1rjb

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[[Image:1rjb.gif|left|200px]]
 
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==Crystal Structure of FLT3==
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The line below this paragraph, containing "STRUCTURE_1rjb", creates the "Structure Box" on the page.
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<StructureSection load='1rjb' size='340' side='right'caption='[[1rjb]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1rjb]] 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=1RJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RJB FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rjb OCA], [https://pdbe.org/1rjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rjb RCSB], [https://www.ebi.ac.uk/pdbsum/1rjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rjb ProSAT]</span></td></tr>
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{{STRUCTURE_1rjb| PDB=1rjb | SCENE= }}
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</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>
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== Function ==
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[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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rj/1rjb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rjb ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure of FLT3'''
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==See Also==
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*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
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== References ==
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==Overview==
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<references/>
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FLT3 is a type III receptor tyrosine kinase that is thought to play a key role in hematopoiesis. Certain classes of FLT3 mutations cause constitutively activated forms of the receptor that are found in significant numbers of patients with acute myelogenous leukemia (AML). The mutations occur either in the activation loop, for example, as point mutations of Asp835 or as internal tandem duplication (ITD) sequences in the juxtamembrane (JM) domain. To further understand the nature of FLT3 autoinhibition and regulation, we have determined the crystal structure of the autoinhibited form of FLT3. This structure shows the autoinhibitory conformation of a complete JM domain in this class of receptor tyrosine kinases. The detailed inhibitory mechanism of the JM domain is revealed, which is likely utilized by other members of type III receptor tyrosine kinases.
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__TOC__
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</StructureSection>
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==About this Structure==
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1RJB is a [[Single protein]] structure of 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=1RJB OCA].
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==Reference==
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The structural basis for autoinhibition of FLT3 by the juxtamembrane domain., Griffith J, Black J, Faerman C, Swenson L, Wynn M, Lu F, Lippke J, Saxena K, Mol Cell. 2004 Jan 30;13(2):169-78. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14759363 14759363]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Transferase]]
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[[Category: Black J]]
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[[Category: Black, J.]]
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[[Category: Faerman C]]
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[[Category: Faerman, C.]]
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[[Category: Griffith J]]
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[[Category: Griffith, J.]]
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[[Category: Lippke J]]
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[[Category: Lippke, J.]]
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[[Category: Lu F]]
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[[Category: Lu, F.]]
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[[Category: Saxena K]]
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[[Category: Saxena, K.]]
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[[Category: Swenson L]]
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[[Category: Swenson, L.]]
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[[Category: Wynn M]]
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[[Category: Wynn, M.]]
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[[Category: Autoinhibition]]
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[[Category: Juxtamembrane domain]]
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[[Category: Kinase]]
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[[Category: Structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:33:47 2008''
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Current revision

Crystal Structure of FLT3

PDB ID 1rjb

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