Eukaryotic translation initiation factor 5 (EIF5)

The protein contains 431 amino acids for an estimated molecular weight of 49223 Da.

 

Catalyzes the hydrolysis of GTP bound to the 40S ribosomal initiation complex (40S.mRNA.Met-tRNA[F].eIF-2.GTP) with the subsequent joining of a 60S ribosomal subunit resulting in the release of eIF-2 and the guanine nucleotide. The subsequent joining of a 60S ribosomal subunit results in the formation of a functional 80S initiation complex (80S.mRNA.Met-tRNA[F]). (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.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 75%
Model score: 99

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VariantDescription
a breast cancer sample; somatic mutation

The reference OMIM entry for this protein is 601710

Eukaryotic translation initiation factor 5; eif5

DESCRIPTION

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).

CLONING

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.

GENE FUNCTION

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.

MAPPING

Hartz (2010) mapped the EIF5 gene to chromosome 14q32.32 based on an alignment of the EIF5 sequence (GenBank GENBANK U494936) with the genomic sequence (GRCh37). ... 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 601710 was added.

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