Eukaryotic translation initiation factor 5A-1 (EIF5A)

The protein contains 154 amino acids for an estimated molecular weight of 16832 Da.

 

mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. 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. With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis. Regulates also TNF-alpha-mediated apoptosis. Mediates effects of polyamines on neuronal process extension and survival. May play an important role in brain development and function, and in skeletal muscle stem cell differentiation. Also described as a 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. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 52
MODL_MODELLER-9.18

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The reference OMIM entry for this protein is 600187

Eukaryotic translation initiation factor 5a; eif5a
Eif5a1

CLONING

The eukaryotic initiation factor 5A is an 18-kD protein composed of 154 amino acids. It contains a unique amino acid residue, hypusine, that is formed posttranslationally via the transfer and hydroxylation of the butylamino-group from the polyamine spermidine to a lys50 within the EIF5A protein. Koettnitz et al. (1994) isolated and characterized the human EIF5A pseudogene. Subsequently, Koettnitz et al. (1995) identified a genomic clone encoding a functional EIF5A. The authors showed that this sequence could successfully complement yeast carrying the HYP2 mutation (the homolog of EIF5A), whereas the pseudogenes could not.

GENE STRUCTURE

Koettnitz et al. (1995) found that the human EIF5A gene contains at least 4 exons and spans at least 4.8 kb.

GENE FUNCTION

Saini et al. (2009) used molecular genetic and biochemical studies to show that EIF5A promotes translation elongation. Depletion or inactivation of EIF5A in the yeast S. cerevisiae resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant EIF5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of EIF5A mimicked the effects of the EEF2 (130610) inhibitor sordarin, indicating that EIF5A might function together with EEF2 to promote ribosomal translocation. Because EIF5A is a structural homolog of the bacterial protein EF-P, Saini et al. (2009) proposed that EIF5A/EF-P is a universally conserved translation elongation factor. To identify tumor suppressor genes in lymphoma (605027), Scuoppo et al. (2012) screened a short hairpin RNA library targeting genes deleted in human lymphomas and functionally confirmed those in a mouse lymphoma model. Of the 9 tumor suppressors identified, 8 corresponded to genes occurring in 3 physically linked 'clusters,' suggesting that the common occurrence of large chromosomal deletions in human tumors reflects selective pressure to attenuate multiple genes. Among the newly identified tumor suppressors were adenosylmethionine decarboxylase-1 (AMD1; 180980) and eukaryotic translation initiation factor 5A (eIF5A), 2 genes associated with hypusine, a unique amino acid produced as a product of polyamine metabolism through a highly conserved pathway. Through a secondary screen surveying the impact of all polyamine enzymes on tumorigenesis, Scuoppo et al. (2012) established the polyamine-hypusine axis as a new tumor suppressor network regulating apoptosis. Unexpectedly, heterozygous deletions encompassing AMD1 and eIF5A often occur together in human lymphomas, and cosuppression of both genes promotes lymphomagenesis in mice. Thus, Scuoppo et al. (2012) concluded that some tumor suppressor functions can be disabled through a 2-step process targeting different genes acting in the same pathway. Translation elongation factor P (EF-P) is critical for virulence in bacteria. EF-P is present in all bacteria and orthologous to archaeal and eukaryotic initiation factor 5A (a/eIF5A). Ude et al. (2013) demonstrated that EF-P is an elongation factor that enhances translation of polyproline-containing proteins: in the absence of EF-P, ribosomes stall at polyproline stretches, whereas the presence of EF-P alleviates the translational stalling. Moreover, Ude et al. (2013) demonstrated the physiologic relevance of EF-P to fine-tune the expression of the polyproline-containing pH receptor CadC to levels necessary for ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for EIF5A

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600187 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed