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| | ==Crystal structure of the Tiam2 PHCCEx domain== | | ==Crystal structure of the Tiam2 PHCCEx domain== |
| - | <StructureSection load='3a8p' size='340' side='right' caption='[[3a8p]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3a8p' size='340' side='right'caption='[[3a8p]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3a8p]] is a 4 chain structure with sequence from [http://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=3A8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3A8P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3a8p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A8P FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3a8n|3a8n]], [[3a8q|3a8q]]</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]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tiam2, Kiaa2016, Stef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3a8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a8p OCA], [https://pdbe.org/3a8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a8p RCSB], [https://www.ebi.ac.uk/pdbsum/3a8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a8p ProSAT]</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=3a8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a8p OCA], [http://pdbe.org/3a8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3a8p RCSB], [http://www.ebi.ac.uk/pdbsum/3a8p PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIAM2_MOUSE TIAM2_MOUSE]] Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates specifically RAC1, but not CDC42 and RHOA. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane.<ref>PMID:10364228</ref> <ref>PMID:11707441</ref> <ref>PMID:12912917</ref> <ref>PMID:14550769</ref> <ref>PMID:17320046</ref> | + | [https://www.uniprot.org/uniprot/TIAM2_MOUSE TIAM2_MOUSE] Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates specifically RAC1, but not CDC42 and RHOA. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane.<ref>PMID:10364228</ref> <ref>PMID:11707441</ref> <ref>PMID:12912917</ref> <ref>PMID:14550769</ref> <ref>PMID:17320046</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a8/3a8p_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a8/3a8p_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Hakoshima, T]] | + | [[Category: Mus musculus]] |
| - | [[Category: Higuchi, Y]] | + | [[Category: Hakoshima T]] |
| - | [[Category: Itoh, N]] | + | [[Category: Higuchi Y]] |
| - | [[Category: Kaibuchi, K]] | + | [[Category: Itoh N]] |
| - | [[Category: Kitano, K]] | + | [[Category: Kaibuchi K]] |
| - | [[Category: Mori, T]] | + | [[Category: Kitano K]] |
| - | [[Category: Terawaki, S]] | + | [[Category: Mori T]] |
| - | [[Category: Watanabe, T]] | + | [[Category: Terawaki S]] |
| - | [[Category: Zhai, Y]] | + | [[Category: Watanabe T]] |
| - | [[Category: Cell projection]]
| + | [[Category: Zhai Y]] |
| - | [[Category: Guanine nucleotide exchange factor]]
| + | |
| - | [[Category: Guanine-nucleotide releasing factor]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Myristate]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
TIAM2_MOUSE Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates specifically RAC1, but not CDC42 and RHOA. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane.[1] [2] [3] [4] [5]
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
Tiam1 and Tiam2 (Tiam1/2) are guanine nucleotide-exchange factors that possess the PH-CC-Ex (pleckstrin homology, coiled coil and extra) region that mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. Crystal structures of the PH-CC-Ex regions revealed a single globular domain, PHCCEx domain, comprising a conventional PH subdomain associated with an antiparallel coiled coil of CC subdomain and a novel three-helical globular Ex subdomain. The PH subdomain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. Mutational and binding studies indicated that CC and Ex subdomains form a positively charged surface for protein binding. We identified two unique acidic sequence motifs in Tiam1/2-interacting proteins for binding to PHCCEx domain, Motif-I in CD44 and ephrinB's and the NMDA receptor, and Motif-II in Par3 and JIP2. Our results suggest the molecular basis by which the Tiam1/2 PHCCEx domain facilitates dual binding to membranes and signalling proteins.
The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module.,Terawaki S, Kitano K, Mori T, Zhai Y, Higuchi Y, Itoh N, Watanabe T, Kaibuchi K, Hakoshima T EMBO J. 2010 Jan 6;29(1):236-50. Epub 2009 Nov 5. PMID:19893486[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hoshino M, Sone M, Fukata M, Kuroda S, Kaibuchi K, Nabeshima Y, Hama C. Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1. J Biol Chem. 1999 Jun 18;274(25):17837-44. PMID:10364228
- ↑ Matsuo N, Hoshino M, Yoshizawa M, Nabeshima Y. Characterization of STEF, a guanine nucleotide exchange factor for Rac1, required for neurite growth. J Biol Chem. 2002 Jan 25;277(4):2860-8. Epub 2001 Nov 13. PMID:11707441 doi:http://dx.doi.org/10.1074/jbc.M106186200
- ↑ Kawauchi T, Chihama K, Nabeshima Y, Hoshino M. The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration. EMBO J. 2003 Aug 15;22(16):4190-201. PMID:12912917 doi:http://dx.doi.org/10.1093/emboj/cdg413
- ↑ Matsuo N, Terao M, Nabeshima Y, Hoshino M. Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology. Mol Cell Neurosci. 2003 Sep;24(1):69-81. PMID:14550769
- ↑ Takefuji M, Mori K, Morita Y, Arimura N, Nishimura T, Nakayama M, Hoshino M, Iwamatsu A, Murohara T, Kaibuchi K, Amano M. Rho-kinase modulates the function of STEF, a Rac GEF, through its phosphorylation. Biochem Biophys Res Commun. 2007 Apr 13;355(3):788-94. Epub 2007 Feb 14. PMID:17320046 doi:http://dx.doi.org/10.1016/j.bbrc.2007.02.028
- ↑ Terawaki S, Kitano K, Mori T, Zhai Y, Higuchi Y, Itoh N, Watanabe T, Kaibuchi K, Hakoshima T. The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module. EMBO J. 2010 Jan 6;29(1):236-50. Epub 2009 Nov 5. PMID:19893486 doi:10.1038/emboj.2009.323
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