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<title>
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Entry
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- *602533 - ONCOGENE DJ1; DJ1
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- OMIM
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</ul>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</li>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</div>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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<span class="small">
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</form>
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<div class="row">
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<p />
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</div>
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<!-- <div id="mimSearch"> -->
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*602533</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/602533">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
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<h4 class="panel-title">
|
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
|
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</a>
|
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</h4>
|
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</div>
|
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000116288;t=ENST00000338639" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=11315" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=602533" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000116288;t=ENST00000338639" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001123377,NM_007262,XM_005263424" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_007262" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=602533" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
|
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=03961&isoform_id=03961_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/PARK7" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/2460318,14198257,16751471,30038760,31543380,50058384,56404943,119591997,183227678,189065215,211947947,530360487,2462502607" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q99497" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
|
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</div>
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</a>
|
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</span>
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</span>
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</div>
|
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=11315" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000116288;t=ENST00000338639" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARK7" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=PARK7" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+11315" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/PARK7" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:11315" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/11315" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000338639.10&hgg_start=7961711&hgg_end=7985505&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:16369" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:16369" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/park7" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602533[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602533[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000116288" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=PARK7" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=PARK7" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PARK7" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/PARK7" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PARK7&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA32946" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:16369" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0033885.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2135637" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/PARK7#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:2135637" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/11315/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002488/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=11315" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00015184;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00015184 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00016789;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00016789 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-041010-5" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:11315" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=PARK7&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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602533
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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ONCOGENE DJ1; DJ1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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PARKINSONISM-ASSOCIATED DEGLYCASE; PARK7<br />
|
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PARK7 GENE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PARK7" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PARK7</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/1/115?start=-3&limit=10&highlight=115">1p36.23</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:7961711-7985505&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:7,961,711-7,985,505</a> </span>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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1p36.23
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Parkinson disease 7, autosomal recessive early-onset
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<a href="/entry/606324"> 606324 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/602533" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/602533" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>DJ1, or PARK7, has pleiotropic function that includes roles as a chaperone with protease activity, a transcriptional regulator, and an antioxidant scavenger and redox sensor. DJ1 is also involved in tumorigenesis and in maintaining mitochondrial homeostasis (summary by <a href="#20" class="mim-tip-reference" title="Ottolini, D., Cali, T., Negro, A., Brini, M. <strong>The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering.</strong> Hum. Molec. Genet. 22: 2152-2168, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23418303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23418303</a>] [<a href="https://doi.org/10.1093/hmg/ddt068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23418303">Ottolini et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23418303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Cloning and Expression</strong>
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<p><a href="#19" class="mim-tip-reference" title="Nagakubo, D., Taira, T., Kitaura, H., Ikeda, M., Tamai, K., Iguchi-Ariga, S. M. M., Ariga, H. <strong>DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.</strong> Biochem. Biophys. Res. Commun. 231: 509-513, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9070310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9070310</a>] [<a href="https://doi.org/10.1006/bbrc.1997.6132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9070310">Nagakubo et al. (1997)</a> used yeast 2-hybrid screening of a HeLa cell library to clone a cDNA that encodes a novel 189-amino acid protein, termed DJ1. Northern blot analysis revealed that DJ1 is ubiquitously expressed as a 1.0-kb transcript. Western blot analysis and immunofluorescence showed that the DJ1 protein is present in both nuclei and cytoplasm of HeLa cells. After addition of serum to cells, DJ1 expression increased and the protein translocated from the cytoplasm to nuclei. A search of the GenBank protein database revealed that DJ1 has approximately 40% identity to the 198-amino acid protein product of the E. coli thiazole monophosphate biosynthesis (ThiJ) gene. A homolog also exists in the nematode C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9070310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Northern blot analysis by <a href="#6" class="mim-tip-reference" title="Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P. <strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong> Science 299: 256-259, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>] [<a href="https://doi.org/10.1126/science.1077209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446870">Bonifati et al. (2003)</a> showed ubiquitous expression of the DJ1 transcript, particularly in liver, skeletal muscle, and kidney. In the brain, expression was also ubiquitous, with higher levels of the transcript in subcortical regions, such as the caudate nucleus, the thalamus, the substantia nigra, and the hippocampus, that are more affected in parkinson disease (see MOLECULAR GENETICS). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Zhang, L., Shimoji, M., Thomas, B., Moore, D. J., Yu, S.-W., Marupudi, N. I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M., Dawson, V. L. <strong>Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.</strong> Hum. Molec. Genet. 14: 2063-2073, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944198</a>] [<a href="https://doi.org/10.1093/hmg/ddi211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944198">Zhang et al. (2005)</a> generated highly specific antibodies to DJ1 protein and investigated the subcellular localization of endogenous DJ1 protein in both mouse brain tissues and human neuroblastoma cells. DJ1 was widely distributed and was highly expressed in brain. Cell fractionation and immunogold electron microscopy revealed an endogenous pool of DJ1 in mitochondrial matrix and intermembrane space. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By screening a rat testis cDNA library, <a href="#26" class="mim-tip-reference" title="Wagenfeld, A., Gromoll, J., Cooper, T. G. <strong>Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization.</strong> Biochem. Biophys. Res. Commun. 251: 545-549, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792810</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9512" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792810">Wagenfeld et al. (1998)</a> cloned a homologous gene in rats, called contraception associated protein-1 (CAP1), encoding a deduced protein that shares 95% and 91% sequence homology to mouse and human DJ1, respectively. A 1.6-kb transcript was detected in all rat tissues examined, with the highest level of expression in the testis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p><a href="#6" class="mim-tip-reference" title="Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P. <strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong> Science 299: 256-259, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>] [<a href="https://doi.org/10.1126/science.1077209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446870">Bonifati et al. (2003)</a> reported that the DJ1 gene contains 8 exons spanning 24 kb. The first 2 exons (1A and 1B) are noncoding and alternatively spliced. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#6" class="mim-tip-reference" title="Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P. <strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong> Science 299: 256-259, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>] [<a href="https://doi.org/10.1126/science.1077209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446870">Bonifati et al. (2003)</a> mapped the DJ1 gene to chromosome 1p36. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#27" class="mim-tip-reference" title="Wilson, M. A., Collins, J. L., Hod, Y., Ringe, D., Petsko, G. A. <strong>The 1.1-Angstrom resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease.</strong> Proc. Nat. Acad. Sci. 100: 9256-9261, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12855764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12855764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12855764[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1133288100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12855764">Wilson et al. (2003)</a> reported the 3-dimensional structure of the DJ1 protein, determined at a resolution of 1.1 angstroms by x-ray crystallography. A highly conserved cysteine residue, which is catalytically essential in homologs of human DJ1, showed an extreme sensitivity to radiation damage and may be subject to other forms of oxidative modification as well. The structure suggested that the loss of function caused by the Parkinson disease-associated mutation L166P (<a href="#0002">602533.0002</a>) is due to destabilization of the dimer interface. Taken together, the crystal structure of human DJ1 plus other observations suggested the possible involvement of this protein in the cellular oxidative stress response and a general etiology of neurodegenerative diseases. <a href="#9" class="mim-tip-reference" title="Cookson, M. R. <strong>Crystallizing ideas about Parkinson's disease.</strong> Proc. Nat. Acad. Sci. 100: 9111-9113, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12886009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12886009</a>] [<a href="https://doi.org/10.1073/pnas.1633722100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12886009">Cookson (2003)</a> commented. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12855764+12886009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Macedo, M. G., Anar, B., Bronner, I. F., Cannella, M., Squitieri, F., Bonifati, V., Hoogeveen, A., Heutink, P., Rizzu, P. <strong>The DJ-1(L166P) mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes.</strong> Hum. Molec. Genet. 12: 2807-2816, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12952867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12952867</a>] [<a href="https://doi.org/10.1093/hmg/ddg304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12952867">Macedo et al. (2003)</a> demonstrated that DJ1 protein formed a dimeric structure under physiologic conditions. Conversely, the L166P mutant protein showed a different elution profile in gel filtration assays as compared with wildtype, suggesting that L166P might form higher-order protein structures. In lymphoblasts from a parkinsonian patient who carried the homozygous mutation, the level of mutant protein was very low as compared with wildtype protein. Transfection experiments indicated that the mutant protein was rapidly degraded. <a href="#16" class="mim-tip-reference" title="Macedo, M. G., Anar, B., Bronner, I. F., Cannella, M., Squitieri, F., Bonifati, V., Hoogeveen, A., Heutink, P., Rizzu, P. <strong>The DJ-1(L166P) mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes.</strong> Hum. Molec. Genet. 12: 2807-2816, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12952867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12952867</a>] [<a href="https://doi.org/10.1093/hmg/ddg304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12952867">Macedo et al. (2003)</a> proposed that the rapid turnover and structural changes of the L166P mutant protein may be crucial in disease pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12952867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Chen, J., Li, L., Chin, L.-S. <strong>Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage.</strong> Hum. Molec. Genet. 19: 2395-2408, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20304780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20304780</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20304780[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20304780">Chen et al. (2010)</a> reported that DJ1 is synthesized as a latent protease zymogen with low intrinsic proteolytic activity. DJ1 protease zymogen was activated by the removal of a 15-amino acid peptide at its C terminus. The activated DJ1 functioned as a cysteine protease with cys106 and his126 as the catalytic diad. Endogenous DJ1 in dopaminergic cells underwent C-terminal cleavage in response to mild oxidative stress, suggesting that DJ1 protease activation occurs in a redox-dependent manner. Moreover, the C-terminally cleaved form of DJ1 with activated protease function exhibited enhanced cytoprotective action against oxidative stress-induced apoptosis. The cytoprotective action of DJ1 was abolished by C106A and H126A mutations. <a href="#7" class="mim-tip-reference" title="Chen, J., Li, L., Chin, L.-S. <strong>Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage.</strong> Hum. Molec. Genet. 19: 2395-2408, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20304780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20304780</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20304780[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20304780">Chen et al. (2010)</a> proposed a role for DJ1 protease in cellular defense against oxidative stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20304780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#19" class="mim-tip-reference" title="Nagakubo, D., Taira, T., Kitaura, H., Ikeda, M., Tamai, K., Iguchi-Ariga, S. M. M., Ariga, H. <strong>DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.</strong> Biochem. Biophys. Res. Commun. 231: 509-513, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9070310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9070310</a>] [<a href="https://doi.org/10.1006/bbrc.1997.6132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9070310">Nagakubo et al. (1997)</a> found that the DJ1 gene has weak transforming ability in NIH 3T3 cells, but transformation by DJ1 is synergistically enhanced by cotransfection with HRAS (<a href="/entry/190020">190020</a>) or MYC (<a href="/entry/190080">190080</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9070310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Takahashi, K., Taira, T., Niki, T., Seino, C., Iguchi-Ariga, S. M. M., Ariga, H. <strong>DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx-alpha to the receptor.