Alternative titles; symbols
HGNC Approved Gene Symbol: EEF1D
Cytogenetic location: 8q24.3 Genomic coordinates (GRCh38): 8:143,579,728-143,597,415 (from NCBI)
Eukaryotic elongation factor-1 (EF1) consists of 4 subunits, EF1-alpha (EEF1A1; 130590), EF1-beta (EEF1B2; 600655), EF1-gamma (EEF1G; 130593), and EF1-delta. 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).
Using Xenopus Ef1-delta to probe a human skin fibroblast cDNA library, Sanders et al. (1993) cloned EF1-delta. The deduced 281-amino acid protein has a calculated molecular mass of 31 kD. It has an N-terminal leucine zipper domain and a C-terminal domain that is similar to that of EF1-beta and is predicted to show GDP/GTP exchange activity. EF1-delta also has a conserved serine phosphorylation site. SDS-PAGE detected EF1-delta at an apparent molecular mass of 38 kD.
By Western blot analysis, Sanders et al. (1996) detected 1 major and 2 minor EF1-delta bands, which they attributed to variable degrees of phosphorylation. Immunofluorescence analysis detected EF1-beta, -gamma, and -delta in a perinuclear distribution in human foreskin fibroblasts, and these subunits colocalized with an endoplasmic reticulum (ER) resident protein. In contrast, EF1-alpha showed strong nuclear staining and diffuse cytoplasmic staining.
Using Western blot and immunohistochemical analyses, Cao et al. (2014) showed that EEF1B-alpha, -delta, and -gamma were widely expressed in human and mouse cell lines and tissues and at different stages of mouse development. Immunofluorescence analysis on sections of mouse spinal cord revealed that all 3 Eef1b subunits colocalized with Eef1a2 (602959) in neurons, and EEF1B-EEF1A2 colocalization was confirmed in HeLa cells.
Gross (2022) mapped the EEF1D gene to chromosome 8q24.3 based on an alignment of the EEF1D sequence (GenBank BC007847) with the genomic sequence (GRCh38).
Human immunodeficiency virus-1 (HIV-1) Tat protein has an N-terminal domain that is a potent activator of transcription from the viral long terminal repeat promoter. Tat is also essential for viral replication and can activate or repress transcription of host cell genes. Using Tat as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, Xiao et al. (1998) isolated EF1-delta. Protein pull-down and Western blot analyses confirmed direct interaction between Tat and EF1-delta. EF1-delta specifically interacted with the Tat C-terminal domain. Titration of purified recombinant Tat into in vitro translation reactions showed that Tat inhibited translation of cellular, but not viral, proteins. Xiao et al. (1998) hypothesized that by binding EF1-delta, Tat redirects the protein synthesis machinery toward producing large amounts of viral proteins.
Using yeast 2-hybrid analysis, Ong et al. (2003) found that kinectin (KTN1; 600381) interacted directly with EF1-delta. Using peptide fragments, Ong et al. (2003) showed that a 60-amino acid domain near the kinectin C terminus was required for EF1-delta binding. Endogenous kinectin colocalized with EF1-delta in the ER. Expression of the kinectin EF1-delta-binding domain disrupted EF1-delta localization, suggesting that kinectin anchors EF1-delta to the ER membrane. Ong et al. (2003) also showed that CDC2 (116940) phosphorylated HeLa cell EF1-delta in vitro.
Cao et al. (2014) showed that knockdown of each EEF1B subunit in human cell lines reduced cell viability, decreased the proportion of cells in S and G2/M phases, and increased the proportion of cells in G0/G1 phase.
Cao, Y., Portela, M., Janikiewicz, J., Doig, J., Abbott, C. M. Characterisation of translation elongation factor eEF1B subunit expression in mammalian cells and tissues and co-localisation with eEF1A2. PLoS One 9: e114117, 2014. [PubMed: 25436608] [Full Text: https://doi.org/10.1371/journal.pone.0114117]
Gross, M. B. Personal Communication. Baltimore, Md. 1/14/2022.
Ong, L.-L., Er, C. P. N., Ho, A., Aung, M. T., Yu, H. Kinectin anchors the translation elongation factor-1-delta to the endoplasmic reticulum. J. Biol. Chem. 278: 32115-32123, 2003. [PubMed: 12773547] [Full Text: https://doi.org/10.1074/jbc.M210917200]
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]
Sanders, J., Raggiaschi, R., Morales, J., Moller, W. The human leucine zipper-containing guanine-nucleotide exchange protein elongation factor-1 delta. Biochim. Biophys. Acta 1174: 87-90, 1993. [PubMed: 8334168] [Full Text: https://doi.org/10.1016/0167-4781(93)90097-w]
Xiao, H., Neuveut, C., Benkirane, M., Jeang, K.-T. Interaction of the second coding exon of Tat with human EF-1-delta delineates a mechanism for HIV-1-mediated shut-off of host mRNA translation. Biochem. Biophys. Res. Commun. 244: 384-389, 1998. [PubMed: 9514931] [Full Text: https://doi.org/10.1006/bbrc.1998.8274]