Eukaryotic translation initiation factor 3 subunit E (EIF3E)
The protein contains 445 amino acids for an estimated molecular weight of 52221 Da.
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, PubMed:27462815). 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). 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). Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway (PubMed:17468741). May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins (PubMed:17310990, PubMed:17324924). (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:rs17856554 |
Biological Process
Formation of cytoplasmic translation initiation complex
Negative regulation of translational initiation
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Positive regulation of mRNA binding
Positive regulation of translation
Regulation of translational initiation
Translational initiation
The reference OMIM entry for this protein is 602210
Eukaryotic translation initiation factor 3, subunit e; eif3e
Eukaryotic translation initiation factor 3, 48-kd; eif3-p48
Oncogene int6; int6
Eukaryotic translation initiation factor 3, subunit 6, formerly; eif3s6, formerly mouse mammary tumor v
CLONING
Eukaryotic initiation factor-3 (eIF3) is the largest of the eIFs and consists of at least 10 nonidentical subunits in mammals. See p66 (EIF3S7; 603915). By searching an EST database with the partial protein sequence of the rabbit eIF3-p48 subunit, Asano et al. (1997) identified cDNAs encoding human p48. The predicted human p48 protein contains 445 amino acids. Recombinant p48 coimmunoprecipitated with eIF3 and with the eIF3-p170 (602039) subunit. Northern blot analysis revealed that p48 is expressed as a 1.6-kb mRNA in HeLa cells. Asano et al. (1997) found that human p48 is identical to the mouse int6 gene product. The mouse int6 gene is a site where mouse mammary tumor virus (MMTV) frequently integrates, which may result in the expression of a truncated int6 protein. These authors also noted that int6 has been identified as a human protein that binds to the human T-cell leukemia virus type I Tax protein, leading to the translocation of int6 from the nucleus to the cytoplasm. They proposed models for p48 oncoprotein function. Miyazaki et al. (1997) presented the complete nucleotide sequence of the human homolog of Int6. The deduced amino acid sequence of the human gene product is identical to the mouse protein and contains 3 potential translation start signals.GENE FUNCTION
Yin6 is a yeast homolog of human INT6, which is implicated in tumorigenesis. Yen et al. (2003) showed that Yin6 binds to and regulates proteasome activity. Overexpression of Yin6 strengthened proteasome function, while inactivation weakened it and caused the accumulation of polyubiquitinated proteins, including Cut2/securin (PTTG1; 604147) and Cdc13/cyclin B (CCNB1; 123836). Yin6 regulated the proteasome by preferentially interacting with Rpn5 (PSMD12; 604450), a conserved proteasome subunit, and affecting its localization/assembly. Yin6 also cooperated with Ras1 (190020) to mediate chromosome segregation; Ras1 similarly regulated the proteasome via Rpn5. In yeast, human INT6 bound Rpn5 and regulated its localization. The authors concluded that human INT6, either alone or cooperatively with RAS, influences proteasome activities via RPN5. They proposed that inactivation of INT6 can lead to accumulation of mitotic regulators affecting cell division and mitotic fidelity.GENE STRUCTURE
Miyazaki et al. (1997) determined that the INT6 gene contains 13 exons that span 45 kb of genomic DNA.MAPPING
Miyazaki et al. (1997) mapped the human INT6 gene to 8q22-q23 by analysis of a Chinese hamster/human somatic cell hybrid in which the only human complement was chromosome 8. They had previously shown that mouse Int6 is located on chromosome 15, 16 cM centromeric of the Myc locus (190080). This region of mouse chromosome 15 is conserved on human chromosome 8q. The processed INT6 pseudogene was localized to 6q.MOLECULAR GENETICS
To determine whether INT6 is a target for mutation during tumor development, Miyazaki et al. (1997) surveyed 100 primary breast tumor DNAs. They found loss of heterozygosity (LOH) in 11 of 39 (28%) of primary breast carcinoma DNAs that were informative for a polymorphic sequence in intron 7 of INT6. Single-strand conformation and hybrid mismatch analyses of the remaining allele in these tumor DNAs failed to detect any mutations. ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 602210 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).