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| | <StructureSection load='3p8c' size='340' side='right'caption='[[3p8c]], [[Resolution|resolution]] 2.29Å' scene=''> | | <StructureSection load='3p8c' size='340' side='right'caption='[[3p8c]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p8c]] is a 5 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=3P8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P8C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p8c]] is a 5 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=3P8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P8C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 2.29Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYFIP1, KIAA0068 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCKAP1, HEM2, KIAA0587, NAP1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), WASF1, KIAA0269, SCAR1, WAVE1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), C3orf10, HSPC300, MDS027 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=3p8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p8c OCA], [https://pdbe.org/3p8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p8c RCSB], [https://www.ebi.ac.uk/pdbsum/3p8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p8c 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=3p8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p8c OCA], [https://pdbe.org/3p8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p8c RCSB], [https://www.ebi.ac.uk/pdbsum/3p8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p8c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/CYFP1_HUMAN CYFP1_HUMAN]] Angelman syndrome.
| + | [https://www.uniprot.org/uniprot/CYFP1_HUMAN CYFP1_HUMAN] Angelman syndrome. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/BRK1_HUMAN BRK1_HUMAN]] Involved in regulation of actin and microtubule organization. Part of a WAVE complex that activates the Arp2/3 complex.<ref>PMID:18560548</ref> [[https://www.uniprot.org/uniprot/CYFP1_HUMAN CYFP1_HUMAN]] Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. May act as an invasion suppressor in cancers.<ref>PMID:9417078</ref> <ref>PMID:16260607</ref> <ref>PMID:19524508</ref> <ref>PMID:21107423</ref> [[https://www.uniprot.org/uniprot/WASF1_HUMAN WASF1_HUMAN]] Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. [[https://www.uniprot.org/uniprot/NCKP1_HUMAN NCKP1_HUMAN]] Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. [[https://www.uniprot.org/uniprot/ABI2_HUMAN ABI2_HUMAN]] May act in regulation of cell growth and transformation by interacting with nonreceptor tyrosine kinases ABL1 and/or ABL2. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Regulates ABL1/c-Abl-mediated phosphorylation of MENA.<ref>PMID:7590236</ref> <ref>PMID:8649853</ref> <ref>PMID:10498863</ref>
| + | [https://www.uniprot.org/uniprot/CYFP1_HUMAN CYFP1_HUMAN] Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. May act as an invasion suppressor in cancers.<ref>PMID:9417078</ref> <ref>PMID:16260607</ref> <ref>PMID:19524508</ref> <ref>PMID:21107423</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Members of the Wiskott-Aldrich syndrome protein (WASP) family control cytoskeletal dynamics by promoting actin filament nucleation with the Arp2/3 complex. The WASP relative WAVE regulates lamellipodia formation within a 400-kilodalton, hetero-pentameric WAVE regulatory complex (WRC). The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols. Here we report the 2.3-angstrom crystal structure of the WRC and complementary mechanistic analyses. The structure shows that the activity-bearing VCA motif of WAVE is sequestered by a combination of intramolecular and intermolecular contacts within the WRC. Rac and kinases appear to destabilize a WRC element that is necessary for VCA sequestration, suggesting the way in which these signals stimulate WRC activity towards the Arp2/3 complex. The spatial proximity of the Rac binding site and the large basic surface of the WRC suggests how the GTPase and phospholipids could cooperatively recruit the complex to membranes.
| + | |
| - | | + | |
| - | Structure and control of the actin regulatory WAVE complex.,Chen Z, Borek D, Padrick SB, Gomez TS, Metlagel Z, Ismail AM, Umetani J, Billadeau DD, Otwinowski Z, Rosen MK Nature. 2010 Nov 25;468(7323):533-8. PMID:21107423<ref>PMID:21107423</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3p8c" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Billadeau, D D]] | + | [[Category: Billadeau DD]] |
| - | [[Category: Borek, D]] | + | [[Category: Borek D]] |
| - | [[Category: Chen, Z]] | + | [[Category: Chen Z]] |
| - | [[Category: Gomez, T S]] | + | [[Category: Gomez TS]] |
| - | [[Category: Ismail, A M]] | + | [[Category: Ismail AM]] |
| - | [[Category: Metlagel, Z]] | + | [[Category: Metlagel Z]] |
| - | [[Category: Otwinowski, Z]] | + | [[Category: Otwinowski Z]] |
| - | [[Category: Padrick, S B]] | + | [[Category: Padrick SB]] |
| - | [[Category: Rosen, M K]] | + | [[Category: Rosen MK]] |
| - | [[Category: Umetani, J]] | + | [[Category: Umetani J]] |
| - | [[Category: Actin polymerization]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Disease
CYFP1_HUMAN Angelman syndrome.
Function
CYFP1_HUMAN Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. May act as an invasion suppressor in cancers.[1] [2] [3] [4]
See Also
References
- ↑ Kobayashi K, Kuroda S, Fukata M, Nakamura T, Nagase T, Nomura N, Matsuura Y, Yoshida-Kubomura N, Iwamatsu A, Kaibuchi K. p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase. J Biol Chem. 1998 Jan 2;273(1):291-5. PMID:9417078
- ↑ Kawano Y, Yoshimura T, Tsuboi D, Kawabata S, Kaneko-Kawano T, Shirataki H, Takenawa T, Kaibuchi K. CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Mol Cell Biol. 2005 Nov;25(22):9920-35. PMID:16260607 doi:http://dx.doi.org/25/22/9920
- ↑ Silva JM, Ezhkova E, Silva J, Heart S, Castillo M, Campos Y, Castro V, Bonilla F, Cordon-Cardo C, Muthuswamy SK, Powers S, Fuchs E, Hannon GJ. Cyfip1 is a putative invasion suppressor in epithelial cancers. Cell. 2009 Jun 12;137(6):1047-61. doi: 10.1016/j.cell.2009.04.013. PMID:19524508 doi:http://dx.doi.org/10.1016/j.cell.2009.04.013
- ↑ Chen Z, Borek D, Padrick SB, Gomez TS, Metlagel Z, Ismail AM, Umetani J, Billadeau DD, Otwinowski Z, Rosen MK. Structure and control of the actin regulatory WAVE complex. Nature. 2010 Nov 25;468(7323):533-8. PMID:21107423 doi:10.1038/nature09623
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