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| | ==The PX-BAR membrane remodeling unit of Sorting Nexin 9== | | ==The PX-BAR membrane remodeling unit of Sorting Nexin 9== |
| - | <StructureSection load='2rai' size='340' side='right' caption='[[2rai]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='2rai' size='340' side='right'caption='[[2rai]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2rai]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RAI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RAI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2rai]] is a 2 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=2RAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RAI 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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2raj|2raj]], [[2rak|2rak]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2raj|2raj]], [[2rak|2rak]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNX9, SH3PX1, SH3PXD3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNX9, SH3PX1, SH3PXD3A ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rai OCA], [http://pdbe.org/2rai PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rai RCSB], [http://www.ebi.ac.uk/pdbsum/2rai PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rai 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=2rai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rai OCA], [https://pdbe.org/2rai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rai RCSB], [https://www.ebi.ac.uk/pdbsum/2rai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rai ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SNX9_HUMAN SNX9_HUMAN]] May be involved in several stages of intracellular trafficking. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate.<ref>PMID:11799118</ref> <ref>PMID:12952949</ref> <ref>PMID:15703209</ref> <ref>PMID:17609109</ref> <ref>PMID:18388313</ref> <ref>PMID:20427313</ref> <ref>PMID:21048941</ref> <ref>PMID:17948057</ref> | + | [[https://www.uniprot.org/uniprot/SNX9_HUMAN SNX9_HUMAN]] May be involved in several stages of intracellular trafficking. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate.<ref>PMID:11799118</ref> <ref>PMID:12952949</ref> <ref>PMID:15703209</ref> <ref>PMID:17609109</ref> <ref>PMID:18388313</ref> <ref>PMID:20427313</ref> <ref>PMID:21048941</ref> <ref>PMID:17948057</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Sorting nexin|Sorting nexin]] | + | *[[Sorting nexin 3D structures|Sorting nexin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Carlsson, S R]] | | [[Category: Carlsson, S R]] |
| | [[Category: Lundmark, R]] | | [[Category: Lundmark, R]] |
| Structural highlights
Function
[SNX9_HUMAN] May be involved in several stages of intracellular trafficking. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate.[1] [2] [3] [4] [5] [6] [7] [8]
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
Sorting nexins (SNXs) form a family of proteins known to interact with components in the endosomal system and to regulate various steps of vesicle transport. Sorting nexin 9 (SNX9) is involved in the late stages of clathrin-mediated endocytosis in non-neuronal cells, where together with the GTPase dynamin, it participates in the formation and scission of the vesicle neck. We report here crystal structures of the functional membrane-remodeling unit of SNX9 and show that it efficiently tubulates lipid membranes in vivo and in vitro. Elucidation of the protein superdomain structure, together with mutational analysis and biochemical and cell biological experiments, demonstrated how the SNX9 PX and BAR domains work in concert in targeting and tubulation of phosphoinositide-containing membranes. The study provides insights into the SNX9-induced membrane modulation mechanism.
The PX-BAR membrane-remodeling unit of sorting nexin 9.,Pylypenko O, Lundmark R, Rasmuson E, Carlsson SR, Rak A EMBO J. 2007 Nov 14;26(22):4788-800. Epub 2007 Oct 18. PMID:17948057[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin Q, Lo CG, Cerione RA, Yang W. The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation. J Biol Chem. 2002 Mar 22;277(12):10134-8. Epub 2002 Jan 17. PMID:11799118 doi:http://dx.doi.org/10.1074/jbc.M110329200
- ↑ Lundmark R, Carlsson SR. Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components. J Biol Chem. 2003 Nov 21;278(47):46772-81. Epub 2003 Sep 2. PMID:12952949 doi:http://dx.doi.org/10.1074/jbc.M307334200
- ↑ Soulet F, Yarar D, Leonard M, Schmid SL. SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell. 2005 Apr;16(4):2058-67. Epub 2005 Feb 9. PMID:15703209 doi:http://dx.doi.org/10.1091/mbc.E04-11-1016
- ↑ Yarar D, Waterman-Storer CM, Schmid SL. SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis. Dev Cell. 2007 Jul;13(1):43-56. PMID:17609109 doi:http://dx.doi.org/10.1016/j.devcel.2007.04.014
- ↑ Shin N, Ahn N, Chang-Ileto B, Park J, Takei K, Ahn SG, Kim SA, Di Paolo G, Chang S. SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2. J Cell Sci. 2008 Apr 15;121(Pt 8):1252-63. doi: 10.1242/jcs.016709. PMID:18388313 doi:http://dx.doi.org/10.1242/jcs.016709
- ↑ Park J, Kim Y, Lee S, Park JJ, Park ZY, Sun W, Kim H, Chang S. SNX18 shares a redundant role with SNX9 and modulates endocytic trafficking at the plasma membrane. J Cell Sci. 2010 May 15;123(Pt 10):1742-50. doi: 10.1242/jcs.064170. Epub 2010, Apr 27. PMID:20427313 doi:http://dx.doi.org/10.1242/jcs.064170
- ↑ Wang JT, Kerr MC, Karunaratne S, Jeanes A, Yap AS, Teasdale RD. The SNX-PX-BAR family in macropinocytosis: the regulation of macropinosome formation by SNX-PX-BAR proteins. PLoS One. 2010 Oct 29;5(10):e13763. doi: 10.1371/journal.pone.0013763. PMID:21048941 doi:10.1371/journal.pone.0013763
- ↑ Pylypenko O, Lundmark R, Rasmuson E, Carlsson SR, Rak A. The PX-BAR membrane-remodeling unit of sorting nexin 9. EMBO J. 2007 Nov 14;26(22):4788-800. Epub 2007 Oct 18. PMID:17948057
- ↑ Pylypenko O, Lundmark R, Rasmuson E, Carlsson SR, Rak A. The PX-BAR membrane-remodeling unit of sorting nexin 9. EMBO J. 2007 Nov 14;26(22):4788-800. Epub 2007 Oct 18. PMID:17948057
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