5f0j

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Current revision (08:38, 12 July 2023) (edit) (undo)
 
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<StructureSection load='5f0j' size='340' side='right'caption='[[5f0j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
<StructureSection load='5f0j' size='340' side='right'caption='[[5f0j]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5f0j]] is a 3 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=5F0J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F0J FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5f0j]] is a 3 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=5F0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F0J FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r17|2r17]], [[2fau|2fau]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5f0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f0j OCA], [https://pdbe.org/5f0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f0j RCSB], [https://www.ebi.ac.uk/pdbsum/5f0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f0j ProSAT]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VPS35, MEM3, TCCCTA00141 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS26A, VPS26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SNX3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5f0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f0j OCA], [http://pdbe.org/5f0j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f0j RCSB], [http://www.ebi.ac.uk/pdbsum/5f0j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f0j ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN]] Defects in VPS35 are the cause of Parkinson disease type 17 (PARK17) [MIM:[http://omim.org/entry/614203 614203]]. PARK17 is an autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:21763482</ref> <ref>PMID:21763483</ref> <ref>PMID:22517097</ref> [[http://www.uniprot.org/uniprot/SNX3_HUMAN SNX3_HUMAN]] MMEP syndrome. The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).
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[https://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN] Defects in VPS35 are the cause of Parkinson disease type 17 (PARK17) [MIM:[https://omim.org/entry/614203 614203]. PARK17 is an autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:21763482</ref> <ref>PMID:21763483</ref> <ref>PMID:22517097</ref>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN]] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA).<ref>PMID:15247922</ref> [[http://www.uniprot.org/uniprot/SNX3_HUMAN SNX3_HUMAN]] Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Plays a role in protein transport between cellular compartments. Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation.<ref>PMID:11433298</ref> <ref>PMID:18767904</ref> [[http://www.uniprot.org/uniprot/VP26A_HUMAN VP26A_HUMAN]] Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins (Probable). The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:15078902, PubMed:15078903). Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922). Required for the endosomal localization of FAM21A (indicative for the WASH complex) (PubMed:22070227). Required for the endosomal localization of TBC1D5 (PubMed:20923837). Mediates retromer cargo reognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (PubMed:22279231). Involved in retromer-independent lysosomal sorting of F2R (PubMed:16407403). Involved in recycling of ADRB2 (PubMed:21602791). Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity).[UniProtKB:P40336]<ref>PMID:15078902</ref> <ref>PMID:15078903</ref> <ref>PMID:15247922</ref> <ref>PMID:16407403</ref> <ref>PMID:22070227</ref> <ref>PMID:22279231</ref> <ref>PMID:20923837</ref> <ref>PMID:21602791</ref> <ref>PMID:21725319</ref> <ref>PMID:23563491</ref>
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[https://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA).<ref>PMID:15247922</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>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Bonifacino, J S]]
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[[Category: Bonifacino JS]]
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[[Category: Gershlick, D]]
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[[Category: Gershlick D]]
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[[Category: Hierro, A]]
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[[Category: Hierro A]]
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[[Category: Lucas, M]]
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[[Category: Lucas M]]
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[[Category: Rojas, A L]]
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[[Category: Rojas AL]]
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[[Category: Vidaurrazaga, A]]
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[[Category: Vidaurrazaga A]]
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[[Category: Protein transport]]
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[[Category: Retromer]]
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[[Category: Sorting nexin]]
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[[Category: Transport protein]]
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Current revision

Structure of retromer VPS26-VPS35 subunits bound to SNX3

PDB ID 5f0j

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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