4hzr - Revision history

OCA at 11:48, 1 March 2024

OCA — Fri, 01 Mar 2024 11:48:21 GMT

←Older revision		Revision as of 11:48, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hzr]] 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HZR FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hzr]] 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HZR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.31Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [https://pdbe.org/4hzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [https://www.ebi.ac.uk/pdbsum/4hzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hzr 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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [https://pdbe.org/4hzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [https://www.ebi.ac.uk/pdbsum/4hzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hzr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ACK1_HUMAN ACK1_HUMAN] Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.<ref>PMID:10652228</ref> <ref>PMID:11278436</ref> <ref>PMID:16257963</ref> <ref>PMID:16247015</ref> <ref>PMID:17038317</ref> <ref>PMID:16472662</ref> <ref>PMID:18435854</ref> <ref>PMID:18262180</ref> <ref>PMID:19815557</ref> <ref>PMID:20383201</ref> <ref>PMID:20333297</ref>		[https://www.uniprot.org/uniprot/ACK1_HUMAN ACK1_HUMAN] Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.<ref>PMID:10652228</ref> <ref>PMID:11278436</ref> <ref>PMID:16257963</ref> <ref>PMID:16247015</ref> <ref>PMID:17038317</ref> <ref>PMID:16472662</ref> <ref>PMID:18435854</ref> <ref>PMID:18262180</ref> <ref>PMID:19815557</ref> <ref>PMID:20383201</ref> <ref>PMID:20333297</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The non-receptor tyrosine kinase Ack1 belongs to a unique multi-domain protein kinase family, Ack. Ack is the only family of SH3 domain containing kinases to have an SH3 domain following the kinase domain; others have their SH3 domains preceding the kinase domain. Previous reports have suggested that Ack1 does not require phosphorylation for activation and the enzyme activity of the isolated kinase domain is low relative to other kinases. It has been shown to dimerize in the cellular environment, which augments its enzyme activity. The molecular mechanism of activation, however, remains unknown. Here we present structural and biochemical data on Ack1 kinase domain, and kinase domain+SH3 domain that suggest that Ack1 in its monomeric state is autoinhibited, like EGFR and CDK. The activation of the kinase domain may require N-lobe mediated symmetric dimerization, which may be facilitated by the N-terminal SAM domain. Results presented here show that SH3 domain, unlike in Src family tyrosine kinases, does not directly control the activation state of the enzyme. Instead we speculate that the SH3 domain may play a regulatory role by facilitating binding of the MIG6 homologous region to the kinase domain. We postulate that features of Ack1 activation and regulation parallel those of receptor tyrosine kinase EGFR with some interesting differences.
-
-	Ack1: activation and regulation by allostery.,Gajiwala KS, Maegley K, Ferre R, He YA, Yu X PLoS One. 2013;8(1):e53994. doi: 10.1371/journal.pone.0053994. Epub 2013 Jan 14. PMID:23342057<ref>PMID:23342057</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4hzr" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:29, 9 November 2022

OCA — Wed, 09 Nov 2022 08:29:45 GMT

←Older revision		Revision as of 08:29, 9 November 2022
Line 1:		Line 1:

	==Crystal structure of Ack1 kinase domain==		==Crystal structure of Ack1 kinase domain==
-	<StructureSection load='4hzr' size='340' side='right' caption='[[4hzr]], [[Resolution\|resolution]] 1.31Å' scene=''>	+	<StructureSection load='4hzr' size='340' side='right'caption='[[4hzr]], [[Resolution\|resolution]] 1.31Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hzr]] is a 2 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4HZR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hzr]] 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HZR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hzs\|4hzs]]</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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [https://pdbe.org/4hzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [https://www.ebi.ac.uk/pdbsum/4hzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hzr ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNK2, ACK1 ([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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [~~http~~://pdbe.org/4hzr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4hzr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4hzr ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ACK1_HUMAN ACK1_HUMAN]] Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.<ref>PMID:10652228</ref> <ref>PMID:11278436</ref> <ref>PMID:16257963</ref> <ref>PMID:16247015</ref> <ref>PMID:17038317</ref> <ref>PMID:16472662</ref> <ref>PMID:18435854</ref> <ref>PMID:18262180</ref> <ref>PMID:19815557</ref> <ref>PMID:20383201</ref> <ref>PMID:20333297</ref>	+	[https://www.uniprot.org/uniprot/ACK1_HUMAN ACK1_HUMAN] Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.<ref>PMID:10652228</ref> <ref>PMID:11278436</ref> <ref>PMID:16257963</ref> <ref>PMID:16247015</ref> <ref>PMID:17038317</ref> <ref>PMID:16472662</ref> <ref>PMID:18435854</ref> <ref>PMID:18262180</ref> <ref>PMID:19815557</ref> <ref>PMID:20383201</ref> <ref>PMID:20333297</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4hzr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4hzr" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Gajiwala, K S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Active state]]~~	+	[[Category: Gajiwala KS]]
-	~~[[Category: Phosphotransfer]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 03:57, 5 August 2016

