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 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. Ubiquitous. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Eph family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Chromosomal Location of mouse Ortholog: 1 C4|1 39.55 cM
Cellular Component:  axon; axon terminus; axonal growth cone; cell body; cell junction; cell projection; cell surface; cytoplasm; dendrite; dendritic shaft; dendritic spine; early endosome membrane; endoplasmic reticulum; endosome; filopodium; glutamatergic synapse; Golgi apparatus; membrane; mitochondrial outer membrane; neuromuscular junction; neuron projection; perikaryon; plasma membrane; postsynaptic density; postsynaptic membrane; presynaptic membrane; receptor complex; Schaffer collateral - CA1 synapse; synapse
Molecular Function:  ATP binding; DH domain binding; ephrin receptor activity; ephrin receptor binding; GPI-linked ephrin receptor activity; identical protein binding; kinase activity; nucleotide binding; PH domain binding; protein binding; protein kinase activity; protein tyrosine kinase activity; protein tyrosine kinase binding; transferase activity; transmembrane receptor protein tyrosine kinase activity; transmembrane-ephrin receptor activity
Biological Process:  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 cell adhesion; negative regulation of cell migration; negative regulation of cellular response to hypoxia; negative regulation of epithelial to mesenchymal transition; negative regulation of ERK1 and ERK2 cascade; negative regulation of long-term synaptic potentiation; negative regulation of neuron projection development; negative regulation of proteolysis involved in protein catabolic process; nephric duct morphogenesis; nervous system development; neuron projection fasciculation; neuron projection guidance; peptidyl-tyrosine phosphorylation; phosphorylation; positive regulation of amyloid-beta formation; positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; positive regulation of cell adhesion; positive regulation of cell migration; positive regulation of cell population proliferation; 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 phosphorylation; 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
Reference #:  Q03137 (UniProtKB)
Alt. Names/Synonyms: 2900005C20Rik; AI385584; Cek8; Eph receptor A4; Epha4; Ephrin type-A receptor 4; Hek8; rb; Sek; Sek1; snoRNA MBII-267; Tyr; Tyro1; Tyrosine-protein kinase receptor MPK-3; Tyrosine-protein kinase receptor SEK-1
Gene Symbols: Epha4
Molecular weight: 109,814 Da
Basal Isoelectric point: 6.12  Predict pI for various phosphorylation states
CST Pathways:  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene