2jy8

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{{STRUCTURE_2jy8| PDB=2jy8 | SCENE= }}
 
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===NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1) in complex with ubiquitin. RDC refined===
 
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{{ABSTRACT_PUBMED_18083707}}
 
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==Disease==
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==NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1) in complex with ubiquitin. RDC refined==
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[[http://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN]] Defects in SQSTM1 are a cause of Paget disease of bone (PDB) [MIM:[http://omim.org/entry/602080 602080]]. PDB is a metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years.<ref>PMID:19931284</ref><ref>PMID:11992264</ref><ref>PMID:12374763</ref><ref>PMID:14584883</ref><ref>PMID:15146436</ref><ref>PMID:15207768</ref><ref>PMID:15125799</ref><ref>PMID:15176995</ref> Note=In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinylated protein aggregates.<ref>PMID:16286508</ref>
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<StructureSection load='2jy8' size='340' side='right'caption='[[2jy8]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2jy8]] 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=2JY8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JY8 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">Solution NMR</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=2jy8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jy8 OCA], [https://pdbe.org/2jy8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jy8 RCSB], [https://www.ebi.ac.uk/pdbsum/2jy8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jy8 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN] Defects in SQSTM1 are a cause of Paget disease of bone (PDB) [MIM:[https://omim.org/entry/602080 602080]. PDB is a metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years.<ref>PMID:19931284</ref> <ref>PMID:11992264</ref> <ref>PMID:12374763</ref> <ref>PMID:14584883</ref> <ref>PMID:15146436</ref> <ref>PMID:15207768</ref> <ref>PMID:15125799</ref> <ref>PMID:15176995</ref> Note=In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinylated protein aggregates.<ref>PMID:16286508</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN] Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures). Links ALIS to the autophagic machinery via direct interaction with MAP1 LC3 family members. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels.<ref>PMID:10356400</ref> <ref>PMID:10747026</ref> <ref>PMID:11244088</ref> <ref>PMID:12471037</ref> <ref>PMID:15340068</ref> <ref>PMID:16079148</ref> <ref>PMID:16286508</ref> <ref>PMID:15953362</ref> <ref>PMID:15911346</ref> <ref>PMID:15802564</ref> <ref>PMID:19931284</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/jy/2jy8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2jy8 ConSurf].
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<div style="clear:both"></div>
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==Function==
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==See Also==
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[[http://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN]] Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures). Links ALIS to the autophagic machinery via direct interaction with MAP1 LC3 family members. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels.<ref>PMID:10356400</ref><ref>PMID:10747026</ref><ref>PMID:11244088</ref><ref>PMID:12471037</ref><ref>PMID:15340068</ref><ref>PMID:16079148</ref><ref>PMID:16286508</ref><ref>PMID:15953362</ref><ref>PMID:15911346</ref><ref>PMID:15802564</ref><ref>PMID:19931284</ref>
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*[[Sequestosome|Sequestosome]]
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== References ==
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==About this Structure==
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<references/>
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[[2jy8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JY8 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:018083707</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Layfield, R.]]
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[[Category: Large Structures]]
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[[Category: Long, J E.]]
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[[Category: Layfield R]]
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[[Category: Searle, M S.]]
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[[Category: Long JE]]
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[[Category: Apoptosis]]
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[[Category: Searle MS]]
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[[Category: Differentiation]]
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[[Category: Disease mutation]]
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[[Category: Endosome]]
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[[Category: Helical bundle]]
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[[Category: Immune response]]
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[[Category: Metal-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Protein binding]]
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[[Category: Three helice]]
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[[Category: Ubiquitin associated domain]]
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[[Category: Ubiquitin binding]]
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[[Category: Zinc-finger]]
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Current revision

NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1) in complex with ubiquitin. RDC refined

PDB ID 2jy8

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