OCA — Fri, 05 Aug 2016 03:57:56 GMT

←Older revision		Revision as of 03:57, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of Ack1 kinase domain==		==Crystal structure of Ack1 kinase domain==
	<StructureSection load='4hzr' size='340' side='right' caption='[[4hzr]], [[Resolution\|resolution]] 1.31Å' scene=''>		<StructureSection load='4hzr' size='340' side='right' caption='[[4hzr]], [[Resolution\|resolution]] 1.31Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hzr]] is a 2 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HZR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hzr]] is a 2 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HZR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hzs\|4hzs]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hzs\|4hzs]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNK2, ACK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNK2, ACK1 ([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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [http://www.ebi.ac.uk/pdbsum/4hzr PDBsum]</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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [http://pdbe.org/4hzr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [http://www.ebi.ac.uk/pdbsum/4hzr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hzr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4hzr" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Gajiwala, K S]]		[[Category: Gajiwala, K S]]
	[[Category: Active state]]		[[Category: Active state]]
	[[Category: Phosphotransfer]]		[[Category: Phosphotransfer]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 22:45, 24 December 2014

OCA — Wed, 24 Dec 2014 22:45:36 GMT

←Older revision		Revision as of 22:45, 24 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4hzr.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of Ack1 kinase domain==
		+	<StructureSection load='4hzr' size='340' side='right' caption='[[4hzr]], [[Resolution\|resolution]] 1.31Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4hzr]] is a 2 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=4HZR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HZR FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hzs\|4hzs]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNK2, ACK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4hzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hzr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hzr RCSB], [http://www.ebi.ac.uk/pdbsum/4hzr PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ACK1_HUMAN ACK1_HUMAN]] Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.<ref>PMID:10652228</ref> <ref>PMID:11278436</ref> <ref>PMID:16257963</ref> <ref>PMID:16247015</ref> <ref>PMID:17038317</ref> <ref>PMID:16472662</ref> <ref>PMID:18435854</ref> <ref>PMID:18262180</ref> <ref>PMID:19815557</ref> <ref>PMID:20383201</ref> <ref>PMID:20333297</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The non-receptor tyrosine kinase Ack1 belongs to a unique multi-domain protein kinase family, Ack. Ack is the only family of SH3 domain containing kinases to have an SH3 domain following the kinase domain; others have their SH3 domains preceding the kinase domain. Previous reports have suggested that Ack1 does not require phosphorylation for activation and the enzyme activity of the isolated kinase domain is low relative to other kinases. It has been shown to dimerize in the cellular environment, which augments its enzyme activity. The molecular mechanism of activation, however, remains unknown. Here we present structural and biochemical data on Ack1 kinase domain, and kinase domain+SH3 domain that suggest that Ack1 in its monomeric state is autoinhibited, like EGFR and CDK. The activation of the kinase domain may require N-lobe mediated symmetric dimerization, which may be facilitated by the N-terminal SAM domain. Results presented here show that SH3 domain, unlike in Src family tyrosine kinases, does not directly control the activation state of the enzyme. Instead we speculate that the SH3 domain may play a regulatory role by facilitating binding of the MIG6 homologous region to the kinase domain. We postulate that features of Ack1 activation and regulation parallel those of receptor tyrosine kinase EGFR with some interesting differences.

-	~~{{STRUCTURE_4hzr\| PDB=4hzr \| SCENE= }}~~	+	Ack1: activation and regulation by allostery.,Gajiwala KS, Maegley K, Ferre R, He YA, Yu X PLoS One. 2013;8(1):e53994. doi: 10.1371/journal.pone.0053994. Epub 2013 Jan 14. PMID:23342057<ref>PMID:23342057</ref>

-	~~===Crystal structure~~ of ~~Ack1 kinase domain===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_23342057}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[4hzr]] is a 2 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=4HZR OCA].~~	+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Gajiwala, K S.]]	+	[[Category: Gajiwala, K S]]
	[[Category: Active state]]		[[Category: Active state]]
	[[Category: Phosphotransfer]]		[[Category: Phosphotransfer]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 12:54, 6 February 2013

OCA — Wed, 06 Feb 2013 12:54:58 GMT

←Older revision		Revision as of 12:54, 6 February 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4hzr.jpg\|left\|200px]]

-	~~The entry~~ 4hzr ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4hzr\| PDB=4hzr \| SCENE= }}

-	~~Authors: Gajiwala, K.S.~~	+	===Crystal structure of Ack1 kinase domain===

-	~~Description: Crystal~~ structure ~~of Ack1 kinase domain~~	+	{{ABSTRACT_PUBMED_23342057}}
		+
		+	==About this Structure==
		+	[[4hzr]] is a 2 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=4HZR OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Gajiwala, K S.]]
		+	[[Category: Active state]]
		+	[[Category: Phosphotransfer]]
		+	[[Category: Transferase]]

OCA at 20:46, 12 December 2012

OCA — Wed, 12 Dec 2012 20:46:28 GMT

←Older revision		Revision as of 20:46, 12 December 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4hzr is ON HOLD	+	The entry 4hzr is ON HOLD until Paper Publication

	Authors: Gajiwala, K.S.		Authors: Gajiwala, K.S.

	Description: Crystal structure of Ack1 kinase domain		Description: Crystal structure of Ack1 kinase domain

OCA: Protected "4hzr" [edit=sysop:move=sysop]

OCA — Wed, 21 Nov 2012 09:11:29 GMT

Protected "4hzr" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:11, 21 November 2012

OCA: New page: '''Unreleased structure''' The entry 4hzr is ON HOLD Authors: Gajiwala, K.S. Description: Crystal structure of Ack1 kinase domain

OCA — Wed, 21 Nov 2012 09:11:27 GMT

New page: '''Unreleased structure''' The entry 4hzr is ON HOLD Authors: Gajiwala, K.S. Description: Crystal structure of Ack1 kinase domain

New page

'''Unreleased structure'''

The entry 4hzr is ON HOLD

Authors: Gajiwala, K.S.

Description: Crystal structure of Ack1 kinase domain