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Function

Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts (PubMed:33547280). Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome (By similarity). Acts as a ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step (By similarity). Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity (PubMed:16987817). With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis (PubMed:15371445). Regulates also TNF-alpha-mediated apoptosis (PubMed:15452064, PubMed:17187778). Mediates effects of polyamines on neuronal process extension and survival (PubMed:17360499). Is required for autophagy by assisting the ribosome in translating the ATG3 protein at a specific amino acid sequence, the 'ASP-ASP-Gly' motif, leading to the increase of the efficiency of ATG3 translation and facilitation of LC3B lipidation and autophagosome formation (PubMed:29712776).

(Microbial infection) Cellular cofactor of human T-cell leukemia virus type I (HTLV-1) Rex protein and of human immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA export of retroviral transcripts.

Involvement in disease

Faundes-Banka syndrome

FABAS

An autosomal dominant disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphic features.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Acetylated by PCAF/KAT2B, regulating its subcellular localization (PubMed:19379712, PubMed:22771473). Deacetylated by SIRT2 (PubMed:22771473).

Lys-50 undergoes hypusination, a unique post-translational modification that consists in the addition of a butylamino group from spermidine to lysine side chain, leading to the formation of the unusual amino acid hypusine. eIF-5As are the only known proteins to undergo this modification, which is essential for their function.

Sequence similarities

Belongs to the eIF-5A family.

Tissue specificity

Expressed in umbilical vein endothelial cells and several cancer cell lines (at protein level).

Cellular localization

  • Cytoplasm
  • Nucleus
  • Endoplasmic reticulum membrane
  • Peripheral membrane protein
  • Cytoplasmic side
  • Hypusine modification promotes the nuclear export and cytoplasmic localization and there was a dynamic shift in the localization from predominantly cytoplasmic to primarily nuclear under apoptotic inducing conditions (PubMed:19379712, PubMed:27306458). Nuclear export of hypusinated protein is mediated by XPO4 (PubMed:10944119, PubMed:27306458).

Alternative names

Eukaryotic translation initiation factor 5A-1, eIF-5A-1, eIF-5A1, Eukaryotic initiation factor 5A isoform 1, Rev-binding factor, eIF-4D, eIF-5A, EIF5A

Target type

Proteins

Molecular weight

16832Da