2hk5

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{{STRUCTURE_2hk5| PDB=2hk5 | SCENE= }}
 
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===Hck Kinase in Complex with Lck targetted Inhibitor PG-1009247===
 
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{{ABSTRACT_PUBMED_16997556}}
 
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==Disease==
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==Hck Kinase in Complex with Lck targetted Inhibitor PG-1009247==
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[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref><ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref><ref>PMID:20452982</ref>
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<StructureSection load='2hk5' size='340' side='right'caption='[[2hk5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2hk5]] 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=2HK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HK5 FirstGlance]. <br>
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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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BM:3-{[2-(1H-BENZIMIDAZOL-1-YL)-6-{[2-(DIETHYLAMINO)ETHYL]AMINO}PYRIMIDIN-4-YL]AMINO}-4-METHYLPHENOL'>1BM</scene></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=2hk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hk5 OCA], [https://pdbe.org/2hk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hk5 RCSB], [https://www.ebi.ac.uk/pdbsum/2hk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hk5 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</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/hk/2hk5_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=2hk5 ConSurf].
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<div style="clear:both"></div>
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==Function==
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==See Also==
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[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref><ref>PMID:7535819</ref><ref>PMID:9406996</ref><ref>PMID:9407116</ref><ref>PMID:10092522</ref><ref>PMID:10779760</ref><ref>PMID:10973280</ref><ref>PMID:12411494</ref><ref>PMID:11741929</ref><ref>PMID:11904303</ref><ref>PMID:11896602</ref><ref>PMID:15010462</ref><ref>PMID:15952790</ref><ref>PMID:15998323</ref><ref>PMID:17535448</ref><ref>PMID:17310994</ref><ref>PMID:19114024</ref><ref>PMID:19903482</ref><ref>PMID:20452982</ref>
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*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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[[2hk5]] is a 1 chain structure with 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=2HK5 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:016997556</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific protein-tyrosine kinase]]
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[[Category: Large Structures]]
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[[Category: Evdokimov, A G.]]
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[[Category: Evdokimov AG]]
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[[Category: Mekel, M J.]]
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[[Category: Mekel MJ]]
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[[Category: Pokross, M E.]]
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[[Category: Pokross ME]]
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[[Category: Sabat, M P.]]
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[[Category: Sabat MP]]
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[[Category: Walter, R L.]]
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[[Category: Walter RL]]
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[[Category: Hck]]
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[[Category: Kinase domain]]
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[[Category: Src-family]]
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[[Category: Transferase]]
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Current revision

Hck Kinase in Complex with Lck targetted Inhibitor PG-1009247

PDB ID 2hk5

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