Alternative titles; symbols
HGNC Approved Gene Symbol: EIF3A
Cytogenetic location: 10q26.11 Genomic coordinates (GRCh38): 10:119,033,670-119,080,817 (from NCBI)
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.
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.
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.
Nagase et al. (1995) mapped the KIAA0139 clone to human chromosome 10. By FISH, Ensinger et al. (1998) mapped the EIF3A gene to 10q26.
Ensinger, C., Obrist, P., Mikuz, G., Merkx, G., Smeets, D., Banziger, R., Bachmann, F., Burger, M. Assignment of the p150 subunit of the eukaryotic initiation factor 3A gene (EIF3A) to human chromosome band 10q26 by in situ hybridisation. Cytogenet. Cell Genet. 83: 74-75, 1998. [PubMed: 9925932] [Full Text: https://doi.org/10.1159/000015130]
Holz, M. K., Ballif, B. A., Gygi, S. P., Blenis, J. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 123: 569-580, 2005. [PubMed: 16286006] [Full Text: https://doi.org/10.1016/j.cell.2005.10.024]
Johnson, K. R., Merrick, W. C., Zoll, W. L., Zhu, Y. Identification of cDNA clones for the large subunit of eukaryotic translation initiation factor 3: comparison of homologues from human, Nicotiana tabacum, Caenorhabditis elegans, and Saccharomyces cerevisiae. J. Biol. Chem. 272: 7106-7113, 1997. [PubMed: 9054404] [Full Text: https://doi.org/10.1074/jbc.272.11.7106]
Kittler, R., Putz, G., Pelletier, L., Poser, I., Heninger, A.-K., Drechsel, D., Fischer, S., Konstantinova, I., Habermann, B., Grabner, H., Yaspo, M.-L., Himmelbauer, H., Korn, B., Neugebauer, K., Pisabarro, M. T., Buchholz, F. An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 432: 1036-1040, 2004. [PubMed: 15616564] [Full Text: https://doi.org/10.1038/nature03159]
Nagase, T., Seki, N., Tanaka, A., Ishikawa, K., Nomura, N. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 2: 167-174, 1995. [PubMed: 8590280] [Full Text: https://doi.org/10.1093/dnares/2.4.167]
Scholler, J. K., Kanner, S. B. The human p167 gene encodes a unique structural protein that contains centrosomin A homology and associates with a multicomponent complex. DNA Cell Biol. 16: 515-531, 1997. [PubMed: 9150439] [Full Text: https://doi.org/10.1089/dna.1997.16.515]