Eukaryotic initiation factor 4A-I (EIF4A1)
The protein contains 406 amino acids for an estimated molecular weight of 46154 Da.
ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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Biological Process
Animal organ regeneration
Cellular protein metabolic process
Cytokine-mediated signaling pathway
Cytoplasmic translational initiation
Gene expression
Nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Nuclear-transcribed mRNA poly(A) tail shortening
Regulation of gene expression
RNA secondary structure unwinding
Translation
Translational initiation
Viral process
The reference OMIM entry for this protein is 602641
Eukaryotic translation initiation factor 4a, isoform 1; eif4a1
Ddx2a
CLONING
The eukaryotic initiation factor-4A family consists of 2 closely related genes, EIF4A1 and EIF4A2 (601102). These factors are required for the binding of mRNA to 40S ribosomal subunits. Nielsen et al. (1985) cloned eif4a1 cDNAs from mouse liver. They identified 2 distinct cDNAs differing in their untranslated regions. The sizes of these cDNAs correspond to 2 discrete mRNA bands of 2.0 and 1.6 kb seen on Northern blots of both mouse and human cells. Nielsen and Trachsel (1988) found that eif4a1 was expressed at similar levels in all mouse tissues examined, while eif4a2 had a much more varied pattern of expression. Kim et al. (1993) cloned the human EIF4A1 cDNA. The EIF4A1 cDNA encodes a predicted 406-amino acid polypeptide with 92.7% amino acid similarity to the mouse protein. Kukimoto et al. (1997) characterized the promoter region of human EIF4A1. The minimal promoter contains TATA and CAAT motifs and consensus sequences for binding to SP1 and AP2.MAPPING
By fluorescence in situ hybridization, Jones et al. (1998) mapped the linked EIF4A1 and CD68 (153634) genes to 17p13. By interspecific backcross analysis, they mapped the mouse Eif4a1 and Cd68 genes to chromosome 11.GENE FUNCTION
Cruz-Migoni et al. (2011) found that BPSL1549, a Burkholderia pseudomallei toxin, promotes deamidation of glu339 of the translation initiation factor Eif4a, abolishing its helicase activity and inhibiting translation. Wolfe et al. (2014) reported an EIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, EIF4A promotes T-cell acute lymphoblastic leukemia development in vivo and is required for leukemia maintenance. Accordingly, inhibition of EIF4A with silvestrol has powerful therapeutic effects against murine and human leukemic cells in vitro and in vivo. Wolfe et al. (2014) used transcriptome-scale ribosome footprinting to identify the hallmarks of EIF4A-dependent transcripts. These include 5-prime untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most EIF4A-dependent and silvestrol-sensitive transcripts were a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Wolfe et al. (2014) concluded that the 5-prime UTRs of select cancer genes harbor a targetable requirement for the EIF4A RNA helicase. Boussemart et al. (2014) demonstrated that the persistent formation of the eIF4F complex, comprising the eIF4E (133440) cap-binding protein, the eIF4G (600495) scaffolding protein, and the eIF4A RNA helicase, is associated with resistance to anti-BRAF (164757), anti-MEK (176872), and anti-BRAF plus anti-MEK drug combinations in BRAF(V600) (164757.0001)-mutant melanoma, colon, and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with 1 of 3 mechanisms: reactivation of MAPK (see 176948) signaling; persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 (602223); or increased proapoptotic BMF (606266)-dependent degradation of eIF4G. The development of an in situ method to detect the eIF4E-eIF4G interactions showed that eIF4F complex formation is decreased in tumors that respond to anti-BRAF therapy and increased in resistant metastases compared to tumors before treatme ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602641 was added.