2396 lines
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Entry
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- *608487 - TRIPARTITE MOTIF-CONTAINING PROTEIN 5; TRIM5
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- OMIM
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<p>
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<span class="h4">*608487</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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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 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="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div id="mimFloatingLinksMenu">
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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 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=ENSG00000132256;t=ENST00000380034" 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=85363" 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=608487" 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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<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=ENSG00000132256;t=ENST00000380034" 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_001410958,NM_033034,NM_033092,NM_033093,XM_005253183,XM_005253184,XM_006718358,XM_011520426,XM_017018460,XM_017018461,XM_047427783,XM_047427784,XR_001748014,XR_007062517,XR_007062518,XR_007062519,XR_007062520,XR_007062521,XR_007062522" 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_033034" 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=608487" 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=07004&isoform_id=07004_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/TRIM5" 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/12407381,12407383,12407385,12407387,12407389,14042375,18204217,38605459,48994821,82780748,83282868,83282870,83282872,83282874,83282876,83282878,83282880,83282882,83282884,83282886,83282888,83282890,83282892,83282894,83282896,83282898,83282900,83282902,83282904,83282906,83282908,83282910,83282912,83282914,83282916,83282918,83282920,83282922,83282924,83282926,83282928,83282930,83282932,83282934,83282936,83282938,83282940,116283357,119589177,119589178,119589179,119589180,119589181,119589182,119589183,159459910,172088008,262180666,262180668,262180670,262180672,262180674,262180676,262180678,262180680,262180682,262180684,283046694,283046696,283046698,344323366,344323368,530395903,530395905,578820894,767966710,1034575971,1034575974,2217285253,2217285259,2287780781,2297339990,2462528357,2462528359,2462528361,2462528363,2462528365,2462528368,2462528374,2462528377,2462528379" 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/Q9C035" 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=85363" 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=ENSG00000132256;t=ENST00000380034" 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=TRIM5" 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=TRIM5" 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+85363" 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/TRIM5" 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:85363" 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/85363" 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=chr11&hgg_gene=ENST00000380259.7&hgg_start=5588635&hgg_end=5685074&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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<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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</a>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608487[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 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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<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=608487[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://www.deciphergenomics.org/gene/TRIM5/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000132256" 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=TRIM5" 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=TRIM5" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=TRIM5&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/PA38109" 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 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:16276" 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://www.mousephenotype.org/data/search?q=MGI:1923931 MGI:3035181 MGI:3646853 MGI:4821183 MGI:4821256 MGI:4821257 MGI:98178" 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/TRIM5#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/batch/summary?idType=MGI&ids=MGI:1923931 MGI:3035181 MGI:3646853 MGI:4821183 MGI:4821256 MGI:4821257 MGI:98178" 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/85363/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://www.orthodb.org/?ncbi=85363" 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=WBGene00015114;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00015114 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00016190;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00016190 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00016191;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00016191 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00018384;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00018384 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00022868;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00022868 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00022870;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00022870 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00022872;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00022872 </a></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:85363" 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=TRIM5&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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<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 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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<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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608487
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</span>
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</span>
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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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TRIPARTITE MOTIF-CONTAINING PROTEIN 5; TRIM5
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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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RNF88
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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=TRIM5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TRIM5</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/11/118?start=-3&limit=10&highlight=118">11p15.4</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:5588635-5685074&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'})">11:5,588,635-5,685,074</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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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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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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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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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>TRIM5 belongs to the large tripartite motif protein family, members of which typically are composed of 3 zinc-binding domains, a RING, unique B-box type 1 and B-box type 2 domains, followed by a coiled-coil (CC) region. TRIM proteins use homomultimerization to identify specific cell compartments.</p>
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</span>
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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="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>Using a consensus B-box domain to screen dbEST databases, <a href="#3" class="mim-tip-reference" title="Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A. <strong>The tripartite motif family identifies cell compartments.</strong> EMBO J. 20: 2140-2151, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11331580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11331580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11331580[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/emboj/20.9.2140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11331580">Reymond et al. (2001)</a> identified 37 TRIM members in mammals, 21 of which were novel, as well as 34 splice variants. TRIM5 has 6 variants termed alpha, beta, gamma, delta, epsilon, and zeta, all of which lack a B-box type 1 domain. Additional domains C-terminal to the CC region are variably present. TRIM5-zeta lacks RING, B-box, and CC domains, but possesses 3 RFP-like domains. Northern blot analysis of adult human tissues detected ubiquitous expression of TRIM5. Using interaction mating and mutation analysis, <a href="#3" class="mim-tip-reference" title="Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A. <strong>The tripartite motif family identifies cell compartments.</strong> EMBO J. 20: 2140-2151, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11331580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11331580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11331580[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/emboj/20.9.2140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11331580">Reymond et al. (2001)</a> confirmed that TRIM5, like most TRIMs, homointeracts through the CC region. Interaction was also detected with TRIM6 (<a href="/entry/607564">607564</a>). Green fluorescent protein microscopy demonstrated expression as cytoplasmic speckles, possibly in novel subcellular compartments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11331580" 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="#8" class="mim-tip-reference" title="Stremlau, M., Owens, C. W., Perron, M. J., Kiessling, M., Autissier, P., Sodroski, J. <strong>The cytoplasmic body component TRIM5-alpha restricts HIV-1 infection in Old World monkeys.</strong> Nature 427: 848-853, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14985764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14985764</a>] [<a href="https://doi.org/10.1038/nature02343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14985764">Stremlau et al. (2004)</a> determined that human TRIM5-alpha contains 493 amino acids and includes a C-terminal b30.2 (SPRY) domain missing in other TRIM5 isoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14985764" 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 fluorescence microscopy and mutation analysis, <a href="#9" class="mim-tip-reference" title="Xu, L., Yang, L., Moitra, P. K., Hashimoto, K., Rallabhandi, P., Kaul, S., Meroni, G., Jensen, J. P., Weissman, A. M., D'Arpa, P. <strong>BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5-delta.</strong> Exp. Cell Res. 288: 84-93, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12878161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12878161</a>] [<a href="https://doi.org/10.1016/s0014-4827(03)00187-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12878161">Xu et al. (2003)</a> showed that TRIM5-delta interacts with BTBD1 (<a href="/entry/608530">608530</a>) and BTBD2 (<a href="/entry/608531">608531</a>), apparently serving as a scaffold for the assembly of endogenous BTBD1/2 proteins, dependent on the presence of the CC region and a wildtype RING domain. TRIM5-delta exhibits ubiquitylation in the presence of UBCH5B (UBE2D2; <a href="/entry/602962">602962</a>), dependent on the presence of zinc-coordinating cysteines in the RING domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12878161" 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="#1" class="mim-tip-reference" title="Kaiser, S. M., Malik, H. S., Emerman, M. <strong>Restriction of an extinct retrovirus by the human TRIM5-alpha antiviral protein.</strong> Science 316: 1756-1758, 2007. Note: Erratum: Science 317: 1036 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17588933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17588933</a>] [<a href="https://doi.org/10.1126/science.1140579" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17588933">Kaiser et al. (2007)</a> reported the reconstruction of the core protein of a 4-million-year-old endogenous virus from the chimpanzee genome (PtERV1) and showed that the human variant of the intrinsic immune protein TRIM5-alpha can actively prevent infection by this virus. However, <a href="#1" class="mim-tip-reference" title="Kaiser, S. M., Malik, H. S., Emerman, M. <strong>Restriction of an extinct retrovirus by the human TRIM5-alpha antiviral protein.