</strong> J. Biol. Chem. 276: 37556-37563, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11477070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11477070</a>] [<a href="https://doi.org/10.1074/jbc.M101730200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11477070">Takahashi et al. (2001)</a> showed that DJ1 bound strongly to PIASx-alpha (<a href="/entry/603567">603567</a>), a modulator of the nuclear androgen receptor (AR; <a href="/entry/313700">313700</a>), and colocalized with PIASx-alpha in the nuclei of monkey Cos-I cells. While PIASx repressed AR transcriptional activity to 40% of the original level, as measured with an androgen responsive element-luciferase reporter, addition of DJ1 abrogated this suppression. Furthermore, DJ1 bound to the AR-interacting domain of PIASx, suggesting that DJ1 antagonized PIASx function by absorbing it and interfering with its binding to AR. <a href="#23" class="mim-tip-reference" title="Takahashi, K., Taira, T., Niki, T., Seino, C., Iguchi-Ariga, S. M. M., Ariga, H. <strong>DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx-alpha to the receptor.</strong> J. Biol. Chem. 276: 37556-37563, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11477070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11477070</a>] [<a href="https://doi.org/10.1074/jbc.M101730200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11477070">Takahashi et al. (2001)</a> concluded that, in somatic cells, DJ1 functions as a positive regulator of AR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11477070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Rizzu, P., Hinkle, D. A., Zhukareva, V., Bonifati, V., Severijnen, L.-A., Martinez, D., Ravid, R., Kamphorst, W., Eberwine, J. H., Lee, V. M.-Y., Trojanowski, J. Q., Heutink, P. <strong>DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia.</strong> Ann. Neurol. 55: 113-118, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14705119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14705119</a>] [<a href="https://doi.org/10.1002/ana.10782" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14705119">Rizzu et al. (2004)</a> presented evidence suggesting that DJ1 colocalizes within a subset of pathologic tau (MAPT; <a href="/entry/157140">157140</a>) inclusions in a diverse group of neurodegenerative disorders known as tauopathies, and that the solubility of DJ1 is altered in association with its aggregation within these inclusions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14705119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Moore, D. J., Zhang, L., Troncoso, J., Lee, M. K., Hattori, N., Mizuno, Y., Dawson, T. M., Dawson, V. L. <strong>Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress.</strong> Hum. Molec. Genet. 14: 71-84, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525661</a>] [<a href="https://doi.org/10.1093/hmg/ddi007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15525661">Moore et al. (2005)</a> showed that pathogenic mutant forms of DJ1 specifically but differentially associate with parkin (<a href="/entry/602544">602544</a>), an E3 ubiquitin ligase. Chemical crosslinking showed that pathogenic DJ1 mutants exhibited impairment in homodimer formation, suggesting that parkin may bind to monomeric DJ1. Parkin failed to specifically ubiquitinate and enhance the degradation of L166P (<a href="#0002">602533.0002</a>) and M26I (<a href="#0003">602533.0003</a>) mutant DJ1, but instead promoted their stability in cultured cells. Oxidative stress also promoted an interaction between DJ1 and parkin, but this did not result in the ubiquitination or degradation of DJ1. DJ1 levels were increased in the insoluble fraction of sporadic PD/DLB brains, but were reduced in the insoluble fraction of parkin-linked autosomal recessive juvenile-onset PD brains. The authors proposed that DJ1 and parkin may be linked in a common molecular pathway at multiple levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15525661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In human dopaminergic neuronal cells, <a href="#29" class="mim-tip-reference" title="Xu, J., Zhong, N., Wang, H., Elias, J. E., Kim, C. Y., Woldman, I., Pifl, C., Gygi, S. P., Geula, C., Yankner, B. A. <strong>The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.</strong> Hum. Molec. Genet. 14: 1231-1241, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15790595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15790595</a>] [<a href="https://doi.org/10.1093/hmg/ddi134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15790595">Xu et al. (2005)</a> showed that the major interacting proteins with DJ1 were NRB54 (NONO; <a href="/entry/300084">300084</a>) and PSF (SFPQ; <a href="/entry/605119">605119</a>), which are multifunctional regulators of transcription and RNA metabolism. PD-associated DJ1 mutants exhibited decreased nuclear distribution and increased mitochondrial localization, resulting in diminished colocalization with coactivator NRB54 and repressor PSF. Wildtype DJ1 inhibited the transcriptional silencing activity of PSF unlike DJ1 mutants, and PSF induced neuronal apoptosis, which was reversed by wildtype DJ1 and to a lesser extent by PD-associated DJ1 mutants. RNAi-knockdown of DJ1 sensitized cells to PSF-induced apoptosis. Both DJ1 and NRB54 blocked oxidative stress and mutant alpha-synuclein (SNCA; <a href="/entry/163890">163890</a>)-induced cell death. The findings showed that DJ1 is a neuroprotective transcriptional coactivator that may act in concert with NRB54 and PSF to regulate the expression of a neuroprotective genetic program. <a href="#29" class="mim-tip-reference" title="Xu, J., Zhong, N., Wang, H., Elias, J. E., Kim, C. Y., Woldman, I., Pifl, C., Gygi, S. P., Geula, C., Yankner, B. A. <strong>The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.</strong> Hum. Molec. Genet. 14: 1231-1241, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15790595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15790595</a>] [<a href="https://doi.org/10.1093/hmg/ddi134" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15790595">Xu et al. (2005)</a> concluded that DJ1 mutations that impair transcriptional coactivator function can render dopaminergic neurons vulnerable to apoptosis and may contribute to the pathogenesis of Parkinson disease (<a href="/entry/168600">168600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15790595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Junn, E., Taniguchi, H., Jeong, B. S., Zhao, X., Ichijo, H., Mouradian, M. M. <strong>Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.</strong> Proc. Nat. Acad. Sci. 102: 9691-9696, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15983381[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0409635102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15983381">Junn et al. (2005)</a> found that DJ1 overexpression in a human dopaminergic neuroblastoma cell line afforded modest protection against oxidative stress-induced cell death. A more robust cytoprotection was afforded by interaction of overexpressed DJ1 with the death protein DAXX (<a href="/entry/603186">603186</a>). DJ1 sequestered DAXX in the nucleus and prevented its translocation to the cytoplasm, where DAXX would normally activate its effector kinase, ASK1 (MAP3K5; <a href="/entry/602448">602448</a>), to trigger the death pathway. DJ1 carrying the L166P mutation did not interact with DAXX and was unable to protect cells from oxidative damage or DAXX/ASK1-induced apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15983381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Meulener, M. C., Xu, K., Thomson, L., Ischiropoulos, H., Bonini, N. M. <strong>Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.</strong> Proc. Nat. Acad. Sci. 103: 12517-12522, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 14978, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16894167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16894167</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16894167[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0601891103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16894167">Meulener et al. (2006)</a> found that human DJ1 could rescue Drosophila lacking Dj1b, the fly homolog of DJ1, from oxidative insult, and that a conserved cysteine (cys104, which is analogous to human cys106) was critical for antioxidant function in vivo. SDS-PAGE analysis showed that DJ1 modification increased with age in flies, mice, and humans. In particular, an increase in acidic DJ1 isoforms with lower activity was observed. Modification of Dj1b increased dramatically in aged flies upon oxidative insult, and aged flies were more vulnerable to oxidative stress. <a href="#17" class="mim-tip-reference" title="Meulener, M. C., Xu, K., Thomson, L., Ischiropoulos, H., Bonini, N. M. <strong>Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.</strong> Proc. Nat. Acad. Sci. 103: 12517-12522, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 14978, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16894167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16894167</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16894167[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0601891103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16894167">Meulener et al. (2006)</a> concluded that the risk factors of age and oxidative stress may regulate DJ1 protein activity, potentially contributing to Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16894167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using small-interfering RNA (siRNA) to disrupt DJ1 expression in a human nonsmall cell lung carcinoma cell line, <a href="#8" class="mim-tip-reference" title="Clements, C. M., McNally, R. S., Conti, B. J., Mak, T. W., Ting, J. P.-Y. <strong>DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2.</strong> Proc. Nat. Acad. Sci. 103: 15091-15096, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17015834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17015834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17015834[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0607260103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17015834">Clements et al. (2006)</a> showed that DJ1 was required for the expression of several genes, including the NRF2 (NFE2L2; <a href="/entry/600492">600492</a>)-regulated antioxidant enzyme NQO1 (<a href="/entry/125860">125860</a>). Without DJ1, NRF2 protein was unstable, and transcriptional responses were decreased both basally and after induction. DJ1 was indispensable for NRF2 stabilization by affecting NRF2 association with KEAP1 (<a href="/entry/606016">606016</a>), an inhibitor protein that promotes ubiquitination and degradation of NRF2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17015834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In human dopaminergic cells, <a href="#25" class="mim-tip-reference" title="Tang, B., Xiong, H., Sun, P., Zhang, Y., Wang, D., Hu, Z., Zhu, Z., Ma, H., Pan, Q., Xia, J., Xia, K., Zhang, Z. <strong>Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.</strong> Hum. Molec. Genet. 15: 1816-1825, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16632486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16632486</a>] [<a href="https://doi.org/10.1093/hmg/ddl104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16632486">Tang et al. (2006)</a> demonstrated that wildtype DJ1 and PINK1 (<a href="/entry/608309">608309</a>), mutation in which causes PARK6 (<a href="/entry/605909">605909</a>), coimmunoprecipitate and interact functionally to protect cells from toxic oxidative MPP-induced cell death. Overexpression of both proteins resulted in a synergistic protective effect, and mutations in both proteins resulted in increased cell death compared to either mutant protein alone, suggesting a common mechanism. Evidence also suggested that DJ1 helps to stabilize PINK1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16632486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Xiong, H., Wang, D., Chen, L., Choo, Y. S., Ma, H., Tang, C., Xia, K., Jiang, W., Ronai, Z., Zhuang, X., Zhang, Z. <strong>Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation.</strong> J. Clin. Invest. 119: 650-660, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19229105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19229105</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19229105[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI37617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19229105">Xiong et al. (2009)</a> demonstrated that parkin, PINK1, and DJ1 interact and form an approximately 200-kD functional ubiquitin E3 ligase complex in human primary neurons. PINK1 was shown to increase the activity of parkin, which degrades itself via the ubiquitin-proteasome system. Pathogenic PINK1 (G309D; <a href="/entry/608309#0001">608309.0001</a>) did not promote ubiquitination and degradation of parkin or the parkin substrate synphilin-1 (<a href="/entry/603779">603779</a>) in transfected cells. Expression of DJ1 increased PINK1 expression, perhaps acting as a stabilizer. Overexpression of parkin substrates or heat shock treatment resulted in parkin accumulation in Pink1- or Dj1-deficient murine cells, and pathogenic parkin mutations resulted in a reduced ability to promote degradation of parkin substrates, all suggesting a decrease in E3 ubiquitin activity. <a href="#28" class="mim-tip-reference" title="Xiong, H., Wang, D., Chen, L., Choo, Y. S., Ma, H., Tang, C., Xia, K., Jiang, W., Ronai, Z., Zhuang, X., Zhang, Z. <strong>Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation.</strong> J. Clin. Invest. 119: 650-660, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19229105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19229105</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19229105[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI37617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19229105">Xiong et al. (2009)</a> suggested that this complex promotes degradation of un- or misfolded proteins, including parkin, and that disruption of the activity of this complex leads to accumulation of abnormal proteins and increased susceptibility to oxidative stress, which is toxic to neurons and may lead to Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19229105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Zucchelli, S., Codrich, M., Marcuzzi, F., Pinto, M., Vilotti, S., Biagioli, M., Ferrer, I., Gustincich, S. <strong>TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains.</strong> Hum. Molec. Genet. 19: 3759-3770, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20634198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20634198</a>] [<a href="https://doi.org/10.1093/hmg/ddq290" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20634198">Zucchelli et al. (2010)</a> found that TRAF6 bound misfolded mutant DJ1 (PARK7; <a href="/entry/602533">602533</a>) and SNCA (<a href="/entry/163890">163890</a>), and that both proteins were substrates of TRAF6 ligase activity in vivo. Rather than conventional lys63 (K63) assembly, TRAF6 promoted atypical ubiquitin linkage formation to both PD targets that shared K6-, K27- and K29- mediated ubiquitination. TRAF6 stimulated the accumulation of insoluble and polyubiquitinated mutant DJ1 into cytoplasmic aggregates. In human postmortem brains of PD patients, TRAF6 protein colocalized with SNCA in Lewy bodies. The authors proposed a novel role for TRAF6 and for atypical ubiquitination in PD pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20634198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Dj1 -/- mouse cells, DJ1-linked PD patient lymphoblasts, and DJ1-knockdown human cell lines with appropriate controls, <a href="#13" class="mim-tip-reference" title="Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., and 11 others. <strong>Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.</strong> Hum. Molec. Genet. 19: 3734-3746, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639397</a>] [<a href="https://doi.org/10.1093/hmg/ddq288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639397">Irrcher et al. (2010)</a> showed that loss of DJ1 resulted in mitochondrial fragmentation and sensitivity to oxidative damage. Reactive oxygen species (ROS) appeared to play a critical role in the defects, as mitochondria isolated from Dj1 -/- animals produced more ROS than controls and ROS scavengers rescued the phenotype. The aberrant mitochondrial phenotype was also reversed by expression of either wildtype human parkin or PINK. Dj1 -/- mouse cells and DJ1-linked PD patient lymphoblasts showed evidence of elevated autophagy, but not mitophagy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using over- and underexpression studies, <a href="#12" class="mim-tip-reference" title="Im, J.-Y., Lee, K.-W., Woo, J.-M., Junn, E., Mouradian, M. M. <strong>DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway.</strong> Hum. Molec. Genet. 21: 3013-3024, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22492997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22492997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22492997[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22492997">Im et al. (2012)</a> found that DJ1 protected HeLa cells and human neuroblastoma cell lines from oxidative stress by inducing expression of thioredoxin (TRX1; <a href="/entry/187700">187700</a>), an important antioxidative enzyme. Studies with Dj1-null mice confirmed the findings. DJ1 increased protein expression and nuclear accumulation of NRF2 and enhanced binding of NRF2 to the antioxidant response element (ARE) in the TRX1 promoter. DJ1 also enhanced H2O2-induced activation of AKT (see <a href="/entry/164730">164730</a>), and this effect depended on the presence of TRX1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22492997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Ottolini, D., Cali, T., Negro, A., Brini, M. <strong>The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering.</strong> Hum. Molec. Genet. 