View source for 7eec


==Crystal structure of EphA7 mutant G656R==
<StructureSection load='7eec' size='340' side='right'caption='[[7eec]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7eec]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EEC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7eec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eec OCA], [https://pdbe.org/7eec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eec RCSB], [https://www.ebi.ac.uk/pdbsum/7eec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eec ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EPHA7_HUMAN EPHA7_HUMAN] Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 AND MAPK3 which are phosphorylated upon activation of EPHA7.<ref>PMID:17726105</ref> 
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== Publication Abstract from PubMed ==
Erythropoietin producing hepatocellular (Eph) forms the largest family of receptor tyrosine kinases (RTK). As a family, Eph regulates physiological events such as cell-cell interaction, cell migration, and adhesion. The Kinase domain is the catalytic core of the Eph receptor and is highly conserved sequentially. EphA7 has been recently regarded as a cancer driver gene and comprises several clinically important mutations. Three of the EphA7 mutations Gly656Glu, Gly656Arg, and Asp751His, present in the kinase domain, are predicted to be highly pathogenic. Furthermore, Gly656Glu and Gly656Arg are reported to be hotspot mutations. Considering the importance of mutations, crystals structure of EphA7 Gly656Glu, Gly656Arg, and Asp751His mutants has been explored. Changes in folding pattern and intramolecular interactions were observed in mutant structures. Secondary structural changes were observed in the hinge region of EphA7 Gly656Arg and Asp751His structure, affecting the transition of kinase domain between open and closed conformations. EphA7 Asp751His mutant structure shows a distorted nucleotide-binding groove. Differences were observed in hydrogen bonding and hydrophobic interactions between the catalytic and highly conserved DFG motif in the EphA7 mutants, which may influence the catalytic activity of kinase domain.

Crystal structure of clinically reported mutations Gly656Arg, Gly656Glu and Asp751His identified in the kinase domain of EphA7.,Chakraborty S, Varma AK Biochem Biophys Res Commun. 2021 Jun 26;568:62-67. doi:, 10.1016/j.bbrc.2021.06.048. PMID:34186436<ref>PMID:34186436</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7eec" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ephrin receptor 3D structures|Ephrin receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chakraborty S]]
[[Category: Varma AK]]