</strong> Science 316: 1756-1758, 2007. Note: Erratum: Science 317: 1036 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17588933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17588933</a>] [<a href="https://doi.org/10.1126/science.1140579" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17588933">Kaiser et al. (2007)</a> suggested that the selective changes that have occurred in the human lineage during the acquisition of resistance to this virus, and perhaps similar viruses, may have left our species more susceptible to infection by HIV-1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17588933" 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="#2" class="mim-tip-reference" title="Pertel, T., Hausmann, S., Morger, D., Zuger, S., Guerra, J., Lascano, J., Reinhard, C., Santoni, F. A., Uchil, P. D., Chatel, L., Bisiaux, A., Albert, M. L., Strambio-De-Castillia, C., Mothes, W., Pizzato, M., Grutter, M. G., Luban, J. <strong>TRIM5 is an innate immune sensor for the retrovirus capsid lattice.</strong> Nature 472: 361-365, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21512573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21512573</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21512573[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/nature09976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21512573">Pertel et al. (2011)</a> demonstrated that TRIM5 promotes innate immune signaling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric ubiquitin-conjugating enzyme UBC13-UEV1A, TRIM5 catalyzes the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (<a href="/entry/602614">602614</a>) kinase complex and stimulate AP1 (see <a href="/entry/165160">165160</a>) and NF-kappa-B (see <a href="/entry/164011">164011</a>) signaling. Interaction with the HIV-1 capsid lattice greatly enhanced the UBC13-UEV1A-dependent E3 activity of TRIM5, and challenge with retroviruses induced the transcription of AP1- and NF-kappa-B-dependent factors with a magnitude that tracked with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contributed to capsid-specific restriction by TRIM5. <a href="#2" class="mim-tip-reference" title="Pertel, T., Hausmann, S., Morger, D., Zuger, S., Guerra, J., Lascano, J., Reinhard, C., Santoni, F. A., Uchil, P. D., Chatel, L., Bisiaux, A., Albert, M. L., Strambio-De-Castillia, C., Mothes, W., Pizzato, M., Grutter, M. G., Luban, J. <strong>TRIM5 is an innate immune sensor for the retrovirus capsid lattice.</strong> Nature 472: 361-365, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21512573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21512573</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21512573[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/nature09976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21512573">Pertel et al. (2011)</a> concluded that the retroviral restriction factor TRIM5 has 2 additional activities that are linked to restriction: it constitutively promotes innate immune signaling, and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21512573" 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="#4" class="mim-tip-reference" title="Ribeiro, C. M. S., Sarrami-Forooshani, R., Setiawan, L. C., Zijlstra-Willems, E. M., van Hamme, J. L., Tigchelaar, W., van der Wel, N. N., Kootstra, N. A., Gringhuis, S. I., Geijtenbeek, T. B. H. <strong>Receptor usage dictates HIV-1 restriction by human TRIM5-alpha in dendritic cell subsets.</strong> Nature 540: 448-452, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27919079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27919079</a>] [<a href="https://doi.org/10.1038/nature20567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27919079">Ribeiro et al. (2016)</a> demonstrated that human E3-ubiquitin ligase TRIM5-alpha potently restricts HIV-1 infection of Langerhans cells but not of subepithelial DCSIGN (CD209; <a href="/entry/604672">604672</a>)+ dendritic cells. HIV-1 restriction by TRIM5-alpha had been considered to be reserved to nonhuman primate TRIM5-alpha orthologs, but the data strongly suggested that human TRIM5-alpha is a cell-specific restriction factor dependent on C-type lectin receptor function. <a href="#4" class="mim-tip-reference" title="Ribeiro, C. M. S., Sarrami-Forooshani, R., Setiawan, L. C., Zijlstra-Willems, E. M., van Hamme, J. L., Tigchelaar, W., van der Wel, N. N., Kootstra, N. A., Gringhuis, S. I., Geijtenbeek, T. B. H. <strong>Receptor usage dictates HIV-1 restriction by human TRIM5-alpha in dendritic cell subsets.</strong> Nature 540: 448-452, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27919079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27919079</a>] [<a href="https://doi.org/10.1038/nature20567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27919079">Ribeiro et al. (2016)</a> suggested that their findings highlighted the importance of HIV-1 binding to langerin (<a href="/entry/604862">604862</a>) for the routing of HIV-1 into the human TRIM5-alpha-mediated restriction pathway. TRIM5-alpha mediates the assembly of an autophagy-activating scaffold to langerin, which targets HIV-1 for autophagic degradation and prevents infection of Langerhans cells. By contrast, HIV-1 binding to DCSIGN+ dendritic cells leads to disassociation of TRIM5-alpha from DCSIGN, which abrogates TRIM5-alpha restriction. Thus, the data of <a href="#4" class="mim-tip-reference" title="Ribeiro, C. M. S., Sarrami-Forooshani, R., Setiawan, L. C., Zijlstra-Willems, E. M., van Hamme, J. L., Tigchelaar, W., van der Wel, N. N., Kootstra, N. A., Gringhuis, S. I., Geijtenbeek, T. B. H. <strong>Receptor usage dictates HIV-1 restriction by human TRIM5-alpha in dendritic cell subsets.</strong> Nature 540: 448-452, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27919079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27919079</a>] [<a href="https://doi.org/10.1038/nature20567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27919079">Ribeiro et al. (2016)</a> strongly suggested that restriction by human TRIM5-alpha is controlled by C-type lectin receptor-dependent uptake of HIV-1, dictating protection or infection of human dendritic cell subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27919079" 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 radiation hybrid analysis, <a href="#3" class="mim-tip-reference" title="Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A. <strong>The tripartite motif family identifies cell compartments.