complexes can be inhibited by eIF2B. ..
  20. Luna R, Arthanari H, Hiraishi H, Akabayov B, Tang L, Cox C, et al. The interaction between eukaryotic initiation factor 1A and eIF5 retains eIF1 within scanning preinitiation complexes. Biochemistry. 2013;52:9510-8 pubmed publisher
    ..These results suggest that the eIF1A-eIF5-CTD interaction during scanning PICs contributes to the maintenance of eIF1 within the open PIC...
  21. 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
    ..The yeast gene that encodes eIF-5, designated TIF5, has been isolated and expressed in Escherichia coli to yield a catalytically active eIF-5 protein...
  22. Algire M, Maag D, Savio P, Acker M, Tarun S, Sachs A, et al. Development and characterization of a reconstituted yeast translation initiation system. RNA. 2002;8:382-97 pubmed
  23. Zhou M, Sandercock A, Fraser C, Ridlova G, Stephens E, Schenauer M, et al. Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3. Proc Natl Acad Sci U S A. 2008;105:18139-44 pubmed publisher
  24. Fekete C, Mitchell S, Cherkasova V, Applefield D, Algire M, Maag D, et al. N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selection. EMBO J. 2007;26:1602-14 pubmed
    ..We conclude that tight binding of eIF1A to the PIC is an important determinant of AUG selection and is modulated in opposite directions by residues in the NTT and CTT of eIF1A. ..
  25. 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
    ..In vivo, overexpression of eIF2 and tRNA(Met)(i) suppresses the temperature-sensitive phenotype of tif5-7A altering eIF5-CTD by increasing interaction of the mutant eIF5 with eIF2 by mass action and restoring its ..
  26. Gai Z, Kitagawa Y, Tanaka Y, Shimizu N, Komoda K, Tanaka I, et al. The binding mechanism of eIF2? with its partner proteins, eIF5 and eIF2B?. Biochem Biophys Res Commun. 2012;423:515-9 pubmed publisher
    ..Such flexibility of eIF2?-NTD is expected to be responsible for its binding capability. ..
  27. Singh C, Watanabe R, Chowdhury W, Hiraishi H, Murai M, Yamamoto Y, et al. Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2? stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode. Mol Cell Biol. 2012;32:3978-89 pubmed publisher
  28. Martin Marcos P, Nanda J, Luna R, Zhang F, Saini A, Cherkasova V, et al. Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements of the preinitiation complex and elevates initiation accuracy. RNA. 2014;20:150-67 pubmed publisher
  29. Jennings M, Zhou Y, Mohammad Qureshi S, Bennett D, Pavitt G. eIF2B promotes eIF5 dissociation from eIF2*GDP to facilitate guanine nucleotide exchange for translation initiation. Genes Dev. 2013;27:2696-707 pubmed publisher
    ..We propose a new model to place eIF2B GDF function in the context of efficient eIF2 recycling and its regulation by eIF2 phosphorylation...
  30. He H, von der Haar T, Singh C, Ii M, Li B, Hinnebusch A, et al. The yeast eukaryotic initiation factor 4G (eIF4G) HEAT domain interacts with eIF1 and eIF5 and is involved in stringent AUG selection. Mol Cell Biol. 2003;23:5431-45 pubmed
    ..These results strongly suggest that the binding of the eIF4G HEAT domain to eIF1 and eIF5 is important for maintaining the integrity of the scanning ribosomal preinitiation complex. ..
  31. 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. ..
  32. Bavli Kertselli I, Melamed D, Bar Ziv L, Volf H, Arava Y. Overexpression of eukaryotic initiation factor 5 rescues the translational defect of tpk1w in a manner that necessitates a novel phosphorylation site. FEBS J. 2015;282:504-20 pubmed publisher
    ..These results implicate phosphorylation of eIF5 at Thr191 by CKII as one of the pathways for regulating translation upon glucose depletion. ..
  33. Das S, Maiti T, Das K, Maitra U. Specific interaction of eukaryotic translation initiation factor 5 (eIF5) with the beta-subunit of eIF2. J Biol Chem. 1997;272:31712-8 pubmed
    ..eIF2.GTP ternary complex, and (b) eIF5 forms a specific complex with eIF2 suggests that the specific interaction between eIF5 and the beta subunit of eIF2 may be critical for the hydrolysis of GTP during translation initiation. ..
  34. Hinnebusch A, Asano K, Olsen D, Phan L, Nielsen K, VALASEK L. Study of translational control of eukaryotic gene expression using yeast. Ann N Y Acad Sci. 2004;1038:60-74 pubmed
    ..Thus, apart from its critical role in the starvation response, GCN4 regulation is a valuable tool for dissecting the contributions of multiple translation factors in the eukaryotic initiation pathway. ..
  35. Singh C, Watanabe R, Zhou D, Jennings M, Fukao A, Lee B, et al. Mechanisms of translational regulation by a human eIF5-mimic protein. Nucleic Acids Res. 2011;39:8314-28 pubmed publisher
    ..Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function. ..
  36. Ghosh A, Jindal S, Bentley A, Hinnebusch A, Komar A. Rps5-Rps16 communication is essential for efficient translation initiation in yeast S. cerevisiae. Nucleic Acids Res. 2014;42:8537-55 pubmed publisher
    ..of 48S PICs to 80S initiation complexes (ICs) and this abnormality and related phenotypes are mitigated by the SUI5 variant of eIF5...