22: 2152-2168, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23418303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23418303</a>] [<a href="https://doi.org/10.1093/hmg/ddt068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23418303">Ottolini et al. (2013)</a> found that DJ1 was expressed at mitochondrial-associated membranes in the endoplasmic reticulum (ER) and that DJ1 maintained mitochondrial morphology and influenced mitochondrial Ca(2+) transients in stimulated HeLa cells. Knockdown of DJ1 resulted in mitochondrial fragmentation and decreased mitochondrial Ca(2+) uptake from the ER following stimulation. Conversely, overexpression of DJ1 augmented stimulation-induced mitochondrial Ca(2+) transients by increasing ER-mitochondrial communication. Overexpression of p53 (<a href="/entry/191170">191170</a>) in HeLa cells impaired the ability of mitochondria to accumulate Ca(2+) following stimulation, disrupted mitochondrial morphology, and reduced mitochondria-ER contact sites. DJ1 overexpression prevented p53 effects and reestablished ER-mitochondrial contacts. The effects of p53 on mitochondria did not require the transcriptional regulatory function of p53. Rescue of mitochondria by DJ1 was associated with enhanced degradation of p53, but it did not require DJ1 upregulation or DJ1 kinase activity. Overexpression of the mitochondrial profusion protein mitofusin-2 (MFN2; <a href="/entry/608507">608507</a>) also reversed the effects of p53 on mitochondria. <a href="#20" class="mim-tip-reference" title="Ottolini, D., Cali, T., Negro, A., Brini, M. <strong>The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering.</strong> Hum. Molec. Genet. 22: 2152-2168, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23418303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23418303</a>] [<a href="https://doi.org/10.1093/hmg/ddt068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23418303">Ottolini et al. (2013)</a> concluded that DJ1 has a direct role in ER-mitochondria coupling and is essential to maintain mitochondrial structure and function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23418303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bjorkblom, B., Adilbayeva, A., Maple-Grodem, J., Piston, D., Okvist, M., Xu, X. M., Brede, C., Larsen, J. P., Moller, S. G. <strong>Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity.</strong> J. Biol. Chem. 288: 22809-22820, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23792957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23792957</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23792957[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M113.482091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23792957">Bjorkblom et al. (2013)</a> found that recombinant human DJ1 bound copper, mercury, and, more weakly, manganese, but not other ions tested. Dj1 also protected mouse embryonic fibroblasts (MEFs) against copper- and mercury-induced cytotoxicity. Exposure of MEFs to a nontoxic concentration of dopamine, together with copper or mercury, resulted in an almost immediate and dramatic surge of intracellular oxidation. The oxidative response was exacerbated in Dj1 -/- MEFs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23792957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Richarme, G., Liu, C., Mihoub, M., Abdallah, J., Leger, T., Joly, N., Liebart, J.-C., Jurkunas, U. V., Nadal, M., Bouloc, P., Dairou, J., Lamouri, A. <strong>Guanine glycation repair by DJ-1/Park7 and its bacterial homologs.</strong> Science 357: 208-211, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28596309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28596309</a>] [<a href="https://doi.org/10.1126/science.aag1095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28596309">Richarme et al. (2017)</a> found that DJ1 and its bacterial homologs Hsp31, YhbO, and YajL can repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, <a href="#21" class="mim-tip-reference" title="Richarme, G., Liu, C., Mihoub, M., Abdallah, J., Leger, T., Joly, N., Liebart, J.-C., Jurkunas, U. V., Nadal, M., Bouloc, P., Dairou, J., Lamouri, A. <strong>Guanine glycation repair by DJ-1/Park7 and its bacterial homologs.</strong> Science 357: 208-211, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28596309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28596309</a>] [<a href="https://doi.org/10.1126/science.aag1095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28596309">Richarme et al. (2017)</a> concluded that DJ1 and its prokaryotic homologs constitute a major nucleotide repair system that they named guanine glycation repair. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28596309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 consanguineous families from genetically isolated communities in the Netherlands and Italy with autosomal recessive early-onset Parkinson disease (PARK7; <a href="/entry/606324">606324</a>), <a href="#6" class="mim-tip-reference" title="Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P. <strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong> Science 299: 256-259, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>] [<a href="https://doi.org/10.1126/science.1077209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446870">Bonifati et al. (2003)</a> identified 2 mutations in the DJ1 gene that cosegregated with the disease (<a href="#0001">602533.0001</a> and <a href="#0002">602533.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 185 unrelated patients with early-onset Parkinson disease, <a href="#1" class="mim-tip-reference" title="Abou-Sleiman, P. M., Healy, D. G., Quinn, N., Lees, A. J., Wood, N. W. <strong>The role of pathogenic DJ-1 mutations in Parkinson's disease.</strong> Ann. Neurol. 54: 283-286, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12953260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12953260</a>] [<a href="https://doi.org/10.1002/ana.10675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12953260">Abou-Sleiman et al. (2003)</a> identified 2 patients with mutations in the DJ1 gene (<a href="#0003">602533.0003</a>-<a href="#0004">602533.0004</a>); one was homozygous and the other was heterozygous. In addition, several variants were found in the DJ1 gene, which likely represented polymorphisms. The authors estimated that the frequency of DJ1 mutations in early-onset Parkinson disease is very low, at approximately 1%. No mutations in the DJ1 gene were identified in a cohort of later-onset sporadic cases of Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12953260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a series of in vitro studies, <a href="#24" class="mim-tip-reference" title="Takahashi-Niki, K., Niki, T., Taira, T., Iguchi-Ariga, S. M. M., Ariga, H. <strong>Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients.</strong> Biochem. Biophys. Res. Commun. 320: 389-397, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15219840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15219840</a>] [<a href="https://doi.org/10.1016/j.bbrc.2004.05.187" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15219840">Takahashi-Niki et al. (2004)</a> found that mutant DJ1 proteins M26I (<a href="#0003">602533.0003</a>), D149A (<a href="#0004">602533.0004</a>), and L166P (<a href="#0002">602533.0002</a>) formed heterodimers with wildtype DJ1. Mutant proteins M26I and L166P were unstable and were degraded by the proteasome system. Cell lines expressing the mutant M26I and L166P proteins showed reduced ability to eliminate exogenous hydrogen peroxide, indicating increased susceptibility to oxidative stress. In contrast, the mutant D149A protein showed increased stability compared to wildtype, and cells expressing the mutant D149A were resistant to hydrogen peroxide-induced cell death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15219840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Zhang, L., Shimoji, M., Thomas, B., Moore, D. J., Yu, S.-W., Marupudi, N. I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M., Dawson, V. L. <strong>Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.</strong> Hum. Molec. Genet. 14: 2063-2073, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944198</a>] [<a href="https://doi.org/10.1093/hmg/ddi211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944198">Zhang et al. (2005)</a> generated human neuroblastoma cells stably transfected with wildtype or mutant (e.g., M26I, L166P, and D149A) DJ1 constructs and performed mitochondrial fractionation and confocal colocalization imaging studies. When compared with wildtype and other mutants, the L166P mutant exhibited a largely reduced protein level. However, the pathogenic mutations did not alter the distribution of DJ1 to mitochondria. <a href="#30" class="mim-tip-reference" title="Zhang, L., Shimoji, M., Thomas, B., Moore, D. J., Yu, S.-W., Marupudi, N. I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M., Dawson, V. L. <strong>Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.</strong> Hum. Molec. Genet. 14: 2063-2073, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944198</a>] [<a href="https://doi.org/10.1093/hmg/ddi211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944198">Zhang et al. 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<p><a href="#15" class="mim-tip-reference" title="Kim, R. H., Smith, P. D., Aleyasin, H., Hayley, S., Mount, M. P., Pownall, S., Wakeham, A., You-Ten, A. J., Kalia, S. K., Horne, P., Westaway, D., Lozano, A. M., Anisman, H., Park, D. S., Mak, T. W. <strong>Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress.</strong> Proc. Nat. Acad. Sci. 102: 5215-5220, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15784737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15784737</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15784737[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0501282102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15784737">Kim et al. (2005)</a> found that mice with a targeted deletion of the Dj1 gene developed normally, had normal numbers of dopaminergic neurons in the substantia nigra, and showed no abnormal gross motor behavior up to 13 months of age. In vitro studies showed that primary cortical neurons from the Dj1-null mice exhibited increased sensitivity to oxidative stress compared to control cells. After challenge with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), Dj1-null mice showed a significant decrease in total activity and a greater loss of striatal dopaminergic neurons compared to control mice. Restoration of Dj1 expression in cell cultures or in Dj1-null mice resulted in a protective effect. Moreover, wildtype mice that received adenoviral delivery of Dj1 showed some resistance to MPTP-induced neuronal damage. <a href="#15" class="mim-tip-reference" title="Kim, R. H., Smith, P. D., Aleyasin, H., Hayley, S., Mount, M. P., Pownall, S., Wakeham, A., You-Ten, A. J., Kalia, S. K., Horne, P., Westaway, D., Lozano, A. M., Anisman, H., Park, D. S., Mak, T. W. <strong>Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress.</strong> Proc. Nat. Acad. Sci. 102: 5215-5220, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15784737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15784737</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15784737[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0501282102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15784737">Kim et al. (2005)</a> concluded that Dj1 protects against neuronal oxidative stress, and that while loss of Dj1 alone may not be sufficient to produce parkinsonism, it may confer hypersensitivity to dopaminergic insults when challenged. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15784737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In vitro and in vivo, <a href="#2" class="mim-tip-reference" title="Aleyasin, H., Rousseaux, M. W. C., Phillips, M., Kim, R. H., Bland, R. J., Callaghan, S., Slack, R. S., During, M. J., Mak, T. W., Park, D. S. <strong>The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.</strong> Proc. Nat. Acad. Sci. 104: 18748-18753, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18003894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18003894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18003894[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0709379104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18003894">Aleyasin et al. (2007)</a> found that Dj1-null mice were significantly more susceptible to glutamate-induced neuronal excitotoxicity compared to controls. Expression of Dj1 provided protection. Further studies showed that the oxidation-sensitive cys106 residue was essential for neuronal protection from excitotoxicity. Dj1 expression decreased markers of oxidative stress after stroke insult in vivo, suggesting that Dj1 protects through alleviation of oxidative stress. <a href="#2" class="mim-tip-reference" title="Aleyasin, H., Rousseaux, M. W. C., Phillips, M., Kim, R. H., Bland, R. J., Callaghan, S., Slack, R. S., During, M. J., Mak, T. W., Park, D. S. <strong>The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.</strong> Proc. Nat. Acad. Sci. 104: 18748-18753, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18003894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18003894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18003894[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0709379104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18003894">Aleyasin et al. (2007)</a> suggested that Dj1 may be important in other neuropathologic conditions besides Parkinson disease, and noted commonalities among different neuropathologies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18003894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Andres-Mateos, E., Perier, C., Zhang, L., Blanchard-Fillion, B., Greco, T. M., Thomas, B., Ko, H. S., Sasaki, M., Ischiropoulos, H., Przedborski, S., Dawson, T. M., Dawson, V. L. <strong>DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase.</strong> Proc. Nat. Acad. Sci. 104: 14807-14812, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17766438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17766438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17766438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0703219104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17766438">Andres-Mateos et al. (2007)</a> found that mice with targeted deletion of Dj1 exons 2 and 3 had no significant changes in the striatal dopaminergic system compared to wildtype mice. However, mitochondria isolated from the mutant mice contained a 2-fold increase in hydrogen peroxide associated with a decrease in mitochondrial aconitase (ACO2; <a href="/entry/100850">100850</a>). Older mutant mice showed a compensatory upregulation of mitochondrial superoxide dismutase (SOD1; <a href="/entry/147450">147450</a>) and glutathione peroxidase activity (see, e.g., GPX1; <a href="/entry/138320">138320</a>). Functional studies and mass spectrometry indicated that DJ1 is an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide through oxidation of cys106. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17766438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, <a href="#10" class="mim-tip-reference" title="Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T., Surmeier, D. J. <strong>Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1.</strong> Nature 468: 696-700, 2010. Note: Erratum: Nature 521: 380 only, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21068725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21068725</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21068725[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21068725">Guzman et al. (2010)</a> showed that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable substantia nigra pars compacta (SNc) dopaminergic neurons. The oxidant stress engaged defenses that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D (<a href="/entry/601753">601753</a>), which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ1 downregulated the expression of 2 uncoupling proteins, UCP4 (SLC25A27) and UCP5 (SLC25A14; <a href="/entry/300242">300242</a>), compromised calcium-induced uncoupling, and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, <a href="#10" class="mim-tip-reference" title="Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T., Surmeier, D. J. <strong>Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1.</strong> Nature 468: 696-700, 2010. Note: Erratum: Nature 521: 380 only, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21068725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21068725</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21068725[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21068725">Guzman et al. (2010)</a> suggested that their results pointed to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson disease (<a href="/entry/168600">168600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21068725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a consanguineous Dutch family with early-onset Parkinson disease (PARK7; <a href="/entry/606324">606324</a>), <a href="#6" class="mim-tip-reference" title="Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P. <strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong> Science 299: 256-259, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>] [<a href="https://doi.org/10.1126/science.1077209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446870">Bonifati et al. (2003)</a> identified a 14-kb homozygous deletion in the DJ1 gene, which deleted exons 1 through 5 and 4 kb of sequence upstream of the open reading frame start. The deletion showed cosegregation with the disease in the 4 affected family members and was absent in over 1,220 chromosomes from the Dutch population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., and 11 others. <strong>Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.</strong> Hum. Molec. Genet. 19: 3734-3746, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639397</a>] [<a href="https://doi.org/10.1093/hmg/ddq288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639397">Irrcher et al. (2010)</a> showed that this deletion mutation in DJ1 resulted in fragmented mitochondria and elevated markers of autophagy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a consanguineous Italian family with autosomal recessive early-onset Parkinson disease (PARK7; <a href="/entry/606324">606324</a>), <a href="#6" class="mim-tip-reference" title="Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P. <strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong> Science 299: 256-259, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>] [<a href="https://doi.org/10.1126/science.1077209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446870">Bonifati et al. (2003)</a> identified a homozygous 497T-C transition in the DJ1 gene, resulting in a leu166-to-pro substitution (L166P) in the protein. The mutation showed cosegregation with the disease in 3 affected sibs and was absent in 320 chromosomes from the Italian population. A molecular model of the mutation was predicted to destabilize the terminal helix of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., and 11 others. <strong>Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.