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</button> <ul id="toc-Biology_/_Functions-sublist" class="vector-toc-list"> <li id="toc-Expression" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Expression"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.1</span> <span>Expression</span> </div> </a> <ul id="toc-Expression-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Antigen_presentation" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Antigen_presentation"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.2</span> <span>Antigen presentation</span> </div> </a> <ul id="toc-Antigen_presentation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Other_functions" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Other_functions"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.3</span> <span>Other functions</span> </div> </a> <ul id="toc-Other_functions-sublist" 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<h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">ERAP2</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. 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lang="bs" hreflang="bs" data-title="ERAP2" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target"><span>Bosanski</span></a></li><li class="interlanguage-link interwiki-eu mw-list-item"><a href="https://eu.wikipedia.org/wiki/ERAP2" title="ERAP2 – Basque" lang="eu" hreflang="eu" data-title="ERAP2" data-language-autonym="Euskara" data-language-local-name="Basque" class="interlanguage-link-target"><span>Euskara</span></a></li><li class="interlanguage-link interwiki-arz mw-list-item"><a href="https://arz.wikipedia.org/wiki/ERAP2" title="ERAP2 – Egyptian Arabic" lang="arz" hreflang="arz" data-title="ERAP2" data-language-autonym="مصرى" data-language-local-name="Egyptian Arabic" class="interlanguage-link-target"><span>مصرى</span></a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/ERAP2" title="ERAP2 – Ukrainian" lang="uk" hreflang="uk" data-title="ERAP2" data-language-autonym="Українська" 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searchaux" style="display:none">Protein-coding gene in the species Homo sapiens</div><table class="infobox" style="width:26.4em"><tbody><tr><th colspan="4" style="text-align:center;font-size:125%;font-weight:bold">ERAP2</th></tr><tr><td colspan="4" style="text-align:center"><span typeof="mw:File"><a href="/wiki/File:Crystal_structure_ERAP2_-_PDB_3SE6.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Crystal_structure_ERAP2_-_PDB_3SE6.jpg/250px-Crystal_structure_ERAP2_-_PDB_3SE6.jpg" decoding="async" width="250" height="250" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Crystal_structure_ERAP2_-_PDB_3SE6.jpg/375px-Crystal_structure_ERAP2_-_PDB_3SE6.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/d/d6/Crystal_structure_ERAP2_-_PDB_3SE6.jpg 2x" data-file-width="500" data-file-height="500" /></a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd">Available structures</th></tr><tr><th rowspan="2" style="background-color:#c3fdb8;width:43px"><a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a></th><td colspan="2" style="background-color:#eee">Human UniProt search: <span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/searchResults.html?display=both&term=Q6P179">PDBe</a> <a rel="nofollow" class="external text" href="https://www.rcsb.org/search?q=rcsb_polymer_entity_container_identifiers.reference_sequence_identifiers.database_name:UniProt%20AND%20rcsb_polymer_entity_container_identifiers.reference_sequence_identifiers.database_accession:Q6P179">RCSB</a> </span></td></tr><tr><td><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr style="background-color:#ddd;text-align:center"><th colspan="2">List of PDB id codes</th></tr><tr><td colspan="2" style="background-color:#eee"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/3SE6">3SE6</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/4E36">4E36</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/4JBS">4JBS</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/5CU5">5CU5</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/5AB2">5AB2</a>, <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/5AB0">5AB0</a></span></p></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><th colspan="4" style="text-align:center;background-color:#ddd">Identifiers</th></tr><tr><th scope="row" style="background-color:#c3fdb8"><span class="plainlinks"><a href="/wiki/Gene_nomenclature" title="Gene nomenclature">Aliases</a></span></th><td colspan="3" style="background:#eee"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/29499">ERAP2</a></span>, L-RAP, LRAP, endoplasmic reticulum aminopeptidase 2</td></tr><tr><th scope="row" style="background-color:#c3fdb8">External IDs</th><td colspan="3" style="background-color:#eee"><span class="plainlinks"><a href="/wiki/Mendelian_Inheritance_in_Man" class="mw-redirect" title="Mendelian Inheritance in Man">OMIM</a>: <a rel="nofollow" class="external text" href="https://omim.org/entry/609497">609497</a>; <a href="/wiki/HomoloGene" title="HomoloGene">HomoloGene</a>: <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=homologene&dopt=HomoloGene&list_uids=75183">75183</a>; <a href="/wiki/GeneCards" title="GeneCards">GeneCards</a>: <a rel="nofollow" class="external text" href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=ERAP2">ERAP2</a>; <a href="/wiki/Orthologous_MAtrix" title="Orthologous MAtrix">OMA</a>:<a rel="nofollow" class="external text" href="https://omabrowser.org/oma/vps/ENSG00000164308">ERAP2 - orthologs</a></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd">Gene location (<a href="/wiki/Human_genome" title="Human genome">Human</a>)</th></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span typeof="mw:File"><a href="/wiki/File:Ideogram_human_chromosome_5.svg" class="mw-file-description" title="Chromosome 5 (human)"><img alt="Chromosome 5 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/6/61/Ideogram_human_chromosome_5.svg/300px-Ideogram_human_chromosome_5.svg.png" decoding="async" width="300" height="120" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/61/Ideogram_human_chromosome_5.svg/450px-Ideogram_human_chromosome_5.