EPHA4 (P54764) - Overview - Molecular Target Synopsis
EPHA4, Ephrin type-A receptor 4
Enzyme Classification 18.104.22.168
Also Known as EPHA4_HUMAN, EPHA4, HEK8, SEK, TYRO1
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. 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. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation (By similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases.
|Protein Length||Ensembl Gene||Ensembl Transcript||Ensembl Protein||Uniprot Isoform|
|986||ENSG00000116106||ENST00000281821, ENST00000409938||ENSP00000281821, ENSP00000386829||P54764-1|
UniProt: EPHA4 is active in the following subcellular-locations: axon, cell junction, cell membrane, cell projection, dendrite, early endosome, postsynaptic cell membrane, postsynaptic density, synapse.
GO terms: EPHA4 is active in the following subcellular-locations: axon, axon terminus, axonal growth cone, cell junction, cell surface, cytoplasm, dendrite, dendritic shaft, dendritic spine, early endosome membrane, endoplasmic reticulum, filopodium, glutamatergic synapse, Golgi apparatus, integral component of plasma membrane, integral component of postsynaptic membrane, integral component of presynaptic membrane, mitochondrial outer membrane, neuromuscular junction, neuron projection, perikaryon, plasma membrane, postsynaptic density, receptor complex, Schaffer collateral - CA1 synapse.