Function: Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 AND MAPK3 which are phosphorylated upon activation of EPHA7. Isoform 4 which lacks the kinase domain may regulate isoform 1 adhesive properties. Ref.8 Ref.9 Ref.10 Ref.11
Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure: Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses
By similarity. Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain). Ref.7
Subcellular location: Cell membrane
Probable; Single-pass type I membrane protein
Probable Ref.8.
Tissue specificity: Widely expressed in embryo. In adult, expression restricted to hippocampus, testis and spleen.
Developmental stage: During visual system development, expressed in an anterior to posterior decreasing gradient stretching through the entire midbrain. This gradient has the reverse orientation to the one defined by the expression of ephrins. Isoform 4 and isoform 5 are expressed at the edges of the embryonic cranial neural fold. Ref.8 Ref.10
Post-translational modification: Phosphorylated. Isoform 4 inhibits isoform 1 phosphorylation and may regulate its function in adhesion. Ref.8
Disruption phenotype: Mice are viable, fertile and show no gross morphological or behavioral defects. However, topographic targeting errors of nasal and temporal retinal axons appear during development of the retinocollicular projections in the visual system. 10 percent of the embryos also display exencephalic overgrowth of forebrain tissues which might be the result of reduced apoptosis. Ref.9 Ref.10
Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.Contains 1 Eph LBD (Eph ligand-binding) domain.Contains 2 fibronectin type-III domains.Contains 1 protein kinase domain.Contains 1 SAM (sterile alpha motif) domain.
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