5mah - Revision history

OCA at 07:26, 1 May 2024

OCA — Wed, 01 May 2024 07:26:06 GMT

←Older revision		Revision as of 07:26, 1 May 2024
Line 12:		Line 12:
	== Function ==		== Function ==
	[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>		[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>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
-
-	The target landscape of clinical kinase drugs.,Klaeger S, Heinzlmeir S, Wilhelm M, Polzer H, Vick B, Koenig PA, Reinecke M, Ruprecht B, Petzoldt S, Meng C, Zecha J, Reiter K, Qiao H, Helm D, Koch H, Schoof M, Canevari G, Casale E, Depaolini SR, Feuchtinger A, Wu Z, Schmidt T, Rueckert L, Becker W, Huenges J, Garz AK, Gohlke BO, Zolg DP, Kayser G, Vooder T, Preissner R, Hahne H, Tonisson N, Kramer K, Gotze K, Bassermann F, Schlegl J, Ehrlich HC, Aiche S, Walch A, Greif PA, Schneider S, Felder ER, Ruland J, Medard G, Jeremias I, Spiekermann K, Kuster B Science. 2017 Dec 1;358(6367). pii: 358/6367/eaan4368. doi:, 10.1126/science.aan4368. PMID:29191878<ref>PMID:29191878</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5mah" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:35, 1 November 2023

OCA — Wed, 01 Nov 2023 18:35:04 GMT

←Older revision		Revision as of 18:35, 1 November 2023
Line 1:		Line 1:

	==Crystal structure of MELK in complex with an inhibitor==		==Crystal structure of MELK in complex with an inhibitor==
-	<StructureSection load='5mah' size='340' side='right' caption='[[5mah]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5mah' size='340' side='right'caption='[[5mah]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mah]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MAH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MAH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mah]] 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=5MAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MAH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7KD:~{N}-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide'>7KD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MELK, KIAA0175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7KD:~{N}-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide'>7KD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5mah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mah OCA], [~~http~~://pdbe.org/5mah PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mah RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mah PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mah 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=5mah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mah OCA], [https://pdbe.org/5mah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mah RCSB], [https://www.ebi.ac.uk/pdbsum/5mah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mah 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Canevari, G~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Casale, E~~]]	+	[[Category: Canevari G]]
-	[[Category: ~~Depaolini, S Re~~]]	+	[[Category: Casale E]]
-	[[Category: Felder, E]]	+	[[Category: Felder E]]
-	[[Category: Heinzlmeir, S]]	+	[[Category: Heinzlmeir S]]
-	[[Category: Kuster, B]]	+	[[Category: Kuster B]]
-	[[Category: ~~Complex]]~~	+	[[Category: Re Depaolini S]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:27, 13 December 2017

OCA — Wed, 13 Dec 2017 07:27:29 GMT

←Older revision		Revision as of 07:27, 13 December 2017
Line 3:		Line 3:
	<StructureSection load='5mah' size='340' side='right' caption='[[5mah]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5mah' size='340' side='right' caption='[[5mah]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mah]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MAH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MAH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mah]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MAH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MAH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7KD:~{N}-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide'>7KD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7KD:~{N}-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide'>7KD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MELK, KIAA0175 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5mah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mah OCA], [http://pdbe.org/5mah PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mah RCSB], [http://www.ebi.ac.uk/pdbsum/5mah PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mah ProSAT]</span></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=5mah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mah OCA], [http://pdbe.org/5mah PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mah RCSB], [http://www.ebi.ac.uk/pdbsum/5mah PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mah ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== 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>		[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.
		+
		+	The target landscape of clinical kinase drugs.,Klaeger S, Heinzlmeir S, Wilhelm M, Polzer H, Vick B, Koenig PA, Reinecke M, Ruprecht B, Petzoldt S, Meng C, Zecha J, Reiter K, Qiao H, Helm D, Koch H, Schoof M, Canevari G, Casale E, Depaolini SR, Feuchtinger A, Wu Z, Schmidt T, Rueckert L, Becker W, Huenges J, Garz AK, Gohlke BO, Zolg DP, Kayser G, Vooder T, Preissner R, Hahne H, Tonisson N, Kramer K, Gotze K, Bassermann F, Schlegl J, Ehrlich HC, Aiche S, Walch A, Greif PA, Schneider S, Felder ER, Ruland J, Medard G, Jeremias I, Spiekermann K, Kuster B Science. 2017 Dec 1;358(6367). pii: 358/6367/eaan4368. doi:, 10.1126/science.aan4368. PMID:29191878<ref>PMID:29191878</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5mah" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Canevari, G]]		[[Category: Canevari, G]]
	[[Category: Casale, E]]		[[Category: Casale, E]]

