3qs7

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<StructureSection load='3qs7' size='340' side='right'caption='[[3qs7]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
<StructureSection load='3qs7' size='340' side='right'caption='[[3qs7]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3qs7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QS7 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3qs7]] is a 8 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=3QS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QS7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qs9|3qs9]]</div></td></tr>
 
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FLT3LG ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FLT3, STK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=3qs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qs7 OCA], [https://pdbe.org/3qs7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qs7 RCSB], [https://www.ebi.ac.uk/pdbsum/3qs7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qs7 ProSAT]</span></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=3qs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qs7 OCA], [https://pdbe.org/3qs7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qs7 RCSB], [https://www.ebi.ac.uk/pdbsum/3qs7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qs7 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[[https://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Defects in FLT3 are a cause of acute myelogenous leukemia (AML) [MIM:[https://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.<ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:14504097</ref> <ref>PMID:9737679</ref> <ref>PMID:18305215</ref> <ref>PMID:11290608</ref> <ref>PMID:8946930</ref> <ref>PMID:11442493</ref>
 
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/FLT3L_HUMAN FLT3L_HUMAN]] Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins. [[https://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.<ref>PMID:7507245</ref> <ref>PMID:10080542</ref> <ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:16627759</ref> <ref>PMID:18490735</ref> <ref>PMID:20111072</ref> <ref>PMID:21067588</ref> <ref>PMID:21262971</ref> <ref>PMID:21516120</ref> <ref>PMID:14504097</ref>
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[https://www.uniprot.org/uniprot/FLT3L_HUMAN FLT3L_HUMAN] Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Savvides SN]]
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[[Category: Savvides, S N]]
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[[Category: Verstraete K]]
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[[Category: Verstraete, K]]
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[[Category: Cytokine-receptor complex]]
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[[Category: Cytokine-signaling protein complex]]
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[[Category: Extracellular complex]]
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[[Category: Four-helical bundle cytokine]]
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[[Category: Immunoglobulin-like domain]]
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[[Category: Receptor tyrosine kinase]]
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Revision as of 08:08, 11 January 2023

Crystal structure of a human Flt3 ligand-receptor ternary complex

PDB ID 3qs7

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