</strong> EMBO J. 20: 2140-2151, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11331580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11331580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11331580[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/emboj/20.9.2140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11331580">Reymond et al. (2001)</a> mapped the TRIM5 gene to chromosome 11p15, in a cluster with TRIM6, TRIM21 (<a href="/entry/109092">109092</a>), TRIM22 (<a href="/entry/606559">606559</a>), TRIM34 (<a href="/entry/605684">605684</a>), and a TRIM pseudogene. The authors noted that, apart from another cluster in the HLA region (chromosome 6p21-23), TRIM genes are dispersed throughout the genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11331580" 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="#8" class="mim-tip-reference" title="Stremlau, M., Owens, C. W., Perron, M. J., Kiessling, M., Autissier, P., Sodroski, J. <strong>The cytoplasmic body component TRIM5-alpha restricts HIV-1 infection in Old World monkeys.</strong> Nature 427: 848-853, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14985764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14985764</a>] [<a href="https://doi.org/10.1038/nature02343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14985764">Stremlau et al. (2004)</a> noted that HIV-1, the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a block before reverse transcription. The block acts on the HIV-1 capsid and is mediated by a dominant repressive factor. By screening HeLa cell lines transduced with a cDNA library from rhesus fibroblasts, <a href="#8" class="mim-tip-reference" title="Stremlau, M., Owens, C. W., Perron, M. J., Kiessling, M., Autissier, P., Sodroski, J. <strong>The cytoplasmic body component TRIM5-alpha restricts HIV-1 infection in Old World monkeys.</strong> Nature 427: 848-853, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14985764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14985764</a>] [<a href="https://doi.org/10.1038/nature02343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14985764">Stremlau et al. (2004)</a> identified HeLa cells expressing rhesus TRIM5-alpha. These cells were resistant to HIV-1 but not simian immunodeficiency virus (SIV) infection. PCR analysis indicated a disruption of viral cDNA synthesis in rhesus TRIM5-alpha-expressing cells. Mutation analysis suggested that both the N-terminal RING and C-terminal SPRY domains of rhesus TRIM5-alpha contribute to its HIV-1 inhibitory activity. Short interfering (si) RNA experiments reducing rhesus TRIM5-alpha expression resulted in increased efficiency of HIV-1 infection. <a href="#8" class="mim-tip-reference" title="Stremlau, M., Owens, C. W., Perron, M. J., Kiessling, M., Autissier, P., Sodroski, J. <strong>The cytoplasmic body component TRIM5-alpha restricts HIV-1 infection in Old World monkeys.</strong> Nature 427: 848-853, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14985764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14985764</a>] [<a href="https://doi.org/10.1038/nature02343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14985764">Stremlau et al. (2004)</a> concluded that monkey TRIM5-alpha is the repressive factor inhibiting HIV-1 reverse transcription and proposed that rhesus TRIM5-alpha may directly bind and ubiquitinate the HIV-1 viral capsid. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14985764" 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="Sayah, D. M., Sokolskaja, E., Berthoux, L., Luban, J. <strong>Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1.</strong> Nature 430: 569-573, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15243629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15243629</a>] [<a href="https://doi.org/10.1038/nature02777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15243629">Sayah et al. (2004)</a> showed that knockdown of owl monkey CYPA (<a href="/entry/123840">123840</a>) by RNA interference (RNAi) correlated with suppression of anti-HIV-1 activity. However, reintroduction of CYPA to RNAi-treated cells did not restore antiviral activity. A search for additional RNAi targets identified TRIMCYP, an RNAi-responsive mRNA encoding a TRIM5/CYPA fusion protein. TRIMCYP accounts for post-entry restriction of HIV-1 in owl monkeys and blocks HIV-1 infection when transferred to otherwise infectable human or rat cells. <a href="#7" class="mim-tip-reference" title="Sayah, D. M., Sokolskaja, E., Berthoux, L., Luban, J. <strong>Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1.</strong> Nature 430: 569-573, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15243629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15243629</a>] [<a href="https://doi.org/10.1038/nature02777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15243629">Sayah et al. (2004)</a> suggested that TRIMCYP arose after the divergence of New and Old World primates when a LINE-1 retrotransposon catalyzed the insertion of a CYPA cDNA into the TRIM5 locus. They concluded that this was the first vertebrate example of a chimeric gene generated by this mechanism of exon shuffling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15243629" 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="Sakuma, R., Noser, J. A., Ohmine, S., Ikeda, Y. <strong>Rhesus monkey TRIM5-alpha restricts HIV-1 production through rapid degradation of viral Gag polyproteins.</strong> Nature Med. 13: 631-635, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17435772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17435772</a>] [<a href="https://doi.org/10.1038/nm1562" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17435772">Sakuma et al. (2007)</a> showed that rhesus Trim5-alpha, but not human TRIM5-alpha, blocked late-phase HIV-1 production through rapid degradation of HIV-1 Gag polyproteins. In agreement with <a href="#5" class="mim-tip-reference" title="Sakuma, R., Noser, J. A., Ohmine, S., Ikeda, Y. <strong>Rhesus monkey TRIM5-alpha restricts HIV-1 production through rapid degradation of viral Gag polyproteins.