</strong> Hum. Molec. Genet. 19: 3734-3746, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639397</a>] [<a href="https://doi.org/10.1093/hmg/ddq288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639397">Irrcher et al. (2010)</a> showed that the L166P mutation in DJ1 resulted in fragmented mitochondria and elevated markers of autophagy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Im, J.-Y., Lee, K.-W., Woo, J.-M., Junn, E., Mouradian, M. M. <strong>DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway.</strong> Hum. Molec. Genet. 21: 3013-3024, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22492997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22492997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22492997[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22492997">Im et al. (2012)</a> found that DJ1 with the L166P substitution was unable to induce TRX1 (<a href="/entry/187700">187700</a>) expression or to protect transfected HeLa cells from H2O2-induced cytotoxicity. Wildtype, but not mutant DJ1, mediated H2O2-induced and DJ1-dependent expression and nuclear translocation of NRF2 (<a href="/entry/600492">600492</a>) and enhanced recruitment of NRF2 to the antioxidant response element in the TRX1 promoter region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22492997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs74315351 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315351;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74315351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs74315351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Ashkenazi Jewish patient with early-onset Parkinson disease (<a href="/entry/606324">606324</a>), <a href="#1" class="mim-tip-reference" title="Abou-Sleiman, P. M., Healy, D. G., Quinn, N., Lees, A. J., Wood, N. W. <strong>The role of pathogenic DJ-1 mutations in Parkinson's disease.</strong> Ann. Neurol. 54: 283-286, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12953260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12953260</a>] [<a href="https://doi.org/10.1002/ana.10675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12953260">Abou-Sleiman et al. (2003)</a> identified a homozygous A-to-G change in exon 2 of the DJ1 gene, resulting in a met26-to-ile (M26I) substitution. The mutation was not present in more than 1,000 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12953260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Im, J.-Y., Lee, K.-W., Woo, J.-M., Junn, E., Mouradian, M. M. <strong>DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway.</strong> Hum. Molec. Genet. 21: 3013-3024, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22492997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22492997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22492997[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22492997">Im et al. (2012)</a> found that DJ1 with the M26I substitution was unable to induce TRX1 (<a href="/entry/187700">187700</a>) expression or to protect transfected HeLa cells from H2O2-induced cytotoxicity. Wildtype, but not mutant DJ1, mediated H2O2-induced and DJ1-dependent expression and nuclear translocation of NRF2 (<a href="/entry/600492">600492</a>) and enhanced recruitment of NRF2 to the antioxidant response element in the TRX1 promoter region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22492997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315352;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs74315352?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74315352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs74315352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Afro-Caribbean patient with early-onset Parkinson disease (<a href="/entry/606324">606324</a>), <a href="#1" class="mim-tip-reference" title="Abou-Sleiman, P. M., Healy, D. G., Quinn, N., Lees, A. J., Wood, N. W. <strong>The role of pathogenic DJ-1 mutations in Parkinson's disease.</strong> Ann. Neurol. 54: 283-286, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12953260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12953260</a>] [<a href="https://doi.org/10.1002/ana.10675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12953260">Abou-Sleiman et al. (2003)</a> identified a heterozygous mutation in exon 4 of the DJ1 gene, resulting in an asp149-to-ala (D149A) substitution. The mutation was not found in 750 white, 160 Ashkenazi, or 40 Afro-Caribbean chromosomes tested, suggesting that it is pathogenic, but the authors noted that they did not identify a second mutation in the DJ1 gene in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12953260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bjorkblom, B., Adilbayeva, A., Maple-Grodem, J., Piston, D., Okvist, M., Xu, X. M., Brede, C., Larsen, J. P., Moller, S. G. <strong>Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity.</strong> J. Biol. Chem. 288: 22809-22820, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23792957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23792957</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23792957[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M113.482091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23792957">Bjorkblom et al. (2013)</a> found that DJ1 with the D149A substitution bound copper with higher affinity than wildtype DJ1. Mutant DJ1 also bound mercury. However, in contrast with wildtype DJ1, mutant Dj1 lacked the ability to protect mouse embryonic fibroblasts from copper- and mercury-induced cytotoxicity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23792957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315353;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs74315353?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74315353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs74315353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>Analyzing the DJ1 gene in 104 patients with early-onset Parkinson disease (<a href="/entry/606324">606324</a>), <a href="#11" class="mim-tip-reference" title="Hering, R., Strauss, K. M., Tao, X., Bauer, A., Woitalla, D., Mietz, E.-M., Petrovic, S., Bauer, P., Schaible, W., Muller, T., Schols, L., Klein, C., Berg, D., Meyer, P. T., Schulz, J. B., Wollnik, B., Tong, L., Kruger, R., Riess, O. <strong>Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).</strong> Hum. Mutat. 24: 321-329, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365989</a>] [<a href="https://doi.org/10.1002/humu.20089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365989">Hering et al. (2004)</a> identified a homozygous 192G-C transversion, resulting in a glu64-to-asp (E64D) substitution, in 1 patient of Turkish ancestry. In the proband, a substantial reduction of dopamine uptake transporter (DAT; <a href="/entry/126455">126455</a>) binding was found in the striatum by PET scan, indicating a serious loss of presynaptic dopaminergic afferents. The proband's sister, also homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who was heterozygous for E64D. By crystallography, <a href="#11" class="mim-tip-reference" title="Hering, R., Strauss, K. M., Tao, X., Bauer, A., Woitalla, D., Mietz, E.-M., Petrovic, S., Bauer, P., Schaible, W., Muller, T., Schols, L., Klein, C., Berg, D., Meyer, P. T., Schulz, J. B., Wollnik, B., Tong, L., Kruger, R., Riess, O. <strong>Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).</strong> Hum. Mutat. 24: 321-329, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365989</a>] [<a href="https://doi.org/10.1002/humu.20089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365989">Hering et al. (2004)</a> demonstrated that the E64D mutation does not alter the structure of the DJ1 protein; however, they observed a tendency toward decreased levels of the mutant protein when overexpressed in HEK293 or COS-7 cells. By immunocytochemistry, about 5% of the cells expressing E64D and up to 80% of the cells expressing the L166P mutation (<a href="#0002">602533.0002</a>) displayed a predominant nuclear localization of the mutant DJ1 protein, in contrast to the homogeneous nuclear and cytoplasmic staining in HEK293 cells overexpressing wildtype DJ1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs200968609 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200968609;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs200968609?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs200968609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs200968609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315354;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs74315354?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74315354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs74315354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007484 OR RCV001644681" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007484, RCV001644681" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007484...</a>
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<p>In 3 affected sibs from a consanguineous southern Italian family with early-onset parkinsonism (<a href="/entry/606324">606324</a>), <a href="#4" class="mim-tip-reference" title="Annesi, G., Savettieri, G., Pugliese, P., D'Amelio, M., Tarantino, P., Ragonese, P., La Bella, V., Piccoli, T., Civitelli, D., Annesi, F., Fierro, B., Piccoli, F., Arabia, G., Caracciolo, M., Canadiano, I. C. C., Quattrone, A. <strong>DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.</strong> Ann. Neurol. 58: 803-807, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240358</a>] [<a href="https://doi.org/10.1002/ana.20666" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16240358">Annesi et al. (2005)</a> identified double homozygosity for mutations in the DJ1 gene. One was a 3385G-A transition in exon 7, resulting in a glu163-to-lys (E163K) substitution, and the other was an 18-bp duplication (168-185dup) in the promoter region. Age at disease onset was 36, 35, and 24 years, respectively. Severe amyotrophic lateral sclerosis and cognitive impairment were prominent in 1 sib, while the other 2 had prominent parkinsonism and behavioral abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 PARKINSON DISEASE, AUTOSOMAL RECESSIVE EARLY-ONSET, DIGENIC, PINK1/DJ1</strong>
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PARK7, ALA39SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853051 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853051;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007485" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007485" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007485</a>
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<p>In 2 Chinese sibs with early-onset Parkinson disease (see <a href="/entry/605909">605909</a>), <a href="#25" class="mim-tip-reference" title="Tang, B., Xiong, H., Sun, P., Zhang, Y., Wang, D., Hu, Z., Zhu, Z., Ma, H., Pan, Q., Xia, J., Xia, K., Zhang, Z. <strong>Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.</strong> Hum. Molec. Genet. 15: 1816-1825, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16632486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16632486</a>] [<a href="https://doi.org/10.1093/hmg/ddl104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16632486">Tang et al. (2006)</a> identified compound heterozygosity for 2 mutations in 2 different genes: a 115G-T transversion in exon 3 of the DJ1 gene resulting in an ala39-to-ser (A39S) substitution in the third beta-sheet of the protein, and a P399L mutation (<a href="/entry/608309#0014">608309.0014</a>) in the predicted kinase domain of the PINK1 gene. The DJ1 and PINK1 mutations were not observed in 240 and 568 control chromosomes, respectively, and both were located in highly conserved residues. The findings were consistent with digenic inheritance of Parkinson disease. A 42-year-old unaffected family member also carried both mutations, suggesting incomplete penetrance. Coimmunoprecipitation studies showed that both wildtype and mutant PINK1 interacted with both wildtype and mutant DJ1. Expression of wildtype DJ1 increased steady-state levels of both mutant and wildtype PINK1, but mutant DJ1 decreased steady-state levels of both mutant and wildtype PINK1, suggesting that wildtype DJ1 can enhance PINK1 stability. Human neuroblastoma cells expressing either mutant PINK1 or DJ1 showed reduced viability following oxidative challenge with MPP compared to control cells, indicating that both proteins protect against cell stress. Coexpression of both wildtype proteins resulted in a synergistic increase in cell viability against MPP-induced stress. In addition, coexpression of both mutant proteins significantly increased susceptibility of cells to death, compared to either mutant alone. These findings indicated that DJ1 and PINK1 function collaboratively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16632486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Abou-Sleiman2003" class="mim-anchor"></a>
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Abou-Sleiman, P. M., Healy, D. G., Quinn, N., Lees, A. J., Wood, N. W.
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<strong>The role of pathogenic DJ-1 mutations in Parkinson's disease.</strong>
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Ann. Neurol. 54: 283-286, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12953260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12953260</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12953260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.10675" target="_blank">Full Text</a>]
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<a id="Aleyasin2007" class="mim-anchor"></a>
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Aleyasin, H., Rousseaux, M. W. C., Phillips, M., Kim, R. H., Bland, R. J., Callaghan, S., Slack, R. S., During, M. J., Mak, T. W., Park, D. S.
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<strong>The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.</strong>
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Proc. Nat. Acad. Sci. 104: 18748-18753, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18003894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18003894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18003894[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18003894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0709379104" target="_blank">Full Text</a>]
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<a id="Andres-Mateos2007" class="mim-anchor"></a>
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<div class="">
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Andres-Mateos, E., Perier, C., Zhang, L., Blanchard-Fillion, B., Greco, T. M., Thomas, B., Ko, H. S., Sasaki, M., Ischiropoulos, H., Przedborski, S., Dawson, T. M., Dawson, V. L.
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<strong>DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase.</strong>
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Proc. Nat. Acad. Sci. 104: 14807-14812, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17766438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17766438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17766438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17766438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0703219104" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Annesi2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Annesi, G., Savettieri, G., Pugliese, P., D'Amelio, M., Tarantino, P., Ragonese, P., La Bella, V., Piccoli, T., Civitelli, D., Annesi, F., Fierro, B., Piccoli, F., Arabia, G., Caracciolo, M., Canadiano, I. C. C., Quattrone, A.
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<strong>DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.</strong>
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Ann. Neurol. 58: 803-807, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.20666" target="_blank">Full Text</a>]
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<a id="Bjorkblom2013" class="mim-anchor"></a>
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Bjorkblom, B., Adilbayeva, A., Maple-Grodem, J., Piston, D., Okvist, M., Xu, X. M., Brede, C., Larsen, J. P., Moller, S. G.
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<strong>Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity.</strong>
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J. Biol. Chem. 288: 22809-22820, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23792957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23792957</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23792957[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23792957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M113.482091" target="_blank">Full Text</a>]
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<a id="Bonifati2003" class="mim-anchor"></a>
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Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P.
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<strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong>
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Science 299: 256-259, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12446870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1077209" target="_blank">Full Text</a>]
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<a id="Chen2010" class="mim-anchor"></a>
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Chen, J., Li, L., Chin, L.-S.
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<strong>Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage.</strong>
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Hum. Molec. Genet. 19: 2395-2408, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20304780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20304780</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20304780[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20304780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq113" target="_blank">Full Text</a>]
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<a id="Clements2006" class="mim-anchor"></a>
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Clements, C. M., McNally, R. S., Conti, B. J., Mak, T. W., Ting, J. P.-Y.
