View source for 2k0b


==NMR structure of the UBA domain of p62 (SQSTM1)==
<StructureSection load='2k0b' size='340' side='right'caption='[[2k0b]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2k0b]] 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=2K0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K0B FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2k0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k0b OCA], [https://pdbe.org/2k0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k0b RCSB], [https://www.ebi.ac.uk/pdbsum/2k0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k0b ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k0/2k0b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2k0b ConSurf].
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== Publication Abstract from PubMed ==
The ubiquitin associated domain of p62 is a small three-helix bundle of approximately 50 residues that mediates the recognition of polyubiquitin chains and ubiquitylated substrates. The solution structure of a 52 residue construct containing this domain has been characterized using heteronuclear nuclear magnetic resonance (NMR) methods. The resulting ensemble of NMR-derived structures was used in molecular dynamics (MD) simulations to investigate the equilibrium conformation and dynamics of this domain. NOE and (15)N relaxation data have been used to validate the structural ensemble produced by the MD simulations and show a good correlation for residues in regions of secondary structure. A similar approach was taken using an ensemble of structures from the MD simulations to calculate electronic circular dichroism (CD) and IR spectra from first principles with an encouraging correlation with the experimental CD and IR data. Proteins 2008. (c) 2007 Wiley-Liss, Inc.

Conformation and dynamics of the three-helix bundle UBA domain of p62 from experiment and simulation.,Evans CL, Long JE, Gallagher TR, Hirst JD, Searle MS Proteins. 2007 Oct 11;71(1):227-240. PMID:17932931<ref>PMID:17932931</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2k0b" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sequestosome|Sequestosome]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cavey JR]]
[[Category: Ciani B]]
[[Category: Gallagher TRA]]
[[Category: Layfield R]]
[[Category: Long JE]]
[[Category: Searle MS]]
[[Category: Sheppard PW]]