</strong> Nature Med. 13: 631-635, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17435772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17435772</a>] [<a href="https://doi.org/10.1038/nm1562" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17435772">Sakuma et al. (2007)</a>, <a href="#10" class="mim-tip-reference" title="Zhang, F., Perez-Caballero, D., Hatziioannou,T., Bieniasz, P. D. <strong>No effect of endogenous TRIM5-alpha on HIV-1 production. (Letter)</strong> Nature Med. 14: 235-236, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18323834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18323834</a>] [<a href="https://doi.org/10.1038/nm0308-235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18323834">Zhang et al. (2008)</a> found that rhesus Trim5-alpha could block late-stage HIV-1, but not macaque SIV, production. However, the amount of Trim5-alpha required for this effect was much higher than that endogenously expressed, and they questioned the biologic significance of the finding. In a reply, <a href="#6" class="mim-tip-reference" title="Sakuma, R., Ohmine, S., Mael, A. A., Noser, J. A., Ikeda, Y. <strong>Reply to Zhang et al. (Letter)</strong> Nature Med. 14: 236-238, 2008."None>Sakuma et al. (2008)</a> suggested that technical differences, such as cell lines and capsid sequences, may explain the need for high Trim5-alpha expression in the experiments of <a href="#10" class="mim-tip-reference" title="Zhang, F., Perez-Caballero, D., Hatziioannou,T., Bieniasz, P. D. <strong>No effect of endogenous TRIM5-alpha on HIV-1 production. (Letter)</strong> Nature Med. 14: 235-236, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18323834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18323834</a>] [<a href="https://doi.org/10.1038/nm0308-235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18323834">Zhang et al. (2008)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17435772+18323834" 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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Kaiser, S. M., Malik, H. S., Emerman, M.
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[<a href="https://doi.org/10.1126/science.1140579" target="_blank">Full Text</a>]
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Pertel, T., Hausmann, S., Morger, D., Zuger, S., Guerra, J., Lascano, J., Reinhard, C., Santoni, F. A., Uchil, P. D., Chatel, L., Bisiaux, A., Albert, M. L., Strambio-De-Castillia, C., Mothes, W., Pizzato, M., Grutter, M. G., Luban, J.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21512573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21512573</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21512573[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=21512573" 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/10.1038/nature09976" target="_blank">Full Text</a>]
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Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A.
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EMBO J. 20: 2140-2151, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11331580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11331580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11331580[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=11331580" 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/emboj/20.9.2140" target="_blank">Full Text</a>]
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Ribeiro, C. M. S., Sarrami-Forooshani, R., Setiawan, L. C., Zijlstra-Willems, E. M., van Hamme, J. L., Tigchelaar, W., van der Wel, N. N., Kootstra, N. A., Gringhuis, S. I., Geijtenbeek, T. B. H.
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<strong>Receptor usage dictates HIV-1 restriction by human TRIM5-alpha in dendritic cell subsets.</strong>
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Nature 540: 448-452, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27919079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27919079</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27919079" 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/10.1038/nature20567" target="_blank">Full Text</a>]
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Sakuma, R., Noser, J. A., Ohmine, S., Ikeda, Y.
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<strong>Rhesus monkey TRIM5-alpha restricts HIV-1 production through rapid degradation of viral Gag polyproteins.</strong>
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Nature Med. 13: 631-635, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17435772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17435772</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17435772" 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/10.1038/nm1562" target="_blank">Full Text</a>]
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Sakuma, R., Ohmine, S., Mael, A. A., Noser, J. A., Ikeda, Y.
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<strong>Reply to Zhang et al. (Letter)</strong>
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Nature Med. 14: 236-238, 2008.
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Sayah, D. M., Sokolskaja, E., Berthoux, L., Luban, J.
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<strong>Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1.</strong>
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Nature 430: 569-573, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15243629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15243629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15243629" 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/10.1038/nature02777" target="_blank">Full Text</a>]
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Stremlau, M., Owens, C. W., Perron, M. J., Kiessling, M., Autissier, P., Sodroski, J.
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<strong>The cytoplasmic body component TRIM5-alpha restricts HIV-1 infection in Old World monkeys.</strong>
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Nature 427: 848-853, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14985764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14985764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14985764" 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/10.1038/nature02343" target="_blank">Full Text</a>]
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Xu, L., Yang, L., Moitra, P. K., Hashimoto, K., Rallabhandi, P., Kaul, S., Meroni, G., Jensen, J. P., Weissman, A. M., D'Arpa, P.