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<strong>DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2.</strong>
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Proc. Nat. Acad. Sci. 103: 15091-15096, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17015834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17015834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17015834[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17015834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0607260103" target="_blank">Full Text</a>]
|
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|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Cookson2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cookson, M. R.
|
|
<strong>Crystallizing ideas about Parkinson's disease.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 9111-9113, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12886009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12886009</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12886009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.1633722100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Guzman2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T., Surmeier, D. J.
|
|
<strong>Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1.</strong>
|
|
Nature 468: 696-700, 2010. Note: Erratum: Nature 521: 380 only, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21068725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21068725</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21068725[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21068725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09536" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Hering2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hering, R., Strauss, K. M., Tao, X., Bauer, A., Woitalla, D., Mietz, E.-M., Petrovic, S., Bauer, P., Schaible, W., Muller, T., Schols, L., Klein, C., Berg, D., Meyer, P. T., Schulz, J. B., Wollnik, B., Tong, L., Kruger, R., Riess, O.
|
|
<strong>Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).</strong>
|
|
Hum. Mutat. 24: 321-329, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20089" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Im2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Im, J.-Y., Lee, K.-W., Woo, J.-M., Junn, E., Mouradian, M. M.
|
|
<strong>DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway.</strong>
|
|
Hum. Molec. Genet. 21: 3013-3024, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22492997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22492997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22492997[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22492997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/dds131" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Irrcher2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., and 11 others.
|
|
<strong>Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.</strong>
|
|
Hum. Molec. Genet. 19: 3734-3746, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639397</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddq288" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Junn2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Junn, E., Taniguchi, H., Jeong, B. S., Zhao, X., Ichijo, H., Mouradian, M. M.
|
|
<strong>Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 9691-9696, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15983381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15983381</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15983381[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15983381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0409635102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Kim2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, R. H., Smith, P. D., Aleyasin, H., Hayley, S., Mount, M. P., Pownall, S., Wakeham, A., You-Ten, A. J., Kalia, S. K., Horne, P., Westaway, D., Lozano, A. M., Anisman, H., Park, D. S., Mak, T. W.
|
|
<strong>Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 5215-5220, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15784737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15784737</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15784737[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15784737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0501282102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Macedo2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Macedo, M. G., Anar, B., Bronner, I. F., Cannella, M., Squitieri, F., Bonifati, V., Hoogeveen, A., Heutink, P., Rizzu, P.
|
|
<strong>The DJ-1(L166P) mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes.</strong>
|
|
Hum. Molec. Genet. 12: 2807-2816, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12952867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12952867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12952867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg304" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Meulener2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meulener, M. C., Xu, K., Thomson, L., Ischiropoulos, H., Bonini, N. M.
|
|
<strong>Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 12517-12522, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 14978, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16894167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16894167</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16894167[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16894167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0601891103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Moore2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moore, D. J., Zhang, L., Troncoso, J., Lee, M. K., Hattori, N., Mizuno, Y., Dawson, T. M., Dawson, V. L.
|
|
<strong>Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress.</strong>
|
|
Hum. Molec. Genet. 14: 71-84, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15525661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Nagakubo1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nagakubo, D., Taira, T., Kitaura, H., Ikeda, M., Tamai, K., Iguchi-Ariga, S. M. M., Ariga, H.
|
|
<strong>DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.</strong>
|
|
Biochem. Biophys. Res. Commun. 231: 509-513, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9070310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9070310</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9070310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1997.6132" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Ottolini2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ottolini, D., Cali, T., Negro, A., Brini, M.
|
|
<strong>The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering.</strong>
|
|
Hum. Molec. Genet. 22: 2152-2168, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23418303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23418303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23418303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddt068" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Richarme2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Richarme, G., Liu, C., Mihoub, M., Abdallah, J., Leger, T., Joly, N., Liebart, J.-C., Jurkunas, U. V., Nadal, M., Bouloc, P., Dairou, J., Lamouri, A.
|
|
<strong>Guanine glycation repair by DJ-1/Park7 and its bacterial homologs.</strong>
|
|
Science 357: 208-211, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28596309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28596309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28596309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.aag1095" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Rizzu2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rizzu, P., Hinkle, D. A., Zhukareva, V., Bonifati, V., Severijnen, L.-A., Martinez, D., Ravid, R., Kamphorst, W., Eberwine, J. H., Lee, V. M.-Y., Trojanowski, J. Q., Heutink, P.
|
|
<strong>DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia.</strong>
|
|
Ann. Neurol. 55: 113-118, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14705119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14705119</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14705119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.10782" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Takahashi2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takahashi, K., Taira, T., Niki, T., Seino, C., Iguchi-Ariga, S. M. M., Ariga, H.
|
|
<strong>DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx-alpha to the receptor.</strong>
|
|
J. Biol. Chem. 276: 37556-37563, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11477070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11477070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11477070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M101730200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Takahashi-Niki2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takahashi-Niki, K., Niki, T., Taira, T., Iguchi-Ariga, S. M. M., Ariga, H.
|
|
<strong>Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients.</strong>
|
|
Biochem. Biophys. Res. Commun. 320: 389-397, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15219840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15219840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15219840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.bbrc.2004.05.187" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="25" class="mim-anchor"></a>
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<a id="Tang2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tang, B., Xiong, H., Sun, P., Zhang, Y., Wang, D., Hu, Z., Zhu, Z., Ma, H., Pan, Q., Xia, J., Xia, K., Zhang, Z.
|
|
<strong>Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.</strong>
|
|
Hum. Molec. Genet. 15: 1816-1825, 2006.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16632486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16632486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16632486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl104" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="26" class="mim-anchor"></a>
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<a id="Wagenfeld1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Wagenfeld, A., Gromoll, J., Cooper, T. G.
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|
<strong>Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization.</strong>
|
|
Biochem. Biophys. Res. Commun. 251: 545-549, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/bbrc.1998.9512" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="27" class="mim-anchor"></a>
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<a id="Wilson2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wilson, M. A., Collins, J. L., Hod, Y., Ringe, D., Petsko, G. A.
|
|
<strong>The 1.1-Angstrom resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 9256-9261, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12855764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12855764</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12855764[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12855764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.1133288100" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="28" class="mim-anchor"></a>
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<a id="Xiong2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xiong, H., Wang, D., Chen, L., Choo, Y. S., Ma, H., Tang, C., Xia, K., Jiang, W., Ronai, Z., Zhuang, X., Zhang, Z.
|
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<strong>Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation.</strong>
|
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J. Clin. Invest. 119: 650-660, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19229105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19229105</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19229105[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19229105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI37617" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="29" class="mim-anchor"></a>
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<a id="Xu2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xu, J., Zhong, N., Wang, H., Elias, J. E., Kim, C. Y., Woldman, I., Pifl, C., Gygi, S. P., Geula, C., Yankner, B. A.
|
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<strong>The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.</strong>
|
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Hum. Molec. Genet. 14: 1231-1241, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15790595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15790595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15790595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi134" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="30" class="mim-anchor"></a>
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<a id="Zhang2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, L., Shimoji, M., Thomas, B., Moore, D. J., Yu, S.-W., Marupudi, N. I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M., Dawson, V. L.
|
|
<strong>Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.</strong>
|
|
Hum. Molec. Genet. 14: 2063-2073, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi211" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="31" class="mim-anchor"></a>
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<a id="Zucchelli2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zucchelli, S., Codrich, M., Marcuzzi, F., Pinto, M., Vilotti, S., Biagioli, M., Ferrer, I., Gustincich, S.
|
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<strong>TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains.</strong>
|
|
Hum. Molec. Genet. 19: 3759-3770, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20634198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20634198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20634198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq290" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 12/08/2017
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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George E. Tiller - updated : 06/21/2017<br>Patricia A. Hartz - updated : 3/24/2015<br>Patricia A. Hartz - updated : 1/7/2014<br>Patricia A. Hartz - updated : 10/10/2013<br>George E. Tiller - updated : 8/5/2013<br>Cassandra L. Kniffin - updated : 5/15/2013<br>Patricia A. Hartz - updated : 8/3/2012<br>Ada Hamosh - updated : 1/25/2011<br>Cassandra L. Kniffin - updated : 10/15/2009<br>George E. Tiller - updated : 11/18/2008<br>George E. Tiller - updated : 5/19/2008<br>Cassandra L. Kniffin - updated : 3/3/2008<br>Cassandra L. Kniffin - updated : 1/17/2008<br>George E. Tiller - updated : 10/31/2007<br>Patricia A. Hartz - updated : 12/1/2006<br>Paul J. Converse - updated : 11/9/2006<br>Cassandra L. Kniffin - updated : 3/6/2006<br>George E. Tiller - updated : 1/31/2006<br>Cassandra L. Kniffin - updated : 10/17/2005<br>Patricia A. Hartz - updated : 8/15/2005<br>Cassandra L. Kniffin - updated : 4/13/2005<br>Victor A. McKusick - updated : 12/9/2004<br>Cassandra L. Kniffin - updated : 6/7/2004<br>Cassandra L. Kniffin - updated : 12/30/2003<br>Victor A. McKusick - updated : 9/8/2003<br>Cassandra L. Kniffin - updated : 1/15/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Jennifer P. Macke : 4/20/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/16/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 12/08/2017<br>alopez : 06/21/2017<br>alopez : 06/21/2017<br>carol : 09/22/2016<br>alopez : 06/15/2015<br>mgross : 3/27/2015<br>mcolton : 3/24/2015<br>mgross : 1/9/2014<br>mcolton : 1/7/2014<br>mgross : 10/10/2013<br>mgross : 10/10/2013<br>alopez : 8/5/2013<br>carol : 5/20/2013<br>ckniffin : 5/15/2013<br>carol : 10/8/2012<br>joanna : 10/4/2012<br>mgross : 8/8/2012<br>terry : 8/8/2012<br>terry : 8/3/2012<br>alopez : 1/31/2011<br>terry : 1/25/2011<br>carol : 7/12/2010<br>carol : 2/24/2010<br>wwang : 10/27/2009<br>ckniffin : 10/15/2009<br>ckniffin : 1/9/2009<br>wwang : 11/18/2008<br>wwang : 5/23/2008<br>terry : 5/19/2008<br>wwang : 3/19/2008<br>ckniffin : 3/3/2008<br>wwang : 3/3/2008<br>ckniffin : 1/17/2008<br>alopez : 11/5/2007<br>terry : 10/31/2007<br>wwang : 12/1/2006<br>mgross : 11/14/2006<br>terry : 11/9/2006<br>wwang : 3/10/2006<br>ckniffin : 3/6/2006<br>wwang : 2/7/2006<br>terry : 1/31/2006<br>wwang : 10/25/2005<br>ckniffin : 10/17/2005<br>wwang : 10/4/2005<br>ckniffin : 9/20/2005<br>ckniffin : 9/20/2005<br>mgross : 8/15/2005<br>wwang : 4/28/2005<br>wwang : 4/25/2005<br>ckniffin : 4/13/2005<br>tkritzer : 1/5/2005<br>terry : 12/9/2004<br>carol : 6/10/2004<br>ckniffin : 6/8/2004<br>ckniffin : 6/7/2004<br>tkritzer : 1/16/2004<br>ckniffin : 12/30/2003<br>cwells : 9/10/2003<br>terry : 9/8/2003<br>carol : 1/16/2003<br>ckniffin : 1/15/2003<br>dholmes : 5/12/1998<br>dholmes : 5/12/1998
