EPHA8
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. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity).
Post-translational modifications
Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-616 is critical for association with FYN. Autophosphorylation on Tyr-839 modulates tyrosine kinase activity (By similarity).
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation (By similarity).
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Cell projection
- Early endosome membrane
- Undergoes clathrin-mediated endocytosis upon EFNA5-binding and is targeted to early endosomes.
Alternative names
EEK, HEK3, KIAA1459, EPHA8, Ephrin type-A receptor 8, EPH- and ELK-related kinase, EPH-like kinase 3, Tyrosine-protein kinase receptor EEK, EK3, hEK3