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==Crystal Structure of Ack1 with compound T74==
==Crystal Structure of Ack1 with compound T74==
<StructureSection load='3eqr' size='340' side='right' caption='[[3eqr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='3eqr' size='340' side='right'caption='[[3eqr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3eqr]] 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=3EQR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EQR FirstGlance]. <br>
<table><tr><td colspan='2'>[[3eqr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EQR 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=T74:N~3~-(2,6-DIMETHYLPHENYL)-1-(3-METHOXY-3-METHYLBUTYL)-N~6~-(4-PIPERAZIN-1-YLPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE-3,6-DIAMINE'>T74</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=T74:N~3~-(2,6-DIMETHYLPHENYL)-1-(3-METHOXY-3-METHYLBUTYL)-N~6~-(4-PIPERAZIN-1-YLPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE-3,6-DIAMINE'>T74</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eqp|3eqp]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3eqp|3eqp]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNK2, ACK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=3eqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eqr OCA], [http://pdbe.org/3eqr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eqr RCSB], [http://www.ebi.ac.uk/pdbsum/3eqr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3eqr 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=3eqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eqr OCA], [https://pdbe.org/3eqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eqr RCSB], [https://www.ebi.ac.uk/pdbsum/3eqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eqr 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>   
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</div>
</div>
<div class="pdbe-citations 3eqr" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 3eqr" style="background-color:#fffaf0;"></div>
==See Also==
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Liu, J]]
[[Category: Liu, J]]

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