Eukaryotic translation initiation factor 6 (EIF6)
The protein contains 245 amino acids for an estimated molecular weight of 26599 Da.
Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity). (updated: Dec. 20, 2017)
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.
- 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.
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
Assembly of large subunit precursor of preribosome
Gene silencing by miRNA
Maturation of 5.8S rRNA
Maturation of LSU-rRNA
Mature ribosome assembly
MiRNA mediated inhibition of translation
Positive regulation of translation
Regulation of fatty acid biosynthetic process
Regulation of glycolytic process
Regulation of megakaryocyte differentiation
Regulation of reactive oxygen species metabolic process
Response to insulin
Ribosomal large subunit biogenesis
Ribosomal subunit export from nucleus
The reference OMIM entry for this protein is 602912
Eukaryotic translation initiation factor 6; eif6
Integrin, beta-4, binding protein of; itgb4bp
P27, beta-4 integrin-binding protein; p27bbp
Eukaryotic translation initiation factor 3a; eif3a
CLONING
The integrin beta-4 subunit (ITGB4; 147557) is highly enriched in hemidesmosomes, specialized structures providing firm mechanical links between basal lamina and the intermediate filament cytoskeleton. A 303-amino acid segment of the ITGB4 cytoplasmic domain that encompasses the first 2 N-terminal fibronectin type III (FNIII) domains and their interconnecting sequence is necessary for mediating ITGB4 signaling events and incorporation into hemidesmosomes. Using a yeast 2-hybrid system to identify polypeptides that interact with this functional region of the ITGB4 cytodomain, Biffo et al. (1997) isolated human epithelial cell cDNAs encoding ITGB4-binding protein (ITGB4BP), which they called p27BBP. Southern blot analysis showed that the human genome contains a single copy of the ITGB4BP gene. Northern blot analysis and in situ hybridization detected Itgb4bp mRNA in all mouse tissues examined, with the highest levels mainly in proliferating epithelia and in epithelial tissues containing Itgb4. The predicted human ITGB4BP protein has 245 amino acids and lacks a signal sequence. Western blot analysis using antibodies against ITGB4BP detected a 27-kD protein in epithelial cell lysates, which is in agreement with the calculated molecular mass of ITGB4BP. Both in yeast and in vitro, ITGB4BP specifically bound to the first 2 FNIII domains of ITGB4. ITGB4BP is an insoluble protein that is present in the nucleus and cytoplasm. It is associated with the intermediate filament pool and is localized at the submembrane level in close apposition with ITGB4. The authors suggested that ITGB4BP links ITGB4 to the intermediate filament cytoskeleton. Eukaryotic translation initiation factor-6 (EIF6) binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. Using antibodies against purified rabbit EIF6 protein to immunoscreen a HeLa cell cDNA expression library, Si et al. (1997) isolated a cDNA encoding EIF6. Northern blot analysis detected an approximately 1.1-kb transcript in all human tissues examined.GENE FUNCTION
Ceci et al. (2003) demonstrated that the ribosomal 60S subunit is activated by release of EIF6. In the cytoplasm, EIF6 is bound to free 60S but not to 80S subunits. Furthermore, EIF6 interacts in the cytoplasm with RACK1 (176981), a receptor for activated protein kinase C (PKC; see 176960). RACK1 is a major component of translating ribosomes, which harbor significant amounts of PKC. Loading 60S subunits with EIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to EIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of EIF6 impaired RACK1/PKC-mediated translational rescue. Ceci et al. (2003) proposed that EIF6 release regulates subunit joining, and that RACK1 provides a physical and functional link between PKC signaling and ribosome activation. To elucidate how microRNAs mediate their repressive effects, Chendrimada et al. (2007) performed biochemical and functional assays to identify new factors in the microRNA pathway. Chendrimada et al. (2007) showed that human RISC (RNA-induced silencing complex) associated with a multiprotein complex containing MOV10 (610742), the homolog of Drosophila translational repressor Armitage, and proteins of the 60S ribosome subunit. Notably, this complex contains the antiassociation fa ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 602912 was added.