View source for 9me3


==Bruton's tyrosine kinase with mutations in the activation loop in complex with compound P301390==
<StructureSection load='9me3' size='340' side='right'caption='[[9me3]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9me3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ME3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ME3 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]] 3.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BJE:3-(4-phenoxyphenyl)-1~{H}-pyrazolo[3,4-d]pyrimidin-4-amine'>A1BJE</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=9me3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9me3 OCA], [https://pdbe.org/9me3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9me3 RCSB], [https://www.ebi.ac.uk/pdbsum/9me3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9me3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BTK_MOUSE BTK_MOUSE] Defects in Btk are the cause of murine X-linked immunodeficiency (XID).
== Function ==
[https://www.uniprot.org/uniprot/BTK_MOUSE BTK_MOUSE] Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis.<ref>PMID:10852954</ref> <ref>PMID:11120822</ref> <ref>PMID:16738337</ref> <ref>PMID:17725607</ref> <ref>PMID:7538439</ref> <ref>PMID:8629002</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Andreotti AH]]
[[Category: Bravo E]]
[[Category: Li X]]
[[Category: Lin DY]]
[[Category: Tonge PJ]]