Alternative titles; symbols
HGNC Approved Gene Symbol: EPHA1
Cytogenetic location: 7q34-q35 Genomic coordinates (GRCh38): 7:143,391,129-143,408,856 (from NCBI)
Maru et al. (1988) reported characterization of the novel receptor tyrosine kinase gene, EPH. The splicing points of kinase domain-encoding exons were completely distinct from those of other protein tyrosine kinase genes, suggesting that this is the earliest evolutionary split within this family. In Northern blot analysis, EPH gene mRNA was detected in liver, lung, kidney, and testes of rat; screening of 25 human cancers of various cell types showed preferential expression in cells of epithelial origin. Overexpression of EPH mRNA was found in a hepatoma and a lung cancer without gene amplification.
Although ephrins form a high-affinity multivalent complex with their receptors present on axons, axons can be rapidly repelled rather than being bound. Hattori et al. (2000) showed that ephrin-A2 (602756) forms a stable complex with the metalloproteinase Kuzbanian (ADAM10; 602192), involving interactions outside the cleavage region and the protease domain. Eph receptor binding triggered ephrin-A2 cleavage in a localized reaction specific to the cognate ligand. The cleavage-inhibiting mutation in ephrin-A2 delayed axon withdrawal. Hattori et al. (2000) concluded that their studies reveal mechanisms for protease recognition and control of cell surface proteins, and, for ephrin-A2, they may provide a means for efficient axon detachment and termination of signaling.
To examine the roles of EphA receptors and ephrin-A ligands in neuronal migration in the neocortex, Torii et al. (2009) analyzed Efna1 (191164)/Efna3 (601381)/Efna5 (601535) triple-knockout mice. These genes account for almost all ephrin-A genes in the developing neocortex. Most analyses were performed at postnatal day 0 or embryonic stages before the establishment of potentially mistargeted afferent and efferent projections. Torii et al. (2009) showed that an EphA and ephrin A (Efna) signaling-dependent shift in the allocation of clonally related neurons is essential for the proper assembly of cortical columns in the neocortex. In contrast to the relatively uniform labeling of the developing cortical plate by various molecular markers and retrograde tracers in wildtype mice, Torii et al. (2009) found alternating labeling of columnar compartments in Efna knockout mice that are caused by impaired lateral dispersion of migrating neurons rather than by altered cell production or death. Furthermore, in utero electroporation showed that lateral dispersion depends on the expression levels of EphAs and Efnas during neuronal migration. Torii et al. (2009) concluded that this theretofore unrecognized mechanism for lateral neuronal dispersion seems to be essential for the proper intermixing of neuronal types in the cortical columns, which, when disrupted, might contribute to neuropsychiatric disorders associated with abnormal columnar organization.
The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases. They have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the Eph subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ligands for Eph receptors have been named ephrins by the Eph Nomenclature Committee (1997). Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The Eph Nomenclature Committee (1997) proposed that Eph receptors interacting preferentially with ephrin-A proteins be called EphA and Eph receptors interacting preferentially with ephrin-B proteins be called EphB.
Using Southern blot analysis of DNAs from human-mouse hybrid clones with an EPH probe, Maru et al. (1988) showed that the EPHA1 gene is present on human chromosome 7. Two other receptor tyrosine kinase genes, MET (164860) and EGFR (131550), are on the same chromosome. By in situ hybridization, Yoshida et al. (1989) assigned the EPH locus to 7q32-q36.
Eph Nomenclature Committee. Unified nomenclature for the Eph family receptors and their ligands, the ephrins. Cell 90: 403-404, 1997. [PubMed: 9267020] [Full Text: https://doi.org/10.1016/s0092-8674(00)80500-0]
Hattori, M., Osterfield, M., Flanagan, J. G. Regulated cleavage of a contact-mediated axon repellent. Science 289: 1360-1365, 2000. [PubMed: 10958785] [Full Text: https://doi.org/10.1126/science.289.5483.1360]
Maru, Y., Hirai, H., Yoshida, M. C., Takaku, F. Evolution, expression, and chromosomal location of a novel receptor tyrosine kinase gene, eph. Molec. Cell. Biol. 8: 3770-3776, 1988. [PubMed: 3221865] [Full Text: https://doi.org/10.1128/mcb.8.9.3770-3776.1988]
Torii, M., Hashimoto-Torii, K., Levitt, P., Rakic, P. Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling. Nature 461: 524-528, 2009. Note: Erratum: Nature 462: 674 only, 2009. [PubMed: 19759535] [Full Text: https://doi.org/10.1038/nature08362]
Yoshida, M. C., Maru, H., Hirai, H., Takau, F. Chromosomal location of a novel receptor tyrosine kinase gene, EPH, on chromosome 7. (Abstract) Cytogenet. Cell Genet. 51: 1113 only, 1989.