EPHA8

This gene encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors 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 ephrin 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 protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. [provided by RefSeq, Jul 2008]

EPH Receptor A8

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 plays also 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).

Axon guidance Source: UniProtKB
Cell adhesion Source: UniProtKB-KW
Cellular response to follicle-stimulating hormone stimulus Source: Ensembl
Ephrin receptor signaling pathway Source: UniProtKB
Neuron projection development Source: UniProtKB
Neuron remodeling Source: UniProtKB
Positive regulation of kinase activity Source: GO_Central
Positive regulation of MAPK cascade Source: UniProtKB
Positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Regulation of cell adhesion Source: UniProtKB
Regulation of cell adhesion mediated by integrin Source: UniProtKB
Substrate-dependent cell migration Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Cell membrane; Early endosome membrane; Cell projection. Undergoes clathrin-mediated endocytosis upon EFNA5-binding and is targeted to early endosomes.

Extracellular: 28-542
Helical: 543-563
Cytoplasmic: 564-1005

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).