EPHA4
Entrez ID: 2043
Full name: EPH receptor A4
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: TK: Eph
Chromosomal location: 2q36.1
Substructure location: Gatekeeper: A-loop: G-loop: αC-helix:
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EPHA4
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 downstre...
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).
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GO - Biological processes (BP):
adherens junction organization, adult walking behavior, axon guidance, cell adhesion, cellular response to amyloid-beta, cochlea development, corticospinal tract morphogenesis, ephrin receptor signaling pathway, fasciculation of motor neuron axon, fasciculation of sensory neuron axon, glial cell mig...
adherens junction organization, adult walking behavior, axon guidance, cell adhesion, cellular response to amyloid-beta, cochlea development, corticospinal tract morphogenesis, ephrin receptor signaling pathway, fasciculation of motor neuron axon, fasciculation of sensory neuron axon, glial cell migration, motor neuron axon guidance, multicellular organism development, negative regulation of axon regeneration, negative regulation of long-term synaptic potentiation, negative regulation of neuron projection development, negative regulation of proteolysis involved in cellular protein catabolic process, nephric duct morphogenesis, neuron projection fasciculation, neuron projection guidance, peptidyl-tyrosine phosphorylation, positive regulation of amyloid-beta formation, positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process, positive regulation of dendrite morphogenesis, positive regulation of JUN kinase activity, positive regulation of kinase activity, positive regulation of protein tyrosine kinase activity, positive regulation of Rho guanyl-nucleotide exchange factor activity, protein autophosphorylation, protein stabilization, regulation of astrocyte differentiation, regulation of axonogenesis, regulation of dendritic spine morphogenesis, regulation of GTPase activity, regulation of modification of synaptic structure, synapse pruning, transmembrane receptor protein tyrosine kinase signaling pathway
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GO - Molecular function (MF):
amyloid-beta binding, ATP binding, DH domain binding, ephrin receptor binding, GPI-linked ephrin receptor activity, identical protein binding, kinase activity, PH domain binding, protein kinase activity, protein tyrosine kinase binding, transmembrane-ephrin receptor activity, transmembrane receptor ...
amyloid-beta binding, ATP binding, DH domain binding, ephrin receptor binding, GPI-linked ephrin receptor activity, identical protein binding, kinase activity, PH domain binding, protein kinase activity, protein tyrosine kinase binding, transmembrane-ephrin receptor activity, transmembrane receptor protein tyrosine kinase activity
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GO - Cellular component (CC):
endoplasmic reticulum, early endosome membrane, Golgi apparatus, mitochondrial outer membrane, integral component of plasma membrane, integral component of postsynaptic membrane, integral component of presynaptic membrane, plasma membrane, postsynaptic density membrane, adherens junction, axon, axon...
endoplasmic reticulum, early endosome membrane, Golgi apparatus, mitochondrial outer membrane, integral component of plasma membrane, integral component of postsynaptic membrane, integral component of presynaptic membrane, plasma membrane, postsynaptic density membrane, adherens junction, axon, axon terminus, axonal growth cone, cell surface, cytoplasm, dendrite, dendritic shaft, dendritic spine, filopodium, glutamatergic synapse, neuromuscular junction, neuron projection, perikaryon, receptor complex, Schaffer collateral - CA1 synapse
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EPH receptor A4
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*NOTE: the Kaplan plots were collected from OncoLnc