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602533
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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|
|
ONCOGENE DJ1; DJ1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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PARKINSONISM-ASSOCIATED DEGLYCASE; PARK7<br />
|
|
PARK7 GENE
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: PARK7</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
|
Cytogenetic location: 1p36.23
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|
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:7,961,711-7,985,505 </span>
|
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</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
|
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Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
|
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</thead>
|
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<tbody>
|
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
1p36.23
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Parkinson disease 7, autosomal recessive early-onset
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
606324
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
3
|
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</span>
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</td>
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</tbody>
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</table>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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<p>DJ1, or PARK7, has pleiotropic function that includes roles as a chaperone with protease activity, a transcriptional regulator, and an antioxidant scavenger and redox sensor. DJ1 is also involved in tumorigenesis and in maintaining mitochondrial homeostasis (summary by Ottolini et al., 2013). </p>
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<h4>
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<strong>Cloning and Expression</strong>
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</h4>
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<p>Nagakubo et al. (1997) used yeast 2-hybrid screening of a HeLa cell library to clone a cDNA that encodes a novel 189-amino acid protein, termed DJ1. Northern blot analysis revealed that DJ1 is ubiquitously expressed as a 1.0-kb transcript. Western blot analysis and immunofluorescence showed that the DJ1 protein is present in both nuclei and cytoplasm of HeLa cells. After addition of serum to cells, DJ1 expression increased and the protein translocated from the cytoplasm to nuclei. A search of the GenBank protein database revealed that DJ1 has approximately 40% identity to the 198-amino acid protein product of the E. coli thiazole monophosphate biosynthesis (ThiJ) gene. A homolog also exists in the nematode C. elegans. </p><p>Northern blot analysis by Bonifati et al. (2003) showed ubiquitous expression of the DJ1 transcript, particularly in liver, skeletal muscle, and kidney. In the brain, expression was also ubiquitous, with higher levels of the transcript in subcortical regions, such as the caudate nucleus, the thalamus, the substantia nigra, and the hippocampus, that are more affected in parkinson disease (see MOLECULAR GENETICS). </p><p>Zhang et al. (2005) generated highly specific antibodies to DJ1 protein and investigated the subcellular localization of endogenous DJ1 protein in both mouse brain tissues and human neuroblastoma cells. DJ1 was widely distributed and was highly expressed in brain. Cell fractionation and immunogold electron microscopy revealed an endogenous pool of DJ1 in mitochondrial matrix and intermembrane space. </p><p>By screening a rat testis cDNA library, Wagenfeld et al. (1998) cloned a homologous gene in rats, called contraception associated protein-1 (CAP1), encoding a deduced protein that shares 95% and 91% sequence homology to mouse and human DJ1, respectively. A 1.6-kb transcript was detected in all rat tissues examined, with the highest level of expression in the testis. </p>
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<strong>Gene Structure</strong>
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<p>Bonifati et al. (2003) reported that the DJ1 gene contains 8 exons spanning 24 kb. The first 2 exons (1A and 1B) are noncoding and alternatively spliced. </p>
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<strong>Mapping</strong>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Bonifati et al. (2003) mapped the DJ1 gene to chromosome 1p36. </p>
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<strong>Biochemical Features</strong>
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</h4>
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<p>Wilson et al. (2003) reported the 3-dimensional structure of the DJ1 protein, determined at a resolution of 1.1 angstroms by x-ray crystallography. A highly conserved cysteine residue, which is catalytically essential in homologs of human DJ1, showed an extreme sensitivity to radiation damage and may be subject to other forms of oxidative modification as well. The structure suggested that the loss of function caused by the Parkinson disease-associated mutation L166P (602533.0002) is due to destabilization of the dimer interface. Taken together, the crystal structure of human DJ1 plus other observations suggested the possible involvement of this protein in the cellular oxidative stress response and a general etiology of neurodegenerative diseases. Cookson (2003) commented. </p><p>Macedo et al. (2003) demonstrated that DJ1 protein formed a dimeric structure under physiologic conditions. Conversely, the L166P mutant protein showed a different elution profile in gel filtration assays as compared with wildtype, suggesting that L166P might form higher-order protein structures. In lymphoblasts from a parkinsonian patient who carried the homozygous mutation, the level of mutant protein was very low as compared with wildtype protein. Transfection experiments indicated that the mutant protein was rapidly degraded. Macedo et al. (2003) proposed that the rapid turnover and structural changes of the L166P mutant protein may be crucial in disease pathogenesis. </p><p>Chen et al. (2010) reported that DJ1 is synthesized as a latent protease zymogen with low intrinsic proteolytic activity. DJ1 protease zymogen was activated by the removal of a 15-amino acid peptide at its C terminus. The activated DJ1 functioned as a cysteine protease with cys106 and his126 as the catalytic diad. Endogenous DJ1 in dopaminergic cells underwent C-terminal cleavage in response to mild oxidative stress, suggesting that DJ1 protease activation occurs in a redox-dependent manner. Moreover, the C-terminally cleaved form of DJ1 with activated protease function exhibited enhanced cytoprotective action against oxidative stress-induced apoptosis. The cytoprotective action of DJ1 was abolished by C106A and H126A mutations. Chen et al. (2010) proposed a role for DJ1 protease in cellular defense against oxidative stress. </p>
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<strong>Gene Function</strong>
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<p>Nagakubo et al. (1997) found that the DJ1 gene has weak transforming ability in NIH 3T3 cells, but transformation by DJ1 is synergistically enhanced by cotransfection with HRAS (190020) or MYC (190080). </p><p>Takahashi et al. (2001) showed that DJ1 bound strongly to PIASx-alpha (603567), a modulator of the nuclear androgen receptor (AR; 313700), and colocalized with PIASx-alpha in the nuclei of monkey Cos-I cells. While PIASx repressed AR transcriptional activity to 40% of the original level, as measured with an androgen responsive element-luciferase reporter, addition of DJ1 abrogated this suppression. Furthermore, DJ1 bound to the AR-interacting domain of PIASx, suggesting that DJ1 antagonized PIASx function by absorbing it and interfering with its binding to AR. Takahashi et al. (2001) concluded that, in somatic cells, DJ1 functions as a positive regulator of AR. </p><p>Rizzu et al. (2004) presented evidence suggesting that DJ1 colocalizes within a subset of pathologic tau (MAPT; 157140) inclusions in a diverse group of neurodegenerative disorders known as tauopathies, and that the solubility of DJ1 is altered in association with its aggregation within these inclusions. </p><p>Moore et al. (2005) showed that pathogenic mutant forms of DJ1 specifically but differentially associate with parkin (602544), an E3 ubiquitin ligase. Chemical crosslinking showed that pathogenic DJ1 mutants exhibited impairment in homodimer formation, suggesting that parkin may bind to monomeric DJ1. Parkin failed to specifically ubiquitinate and enhance the degradation of L166P (602533.0002) and M26I (602533.0003) mutant DJ1, but instead promoted their stability in cultured cells. Oxidative stress also promoted an interaction between DJ1 and parkin, but this did not result in the ubiquitination or degradation of DJ1. DJ1 levels were increased in the insoluble fraction of sporadic PD/DLB brains, but were reduced in the insoluble fraction of parkin-linked autosomal recessive juvenile-onset PD brains. The authors proposed that DJ1 and parkin may be linked in a common molecular pathway at multiple levels. </p><p>In human dopaminergic neuronal cells, Xu et al. (2005) showed that the major interacting proteins with DJ1 were NRB54 (NONO; 300084) and PSF (SFPQ; 605119), which are multifunctional regulators of transcription and RNA metabolism. PD-associated DJ1 mutants exhibited decreased nuclear distribution and increased mitochondrial localization, resulting in diminished colocalization with coactivator NRB54 and repressor PSF. Wildtype DJ1 inhibited the transcriptional silencing activity of PSF unlike DJ1 mutants, and PSF induced neuronal apoptosis, which was reversed by wildtype DJ1 and to a lesser extent by PD-associated DJ1 mutants. RNAi-knockdown of DJ1 sensitized cells to PSF-induced apoptosis. Both DJ1 and NRB54 blocked oxidative stress and mutant alpha-synuclein (SNCA; 163890)-induced cell death. The findings showed that DJ1 is a neuroprotective transcriptional coactivator that may act in concert with NRB54 and PSF to regulate the expression of a neuroprotective genetic program. Xu et al. (2005) concluded that DJ1 mutations that impair transcriptional coactivator function can render dopaminergic neurons vulnerable to apoptosis and may contribute to the pathogenesis of Parkinson disease (168600). </p><p>Junn et al. (2005) found that DJ1 overexpression in a human dopaminergic neuroblastoma cell line afforded modest protection against oxidative stress-induced cell death. A more robust cytoprotection was afforded by interaction of overexpressed DJ1 with the death protein DAXX (603186). DJ1 sequestered DAXX in the nucleus and prevented its translocation to the cytoplasm, where DAXX would normally activate its effector kinase, ASK1 (MAP3K5; 602448), to trigger the death pathway. DJ1 carrying the L166P mutation did not interact with DAXX and was unable to protect cells from oxidative damage or DAXX/ASK1-induced apoptosis. </p><p>Meulener et al. (2006) found that human DJ1 could rescue Drosophila lacking Dj1b, the fly homolog of DJ1, from oxidative insult, and that a conserved cysteine (cys104, which is analogous to human cys106) was critical for antioxidant function in vivo. SDS-PAGE analysis showed that DJ1 modification increased with age in flies, mice, and humans. In particular, an increase in acidic DJ1 isoforms with lower activity was observed. Modification of Dj1b increased dramatically in aged flies upon oxidative insult, and aged flies were more vulnerable to oxidative stress. Meulener et al. (2006) concluded that the risk factors of age and oxidative stress may regulate DJ1 protein activity, potentially contributing to Parkinson disease. </p><p>Using small-interfering RNA (siRNA) to disrupt DJ1 expression in a human nonsmall cell lung carcinoma cell line, Clements et al. (2006) showed that DJ1 was required for the expression of several genes, including the NRF2 (NFE2L2; 600492)-regulated antioxidant enzyme NQO1 (125860). Without DJ1, NRF2 protein was unstable, and transcriptional responses were decreased both basally and after induction. DJ1 was indispensable for NRF2 stabilization by affecting NRF2 association with KEAP1 (606016), an inhibitor protein that promotes ubiquitination and degradation of NRF2. </p><p>In human dopaminergic cells, Tang et al. (2006) demonstrated that wildtype DJ1 and PINK1 (608309), mutation in which causes PARK6 (605909), coimmunoprecipitate and interact functionally to protect cells from toxic oxidative MPP-induced cell death. Overexpression of both proteins resulted in a synergistic protective effect, and mutations in both proteins resulted in increased cell death compared to either mutant protein alone, suggesting a common mechanism. Evidence also suggested that DJ1 helps to stabilize PINK1. </p><p>Xiong et al. (2009) demonstrated that parkin, PINK1, and DJ1 interact and form an approximately 200-kD functional ubiquitin E3 ligase complex in human primary neurons. PINK1 was shown to increase the activity of parkin, which degrades itself via the ubiquitin-proteasome system. Pathogenic PINK1 (G309D; 608309.0001) did not promote ubiquitination and degradation of parkin or the parkin substrate synphilin-1 (603779) in transfected cells. Expression of DJ1 increased PINK1 expression, perhaps acting as a stabilizer. Overexpression of parkin substrates or heat shock treatment resulted in parkin accumulation in Pink1- or Dj1-deficient murine cells, and pathogenic parkin mutations resulted in a reduced ability to promote degradation of parkin substrates, all suggesting a decrease in E3 ubiquitin activity. Xiong et al. (2009) suggested that this complex promotes degradation of un- or misfolded proteins, including parkin, and that disruption of the activity of this complex leads to accumulation of abnormal proteins and increased susceptibility to oxidative stress, which is toxic to neurons and may lead to Parkinson disease. </p><p>Zucchelli et al. (2010) found that TRAF6 bound misfolded mutant DJ1 (PARK7; 602533) and SNCA (163890), and that both proteins were substrates of TRAF6 ligase activity in vivo. Rather than conventional lys63 (K63) assembly, TRAF6 promoted atypical ubiquitin linkage formation to both PD targets that shared K6-, K27- and K29- mediated ubiquitination. TRAF6 stimulated the accumulation of insoluble and polyubiquitinated mutant DJ1 into cytoplasmic aggregates. In human postmortem brains of PD patients, TRAF6 protein colocalized with SNCA in Lewy bodies. The authors proposed a novel role for TRAF6 and for atypical ubiquitination in PD pathogenesis. </p><p>Using Dj1 -/- mouse cells, DJ1-linked PD patient lymphoblasts, and DJ1-knockdown human cell lines with appropriate controls, Irrcher et al. (2010) showed that loss of DJ1 resulted in mitochondrial fragmentation and sensitivity to oxidative damage. Reactive oxygen species (ROS) appeared to play a critical role in the defects, as mitochondria isolated from Dj1 -/- animals produced more ROS than controls and ROS scavengers rescued the phenotype. The aberrant mitochondrial phenotype was also reversed by expression of either wildtype human parkin or PINK. Dj1 -/- mouse cells and DJ1-linked PD patient lymphoblasts showed evidence of elevated autophagy, but not mitophagy. </p><p>Using over- and underexpression studies, Im et al. (2012) found that DJ1 protected HeLa cells and human neuroblastoma cell lines from oxidative stress by inducing expression of thioredoxin (TRX1; 187700), an important antioxidative enzyme. Studies with Dj1-null mice confirmed the findings. DJ1 increased protein expression and nuclear accumulation of NRF2 and enhanced binding of NRF2 to the antioxidant response element (ARE) in the TRX1 promoter. DJ1 also enhanced H2O2-induced activation of AKT (see 164730), and this effect depended on the presence of TRX1. </p><p>Ottolini et al. (2013) found that DJ1 was expressed at mitochondrial-associated membranes in the endoplasmic reticulum (ER) and that DJ1 maintained mitochondrial morphology and influenced mitochondrial Ca(2+) transients in stimulated HeLa cells. Knockdown of DJ1 resulted in mitochondrial fragmentation and decreased mitochondrial Ca(2+) uptake from the ER following stimulation. Conversely, overexpression of DJ1 augmented stimulation-induced mitochondrial Ca(2+) transients by increasing ER-mitochondrial communication. Overexpression of p53 (191170) in HeLa cells impaired the ability of mitochondria to accumulate Ca(2+) following stimulation, disrupted mitochondrial morphology, and reduced mitochondria-ER contact sites. DJ1 overexpression prevented p53 effects and reestablished ER-mitochondrial contacts. The effects of p53 on mitochondria did not require the transcriptional regulatory function of p53. Rescue of mitochondria by DJ1 was associated with enhanced degradation of p53, but it did not require DJ1 upregulation or DJ1 kinase activity. Overexpression of the mitochondrial profusion protein mitofusin-2 (MFN2; 608507) also reversed the effects of p53 on mitochondria. Ottolini et al. (2013) concluded that DJ1 has a direct role in ER-mitochondria coupling and is essential to maintain mitochondrial structure and function. </p><p>Bjorkblom et al. (2013) found that recombinant human DJ1 bound copper, mercury, and, more weakly, manganese, but not other ions tested. Dj1 also protected mouse embryonic fibroblasts (MEFs) against copper- and mercury-induced cytotoxicity. Exposure of MEFs to a nontoxic concentration of dopamine, together with copper or mercury, resulted in an almost immediate and dramatic surge of intracellular oxidation. The oxidative response was exacerbated in Dj1 -/- MEFs. </p><p>Richarme et al. (2017) found that DJ1 and its bacterial homologs Hsp31, YhbO, and YajL can repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, Richarme et al. (2017) concluded that DJ1 and its prokaryotic homologs constitute a major nucleotide repair system that they named guanine glycation repair. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</h4>
