EPHA4

This gene belongs to 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

EPH Receptor A4

Receptor tyrosine kinase which binds membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity).

Adherens junction organization Source: Ensembl
Adult walking behavior Source: Ensembl
Axon guidance Source: GO_Central
Cell adhesion Source: UniProtKB-KW
Cellular response to amyloid-beta Source: ARUK-UCL
Cochlea development Source: Ensembl
Corticospinal tract morphogenesis Source: UniProtKB
Ephrin receptor signaling pathway Source: ARUK-UCL
Fasciculation of motor neuron axon Source: UniProtKB
Fasciculation of sensory neuron axon Source: UniProtKB
Glial cell migration Source: Ensembl
Motor neuron axon guidance Source: UniProtKB
Negative regulation of axon regeneration Source: UniProtKB
Negative regulation of cell migration Source: ARUK-UCL
Negative regulation of long-term synaptic potentiation Source: ARUK-UCL
Negative regulation of neuron projection development Source: ARUK-UCL
Negative regulation of proteolysis involved in cellular protein catabolic process Source: ARUK-UCL
Nephric duct morphogenesis Source: Ensembl
Neuron projection fasciculation Source: ARUK-UCL
Neuron projection guidance Source: ARUK-UCL
Peptidyl-tyrosine phosphorylation Source: UniProtKB
Positive regulation of amyloid-beta formation Source: ARUK-UCL
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: ARUK-UCL
Positive regulation of cell adhesion Source: ARUK-UCL
Positive regulation of dendrite morphogenesis Source: Ensembl
Positive regulation of JUN kinase activity Source: Ensembl
Positive regulation of kinase activity Source: GO_Central
Positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
Positive regulation of Rho guanyl-nucleotide exchange factor activity Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Protein stabilization Source: ARUK-UCL
Regulation of astrocyte differentiation Source: UniProtKB
Regulation of axonogenesis Source: UniProtKB
Regulation of dendritic spine morphogenesis Source: UniProtKB
Regulation of GTPase activity Source: UniProtKB
Regulation of modification of synaptic structure Source: ARUK-UCL
Synapse pruning Source: Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Early endosome; Cell membrane; Postsynaptic density membrane; Axon; Dendrite; Adherens junction. Clustered upon activation and targeted to early endosome.

Extracellular: 20-547
Helical: 548-569
Cytoplasmic: 570-986