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| | ==Solution Structure of the PX domain of Sorting Nexin 1== | | ==Solution Structure of the PX domain of Sorting Nexin 1== |
| - | <StructureSection load='2i4k' size='340' side='right'caption='[[2i4k]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2i4k' size='340' side='right'caption='[[2i4k]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2i4k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I4K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2i4k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I4K FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SNX1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=2i4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i4k OCA], [https://pdbe.org/2i4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i4k RCSB], [https://www.ebi.ac.uk/pdbsum/2i4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i4k 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=2i4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i4k OCA], [https://pdbe.org/2i4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i4k RCSB], [https://www.ebi.ac.uk/pdbsum/2i4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i4k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SNX1_HUMAN SNX1_HUMAN]] May be involved in several stages of intracellular trafficking. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi. Component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).<ref>PMID:12198132</ref> <ref>PMID:15498486</ref> <ref>PMID:17101778</ref>
| + | [https://www.uniprot.org/uniprot/SNX1_HUMAN SNX1_HUMAN] May be involved in several stages of intracellular trafficking. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi. Component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).<ref>PMID:12198132</ref> <ref>PMID:15498486</ref> <ref>PMID:17101778</ref> |
| | == 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: Gill, G N]] | + | [[Category: Gill GN]] |
| - | [[Category: Hounslow, A M]] | + | [[Category: Hounslow AM]] |
| - | [[Category: Lazar, C S]] | + | [[Category: Lazar CS]] |
| - | [[Category: Waltho, J P]] | + | [[Category: Waltho JP]] |
| - | [[Category: Watson, M J]] | + | [[Category: Watson MJ]] |
| - | [[Category: Zhong, Q]] | + | [[Category: Zhong Q]] |
| - | [[Category: Alpha helice]]
| + | |
| - | [[Category: 3-stranded beta sheet]]
| + | |
| - | [[Category: Proline rich loop]]
| + | |
| - | [[Category: Protein transport]]
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| Structural highlights
Function
SNX1_HUMAN May be involved in several stages of intracellular trafficking. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi. Component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).[1] [2] [3]
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
The sorting nexin (SNX) family of proteins is characterized by sequence-related phox homology (PX) domains. A minority of PX domains bind with high affinity to phosphatidylinositol 3-phosphate [PI(3)P], whereas the majority of PX domains exhibit low affinity that is insufficient to target them to vesicles. SNX1 is located on endosomes, but its low affinity PX domain fails to localize in vivo. The NMR structure of the PX domain of SNX1 reveals an overall fold that is similar to high-affinity PX domains. However, the phosphatidylinositol (PI) binding pocket of the SNX1 PX domain is incomplete; regions of the pocket that are well defined in high-affinity PX domains are highly mobile in SNX1. Some of this mobility is lost upon binding PI(3)P. The C-terminal domain of SNX1 is a long helical dimer that localizes to vesicles but not to the early endosome antigen-1-containing vesicles where endogenous SNX1 resides. Thus, the obligate dimerization of SNX1 that is driven by the C-terminal domain creates a high-affinity PI binding species that properly targets the holo protein to endosomes.
Determinants of the endosomal localization of sorting nexin 1.,Zhong Q, Watson MJ, Lazar CS, Hounslow AM, Waltho JP, Gill GN Mol Biol Cell. 2005 Apr;16(4):2049-57. Epub 2005 Jan 26. PMID:15673616[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cozier GE, Carlton J, McGregor AH, Gleeson PA, Teasdale RD, Mellor H, Cullen PJ. The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation. J Biol Chem. 2002 Dec 13;277(50):48730-6. Epub 2002 Aug 26. PMID:12198132 doi:10.1074/jbc.M206986200
- ↑ Carlton J, Bujny M, Peter BJ, Oorschot VM, Rutherford A, Mellor H, Klumperman J, McMahon HT, Cullen PJ. Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides. Curr Biol. 2004 Oct 26;14(20):1791-800. PMID:15498486 doi:10.1016/j.cub.2004.09.077
- ↑ Rojas R, Kametaka S, Haft CR, Bonifacino JS. Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors. Mol Cell Biol. 2007 Feb;27(3):1112-24. Epub 2006 Nov 13. PMID:17101778 doi:10.1128/MCB.00156-06
- ↑ Zhong Q, Watson MJ, Lazar CS, Hounslow AM, Waltho JP, Gill GN. Determinants of the endosomal localization of sorting nexin 1. Mol Biol Cell. 2005 Apr;16(4):2049-57. Epub 2005 Jan 26. PMID:15673616 doi:10.1091/mbc.E04-06-0504
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