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<span class="mim-text-font">
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<p>In 2 consanguineous families from genetically isolated communities in the Netherlands and Italy with autosomal recessive early-onset Parkinson disease (PARK7; 606324), Bonifati et al. (2003) identified 2 mutations in the DJ1 gene that cosegregated with the disease (602533.0001 and 602533.0002). </p><p>Among 185 unrelated patients with early-onset Parkinson disease, Abou-Sleiman et al. (2003) identified 2 patients with mutations in the DJ1 gene (602533.0003-602533.0004); one was homozygous and the other was heterozygous. In addition, several variants were found in the DJ1 gene, which likely represented polymorphisms. The authors estimated that the frequency of DJ1 mutations in early-onset Parkinson disease is very low, at approximately 1%. No mutations in the DJ1 gene were identified in a cohort of later-onset sporadic cases of Parkinson disease. </p><p>In a series of in vitro studies, Takahashi-Niki et al. (2004) found that mutant DJ1 proteins M26I (602533.0003), D149A (602533.0004), and L166P (602533.0002) formed heterodimers with wildtype DJ1. Mutant proteins M26I and L166P were unstable and were degraded by the proteasome system. Cell lines expressing the mutant M26I and L166P proteins showed reduced ability to eliminate exogenous hydrogen peroxide, indicating increased susceptibility to oxidative stress. In contrast, the mutant D149A protein showed increased stability compared to wildtype, and cells expressing the mutant D149A were resistant to hydrogen peroxide-induced cell death. </p><p>Zhang et al. (2005) generated human neuroblastoma cells stably transfected with wildtype or mutant (e.g., M26I, L166P, and D149A) DJ1 constructs and performed mitochondrial fractionation and confocal colocalization imaging studies. When compared with wildtype and other mutants, the L166P mutant exhibited a largely reduced protein level. However, the pathogenic mutations did not alter the distribution of DJ1 to mitochondria. Zhang et al. (2005) concluded that DJ1 is an integral mitochondrial protein that may have important functions in regulating mitochondrial physiology. </p>
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<strong>Animal Model</strong>
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<p>Kim et al. (2005) found that mice with a targeted deletion of the Dj1 gene developed normally, had normal numbers of dopaminergic neurons in the substantia nigra, and showed no abnormal gross motor behavior up to 13 months of age. In vitro studies showed that primary cortical neurons from the Dj1-null mice exhibited increased sensitivity to oxidative stress compared to control cells. After challenge with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), Dj1-null mice showed a significant decrease in total activity and a greater loss of striatal dopaminergic neurons compared to control mice. Restoration of Dj1 expression in cell cultures or in Dj1-null mice resulted in a protective effect. Moreover, wildtype mice that received adenoviral delivery of Dj1 showed some resistance to MPTP-induced neuronal damage. Kim et al. (2005) concluded that Dj1 protects against neuronal oxidative stress, and that while loss of Dj1 alone may not be sufficient to produce parkinsonism, it may confer hypersensitivity to dopaminergic insults when challenged. </p><p>In vitro and in vivo, Aleyasin et al. (2007) found that Dj1-null mice were significantly more susceptible to glutamate-induced neuronal excitotoxicity compared to controls. Expression of Dj1 provided protection. Further studies showed that the oxidation-sensitive cys106 residue was essential for neuronal protection from excitotoxicity. Dj1 expression decreased markers of oxidative stress after stroke insult in vivo, suggesting that Dj1 protects through alleviation of oxidative stress. Aleyasin et al. (2007) suggested that Dj1 may be important in other neuropathologic conditions besides Parkinson disease, and noted commonalities among different neuropathologies. </p><p>Andres-Mateos et al. (2007) found that mice with targeted deletion of Dj1 exons 2 and 3 had no significant changes in the striatal dopaminergic system compared to wildtype mice. However, mitochondria isolated from the mutant mice contained a 2-fold increase in hydrogen peroxide associated with a decrease in mitochondrial aconitase (ACO2; 100850). Older mutant mice showed a compensatory upregulation of mitochondrial superoxide dismutase (SOD1; 147450) and glutathione peroxidase activity (see, e.g., GPX1; 138320). Functional studies and mass spectrometry indicated that DJ1 is an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide through oxidation of cys106. </p><p>Using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, Guzman et al. (2010) showed that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable substantia nigra pars compacta (SNc) dopaminergic neurons. The oxidant stress engaged defenses that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D (601753), which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ1 downregulated the expression of 2 uncoupling proteins, UCP4 (SLC25A27) and UCP5 (SLC25A14; 300242), compromised calcium-induced uncoupling, and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, Guzman et al. (2010) suggested that their results pointed to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson disease (168600). </p>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>7 Selected Examples):</strong>
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<h4>
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<span class="mim-font">
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<strong>.0001 PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET</strong>
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PARK7, 14-KB DEL
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ClinVar: RCV000007479
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<p>In a consanguineous Dutch family with early-onset Parkinson disease (PARK7; 606324), Bonifati et al. (2003) identified a 14-kb homozygous deletion in the DJ1 gene, which deleted exons 1 through 5 and 4 kb of sequence upstream of the open reading frame start. The deletion showed cosegregation with the disease in the 4 affected family members and was absent in over 1,220 chromosomes from the Dutch population. </p><p>Irrcher et al. (2010) showed that this deletion mutation in DJ1 resulted in fragmented mitochondria and elevated markers of autophagy. </p>
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<h4>
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<span class="mim-font">
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<strong>.0002 PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET</strong>
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PARK7, LEU166PRO
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SNP: rs28938172,
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ClinVar: RCV000007480
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<span class="mim-text-font">
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<p>In a consanguineous Italian family with autosomal recessive early-onset Parkinson disease (PARK7; 606324), Bonifati et al. (2003) identified a homozygous 497T-C transition in the DJ1 gene, resulting in a leu166-to-pro substitution (L166P) in the protein. The mutation showed cosegregation with the disease in 3 affected sibs and was absent in 320 chromosomes from the Italian population. A molecular model of the mutation was predicted to destabilize the terminal helix of the protein. </p><p>Irrcher et al. (2010) showed that the L166P mutation in DJ1 resulted in fragmented mitochondria and elevated markers of autophagy. </p><p>Im et al. (2012) found that DJ1 with the L166P substitution was unable to induce TRX1 (187700) expression or to protect transfected HeLa cells from H2O2-induced cytotoxicity. Wildtype, but not mutant DJ1, mediated H2O2-induced and DJ1-dependent expression and nuclear translocation of NRF2 (600492) and enhanced recruitment of NRF2 to the antioxidant response element in the TRX1 promoter region. </p>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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PARK7, MET26ILE
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<br />
|
|
|
|
SNP: rs74315351,
|
|
|
|
|
|
|
|
ClinVar: RCV000007481
|
|
|
|
|
|
</span>
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</div>
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|
<div>
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<span class="mim-text-font">
|
|
<p>In an Ashkenazi Jewish patient with early-onset Parkinson disease (606324), Abou-Sleiman et al. (2003) identified a homozygous A-to-G change in exon 2 of the DJ1 gene, resulting in a met26-to-ile (M26I) substitution. The mutation was not present in more than 1,000 control chromosomes. </p><p>Im et al. (2012) found that DJ1 with the M26I substitution was unable to induce TRX1 (187700) expression or to protect transfected HeLa cells from H2O2-induced cytotoxicity. Wildtype, but not mutant DJ1, mediated H2O2-induced and DJ1-dependent expression and nuclear translocation of NRF2 (600492) and enhanced recruitment of NRF2 to the antioxidant response element in the TRX1 promoter region. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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PARK7, ASP149ALA
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<br />
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|
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SNP: rs74315352,
|
|
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|
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gnomAD: rs74315352,
|
|
|
|
|
|
ClinVar: RCV000007482
|
|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Afro-Caribbean patient with early-onset Parkinson disease (606324), Abou-Sleiman et al. (2003) identified a heterozygous mutation in exon 4 of the DJ1 gene, resulting in an asp149-to-ala (D149A) substitution. The mutation was not found in 750 white, 160 Ashkenazi, or 40 Afro-Caribbean chromosomes tested, suggesting that it is pathogenic, but the authors noted that they did not identify a second mutation in the DJ1 gene in this patient. </p><p>Bjorkblom et al. (2013) found that DJ1 with the D149A substitution bound copper with higher affinity than wildtype DJ1. Mutant DJ1 also bound mercury. However, in contrast with wildtype DJ1, mutant Dj1 lacked the ability to protect mouse embryonic fibroblasts from copper- and mercury-induced cytotoxicity. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
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|
</div>
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|
</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
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PARK7, GLU64ASP
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs74315353,
|
|
|
|
|
|
gnomAD: rs74315353,
|
|
|
|
|
|
ClinVar: RCV000007483
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Analyzing the DJ1 gene in 104 patients with early-onset Parkinson disease (606324), Hering et al. (2004) identified a homozygous 192G-C transversion, resulting in a glu64-to-asp (E64D) substitution, in 1 patient of Turkish ancestry. In the proband, a substantial reduction of dopamine uptake transporter (DAT; 126455) binding was found in the striatum by PET scan, indicating a serious loss of presynaptic dopaminergic afferents. The proband's sister, also homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who was heterozygous for E64D. By crystallography, Hering et al. (2004) demonstrated that the E64D mutation does not alter the structure of the DJ1 protein; however, they observed a tendency toward decreased levels of the mutant protein when overexpressed in HEK293 or COS-7 cells. By immunocytochemistry, about 5% of the cells expressing E64D and up to 80% of the cells expressing the L166P mutation (602533.0002) displayed a predominant nuclear localization of the mutant DJ1 protein, in contrast to the homogeneous nuclear and cytoplasmic staining in HEK293 cells overexpressing wildtype DJ1. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
</div>
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|
<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PARK7, GLU163LYS AND 18-BP DUP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200968609, rs74315354,
|
|
|
|
|
|
gnomAD: rs200968609, rs74315354,
|
|
|
|
|
|
ClinVar: RCV000007484, RCV001644681
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected sibs from a consanguineous southern Italian family with early-onset parkinsonism (606324), Annesi et al. (2005) identified double homozygosity for mutations in the DJ1 gene. One was a 3385G-A transition in exon 7, resulting in a glu163-to-lys (E163K) substitution, and the other was an 18-bp duplication (168-185dup) in the promoter region. Age at disease onset was 36, 35, and 24 years, respectively. Severe amyotrophic lateral sclerosis and cognitive impairment were prominent in 1 sib, while the other 2 had prominent parkinsonism and behavioral abnormalities. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PARKINSON DISEASE, AUTOSOMAL RECESSIVE EARLY-ONSET, DIGENIC, PINK1/DJ1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
PARK7, ALA39SER
|
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|
|
|
<br />
|
|
|
|
SNP: rs137853051,
|
|
|
|
|
|
|
|
ClinVar: RCV000007485
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Chinese sibs with early-onset Parkinson disease (see 605909), Tang et al. (2006) identified compound heterozygosity for 2 mutations in 2 different genes: a 115G-T transversion in exon 3 of the DJ1 gene resulting in an ala39-to-ser (A39S) substitution in the third beta-sheet of the protein, and a P399L mutation (608309.0014) in the predicted kinase domain of the PINK1 gene. The DJ1 and PINK1 mutations were not observed in 240 and 568 control chromosomes, respectively, and both were located in highly conserved residues. The findings were consistent with digenic inheritance of Parkinson disease. A 42-year-old unaffected family member also carried both mutations, suggesting incomplete penetrance. Coimmunoprecipitation studies showed that both wildtype and mutant PINK1 interacted with both wildtype and mutant DJ1. Expression of wildtype DJ1 increased steady-state levels of both mutant and wildtype PINK1, but mutant DJ1 decreased steady-state levels of both mutant and wildtype PINK1, suggesting that wildtype DJ1 can enhance PINK1 stability. Human neuroblastoma cells expressing either mutant PINK1 or DJ1 showed reduced viability following oxidative challenge with MPP compared to control cells, indicating that both proteins protect against cell stress. Coexpression of both wildtype proteins resulted in a synergistic increase in cell viability against MPP-induced stress. In addition, coexpression of both mutant proteins significantly increased susceptibility of cells to death, compared to either mutant alone. These findings indicated that DJ1 and PINK1 function collaboratively. </p>
|
|
</span>
|
|
</div>
|
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|
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|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abou-Sleiman, P. M., Healy, D. G., Quinn, N., Lees, A. J., Wood, N. W.
