HGNC Approved Gene Symbol: EIF5
Cytogenetic location: 14q32.32 Genomic coordinates (GRCh38): 14:103,334,237-103,345,025 (from NCBI)
Eukaryotic translation initiation factor-5 (EIF5) interacts with the 40S initiation complex to promote hydrolysis of bound GTP with concomitant joining of the 60S ribosomal subunit to the 40S initiation complex. The resulting functional 80S ribosomal initiation complex is then active in peptidyl transfer and chain elongations (summary by Si et al., 1996).
Si et al. (1996) cloned the gene encoding human EIF5. The gene encodes a predicted 431-amino acid polypeptide that shares significant homology with the rat sequence. The authors also characterized multiple mRNAs expressed from the rat EIF5 gene and found that they differ only in the lengths of their 3-prime untranslated regions. The transcript length variations are tissue specific and arise from use of alternative polyadenylation signals.
Das et al. (2001) characterized recombinant rat Eif5. They identified an N-terminal GTPase-activating domain in addition to the C-terminal Eif2-beta (EIF2S2; 603908)-binding region. Mutation analysis revealed 1 critical arginine and 2 critical lysine residues near the N terminus that were essential for Eif5 function. Das et al. (2001) concluded that Eif5 functions as a GTPase-activating protein.
EIF5 functions in start site selection as a GTPase accelerating protein (GAP) for the EIF2-GTP-tRNAi(Met) ternary complex within the ribosome-bound preinitiation complex (summary by Jennings and Pavitt, 2010). Jennings and Pavitt (2010) defined new regulatory functions of EIF5 in the recycling of EIF2 from its inactive EIF2-GDP state between successive rounds of translation initiation. First, the authors showed that EIF5 stabilizes the binding of GDP to EIF2 and is therefore a bifunctional protein that acts as a GDP dissociation inhibitor (GDI). Jennings and Pavitt (2010) found that this activity is independent of the GAP function and identified conserved residues within EIF5 that are necessary for this role. In addition, Jennings and Pavitt (2010) showed that EIF5 is a critical component of the EIF2(alpha-P) regulatory complex that inhibits the activity of the guanine-nucleotide exchange factor (GEF) EIF2B (603908). Jennings and Pavitt (2010) concluded that their findings defined a new step in the translation initiation pathway, one that is critical for normal translational controls.
Hartz (2010) mapped the EIF5 gene to chromosome 14q32.32 based on an alignment of the EIF5 sequence (GenBank U494936) with the genomic sequence (GRCh37).
Das, S., Ghosh, R., Maitra, U. Eukaryotic translation initiation factor 5 functions as a GTPase-activating protein. J. Biol. Chem. 276: 6720-6726, 2001. [PubMed: 11092890] [Full Text: https://doi.org/10.1074/jbc.M008863200]
Hartz, P. A. Personal Communication. Baltimore, Md. 5/5/2010.
Jennings, M. D., Pavitt, G. D. eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature 465: 378-381, 2010. Note: Erratum: Nature 468: 122 only, 2010. [PubMed: 20485439] [Full Text: https://doi.org/10.1038/nature09003]
Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature of initiation, elongation and termination factors for translation in Eukaryotes. Recommendations 1988. Europ. J. Biochem. 186: 1-3, 1989. [PubMed: 2598922] [Full Text: https://doi.org/10.1111/j.1432-1033.1989.tb15169.x]
Si, K., Das, K., Maitra, U. Characterization of multiple mRNAs that encode mammalian translation initiation factor 5 (eIF-5). J. Biol. Chem. 271: 16934-16938, 1996. [PubMed: 8663286] [Full Text: https://doi.org/10.1074/jbc.271.28.16934]