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Other entities represented in this entry:
HGNC Approved Gene Symbol: EEF1A1
Cytogenetic location: 6q13 Genomic coordinates (GRCh38): 6:73,515,750-73,521,032 (from NCBI)
Eukaryotic elongation factor-1 (EF1) consists of 4 subunits, EF1-alpha, EF1-beta (EEF1B2; 600655), EF1-gamma (EEF1G; 130593), and EF1-delta (EEF1D; 130592). EIF-alpha-GTP transfers aminoacyl-tRNA to the ribosome, and the release of animoacyl-tRNA from EIF-alpha-GTP is driven by GTP hydrolysis. EF1-alpha-GDP is recycled to EF1-alpha-GTP by the EF1-beta, -gamma, and -delta subunits (Sanders et al., 1996).
Brands et al. (1986) determined the primary structure of human EEF1A by cDNA sequencing. The deduced 462-amino acid protein shows conservation of more than 80% when compared with yeast and Artema Ef1-alpha.
By immunofluorescence analysis, Sanders et al. (1996) found that EF1-alpha showed strong nuclear staining and diffuse cytoplasmic staining in human foreskin fibroblasts. In contrast, EF1-beta, -gamma, and -delta showed a perinuclear distribution and colocalized with an endoplasmic reticulum resident protein.
CCS3 Splice Variant
Using PLZF (ZNF145; 176797) as bait in a yeast 2-hybrid screen of an ovary cDNA library, Rho et al. (2006) cloned an EEF1A1 splice variant that they called CCS3. The deduced 361-amino acid CCS3 protein lacks the 101 N-terminal amino acids of full-length EEF1A1. Western blot analysis detected both CCS3 and full-length EEF1A1 in human cell lines.
Using human tissue culture cells, Morris et al. (2004) showed that promoter-directed small interfering RNA (siRNA) inhibits transcription of an integrated, proviral EF1A promoter-green fluorescent protein reporter gene and of endogenous EF1A. Silencing was associated with DNA methylation of the targeted sequence, and it required either active transport of siRNA into the nucleus or permeabilization of the nuclear envelope by lentiviral transduction. Morris et al. (2004) concluded that siRNA-directed transcriptional silencing is conserved in mammals, providing a means to inhibit mammalian gene function.
The heat-shock transcription factor HSF1 (140580) is present in unstressed cells in an inactive monomeric form and becomes activated by heat and other stress stimuli. HSF1 activation involves trimerization and acquisition of a site-specific DNA-binding activity, which is negatively regulated by interaction with certain heat-shock proteins. Shamovsky et al. (2006) showed that HSF1 activation by heat shock is an active process that is mediated by a ribonucleoprotein complex containing translation elongation factor eEF1A and a previously unknown noncoding RNA that they termed heat-shock RNA-1 (HSR1; 610157). HSR1 is constitutively expressed in human and rodent cells and its homologs are functionally interchangeable. Both HSR1 and eEF1A are required for HSF1 activation in vitro; antisense oligonucleotides or short interfering RNA against HSR1 impaired the heat-shock response in vivo, rendering cells thermosensitive. Shamovsky et al. (2006) suggested that the central role of HSR1 during heat shock implies that targeting this RNA could serve as a new therapeutic model for cancer, inflammation, and other conditions associated with HSF1 deregulation.
Using mass spectrometric analysis, Belyi et al. (2006) identified EF1A as the protein glucosylated after infection with Legionella pneumophila, the causative agent of Legionnaire disease (see 608556). Glucosylation occurs at ser53 in the GTPase domain of EF1A and results in inhibition of eukaryotic protein synthesis and target cell death.
Using quantitative mass spectrometric analysis, Shimazu et al. (2014) identified EF1A as a substrate for mouse Mettl10 (EEF1AKMT2; 617794) methyltransferase activity following expression in HeLa cells. Of the 5 lysine methylation sites in EF1A1, Mettl10 methylated lys318. Depletion of METTL10 in HEK293T cells via short interfering RNA significantly reduced both di- and trimethylation of EIF1A at lys318 and increased the level of the unmethylated form of EF1A1.
Hamey et al. (2016) found that purified recombinant human EEF1AKMT1 (617793) methylated lys79 in recombinant human EEF1A1 in vitro.
CCS3 Isoform
Using yeast 2-hybrid analysis and protein pull-down assays, Rho et al. (2006) showed that CCS3 interacted with PLZF. Mutation analysis revealed that repressor domain-2 and the zinc finger domain of PLZF were required for the interaction. RT-PCR showed that CCS3 was downregulated in human cervical cancer cell lines and in 7 of 8 human cervical cancers compared with normal human cell lines and tissues. Overexpression of CCS3 inhibited cell growth by inducing apoptosis, and CCS3 suppressed human cyclin A2 (CCNA2; 123835) promoter activity in a reporter gene assay. Rho et al. (2006) concluded that CCS3 functions as a transcriptional repressor and is required for the transcriptional effects of PLZF.
