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6aj4

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<StructureSection load='6aj4' size='340' side='right'caption='[[6aj4]], [[Resolution|resolution]] 3.26&Aring;' scene=''>
<StructureSection load='6aj4' size='340' side='right'caption='[[6aj4]], [[Resolution|resolution]] 3.26&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6aj4]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AJ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AJ4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6aj4]] is a 8 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=6AJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AJ4 FirstGlance]. <br>
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</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=6aj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aj4 OCA], [http://pdbe.org/6aj4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aj4 RCSB], [http://www.ebi.ac.uk/pdbsum/6aj4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aj4 ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.256&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6aj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aj4 OCA], [https://pdbe.org/6aj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aj4 RCSB], [https://www.ebi.ac.uk/pdbsum/6aj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aj4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN]] Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome. The disease is caused by mutations affecting the gene represented in this entry.
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[https://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN] Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN]] Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity).[UniProtKB:Q8R1A4]<ref>PMID:16982419</ref> [[http://www.uniprot.org/uniprot/CDC42_HUMAN CDC42_HUMAN]] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.<ref>PMID:14978216</ref> <ref>PMID:15642749</ref> <ref>PMID:17038317</ref>
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[https://www.uniprot.org/uniprot/DOCK7_HUMAN DOCK7_HUMAN] Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity).[UniProtKB:Q8R1A4]<ref>PMID:16982419</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The Dedicator Of CytoKinesis (DOCK) family of atypical guanine nucleotide exchange factors activates the Rho family GTPases Rac and/or Cdc42 through DOCK homology region 2 (DHR-2). Previous structural analyses of the DHR-2 domains of DOCK2 and DOCK9 have shown that they preferentially bind Rac1 and Cdc42, respectively; however, the molecular mechanism by which DHR-2 distinguishes between these GTPases is unclear. Here we report the crystal structure of the Cdc42-bound form of the DOCK7 DHR-2 domain showing dual specificity for Rac1 and Cdc42. The structure revealed increased substrate tolerance of DOCK7 at the interfaces with switch 1 and residue 56 of Cdc42. Furthermore, molecular dynamics simulations showed a closed-to-open conformational change in the DOCK7 DHR-2 domain between the Cdc42- and Rac1-bound states by lobe B displacement. Our results suggest that lobe B acts as a sensor for identifying different switch 1 conformations and explain how DOCK7 recognizes both Rac1 and Cdc42.
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Structural Basis for the Dual Substrate Specificity of DOCK7 Guanine Nucleotide Exchange Factor.,Kukimoto-Niino M, Tsuda K, Ihara K, Mishima-Tsumagari C, Honda K, Ohsawa N, Shirouzu M Structure. 2019 Feb 16. pii: S0969-2126(19)30045-0. doi:, 10.1016/j.str.2019.02.001. PMID:30853411<ref>PMID:30853411</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6aj4" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Dedicator of cytokinesis protein 3D structures|Dedicator of cytokinesis protein 3D structures]]
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*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Kukimoto-Niino, M]]
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[[Category: Kukimoto-Niino M]]
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[[Category: Shirouzu, M]]
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[[Category: Shirouzu M]]
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[[Category: Cdc42]]
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[[Category: Dhr-2]]
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[[Category: Dock]]
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[[Category: Gef]]
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[[Category: Gtpase]]
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[[Category: Rac]]
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[[Category: Rho]]
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[[Category: Signaling protein]]
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Current revision

Crystal structure of the DHR-2 domain of DOCK7 in complex with Cdc42

PDB ID 6aj4

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