EPH receptor A4 explained

EPH receptor A4 (ephrin type-A receptor 4) is a protein that in humans is encoded by the EPHA4 gene.^{[1] [2]}

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

Notes and References

1. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee . Cell . 90 . 3 . 403–4 . Sep 1997 . 9267020 . 10.1016/S0092-8674(00)80500-0 . Ephnomenclaturecommittee . 26773768 . free .
2. Web site: Entrez Gene: EPHA4 EPH receptor A4.