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==Structure of Maternal Embryonic Leucine Zipper Kinase==
==Structure of Maternal Embryonic Leucine Zipper Kinase==
<StructureSection load='5twy' size='340' side='right' caption='[[5twy]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
<StructureSection load='5twy' size='340' side='right'caption='[[5twy]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5twy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TWY FirstGlance]. <br>
<table><tr><td colspan='2'>[[5twy]] is a 2 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=5TWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TWY FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7LY:2-(benzyloxy)-4-(1H-pyrazol-4-yl)-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzamide'>7LY</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.91&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tvt|5tvt]], [[5twl|5twl]], [[5twu|5twu]], [[5twz|5twz]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7LY:2-(benzyloxy)-4-(1H-pyrazol-4-yl)-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzamide'>7LY</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5twy OCA], [http://pdbe.org/5twy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5twy RCSB], [http://www.ebi.ac.uk/pdbsum/5twy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5twy 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=5twy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5twy OCA], [https://pdbe.org/5twy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5twy RCSB], [https://www.ebi.ac.uk/pdbsum/5twy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5twy ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.  
[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN] Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>
[https://www.uniprot.org/uniprot/MELK_HUMAN MELK_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.<ref>PMID:11802789</ref> <ref>PMID:12400006</ref> <ref>PMID:14699119</ref> <ref>PMID:15908796</ref> <ref>PMID:16216881</ref> <ref>PMID:17280616</ref>  
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Dhe-Paganon, S]]
[[Category: Homo sapiens]]
[[Category: Seo, H S]]
[[Category: Large Structures]]
[[Category: Breast cancer]]
[[Category: Dhe-Paganon S]]
[[Category: Inhibitor]]
[[Category: Seo H-S]]
[[Category: Kinase]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 14:23, 6 March 2024

Structure of Maternal Embryonic Leucine Zipper Kinase

5twy, resolution 2.91Å

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