Translation elongation factor IF5A-like (IPR001884)

Short name: IF5A-like

Overlapping homologous superfamilies

Family relationships


Eukaryotic eIF-5A was initially thought to function as a translation initiation factor, based on its ability to stimulate methionyl-puromycin synthesis. However, subsequent work revealed a role for eIF5A in translation elongation [PMID: 19424157, PMID: 28392174]. Depletion or inactivation of eIF-5A in the yeast Saccharomyces cerevisiae (Baker's yeast) resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF-5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF-5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF-5A might function together with eEF2 to promote ribosomal translocation. Finally, it was shown that eIF5A is specifically required to promote peptide-bond formation between consecutive proline residues. It has been proposed to stimulate the peptidyl-transferase activity of the ribosome and facilitate the reactivity of poor substrates like proline [PMID: 23727016].

eIF-5A is a cofactor for the Rev and Rex transactivator proteins of human immunodeficiency virus-1 and T-cell leukaemia virus I, respectively [PMID: 8347280, PMID: 1903841, PMID: 9753699]. IF-5A is the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (Ne-(4-amino-2-hydroxybutyl)lysine) that is an absolute functional requirement. The first step in the post-translational modification of lysine to hypusine is catalyzed by the enzyme deoxyhypusine synthase, the structure of which has been reported [PMID: 9493264].

The archaeal IF-5A proteins have not been studied as comprehensively as their eukaryotic homologues, though the crystal structure of the Pyrobaculum aerophilum protein has been determined. Unmodified P. aerophilum IF-5A is found to be a beta structure with two domains and three separate hydrophobic cores. The lysine (Lys42) that is post-translationally modified by deoxyhypusine synthase is found at one end of the IF-5A molecule in a turn between beta strands beta4 and beta5; this lysine residue is freely solvent accessible. The C-terminal domain is found to be homologous to the cold-shock protein CspA of E. coli, which has a well characterised RNA-binding fold, suggesting that IF-5A is involved in RNA binding [PMID: 9753699].

This family also includes the Woronin body major protein Hex1, whose sequence and structure are similar to eukaryotic initiation factor 5A (eIF5A), suggesting they share a common ancestor during evolution [PMID: 12640443].

GO terms

Biological Process

GO:0045901 positive regulation of translational elongation

Molecular Function

GO:0003723 RNA binding
GO:0043022 ribosome binding
GO:0003746 translation elongation factor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.