Ditzel et al. (2000) identified EEF1A1 as an autoantibody in 66% of patients with Felty syndrome (134750), a disorder characterized by the association of rheumatoid arthritis, splenomegaly, and peripheral destruction of neutrophils leading to neutropenia.
Opdenakker et al. (1987) concluded that there are more than 10 copies per haploid genome of EEF1A in humans. Using in situ hybridization of a cDNA probe to normal metaphase chromosomes, they showed multiple chromosomal localizations of the elongation factor genes, with peak hybridization on chromosomes 1, 2, 4, 5, 6, 7, and 15.
By fluorescence in situ hybridization (FISH) and PCR analysis of a somatic cell hybrid panel, Lund et al. (1996) mapped the EEF1A1 gene to chromosome 6q14. By FISH, they mapped the EEF1A2 gene (602959) to 20q13.3.
Belyi, Y., Niggeweg, R., Opitz, B., Vogelsgesang, M., Hippenstiel, S., Wilm, M., Aktories, K. Legionella pneumophila glucosyltransferase inhibits host elongation factor 1A. Proc. Nat. Acad. Sci. 103: 16953-16958, 2006. [PubMed: 17068130] [Full Text: https://doi.org/10.1073/pnas.0601562103]
Brands, J. H. G. M., Maassen, J. A., Van Hemert, F. J., Amons, R., Moller, W. The primary structure of the alpha subunit of human elongation factor 1: structural aspects of guanine-nucleotide-binding sites. Europ. J. Biochem. 155: 167-171, 1986. [PubMed: 3512269] [Full Text: https://doi.org/10.1111/j.1432-1033.1986.tb09472.x]
Ditzel, H. J., Masaki, Y., Nielsen, H., Farnaes, L., Burton, D. R. Cloning and expression of a novel human antibody--antigen pair associated with Felty's syndrome. Proc. Nat. Acad. Sci. 97: 9234-9239, 2000. [PubMed: 10922075] [Full Text: https://doi.org/10.1073/pnas.97.16.9234]
Hamey, J. J., Winter, D. L., Yagoub, D., Overall, C. M., Hart-Smith, G., Wilkins, M. R. Novel N-terminal and lysine methyltransferases that target translation elongation factor 1A in yeast and human. Molec. Cell. Proteomics 15: 164-176, 2016. [PubMed: 26545399] [Full Text: https://doi.org/10.1074/mcp.M115.052449]
Lund, A., Knudsen, S. M., Vissing, H., Clark, B., Tommerup, N. Assignment of human elongation factor 1-alpha genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3. Genomics 36: 359-361, 1996. [PubMed: 8812466] [Full Text: https://doi.org/10.1006/geno.1996.0475]
Morris, K. V., Chan, S. W.-L., Jacobsen, S. E., Looney, D. J. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305: 1289-1292, 2004. [PubMed: 15297624] [Full Text: https://doi.org/10.1126/science.1101372]
Opdenakker, G., Cabeza-Arvelaiz, Y., Fiten, P., Dijkmans, R., Van Damme, J., Volckaert, G., Billiau, A., Van Elsen, A., Van der Schueren, B., Van den Berghe, H., Cassiman, J.-J. Human elongation factor 1-alpha: a polymorphic and conserved multigene family with multiple chromosomal localizations. Hum. Genet. 75: 339-344, 1987. [PubMed: 3570288] [Full Text: https://doi.org/10.1007/BF00284104]
Rho, S. B., Park, Y. G., Park, K., Lee, S.-H., Lee, J.-H. A novel cervical cancer suppressor 3 (CCS-3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis. FEBS Lett. 580: 4073-4080, 2006. [PubMed: 16828757] [Full Text: https://doi.org/10.1016/j.febslet.2006.06.047]
Sanders, J., Brandsma, M., Janssen, G. M. C., Dijk, J., Moller, W. Immunofluorescence studies of human fibroblasts demonstrate the presence of the complex of elongation factor-1-beta-gamma-delta in the endoplasmic reticulum. J. Cell Sci. 109: 1113-1117, 1996. [PubMed: 8743958] [Full Text: https://doi.org/10.1242/jcs.109.5.1113]
Shamovsky, I., Ivannikov, M., Kandel, E. S., Gershon, D., Nudler, E. RNA-mediated response to heat shock in mammalian cells. Nature 440: 556-560, 2006. [PubMed: 16554823] [Full Text: https://doi.org/10.1038/nature04518]
Shimazu, T., Barjau, J., Sohtome, Y., Sodeoka, M., Shinkai, Y. Selenium-based S-adenosylmethionine analog reveals the mammalian seven-beta-strand methyltransferase METTL10 to be an EF1A1 lysine methyltransferase. PLoS One 9: e105394, 2014. Note: Electronic Article. [PubMed: 25144183] [Full Text: https://doi.org/10.1371/journal.pone.0105394]