EPH receptor A4

EPH receptor A4 (ephrin type-A receptor 4) is a protein that in humans is encoded by the EPHA4 gene.

EPHA4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LW8, 2WO1, 2WO2, 2WO3, 3CKH, 3GXU, 4BK4, 4BK5, 4BKA, 4BKF, 4M4P, 4M4R, 4W4Z, 4W50, 5JR2
Identifiers
Aliases	EPHA4, Epha4, 2900005C20Rik, AI385584, Cek8, Hek8, Sek, Sek1, Tyro1, rb, EPH receptor A4, HEK8, SEK, TYRO1, EK8
External IDs	OMIM: 602188; MGI: 98277; HomoloGene: 20933; GeneCards: EPHA4; OMA:EPHA4 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q36.1 Start 221,418,027 bp End 221,574,202 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 C4|1 39.55 cM Start 77,343,822 bp End 77,491,725 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 frontal pole middle temporal gyrus lateral nuclear group of thalamus endothelial cell primary visual cortex superior frontal gyrus parietal lobe postcentral gyrus palpebral conjunctiva Top expressed in Rostral migratory stream medial ganglionic eminence ventricular zone dorsal striatum genital tubercle dentate gyrus of hippocampal formation granule cell medial dorsal nucleus lateral geniculate nucleus nucleus accumbens tail of embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding GPI-linked ephrin receptor activity ephrin receptor binding DH domain binding transmembrane-ephrin receptor activity kinase activity protein binding identical protein binding transmembrane receptor protein tyrosine kinase activity PH domain binding protein tyrosine kinase activity ATP binding ephrin receptor activity amyloid-beta binding protein tyrosine kinase binding Cellular component cytoplasm axon terminus integral component of membrane cell body perikaryon postsynaptic membrane Golgi apparatus endosome cell projection early endosome membrane membrane postsynaptic density filopodium neuromuscular junction plasma membrane dendritic spine axonal growth cone integral component of plasma membrane synapse cell surface mitochondrial outer membrane cell junction axon dendrite early endosome endoplasmic reticulum neuron projection dendritic shaft receptor complex Schaffer collateral - CA1 synapse glutamatergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane Biological process negative regulation of axon regeneration fasciculation of motor neuron axon phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway positive regulation of JUN kinase activity regulation of GTPase activity nervous system development regulation of axonogenesis multicellular organism development protein phosphorylation regulation of astrocyte differentiation cell adhesion positive regulation of dendrite morphogenesis nephric duct morphogenesis protein autophosphorylation corticospinal tract morphogenesis peptidyl-tyrosine phosphorylation fasciculation of sensory neuron axon motor neuron axon guidance positive regulation of Rho guanyl-nucleotide exchange factor activity regulation of dendritic spine morphogenesis glial cell migration adult walking behavior axon guidance ephrin receptor signaling pathway negative regulation of neuron projection development protein stabilization positive regulation of protein tyrosine kinase activity neuron projection guidance synapse pruning neuron projection fasciculation negative regulation of long-term synaptic potentiation positive regulation of amyloid-beta formation positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process negative regulation of proteolysis involved in cellular protein catabolic process cellular response to amyloid-beta regulation of modification of synaptic structure Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2043 13838 Ensembl ENSG00000116106 ENSMUSG00000026235 UniProt P54764 Q03137 RefSeq (mRNA) NM_001304536 NM_001304537 NM_004438 NM_001363748 NM_007936 RefSeq (protein) NP_001291465 NP_001291466 NP_004429 NP_001350677 NP_031962 Location (UCSC) Chr 2: 221.42 – 221.57 Mb Chr 1: 77.34 – 77.49 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

In 2012, a publication in Nature Medicine revealed a connection between EPHA4 and the neurodegenerative disease Amyotrophic lateral sclerosis (ALS), where a defective gene allows ALS patients to live considerably longer than patients with an intact gene. This opens up for development of treatment for this currently untreatable disease.

Further reading

• Flanagan JG, Vanderhaeghen P (1998). "The ephrins and Eph receptors in neural development". Annu. Rev. Neurosci. 21: 309–45. doi:10.1146/annurev.neuro.21.1.309. PMID 9530499.
• Zhou R (1998). "The Eph family receptors and ligands". Pharmacol. Ther. 77 (3): 151–81. doi:10.1016/S0163-7258(97)00112-5. PMID 9576626.
• Holder N, Klein R (1999). "Eph receptors and ephrins: effectors of morphogenesis". Development. 126 (10): 2033–44. doi:10.1242/dev.126.10.2033. PMID 10207129.
• Wilkinson DG (2000). "Eph receptors and ephrins: regulators of guidance and assembly; Chapter: Eph receptors and ephrins: Regulators of guidance and assembly". Int. Rev. Cytol. International Review of Cytology. 196: 177–244. doi:10.1016/S0074-7696(00)96005-4. ISBN 978-0-12-364600-2. PMID 10730216.
• Xu Q, Mellitzer G, Wilkinson DG (2001). "Roles of Eph receptors and ephrins in segmental patterning". Philos. Trans. R. Soc. Lond. B Biol. Sci. 355 (1399): 993–1002. doi:10.1098/rstb.2000.0635. PMC 1692797. PMID 11128993.
• Wilkinson DG (2001). "Multiple roles of EPH receptors and ephrins in neural development". Nat. Rev. Neurosci. 2 (3): 155–64. doi:10.1038/35058515. PMID 11256076. S2CID 205014301.
• Fox GM, Holst PL, Chute HT, et al. (1995). "cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases". Oncogene. 10 (5): 897–905. PMID 7898931.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Ellis C, Kasmi F, Ganju P, et al. (1996). "A juxtamembrane autophosphorylation site in the Eph family receptor tyrosine kinase, Sek, mediates high affinity interaction with p59fyn". Oncogene. 12 (8): 1727–36. PMID 8622893.
• Gale NW, Holland SJ, Valenzuela DM, et al. (1996). "Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis". Neuron. 17 (1): 9–19. doi:10.1016/S0896-6273(00)80276-7. PMID 8755474. S2CID 1075856.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Aasheim HC, Terstappen LW, Logtenberg T (1997). "Regulated expression of the Eph-related receptor tyrosine kinase Hek11 in early human B lymphopoiesis". Blood. 90 (9): 3613–22. doi:10.1182/blood.V90.9.3613. PMID 9345045.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Bergemann AD, Zhang L, Chiang MK, et al. (1998). "Ephrin-B3, a ligand for the receptor EphB3, expressed at the midline of the developing neural tube". Oncogene. 16 (4): 471–80. doi:10.1038/sj.onc.1201557. PMID 9484836. S2CID 2497788.
• Janis LS, Cassidy RM, Kromer LF (1999). "Ephrin-A binding and EphA receptor expression delineate the matrix compartment of the striatum". J. Neurosci. 19 (12): 4962–71. doi:10.1523/JNEUROSCI.19-12-04962.1999. PMC 6782661. PMID 10366629.