OCA at 06:45, 27 November 2019

2019-11-27T06:45:48Z

←Older revision		Revision as of 06:45, 27 November 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6itv is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of activated c-KIT in complex with compound==
-		+	<StructureSection load='6itv' size='340' side='right'caption='[[6itv]], [[Resolution\|resolution]] 1.88Å' scene=''>
-	~~Authors~~: Wu, T.S., Wu, S.Y.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6itv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ITV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ITV FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~activated c-~~KIT in ~~complex~~ with ~~compound~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AWO:N-(5-ethyl-1,2-oxazol-3-yl)-N-[4-(2-{[6-(4-ethylpyrazin-1(4H)-yl)pyrimidin-4-yl]amino}-1,3-thiazol-5-yl)phenyl]urea'>AWO</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	[[Category: Wu, T.S]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
-	[[Category: Wu, S.Y]]	+	<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=6itv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6itv OCA], [http://pdbe.org/6itv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6itv RCSB], [http://www.ebi.ac.uk/pdbsum/6itv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6itv ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KIT_HUMAN KIT_HUMAN]] Defects in KIT are a cause of piebald trait (PBT) [MIM:[http://omim.org/entry/172800 172800]]; also known as piebaldism. PBT is an autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.<ref>PMID:1376329</ref> <ref>PMID:1370874</ref> <ref>PMID:1717985</ref> <ref>PMID:7687267</ref> <ref>PMID:8680409</ref> <ref>PMID:9029028</ref> <ref>PMID:9450866</ref> <ref>PMID:9699740</ref> <ref>PMID:11074500</ref> Defects in KIT are a cause of gastrointestinal stromal tumor (GIST) [MIM:[http://omim.org/entry/606764 606764]].<ref>PMID:9029028</ref> <ref>PMID:9697690</ref> <ref>PMID:9438854</ref> <ref>PMID:11505412</ref> <ref>PMID:15824741</ref> Defects in KIT have been associated with testicular germ cell tumor (TGCT) [MIM:[http://omim.org/entry/273300 273300]]. A common solid malignancy in males. Germ cell tumors of the testis constitute 95% of all testicular neoplasms.<ref>PMID:9029028</ref> Defects in KIT are a cause of acute myelogenous leukemia (AML) [MIM:[http://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 KIT are detected 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 kinase domain can result in a constitutively activated kinase.<ref>PMID:9029028</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KIT_HUMAN KIT_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.<ref>PMID:7520444</ref> <ref>PMID:9528781</ref> <ref>PMID:10397721</ref> <ref>PMID:12444928</ref> <ref>PMID:12878163</ref> <ref>PMID:12511554</ref> <ref>PMID:17904548</ref> <ref>PMID:19265199</ref> <ref>PMID:21640708</ref> <ref>PMID:21135090</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Wu, S Y]]
		+	[[Category: Wu, T S]]
		+	[[Category: Oncoprotein]]
		+	[[Category: Receptor tyrosine kinase dfg motif conformational control inhibitor]]

OCA at 05:00, 26 June 2019

2019-06-26T05:00:29Z

←Older revision		Revision as of 05:00, 26 June 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6itv is ON HOLD	+	The entry 6itv is ON HOLD until Paper Publication

	Authors: Wu, T.S., Wu, S.Y.		Authors: Wu, T.S., Wu, S.Y.

OCA: Protected "6itv" [edit=sysop:move=sysop]

2018-12-05T05:10:24Z

Protected "6itv" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:10, 5 December 2018

OCA: New page: '''Unreleased structure''' The entry 6itv is ON HOLD Authors: Wu, T.S., Wu, S.Y. Description: Crystal structure of activated c-KIT in complex with compound [[Category: Unreleased Struc...

2018-12-05T05:10:23Z

New page: '''Unreleased structure''' The entry 6itv is ON HOLD Authors: Wu, T.S., Wu, S.Y. Description: Crystal structure of activated c-KIT in complex with compound [[Category: Unreleased Struc...

New page

'''Unreleased structure'''

The entry 6itv is ON HOLD

Authors: Wu, T.S., Wu, S.Y.

Description: Crystal structure of activated c-KIT in complex with compound
[[Category: Unreleased Structures]]
[[Category: Wu, T.S]]
[[Category: Wu, S.Y]]

6itv - Revision history

OCA at 06:45, 27 November 2019

OCA at 05:00, 26 June 2019

OCA: Protected "6itv" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6itv is ON HOLD Authors: Wu, T.S., Wu, S.Y. Description: Crystal structure of activated c-KIT in complex with compound [[Category: Unreleased Struc...