3f6k

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{{STRUCTURE_3f6k| PDB=3f6k | SCENE= }}
 
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===Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with neurotensin===
 
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{{ABSTRACT_PUBMED_19122660}}
 
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==Disease==
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==Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with neurotensin==
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[[http://www.uniprot.org/uniprot/SORT_HUMAN SORT_HUMAN]] Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.
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<StructureSection load='3f6k' size='340' side='right'caption='[[3f6k]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3f6k]] is a 2 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=3F6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F6K FirstGlance]. <br>
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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&#8491;</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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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=3f6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6k OCA], [https://pdbe.org/3f6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f6k RCSB], [https://www.ebi.ac.uk/pdbsum/3f6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6k ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SORT_HUMAN SORT_HUMAN] Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.
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== Function ==
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[https://www.uniprot.org/uniprot/SORT_HUMAN SORT_HUMAN] Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.<ref>PMID:10085125</ref> <ref>PMID:11331584</ref> <ref>PMID:11390366</ref> <ref>PMID:12209882</ref> <ref>PMID:14657016</ref> <ref>PMID:12598608</ref> <ref>PMID:15313463</ref> <ref>PMID:14985763</ref> <ref>PMID:15930396</ref> <ref>PMID:15987945</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f6k_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f6k ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-A resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed beta-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of nerve growth factor-beta, are present in the tunnel and that competition for binding relates to the restricted space inside the propeller.
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==Function==
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Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain.,Quistgaard EM, Madsen P, Groftehauge MK, Nissen P, Petersen CM, Thirup SS Nat Struct Mol Biol. 2009 Jan;16(1):96-8. Epub 2009 Jan 4. PMID:19122660<ref>PMID:19122660</ref>
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[[http://www.uniprot.org/uniprot/SORT_HUMAN SORT_HUMAN]] Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.<ref>PMID:10085125</ref><ref>PMID:11331584</ref><ref>PMID:11390366</ref><ref>PMID:12209882</ref><ref>PMID:14657016</ref><ref>PMID:12598608</ref><ref>PMID:15313463</ref><ref>PMID:14985763</ref><ref>PMID:15930396</ref><ref>PMID:15987945</ref> [[http://www.uniprot.org/uniprot/NEUT_HUMAN NEUT_HUMAN]] Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3f6k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6K OCA].
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</div>
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<div class="pdbe-citations 3f6k" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:019122660</ref><references group="xtra"/><references/>
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*[[Neurotensin receptor|Neurotensin receptor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Groftehauge, M K.]]
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[[Category: Large Structures]]
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[[Category: Madsen, P.]]
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[[Category: Groftehauge MK]]
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[[Category: Nissen, P.]]
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[[Category: Madsen P]]
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[[Category: Petersen, C M.]]
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[[Category: Nissen P]]
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[[Category: Quistgaard, E M.]]
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[[Category: Petersen CM]]
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[[Category: Thirup, S.]]
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[[Category: Quistgaard EM]]
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[[Category: 10-bladed beta-propeller]]
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[[Category: Thirup S]]
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[[Category: Cys-rich domain]]
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[[Category: Cytoplasmic vesicle]]
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[[Category: Developmental protein]]
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[[Category: Differentiation]]
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[[Category: Endocytosis]]
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[[Category: Endoplasmic reticulum]]
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[[Category: Endosome]]
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[[Category: Glycoprotein]]
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[[Category: Golgi apparatus]]
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[[Category: Lysosome]]
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[[Category: Membrane]]
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[[Category: Phosphoprotein]]
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[[Category: Protein sorting receptor]]
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[[Category: Protein-peptide complex]]
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[[Category: Receptor]]
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[[Category: Secreted]]
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[[Category: Signaling protein]]
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[[Category: Sortilin vps10p-d]]
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[[Category: Ssortilin]]
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[[Category: Transmembrane]]
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[[Category: Transport]]
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Current revision

Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with neurotensin

PDB ID 3f6k

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