|
|
<strong>The role of pathogenic DJ-1 mutations in Parkinson's disease.</strong>
|
|
Ann. Neurol. 54: 283-286, 2003.
|
|
|
|
|
|
[PubMed: 12953260]
|
|
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|
|
|
[Full Text: https://doi.org/10.1002/ana.10675]
|
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Aleyasin, H., Rousseaux, M. W. C., Phillips, M., Kim, R. H., Bland, R. J., Callaghan, S., Slack, R. S., During, M. J., Mak, T. W., Park, D. S.
|
|
<strong>The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 18748-18753, 2007.
|
|
|
|
|
|
[PubMed: 18003894]
|
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|
|
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[Full Text: https://doi.org/10.1073/pnas.0709379104]
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Andres-Mateos, E., Perier, C., Zhang, L., Blanchard-Fillion, B., Greco, T. M., Thomas, B., Ko, H. S., Sasaki, M., Ischiropoulos, H., Przedborski, S., Dawson, T. M., Dawson, V. L.
|
|
<strong>DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 14807-14812, 2007.
|
|
|
|
|
|
[PubMed: 17766438]
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|
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[Full Text: https://doi.org/10.1073/pnas.0703219104]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Annesi, G., Savettieri, G., Pugliese, P., D'Amelio, M., Tarantino, P., Ragonese, P., La Bella, V., Piccoli, T., Civitelli, D., Annesi, F., Fierro, B., Piccoli, F., Arabia, G., Caracciolo, M., Canadiano, I. C. C., Quattrone, A.
|
|
<strong>DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.</strong>
|
|
Ann. Neurol. 58: 803-807, 2005.
|
|
|
|
|
|
[PubMed: 16240358]
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|
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[Full Text: https://doi.org/10.1002/ana.20666]
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</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Bjorkblom, B., Adilbayeva, A., Maple-Grodem, J., Piston, D., Okvist, M., Xu, X. M., Brede, C., Larsen, J. P., Moller, S. G.
|
|
<strong>Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity.</strong>
|
|
J. Biol. Chem. 288: 22809-22820, 2013.
|
|
|
|
|
|
[PubMed: 23792957]
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|
|
[Full Text: https://doi.org/10.1074/jbc.M113.482091]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bonifati, V., Rizzu, P., van Baren, M. J., Schaap, O., Breedveld, G. J., Krieger, E., Dekker, M. C. J., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J. W., Vanacore, N., van Swieten, J. C., Brice, A., Meco, G., van Duijn, C. M., Oostra, B. A., Heutink, P.
|
|
<strong>Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.</strong>
|
|
Science 299: 256-259, 2003.
|
|
|
|
|
|
[PubMed: 12446870]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1077209]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, J., Li, L., Chin, L.-S.
|
|
<strong>Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage.</strong>
|
|
Hum. Molec. Genet. 19: 2395-2408, 2010.
|
|
|
|
|
|
[PubMed: 20304780]
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|
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddq113]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clements, C. M., McNally, R. S., Conti, B. J., Mak, T. W., Ting, J. P.-Y.
|
|
<strong>DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 15091-15096, 2006.
|
|
|
|
|
|
[PubMed: 17015834]
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|
|
[Full Text: https://doi.org/10.1073/pnas.0607260103]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Cookson, M. R.
|
|
<strong>Crystallizing ideas about Parkinson's disease.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 9111-9113, 2003.
|
|
|
|
|
|
[PubMed: 12886009]
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|
|
[Full Text: https://doi.org/10.1073/pnas.1633722100]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T., Surmeier, D. J.
|
|
<strong>Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1.</strong>
|
|
Nature 468: 696-700, 2010. Note: Erratum: Nature 521: 380 only, 2015.
|
|
|
|
|
|
[PubMed: 21068725]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09536]
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</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Hering, R., Strauss, K. M., Tao, X., Bauer, A., Woitalla, D., Mietz, E.-M., Petrovic, S., Bauer, P., Schaible, W., Muller, T., Schols, L., Klein, C., Berg, D., Meyer, P. T., Schulz, J. B., Wollnik, B., Tong, L., Kruger, R., Riess, O.
|
|
<strong>Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).</strong>
|
|
Hum. Mutat. 24: 321-329, 2004.
|
|
|
|
|
|
[PubMed: 15365989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20089]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Im, J.-Y., Lee, K.-W., Woo, J.-M., Junn, E., Mouradian, M. M.
|
|
<strong>DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway.</strong>
|
|
Hum. Molec. Genet. 21: 3013-3024, 2012.
|
|
|
|
|
|
[PubMed: 22492997]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/dds131]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani-Asl, A., Callaghan, S., MacLaurin, J. G., and 11 others.
|
|
<strong>Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.</strong>
|
|
Hum. Molec. Genet. 19: 3734-3746, 2010.
|
|
|
|
|
|
[PubMed: 20639397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq288]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Junn, E., Taniguchi, H., Jeong, B. S., Zhao, X., Ichijo, H., Mouradian, M. M.
|
|
<strong>Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 9691-9696, 2005.
|
|
|
|
|
|
[PubMed: 15983381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0409635102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, R. H., Smith, P. D., Aleyasin, H., Hayley, S., Mount, M. P., Pownall, S., Wakeham, A., You-Ten, A. J., Kalia, S. K., Horne, P., Westaway, D., Lozano, A. M., Anisman, H., Park, D. S., Mak, T. W.
|
|
<strong>Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 5215-5220, 2005.
|
|
|
|
|
|
[PubMed: 15784737]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0501282102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Macedo, M. G., Anar, B., Bronner, I. F., Cannella, M., Squitieri, F., Bonifati, V., Hoogeveen, A., Heutink, P., Rizzu, P.
|
|
<strong>The DJ-1(L166P) mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes.</strong>
|
|
Hum. Molec. Genet. 12: 2807-2816, 2003.
|
|
|
|
|
|
[PubMed: 12952867]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg304]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meulener, M. C., Xu, K., Thomson, L., Ischiropoulos, H., Bonini, N. M.
|
|
<strong>Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 12517-12522, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 14978, 2006.
|
|
|
|
|
|
[PubMed: 16894167]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0601891103]
|
|
|
|
|
|
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|
|
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|
|
|
|
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|
|
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|
|
Moore, D. J., Zhang, L., Troncoso, J., Lee, M. K., Hattori, N., Mizuno, Y., Dawson, T. M., Dawson, V. L.
|
|
<strong>Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress.</strong>
|
|
Hum. Molec. Genet. 14: 71-84, 2005.
|
|
|
|
|
|
[PubMed: 15525661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagakubo, D., Taira, T., Kitaura, H., Ikeda, M., Tamai, K., Iguchi-Ariga, S. M. M., Ariga, H.
|
|
<strong>DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.</strong>
|
|
Biochem. Biophys. Res. Commun. 231: 509-513, 1997.
|
|
|
|
|
|
[PubMed: 9070310]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1997.6132]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ottolini, D., Cali, T., Negro, A., Brini, M.
|
|
<strong>The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering.</strong>
|
|
Hum. Molec. Genet. 22: 2152-2168, 2013.
|
|
|
|
|
|
[PubMed: 23418303]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddt068]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Richarme, G., Liu, C., Mihoub, M., Abdallah, J., Leger, T., Joly, N., Liebart, J.-C., Jurkunas, U. V., Nadal, M., Bouloc, P., Dairou, J., Lamouri, A.
|
|
<strong>Guanine glycation repair by DJ-1/Park7 and its bacterial homologs.</strong>
|
|
Science 357: 208-211, 2017.
|
|
|
|
|
|
[PubMed: 28596309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aag1095]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
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|
|
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|
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Rizzu, P., Hinkle, D. A., Zhukareva, V., Bonifati, V., Severijnen, L.-A., Martinez, D., Ravid, R., Kamphorst, W., Eberwine, J. H., Lee, V. M.-Y., Trojanowski, J. Q., Heutink, P.
|
|
<strong>DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia.</strong>
|
|
Ann. Neurol. 55: 113-118, 2004.
|
|
|
|
|
|
[PubMed: 14705119]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10782]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takahashi, K., Taira, T., Niki, T., Seino, C., Iguchi-Ariga, S. M. M., Ariga, H.
|
|
<strong>DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx-alpha to the receptor.</strong>
|
|
J. Biol. Chem. 276: 37556-37563, 2001.
|
|
|
|
|
|
[PubMed: 11477070]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M101730200]
|
|
|
|
|
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|
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|
|
|
|
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|
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|
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Takahashi-Niki, K., Niki, T., Taira, T., Iguchi-Ariga, S. M. M., Ariga, H.
|
|
<strong>Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients.</strong>
|
|
Biochem. Biophys. Res. Commun. 320: 389-397, 2004.
|
|
|
|
|
|
[PubMed: 15219840]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2004.05.187]
|
|
|
|
|
|
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|
|
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|
|
|
|
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|
|
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|
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Tang, B., Xiong, H., Sun, P., Zhang, Y., Wang, D., Hu, Z., Zhu, Z., Ma, H., Pan, Q., Xia, J., Xia, K., Zhang, Z.
|
|
<strong>Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.</strong>
|
|
Hum. Molec. Genet. 15: 1816-1825, 2006.
|
|
|
|
|
|
[PubMed: 16632486]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddl104]
|
|
|
|
|
|
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|
|
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|
|
|
|
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|
|
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Wagenfeld, A., Gromoll, J., Cooper, T. G.
|
|
<strong>Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization.</strong>
|
|
Biochem. Biophys. Res. Commun. 251: 545-549, 1998.
|
|
|
|
|
|
[PubMed: 9792810]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1998.9512]
|
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|
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|
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|
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|
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|
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Wilson, M. A., Collins, J. L., Hod, Y., Ringe, D., Petsko, G. A.
|
|
<strong>The 1.1-Angstrom resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 9256-9261, 2003.
|
|
|
|
|
|
[PubMed: 12855764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1133288100]
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</p>
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Xiong, H., Wang, D., Chen, L., Choo, Y. S., Ma, H., Tang, C., Xia, K., Jiang, W., Ronai, Z., Zhuang, X., Zhang, Z.
|
|
<strong>Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation.</strong>
|
|
J. Clin. Invest. 119: 650-660, 2009.
|
|
|
|
|
|
[PubMed: 19229105]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI37617]
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</p>
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</li>
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<li>
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Xu, J., Zhong, N., Wang, H., Elias, J. E., Kim, C. Y., Woldman, I., Pifl, C., Gygi, S. P., Geula, C., Yankner, B. A.
|
|
<strong>The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.</strong>
|
|
Hum. Molec. Genet. 14: 1231-1241, 2005.
|
|
|
|
|
|
[PubMed: 15790595]
|
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|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi134]
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</p>
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</li>
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Zhang, L., Shimoji, M., Thomas, B., Moore, D. J., Yu, S.-W., Marupudi, N. I., Torp, R., Torgner, I. A., Ottersen, O. P., Dawson, T. M., Dawson, V. L.
|
|
<strong>Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.</strong>
|
|
Hum. Molec. Genet. 14: 2063-2073, 2005.
|
|
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|
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[PubMed: 15944198]
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[Full Text: https://doi.org/10.1093/hmg/ddi211]
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Zucchelli, S., Codrich, M., Marcuzzi, F., Pinto, M., Vilotti, S., Biagioli, M., Ferrer, I., Gustincich, S.
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<strong>TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains.</strong>
|
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Hum. Molec. Genet. 19: 3759-3770, 2010.
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|
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[PubMed: 20634198]
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[Full Text: https://doi.org/10.1093/hmg/ddq290]
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Ada Hamosh - updated : 12/08/2017<br>George E. Tiller - updated : 06/21/2017<br>Patricia A. Hartz - updated : 3/24/2015<br>Patricia A. Hartz - updated : 1/7/2014<br>Patricia A. Hartz - updated : 10/10/2013<br>George E. Tiller - updated : 8/5/2013<br>Cassandra L. Kniffin - updated : 5/15/2013<br>Patricia A. Hartz - updated : 8/3/2012<br>Ada Hamosh - updated : 1/25/2011<br>Cassandra L. Kniffin - updated : 10/15/2009<br>George E. Tiller - updated : 11/18/2008<br>George E. Tiller - updated : 5/19/2008<br>Cassandra L. Kniffin - updated : 3/3/2008<br>Cassandra L. Kniffin - updated : 1/17/2008<br>George E. Tiller - updated : 10/31/2007<br>Patricia A. Hartz - updated : 12/1/2006<br>Paul J. Converse - updated : 11/9/2006<br>Cassandra L. Kniffin - updated : 3/6/2006<br>George E. Tiller - updated : 1/31/2006<br>Cassandra L. Kniffin - updated : 10/17/2005<br>Patricia A. Hartz - updated : 8/15/2005<br>Cassandra L. Kniffin - updated : 4/13/2005<br>Victor A. McKusick - updated : 12/9/2004<br>Cassandra L. Kniffin - updated : 6/7/2004<br>Cassandra L. Kniffin - updated : 12/30/2003<br>Victor A. McKusick - updated : 9/8/2003<br>Cassandra L. Kniffin - updated : 1/15/2003
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