Alternative titles; symbols
HGNC Approved Gene Symbol: EPHA3
Cytogenetic location: 3p11.1 Genomic coordinates (GRCh38): 3:89,107,621-89,482,134 (from NCBI)
See EPH (EPHA1; 179610) for background on Eph receptors and their ligands, the ephrins. Kinases that phosphorylate proteins on tyrosine residues (protein tyrosine kinases; PTKs), such as EPHA3, form a structurally related group of molecules that exhibit functional diversity. Genetic alterations that lead to the inappropriate activation or expression of PTKs may be oncogenic. Many growth factor receptors are PTKs, e.g., the receptors for epidermal growth factor (EGFR; 131550), platelet-derived growth factor (PDGFR1, 173410; PDGFR2, 173490), colony-stimulating factor-1 (CSF1R; 164770), and stem cell growth factor (164920).
Wicks et al. (1992) isolated and sequenced a 4.5-kb cDNA encoding the HEK receptor tyrosine kinase. Sequence comparison with other PTKs showed a high degree of homology with members of the EPH and ELK (EPHB1; 600600) families of receptor tyrosine kinases. There was an apparent restriction of HEK expression to lymphoid tumor cell lines, raising the possibility that HEK may play a role in some human lymphoid malignancies and also in normal lymphoid function and differentiation.
By purifying the protein from a pre-B acute lymphoblastic leukemia cell line and amino acid sequencing, Boyd et al. (1992) identified this molecule as a member of the eph/elk family of tyrosine kinases. They assigned this molecule the provisional name HEK, for human eph/elk-like kinase.
Northern blot analysis by Fox et al. (1995) revealed that HEK4 is expressed as a single 7-kb transcript in a variety of human tissues, with the highest level of expression in placenta.
Gallarda et al. (2008) reported that, within axial nerves, establishment of discrete afferent and efferent pathways depends on coordinate signaling between coextending sensory and motor projections. These heterotypic axon-axon interactions require motor axonal EphA3/EphA4 (602188) receptor tyrosine kinases activated by cognate sensory axonal ephrin-A ligands. Genetic elimination of transaxonal ephrin-A-to-EphA signaling in mice triggers drastic motorsensory miswiring, culminating in functional efferents within proximal afferent pathways. Gallarda et al. (2008) concluded that effective assembly of a key circuit underlying motor behaviors thus critically depends on transaxonal signaling interactions resolving motor and sensory projections into discrete pathways.
By Southern blot analysis of somatic cell hybrids and fluorescence in situ hybridization, Wicks et al. (1994) localized the ETK gene to 3p11.2.
Boyd, A. W., Ward, L. D., Wicks, I. P., Simpson, R. J., Salvaris, E., Wilks, A., Welch, K., Loudovaris, M., Rockman, S., Busmanis, I. Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. J. Biol. Chem. 267: 3262-3267, 1992. [PubMed: 1737782]
Fox, G. M., Holst, P. L., Chute, H. T., Lindberg, R. A., Janssen, A. M., Basu, R., Welcher, A. A. cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases. Oncogene 10: 897-905, 1995. [PubMed: 7898931]
Gallarda, B. W., Bonanomi, D., Mueller, D., Brown, A., Alaynick, W. A., Andrews S. E., Lemke, G., Pfaff, S. L., Marquardt, T. Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling. Science 320: 233-236, 2008. [PubMed: 18403711] [Full Text: https://doi.org/10.1126/science.1153758]
Wicks, I. P., Lapsys, N. M., Baker, E., Campbell, L. J., Boyd, A. W., Sutherland, G. R. Localization of a human receptor tyrosine kinase (ETK1) to chromosome region 3p11.2. Genomics 19: 38-41, 1994. [PubMed: 8188238] [Full Text: https://doi.org/10.1006/geno.1994.1009]
Wicks, I. P., Wilkinson, D., Salvaris, E., Boyd, A. W. Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. Proc. Nat. Acad. Sci. 89: 1611-1615, 1992. [PubMed: 1311845] [Full Text: https://doi.org/10.1073/pnas.89.5.1611]