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<strong>BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5-delta.</strong>
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Exp. Cell Res. 288: 84-93, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12878161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12878161</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12878161" 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/s0014-4827(03)00187-3" target="_blank">Full Text</a>]
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Zhang, F., Perez-Caballero, D., Hatziioannou,T., Bieniasz, P. D.
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<strong>No effect of endogenous TRIM5-alpha on HIV-1 production. (Letter)</strong>
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Nature Med. 14: 235-236, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18323834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18323834</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18323834" 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/10.1038/nm0308-235" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 01/10/2017
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Ada Hamosh - updated : 7/8/2011<br>Paul J. Converse - updated : 5/29/2008<br>Ada Hamosh - updated : 7/24/2007<br>Ada Hamosh - updated : 8/26/2004
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Paul J. Converse : 2/26/2004
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alopez : 01/10/2017
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carol : 10/18/2016<br>alopez : 11/13/2012<br>alopez : 7/12/2011<br>alopez : 7/12/2011<br>terry : 7/8/2011<br>mgross : 6/2/2008<br>terry : 5/29/2008<br>alopez : 7/25/2007<br>terry : 7/24/2007<br>tkritzer : 8/27/2004<br>terry : 8/26/2004<br>mgross : 3/16/2004<br>alopez : 2/26/2004<br>alopez : 2/26/2004<br>alopez : 2/26/2004
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<strong>*</strong> 608487
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TRIPARTITE MOTIF-CONTAINING PROTEIN 5; TRIM5
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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RNF88
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<strong><em>HGNC Approved Gene Symbol: TRIM5</em></strong>
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Cytogenetic location: 11p15.4
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Genomic coordinates <span class="small">(GRCh38)</span> : 11:5,588,635-5,685,074 </span>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>TEXT</strong>
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<p>TRIM5 belongs to the large tripartite motif protein family, members of which typically are composed of 3 zinc-binding domains, a RING, unique B-box type 1 and B-box type 2 domains, followed by a coiled-coil (CC) region. TRIM proteins use homomultimerization to identify specific cell compartments.</p>
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<strong>Cloning and Expression</strong>
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<p>Using a consensus B-box domain to screen dbEST databases, Reymond et al. (2001) identified 37 TRIM members in mammals, 21 of which were novel, as well as 34 splice variants. TRIM5 has 6 variants termed alpha, beta, gamma, delta, epsilon, and zeta, all of which lack a B-box type 1 domain. Additional domains C-terminal to the CC region are variably present. TRIM5-zeta lacks RING, B-box, and CC domains, but possesses 3 RFP-like domains. Northern blot analysis of adult human tissues detected ubiquitous expression of TRIM5. Using interaction mating and mutation analysis, Reymond et al. (2001) confirmed that TRIM5, like most TRIMs, homointeracts through the CC region. Interaction was also detected with TRIM6 (607564). Green fluorescent protein microscopy demonstrated expression as cytoplasmic speckles, possibly in novel subcellular compartments. </p><p>Stremlau et al. (2004) determined that human TRIM5-alpha contains 493 amino acids and includes a C-terminal b30.2 (SPRY) domain missing in other TRIM5 isoforms. </p>
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<strong>Gene Function</strong>
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<p>By fluorescence microscopy and mutation analysis, Xu et al. (2003) showed that TRIM5-delta interacts with BTBD1 (608530) and BTBD2 (608531), apparently serving as a scaffold for the assembly of endogenous BTBD1/2 proteins, dependent on the presence of the CC region and a wildtype RING domain. TRIM5-delta exhibits ubiquitylation in the presence of UBCH5B (UBE2D2; 602962), dependent on the presence of zinc-coordinating cysteines in the RING domain. </p><p>Kaiser et al. (2007) reported the reconstruction of the core protein of a 4-million-year-old endogenous virus from the chimpanzee genome (PtERV1) and showed that the human variant of the intrinsic immune protein TRIM5-alpha can actively prevent infection by this virus. However, Kaiser et al. (2007) suggested that the selective changes that have occurred in the human lineage during the acquisition of resistance to this virus, and perhaps similar viruses, may have left our species more susceptible to infection by HIV-1. </p><p>Pertel et al. (2011) demonstrated that TRIM5 promotes innate immune signaling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric ubiquitin-conjugating enzyme UBC13-UEV1A, TRIM5 