7r7k

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<StructureSection load='7r7k' size='340' side='right'caption='[[7r7k]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
<StructureSection load='7r7k' size='340' side='right'caption='[[7r7k]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7r7k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R7K FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7r7k]] 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=7R7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R7K FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25J:4-(6-amino-5-{(1R)-1-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]ethoxy}pyridin-3-yl)-2,3-dihydro-1H-isoindol-1-one'>25J</scene></td></tr>
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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]] 1.831&#8491;</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25J:4-(6-amino-5-{(1R)-1-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]ethoxy}pyridin-3-yl)-2,3-dihydro-1H-isoindol-1-one'>25J</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=7r7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r7k OCA], [https://pdbe.org/7r7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r7k RCSB], [https://www.ebi.ac.uk/pdbsum/7r7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r7k 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=7r7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r7k OCA], [https://pdbe.org/7r7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r7k RCSB], [https://www.ebi.ac.uk/pdbsum/7r7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r7k ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/ALK_HUMAN ALK_HUMAN]] Note=A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. Note=A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. Note=A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. Defects in ALK are the cause of susceptibility to neuroblastoma type 3 (NBLST3) [MIM:[https://omim.org/entry/613014 613014]]. Neuroblastoma is a common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.<ref>PMID:18724359</ref> <ref>PMID:18923523</ref> <ref>PMID:18923525</ref> Note=The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth.
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[https://www.uniprot.org/uniprot/ALK_HUMAN ALK_HUMAN] Note=A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. Note=A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. Note=A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. Defects in ALK are the cause of susceptibility to neuroblastoma type 3 (NBLST3) [MIM:[https://omim.org/entry/613014 613014]. Neuroblastoma is a common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.<ref>PMID:18724359</ref> <ref>PMID:18923523</ref> <ref>PMID:18923525</ref> Note=The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth.
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/ALK_HUMAN ALK_HUMAN]] Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.<ref>PMID:11387242</ref> <ref>PMID:11121404</ref> <ref>PMID:11278720</ref> <ref>PMID:11809760</ref> <ref>PMID:12107166</ref> <ref>PMID:12122009</ref> <ref>PMID:15226403</ref> <ref>PMID:15908427</ref> <ref>PMID:16317043</ref> <ref>PMID:17274988</ref> <ref>PMID:16878150</ref>
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[https://www.uniprot.org/uniprot/ALK_HUMAN ALK_HUMAN] Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.<ref>PMID:11387242</ref> <ref>PMID:11121404</ref> <ref>PMID:11278720</ref> <ref>PMID:11809760</ref> <ref>PMID:12107166</ref> <ref>PMID:12122009</ref> <ref>PMID:15226403</ref> <ref>PMID:15908427</ref> <ref>PMID:16317043</ref> <ref>PMID:17274988</ref> <ref>PMID:16878150</ref>
<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: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: McTigue M]]
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[[Category: McTigue, M]]
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[[Category: Kinase]]
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[[Category: Transferase]]
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Current revision

Structure of Human Anaplastic Lymphoma Kinase Domain in complex with (4-[6-amino-5-[(1~{R})-1-[5-fluoro-2-(triazol-2-yl)phenyl]ethoxy]-3-pyridyl]isoindolin-1-one)

PDB ID 7r7k

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