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| | ==Crystal structure of the DH domain of FARP2== | | ==Crystal structure of the DH domain of FARP2== |
| - | <StructureSection load='4gyv' size='340' side='right' caption='[[4gyv]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4gyv' size='340' side='right'caption='[[4gyv]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gyv]] is a 9 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=4GYV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GYV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gyv]] is a 9 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=4GYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GYV FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gzu|4gzu]]</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=4gyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gyv OCA], [https://pdbe.org/4gyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gyv RCSB], [https://www.ebi.ac.uk/pdbsum/4gyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gyv ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Farp2, Kiaa0793 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gyv OCA], [http://pdbe.org/4gyv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gyv RCSB], [http://www.ebi.ac.uk/pdbsum/4gyv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gyv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FARP2_MOUSE FARP2_MOUSE]] Rho-guanine nucleotide exchange factor that activates RAC1. Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton.<ref>PMID:12351724</ref> <ref>PMID:16286926</ref> | + | [https://www.uniprot.org/uniprot/FARP2_MOUSE FARP2_MOUSE] Rho-guanine nucleotide exchange factor that activates RAC1. Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton.<ref>PMID:12351724</ref> <ref>PMID:16286926</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: He, X]] | + | [[Category: Mus musculus]] |
| - | [[Category: Zhang, X]] | + | [[Category: He X]] |
| - | [[Category: Dh]] | + | [[Category: Zhang X]] |
| - | [[Category: Farp2]]
| + | |
| - | [[Category: Gef]]
| + | |
| - | [[Category: Guanine nucleotide exchange factor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
FARP2_MOUSE Rho-guanine nucleotide exchange factor that activates RAC1. Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton.[1] [2]
Publication Abstract from PubMed
FARP2 is a Dbl-family guanine nucleotide exchange factor (GEF) that contains a 4.1, ezrin, radixin and moesin (FERM) domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. FARP2 activates Rac1 or Cdc42 in response to upstream signals, thereby regulating processes such as neuronal axon guidance and bone homeostasis. How the GEF activity of FARP2 is regulated remained poorly understood. We have determined the crystal structures of the catalytic DH domain and the DH-PH-PH domains of FARP2. The structures reveal an auto-inhibited conformation in which the GEF substrate-binding site is blocked collectively by the last helix in the DH domain and the two PH domains. This conformation is stabilized by multiple interactions among the domains and two well-structured inter-domain linkers. Our cell-based activity assays confirm the suppression of the FARP2 GEF activity by these auto-inhibitory elements.
Structural Basis for Autoinhibition of the Guanine Nucleotide Exchange Factor FARP2.,He X, Kuo YC, Rosche TJ, Zhang X Structure. 2013 Mar 5;21(3):355-64. doi: 10.1016/j.str.2013.01.001. Epub 2013 Jan, 31. PMID:23375260[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kubo T, Yamashita T, Yamaguchi A, Sumimoto H, Hosokawa K, Tohyama M. A novel FERM domain including guanine nucleotide exchange factor is involved in Rac signaling and regulates neurite remodeling. J Neurosci. 2002 Oct 1;22(19):8504-13. PMID:12351724
- ↑ Toyofuku T, Yoshida J, Sugimoto T, Zhang H, Kumanogoh A, Hori M, Kikutani H. FARP2 triggers signals for Sema3A-mediated axonal repulsion. Nat Neurosci. 2005 Dec;8(12):1712-9. Epub 2005 Nov 13. PMID:16286926 doi:nn1596
- ↑ He X, Kuo YC, Rosche TJ, Zhang X. Structural Basis for Autoinhibition of the Guanine Nucleotide Exchange Factor FARP2. Structure. 2013 Mar 5;21(3):355-64. doi: 10.1016/j.str.2013.01.001. Epub 2013 Jan, 31. PMID:23375260 doi:http://dx.doi.org/10.1016/j.str.2013.01.001
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