catalyzes the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (602614) kinase complex and stimulate AP1 (see 165160) and NF-kappa-B (see 164011) signaling. Interaction with the HIV-1 capsid lattice greatly enhanced the UBC13-UEV1A-dependent E3 activity of TRIM5, and challenge with retroviruses induced the transcription of AP1- and NF-kappa-B-dependent factors with a magnitude that tracked with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contributed to capsid-specific restriction by TRIM5. Pertel et al. (2011) concluded that the retroviral restriction factor TRIM5 has 2 additional activities that are linked to restriction: it constitutively promotes innate immune signaling, and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice. </p><p>Ribeiro et al. (2016) demonstrated that human E3-ubiquitin ligase TRIM5-alpha potently restricts HIV-1 infection of Langerhans cells but not of subepithelial DCSIGN (CD209; 604672)+ dendritic cells. HIV-1 restriction by TRIM5-alpha had been considered to be reserved to nonhuman primate TRIM5-alpha orthologs, but the data strongly suggested that human TRIM5-alpha is a cell-specific restriction factor dependent on C-type lectin receptor function. Ribeiro et al. (2016) suggested that their findings highlighted the importance of HIV-1 binding to langerin (604862) for the routing of HIV-1 into the human TRIM5-alpha-mediated restriction pathway. TRIM5-alpha mediates the assembly of an autophagy-activating scaffold to langerin, which targets HIV-1 for autophagic degradation and prevents infection of Langerhans cells. By contrast, HIV-1 binding to DCSIGN+ dendritic cells leads to disassociation of TRIM5-alpha from DCSIGN, which abrogates TRIM5-alpha restriction. Thus, the data of Ribeiro et al. (2016) strongly suggested that restriction by human TRIM5-alpha is controlled by C-type lectin receptor-dependent uptake of HIV-1, dictating protection or infection of human dendritic cell subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans. </p>
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<strong>Mapping</strong>
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<p>By radiation hybrid analysis, Reymond et al. (2001) mapped the TRIM5 gene to chromosome 11p15, in a cluster with TRIM6, TRIM21 (109092), TRIM22 (606559), TRIM34 (605684), and a TRIM pseudogene. The authors noted that, apart from another cluster in the HLA region (chromosome 6p21-23), TRIM genes are dispersed throughout the genome. </p>
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<strong>Animal Model</strong>
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<p>Stremlau et al. (2004) noted that HIV-1, the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a block before reverse transcription. The block acts on the HIV-1 capsid and is mediated by a dominant repressive factor. By screening HeLa cell lines transduced with a cDNA library from rhesus fibroblasts, Stremlau et al. (2004) identified HeLa cells expressing rhesus TRIM5-alpha. These cells were resistant to HIV-1 but not simian immunodeficiency virus (SIV) infection. PCR analysis indicated a disruption of viral cDNA synthesis in rhesus TRIM5-alpha-expressing cells. Mutation analysis suggested that both the N-terminal RING and C-terminal SPRY domains of rhesus TRIM5-alpha contribute to its HIV-1 inhibitory activity. Short interfering (si) RNA experiments reducing rhesus TRIM5-alpha expression resulted in increased efficiency of HIV-1 infection. Stremlau et al. (2004) concluded that monkey TRIM5-alpha is the repressive factor inhibiting HIV-1 reverse transcription and proposed that rhesus TRIM5-alpha may directly bind and ubiquitinate the HIV-1 viral capsid. </p><p>Sayah et al. (2004) showed that knockdown of owl monkey CYPA (123840) by RNA interference (RNAi) correlated with suppression of anti-HIV-1 activity. However, reintroduction of CYPA to RNAi-treated cells did not restore antiviral activity. A search for additional RNAi targets identified TRIMCYP, an RNAi-responsive mRNA encoding a TRIM5/CYPA fusion protein. TRIMCYP accounts for post-entry restriction of HIV-1 in owl monkeys and blocks HIV-1 infection when transferred to otherwise infectable human or rat cells. Sayah et al. (2004) suggested that TRIMCYP arose after the divergence of New and Old World primates when a LINE-1 retrotransposon catalyzed the insertion of a CYPA cDNA into the TRIM5 locus. They concluded that this was the first vertebrate example of a chimeric gene generated by this mechanism of exon shuffling. </p><p>Sakuma et al. (2007) showed that rhesus Trim5-alpha, but not human TRIM5-alpha, blocked late-phase HIV-1 production through rapid degradation of HIV-1 Gag polyproteins. In agreement with Sakuma et al. (2007), Zhang et al. (2008) found that rhesus Trim5-alpha could block late-stage HIV-1, but not macaque SIV, production. However, the amount of Trim5-alpha required for this effect was much higher than that endogenously expressed, and they questioned the biologic significance of the finding. In a reply, Sakuma et al. (2008) suggested that technical differences, such as cell lines and capsid sequences, may explain the need for high Trim5-alpha expression in the experiments of Zhang et al. (2008). </p>
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<strong>REFERENCES</strong>
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Kaiser, S. M., Malik, H. S., Emerman, M.
