Eukaryotic translation initiation factor 3 subunit A (EIF3A)
The protein contains 1382 amino acids for an estimated molecular weight of 166569 Da.
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632, PubMed:11169732). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815).', '(Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634).', '(Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs967185 | |
| dbSNP:rs431898 | |
| dbSNP:rs532138 |
Biological Process
Formation of cytoplasmic translation initiation complex
IRES-dependent viral translational initiation
Negative regulation of ERK1 and ERK2 cascade
Translation reinitiation
Translational initiation
Viral translational termination-reinitiation
Cellular Component
Cytoplasm
Cytosol
Eukaryotic 43S preinitiation complex
Eukaryotic 48S preinitiation complex
Eukaryotic translation initiation factor 3 complex
Eukaryotic translation initiation factor 3 complex, eIF3e
Eukaryotic translation initiation factor 3 complex, eIF3m
Membrane
Microtubule
Multi-eIF complex
Nucleolus
Nucleoplasm
Nucleus
Postsynaptic density
The reference OMIM entry for this protein is 602039
Eukaryotic translation initiation factor 3, subunit a; eif3a
Eukaryotic translation initiation factor 3, theta; eif3-theta
Eif3, p180 subunit
Eif3, p170 subunit
Cytoplasmic protein p167
Centrosomin b, mouse, homolog of
Eukaryotic translat
Eukaryotic translation initiation factors (EIFs) initiate protein synthesis from mRNAs. EIF3, at 650 kD, is the largest of the EIFs. According to Johnson et al. (1997), EIF3 has been implicated in several roles, including binding to the 40S ribosomal subunit and to other EIFs, possibly to align the factors for initial binding to the 40S subunit and the subsequent identification of the AUG initiation codon. The EIF3 protein synthesis initiation factor is composed of at least 8 subunits, the largest of which is p180.
CLONING
Nagase et al. (1995) identified an open reading frame with significant homology to mouse centrosomin B. Nagase et al. (1995) noted that this clone, which they termed KIAA0139, was ubiquitously expressed and contained 21 units of an unusual 10-amino acid repeat. The full-length cDNA was later cloned and characterized independently by Johnson et al. (1997) and Scholler and Kanner (1997). Johnson et al. (1997) used expression screening of a human liver cDNA library to isolate a clone, which they termed p180. The cDNA predicted a protein of 1,382 amino acids, which Johnson et al. (1997) identified as the human homolog of centrosomin, the large subunit of mouse eif3. Johnson et al. (1997) also showed that p180 has homologs in yeast, nematodes, and plants. Scholler and Kanner (1997) used expression screening of a human T-cell cDNA library to isolate a clone, termed p167 by them, that was nearly identical to that isolated by Johnson et al. (1997). Scholler and Kanner (1997) showed that p167 was a cytoplasmic protein that is not phosphorylated and is part of a multisubunit complex.GENE FUNCTION
Using a library of endoribonuclease-prepared short interfering RNAs (esiRNAs), Kittler et al. (2004) identified 37 genes required for cell division, one of which was EIF3S10. These 37 genes included several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown. Holz et al. (2005) showed that MTOR (FRAP1; 601231) and S6K1 (RPS6KB1; 608938) maneuvered on and off the EIF3 translation initiation complex in HEK293 cells in a signal-dependent, choreographed fashion. When inactive, S6K1 associated with the EIF3 complex, while the S6K1 activator MTOR, in association with its binding partner RAPTOR (607130), did not. Hormone- or mitogen-mediated cell stimulation promoted MTOR/RAPTOR binding to the EIF3 complex and phosphorylation of S6K1. Phosphorylation resulted in S6K1 dissociation and activation, followed by phosphorylation of S6K1 targets, including EIF4B (603928), which, upon phosphorylation, was recruited into the EIF3 complex. Holz et al. (2005) concluded that the EIF3 preinitiation complex acts as a scaffold to coordinate responses to stimuli that promote efficient protein synthesis.MAPPING
Nagase et al. (1995) mapped the KIAA0139 clone to human chromosome 10. By FISH, Ensinger et al. (1998) mapped the EIF3A gene to 10q26. ... More on the omim web site
July 5, 2019: Protein entry updated
Automatic update: OMIM entry 602039 was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).