View source for 4bka

{{STRUCTURE_4bka|  PDB=4bka  |  SCENE=  }} 
===crystal structure of the human EphA4 ectodomain in complex with human ephrin A5===

==Function==
[[http://www.uniprot.org/uniprot/EPHA4_HUMAN EPHA4_HUMAN]] 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. Beside 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.<ref>PMID:17143272</ref>  [[http://www.uniprot.org/uniprot/EFNA5_HUMAN EFNA5_HUMAN]] Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors 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. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion.<ref>PMID:10601038</ref> <ref>PMID:11870224</ref>  

==About this Structure==
[[4bka]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BKA OCA]. 

==Reference==
<references group="xtra"/><references/>
[[Category: Homo sapiens]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Aricescu, A R.]]
[[Category: Harlos, K.]]
[[Category: Jones, E Y.]]
[[Category: Kaufmann, R.]]
[[Category: Klein, R.]]
[[Category: Mitakidis, N.]]
[[Category: Ruiz, D del Toro.]]
[[Category: Schaupp, A.]]
[[Category: Seiradake, E.]]
[[Category: Cell adhesion]]
[[Category: Cell repulsion]]
[[Category: Egf]]
[[Category: Eph ectodomain]]
[[Category: Eph-ephrin]]
[[Category: Erythropoetin-producing hepatocellular receptor]]
[[Category: Fn]]
[[Category: Lbd]]
[[Category: Receptor cis interaction]]
[[Category: Receptor clustering]]
[[Category: Sushi]]