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| | <StructureSection load='1lb1' size='340' side='right'caption='[[1lb1]], [[Resolution|resolution]] 2.81Å' scene=''> | | <StructureSection load='1lb1' size='340' side='right'caption='[[1lb1]], [[Resolution|resolution]] 2.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1lb1]] is a 8 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=1LB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LB1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1lb1]] is a 8 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=1LB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LB1 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;'>[[1kz7|1kz7]], [[1kzg|1kzg]], [[1foe|1foe]], [[1ki1|1ki1]]</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]] 2.81Å</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]), RhoA ([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=1lb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lb1 OCA], [https://pdbe.org/1lb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lb1 RCSB], [https://www.ebi.ac.uk/pdbsum/1lb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lb1 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=1lb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lb1 OCA], [https://pdbe.org/1lb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lb1 RCSB], [https://www.ebi.ac.uk/pdbsum/1lb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lb1 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/RHOA_HUMAN RHOA_HUMAN]] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:8910519</ref> <ref>PMID:9121475</ref> <ref>PMID:12900402</ref> <ref>PMID:16103226</ref> <ref>PMID:16236794</ref> <ref>PMID:19934221</ref> <ref>PMID:20937854</ref> <ref>PMID:20974804</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: Betts, L]] | + | [[Category: Betts L]] |
| - | [[Category: Der, C J]] | + | [[Category: Der CJ]] |
| - | [[Category: Pruitt, W M]] | + | [[Category: Pruitt WM]] |
| - | [[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: Db]]
| + | |
| - | [[Category: Dh domain]]
| + | |
| - | [[Category: Guanine nucleotide exchange factor]]
| + | |
| - | [[Category: Ph domain]]
| + | |
| - | [[Category: Rhoa]]
| + | |
| - | [[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
Activation of Rho-family GTPases involves the removal of bound GDP and the subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family members. To rationalize this specificity, we have determined crystal structures of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of the exchange factors intersectin and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural features necessary for the proper pairing of Dbl-exchange factors with Rho GTPases and now allow for the detailed manipulation of signaling pathways mediated by these oncoproteins in vivo.
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.,Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J Nat Struct Biol. 2002 Jun;9(6):468-75. PMID:12006984[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J. Structural basis for the selective activation of Rho GTPases by Dbl exchange factors. Nat Struct Biol. 2002 Jun;9(6):468-75. PMID:12006984 doi:10.1038/nsb796
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