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| | <StructureSection load='1kzg' size='340' side='right'caption='[[1kzg]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='1kzg' size='340' side='right'caption='[[1kzg]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1kzg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KZG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1kzg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KZG FirstGlance]. <br> |
| - | </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]], [[1kz7|1kz7]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dbs ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Cdc42 ([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=1kzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kzg OCA], [https://pdbe.org/1kzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kzg RCSB], [https://www.ebi.ac.uk/pdbsum/1kzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kzg 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=1kzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kzg OCA], [https://pdbe.org/1kzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kzg RCSB], [https://www.ebi.ac.uk/pdbsum/1kzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kzg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MCF2L_MOUSE MCF2L_MOUSE]] Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42. Catalyzes guanine nucleotide exchange on RHOA and CDC42 and interacts specifically with the GTP-bound form of RAC1, suggesting that it functions as an effector of RAC1. May also participate in axonal transport in the brain. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). [[https://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>
| + | [https://www.uniprot.org/uniprot/MCF2L_MOUSE MCF2L_MOUSE] Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42. Catalyzes guanine nucleotide exchange on RHOA and CDC42 and interacts specifically with the GTP-bound form of RAC1, suggesting that it functions as an effector of RAC1. May also participate in axonal transport in the brain. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). |
| | == 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: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Campbell, S L]] | + | [[Category: Campbell SL]] |
| - | [[Category: Rossman, K L]] | + | [[Category: Rossman KL]] |
| - | [[Category: Siderovski, D P]] | + | [[Category: Siderovski DP]] |
| - | [[Category: Snyder, J T]] | + | [[Category: Snyder JT]] |
| - | [[Category: Sondek, J]] | + | [[Category: Sondek J]] |
| - | [[Category: Worthylake, D K]] | + | [[Category: Worthylake DK]] |
| - | [[Category: Cdc42]]
| + | |
| - | [[Category: Db]]
| + | |
| - | [[Category: Dh/ph]]
| + | |
| - | [[Category: Guanine nucleotide exchange factor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Small g-protein]]
| + | |
| Structural highlights
Function
MCF2L_MOUSE Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42. Catalyzes guanine nucleotide exchange on RHOA and CDC42 and interacts specifically with the GTP-bound form of RAC1, suggesting that it functions as an effector of RAC1. May also participate in axonal transport in the brain. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity).
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
Dbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho guanosine triphosphatases (GTPases) and invariably possess tandem Dbl (DH) and pleckstrin homology (PH) domains. While it is known that the DH domain is the principal catalytic subunit, recent biochemical data indicate that for some Dbl-family proteins, such as Dbs and Trio, PH domains may cooperate with their associated DH domains in promoting guanine nucleotide exchange of Rho GTPases. In order to gain an understanding of the involvement of these PH domains in guanine nucleotide exchange, we have determined the crystal structure of a DH/PH fragment from Dbs in complex with Cdc42. The complex features the PH domain in a unique conformation distinct from the PH domains in the related structures of Sos1 and Tiam1.Rac1. Consequently, the Dbs PH domain participates with the DH domain in binding Cdc42, primarily through a set of interactions involving switch 2 of the GTPase. Comparative sequence analysis suggests that a subset of Dbl-family proteins will utilize their PH domains similarly to Dbs.
A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange.,Rossman KL, Worthylake DK, Snyder JT, Siderovski DP, Campbell SL, Sondek J EMBO J. 2002 Mar 15;21(6):1315-26. PMID:11889037[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rossman KL, Worthylake DK, Snyder JT, Siderovski DP, Campbell SL, Sondek J. A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange. EMBO J. 2002 Mar 15;21(6):1315-26. PMID:11889037 doi:10.1093/emboj/21.6.1315
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