5u6b
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the Axl kinase domain in complex with a macrocyclic inhibitor== | |
| - | + | <StructureSection load='5u6b' size='340' side='right'caption='[[5u6b]], [[Resolution|resolution]] 2.84Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[5u6b]] is a 4 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=5U6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U6B 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]] 2.84Å</td></tr> | |
| - | [[Category: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7YS:(10R)-7-amino-11-chloro-12-fluoro-1-(2-hydroxyethyl)-3,10,16-trimethyl-16,17-dihydro-1H-8,4-(azeno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecin-15(10H)-one'>7YS</scene></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=5u6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6b OCA], [https://pdbe.org/5u6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u6b RCSB], [https://www.ebi.ac.uk/pdbsum/5u6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/UFO_HUMAN UFO_HUMAN] Note=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/UFO_HUMAN UFO_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. In case of filovirus infection, seems to function as a cell entry factor.<ref>PMID:1656220</ref> <ref>PMID:10403904</ref> <ref>PMID:11484958</ref> <ref>PMID:12364394</ref> <ref>PMID:12490074</ref> <ref>PMID:15507525</ref> <ref>PMID:15733062</ref> <ref>PMID:17005688</ref> <ref>PMID:18840707</ref> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gajiwala KS]] | ||
| + | [[Category: Grodsky N]] | ||
Current revision
Structure of the Axl kinase domain in complex with a macrocyclic inhibitor
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