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| | <StructureSection load='3bji' size='340' side='right'caption='[[3bji]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='3bji' size='340' side='right'caption='[[3bji]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3bji]] is a 4 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=3BJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BJI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3bji]] is a 4 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=3BJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BJI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1foe|1foe]], [[1f5x|1f5x]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VAV1, VAV ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAC1 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3bji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bji OCA], [https://pdbe.org/3bji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bji RCSB], [https://www.ebi.ac.uk/pdbsum/3bji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bji 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=3bji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bji OCA], [https://pdbe.org/3bji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bji RCSB], [https://www.ebi.ac.uk/pdbsum/3bji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bji ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VAV_HUMAN VAV_HUMAN]] Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. [[https://www.uniprot.org/uniprot/RAC1_HUMAN RAC1_HUMAN]] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref>
| + | [https://www.uniprot.org/uniprot/VAV_HUMAN VAV_HUMAN] Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: ATCG3D, Accelerated Technologies Center for Gene to 3D Structure]]
| + | [[Category: Brooun A]] |
| - | [[Category: Brooun, A]] | + | [[Category: Chrencik JE]] |
| - | [[Category: Chrencik, J E]] | + | [[Category: Kuhn P]] |
| - | [[Category: Kuhn, P]] | + | |
| - | [[Category: Accelerated technologies center for gene to 3d structure]]
| + | |
| - | [[Category: Adp-ribosylation]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Atcg3d]]
| + | |
| - | [[Category: Atypical cysteine rich domain]]
| + | |
| - | [[Category: Gef/gtpase]]
| + | |
| - | [[Category: Gtp-binding]]
| + | |
| - | [[Category: Guanine-nucleotide releasing factor]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phorbol-ester binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Prenylation]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| - | [[Category: Proto-oncogene]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
VAV_HUMAN Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The guanine nucleotide exchange factor (GEF) Vav1 plays an important role in T-cell activation and tumorigenesis. In the GEF superfamily, Vav1 has the ability to interact with multiple families of Rho GTPases. The structure of the Vav1 DH-PH-CRD/Rac1 complex to 2.6 A resolution reveals a unique intramolecular network of contacts between the Vav1 cysteine-rich domain (CRD) and the C-terminal helix of the Vav1 Dbl homology (DH) domain. These unique interactions stabilize the Vav1 DH domain for its intimate association with the Switch II region of Rac1 that is critical for the displacement of the guanine nucleotide. Small angle x-ray scattering (SAXS) studies support this domain arrangement for the complex in solution. Further, mutational analyses confirms that the atypical CRD is critical for maintaining both optimal guanine nucleotide exchange activity and broader specificity of Vav family GEFs. Taken together, the data outline the detailed nature of Vav1's ability to contact a range of Rho GTPases using a novel protein-protein interaction network.
Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1.,Chrencik JE, Brooun A, Zhang H, Mathews II, Hura GL, Foster SA, Perry JJ, Streiff M, Ramage P, Widmer H, Bokoch GM, Tainer JA, Weckbecker G, Kuhn P J Mol Biol. 2008 Jul 25;380(5):828-43. Epub 2008 May 17. PMID:18589439[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chrencik JE, Brooun A, Zhang H, Mathews II, Hura GL, Foster SA, Perry JJ, Streiff M, Ramage P, Widmer H, Bokoch GM, Tainer JA, Weckbecker G, Kuhn P. Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1. J Mol Biol. 2008 Jul 25;380(5):828-43. Epub 2008 May 17. PMID:18589439 doi:http://dx.doi.org/10.1016/j.jmb.2008.05.024
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