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<strong>Restriction of an extinct retrovirus by the human TRIM5-alpha antiviral protein.</strong>
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Science 316: 1756-1758, 2007. Note: Erratum: Science 317: 1036 only, 2007.
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[PubMed: 17588933]
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[Full Text: https://doi.org/10.1126/science.1140579]
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Pertel, T., Hausmann, S., Morger, D., Zuger, S., Guerra, J., Lascano, J., Reinhard, C., Santoni, F. A., Uchil, P. D., Chatel, L., Bisiaux, A., Albert, M. L., Strambio-De-Castillia, C., Mothes, W., Pizzato, M., Grutter, M. G., Luban, J.
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<strong>TRIM5 is an innate immune sensor for the retrovirus capsid lattice.</strong>
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Nature 472: 361-365, 2011.
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[PubMed: 21512573]
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[Full Text: https://doi.org/10.1038/nature09976]
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Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P. G., Ballabio, A.
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<strong>The tripartite motif family identifies cell compartments.</strong>
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EMBO J. 20: 2140-2151, 2001.
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[PubMed: 11331580]
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[Full Text: https://doi.org/10.1093/emboj/20.9.2140]
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Ribeiro, C. M. S., Sarrami-Forooshani, R., Setiawan, L. C., Zijlstra-Willems, E. M., van Hamme, J. L., Tigchelaar, W., van der Wel, N. N., Kootstra, N. A., Gringhuis, S. I., Geijtenbeek, T. B. H.
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<strong>Receptor usage dictates HIV-1 restriction by human TRIM5-alpha in dendritic cell subsets.</strong>
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Nature 540: 448-452, 2016.
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[PubMed: 27919079]
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[Full Text: https://doi.org/10.1038/nature20567]
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Sakuma, R., Noser, J. A., Ohmine, S., Ikeda, Y.
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<strong>Rhesus monkey TRIM5-alpha restricts HIV-1 production through rapid degradation of viral Gag polyproteins.</strong>
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Nature Med. 13: 631-635, 2007.
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[PubMed: 17435772]
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[Full Text: https://doi.org/10.1038/nm1562]
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Sakuma, R., Ohmine, S., Mael, A. A., Noser, J. A., Ikeda, Y.
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<strong>Reply to Zhang et al. (Letter)</strong>
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Nature Med. 14: 236-238, 2008.
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<p class="mim-text-font">
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Sayah, D. M., Sokolskaja, E., Berthoux, L., Luban, J.
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<strong>Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1.</strong>
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Nature 430: 569-573, 2004.
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[PubMed: 15243629]
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[Full Text: https://doi.org/10.1038/nature02777]
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<p class="mim-text-font">
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Stremlau, M., Owens, C. W., Perron, M. J., Kiessling, M., Autissier, P., Sodroski, J.
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<strong>The cytoplasmic body component TRIM5-alpha restricts HIV-1 infection in Old World monkeys.</strong>
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Nature 427: 848-853, 2004.
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[PubMed: 14985764]
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[Full Text: https://doi.org/10.1038/nature02343]
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<p class="mim-text-font">
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Xu, L., Yang, L., Moitra, P. K., Hashimoto, K., Rallabhandi, P., Kaul, S., Meroni, G., Jensen, J. P., Weissman, A. M., D'Arpa, P.
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<strong>BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5-delta.</strong>
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Exp. Cell Res. 288: 84-93, 2003.
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[PubMed: 12878161]
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[Full Text: https://doi.org/10.1016/s0014-4827(03)00187-3]
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<p class="mim-text-font">
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Zhang, F., Perez-Caballero, D., Hatziioannou,T., Bieniasz, P. D.
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<strong>No effect of endogenous TRIM5-alpha on HIV-1 production. (Letter)</strong>
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Nature Med. 14: 235-236, 2008.
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[PubMed: 18323834]
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[Full Text: https://doi.org/10.1038/nm0308-235]
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Contributors:
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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 : 01/10/2017<br>Ada Hamosh - updated : 7/8/2011<br>Paul J. Converse - updated : 5/29/2008<br>Ada Hamosh - updated : 7/24/2007<br>Ada Hamosh - updated : 8/26/2004
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<span class="mim-text-font">
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Paul J. Converse : 2/26/2004
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