OCA at 07:09, 6 December 2017

OCA — Wed, 06 Dec 2017 07:09:39 GMT

←Older revision		Revision as of 07:09, 6 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5mah ~~is ON HOLD until Dec 31 2018~~	+	==Crystal structure of MELK in complex with an inhibitor==
-		+	<StructureSection load='5mah' size='340' side='right' caption='[[5mah]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~: ~~Canevari, G~~., ~~Re Depaolini~~, S., ~~Casale~~, E., ~~Felder~~, E., ~~Kuster~~, B., ~~Heinzlmeir~~, S.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5mah]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MAH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MAH FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of MELK~~ in ~~complex with~~ an ~~inhibitor~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7KD:~{N}-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide'>7KD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5mah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mah OCA], [http://pdbe.org/5mah PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mah RCSB], [http://www.ebi.ac.uk/pdbsum/5mah PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mah ProSAT]</span></td></tr>
		+	</table>
		+	== 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.
		+	== 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Canevari, G]]
	[[Category: Casale, E]]		[[Category: Casale, E]]
		+	[[Category: Depaolini, S Re]]
		+	[[Category: Felder, E]]
	[[Category: Heinzlmeir, S]]		[[Category: Heinzlmeir, S]]
	[[Category: Kuster, B]]		[[Category: Kuster, B]]
-	[[Category: ~~Re Depaolini, S~~]]	+	[[Category: Complex]]
-	[[Category: ~~Canevari, G~~]]	+	[[Category: Inhibitor]]
-	[[Category: ~~Felder, E~~]]	+	[[Category: Kinase]]
		+	[[Category: Transferase]]

OCA at 05:57, 18 October 2017

OCA — Wed, 18 Oct 2017 05:57:30 GMT

←Older revision		Revision as of 05:57, 18 October 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5mah is ON HOLD until ~~Nov 03~~ 2018	+	The entry 5mah is ON HOLD until Dec 31 2018

	Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S.		Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S.
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Casale, E]]		[[Category: Casale, E]]
-	[[Category: Canevari, G]]
	[[Category: Heinzlmeir, S]]		[[Category: Heinzlmeir, S]]
	[[Category: Kuster, B]]		[[Category: Kuster, B]]
	[[Category: Re Depaolini, S]]		[[Category: Re Depaolini, S]]
		+	[[Category: Canevari, G]]
	[[Category: Felder, E]]		[[Category: Felder, E]]

OCA at 11:09, 9 March 2017

OCA — Thu, 09 Mar 2017 11:09:42 GMT

←Older revision		Revision as of 11:09, 9 March 2017
Line 10:		Line 10:
	[[Category: Canevari, G]]		[[Category: Canevari, G]]
	[[Category: Heinzlmeir, S]]		[[Category: Heinzlmeir, S]]
-	[[Category: Felder, E]]
	[[Category: Kuster, B]]		[[Category: Kuster, B]]
	[[Category: Re Depaolini, S]]		[[Category: Re Depaolini, S]]
		+	[[Category: Felder, E]]

OCA at 13:23, 2 January 2017

OCA — Mon, 02 Jan 2017 13:23:29 GMT

←Older revision		Revision as of 13:23, 2 January 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5mah is ON HOLD	+	The entry 5mah is ON HOLD until Nov 03 2018

	Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S.		Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S.

OCA: Protected "5mah" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 16:34:09 GMT

Protected "5mah" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:34, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5mah is ON HOLD Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S. Description: Crystal structure of MELK ...

OCA — Fri, 09 Dec 2016 16:34:07 GMT

New page: '''Unreleased structure''' The entry 5mah is ON HOLD Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S. Description: Crystal structure of MELK ...

New page

'''Unreleased structure'''

The entry 5mah is ON HOLD

Authors: Canevari, G., Re Depaolini, S., Casale, E., Felder, E., Kuster, B., Heinzlmeir, S.

Description: Crystal structure of MELK in complex with an inhibitor
[[Category: Unreleased Structures]]
[[Category: Casale, E]]
[[Category: Canevari, G]]
[[Category: Heinzlmeir, S]]
[[Category: Felder, E]]
[[Category: Kuster, B]]
[[Category: Re Depaolini, S]]