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/61/Ideogram_human_chromosome_5.svg/600px-Ideogram_human_chromosome_5.svg.png 2x" data-file-width="500" data-file-height="200" /></a></span></td></tr><tr><th scope="row" width="15%" style="background-color:#c3fdb8"><a href="/wiki/Chromosome" title="Chromosome">Chr.</a></th><td colspan="3" width="85%" style="background-color:#eee"><span class="plainlinks"><a href="/wiki/Chromosome_5_(human)" class="mw-redirect" title="Chromosome 5 (human)">Chromosome 5 (human)</a><sup id="cite_ref-refGRCh38Ensembl_1-0" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><div align="center"><div style="position: relative; width: 300px;"><span typeof="mw:File"><a href="/wiki/File:Human_chromosome_5_ideogram.svg" class="mw-file-description" title="Chromosome 5 (human)"><img alt="Chromosome 5 (human)" src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a2/Human_chromosome_5_ideogram.svg/300px-Human_chromosome_5_ideogram.svg.png" decoding="async" width="300" height="58" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a2/Human_chromosome_5_ideogram.svg/450px-Human_chromosome_5_ideogram.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a2/Human_chromosome_5_ideogram.svg/600px-Human_chromosome_5_ideogram.svg.png 2x" data-file-width="1125" data-file-height="216" /></a></span><div style="position: absolute; left: 151.5965098976px; top: 2px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:HSR_1996_II_3.5e.svg" class="mw-file-description" title="Genomic location for ERAP2"><img alt="Genomic location for ERAP2" src="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/14px-HSR_1996_II_3.5e.svg.png" decoding="async" width="14" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/21px-HSR_1996_II_3.5e.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/d8/HSR_1996_II_3.5e.svg/28px-HSR_1996_II_3.5e.svg.png 2x" data-file-width="142" data-file-height="142" /></a></span></div><div style="position: absolute; left: 157.6px; top: 19px; padding: 0;"><span typeof="mw:File"><a href="/wiki/File:Red_rectangle_2x18.png" class="mw-file-description" title="Genomic location for ERAP2"><img alt="Genomic location for ERAP2" src="//upload.wikimedia.org/wikipedia/commons/6/6a/Red_rectangle_2x18.png" decoding="async" width="2" height="18" class="mw-file-element" data-file-width="2" data-file-height="18" /></a></span></div></div></div></td></tr><tr><th scope="row" rowspan="2" width="15%" style="background-color:#c3fdb8"><a href="/wiki/Locus_(genetics)" title="Locus (genetics)">Band</a></th><td rowspan="2" width="35%" style="background-color:#eee"><span class="plainlinks">5q15</span></td><th scope="row" style="background-color:#c3fdb8">Start</th><td style="background-color:#eee"><span class="plainlinks">96,875,986 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-1" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr><tr><th scope="row" style="background-color:#c3fdb8">End</th><td style="background-color:#eee"><span class="plainlinks">96,919,703 <a href="/wiki/Base_pair" title="Base pair">bp</a><sup id="cite_ref-refGRCh38Ensembl_1-2" class="reference"><a href="#cite_note-refGRCh38Ensembl-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd"><a href="/wiki/Gene_expression" title="Gene expression">RNA expression</a> pattern</th></tr><tr><th scope="row" style="background-color:#c3fdb8"><a rel="nofollow" class="external text" href="https://www.bgee.org/">Bgee</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th><b><a href="/wiki/Human_genome" title="Human genome">Human</a></b></th><th><b><a href="/wiki/Laboratory_mouse" title="Laboratory mouse">Mouse</a> (ortholog)</b></th></tr><tr><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000164308">Top expressed in</a></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px"><li style="line-height: 137%;">buccal mucosa cell</li><br /><li style="line-height: 137%;">granulocyte</li><br /><li style="line-height: 137%;">lymph node</li><br /><li style="line-height: 137%;">superficial temporal artery</li><br /><li style="line-height: 137%;">visceral pleura</li><br /><li style="line-height: 137%;">epithelium of nasopharynx</li><br /><li style="line-height: 137%;">monocyte</li><br /><li style="line-height: 137%;">epithelium of colon</li><br /><li style="line-height: 137%;">appendix</li><br /><li style="line-height: 137%;">Achilles tendon</li></ul></div></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="1"><span class="plainlinks" style="margin:-3px"></span></td></tr><tr><td colspan="1"><div class="plainlinks" style="margin:-12px 0px -10px 0px"><ul style="line-height:15%;margin:9px">n/a</ul></div></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.bgee.org/gene/ENSG00000164308">More reference expression data</a></span></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a rel="nofollow" class="external text" href="http://biogps.org/">BioGPS</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><td colspan="4" style="text-align:center;background-color:#eee">n/a</td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><span class="plainlinks"></span></td></tr></tbody></table></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible collapsed" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd"><a href="/wiki/Gene_ontology" class="mw-redirect" title="Gene ontology">Gene ontology</a></th></tr><tr><td style="background-color:#c3fdb8;font-weight:bold">Molecular function</td><td style="background-color:#eee"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0004177">aminopeptidase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008237">metallopeptidase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008233">peptidase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016787">hydrolase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008270">zinc ion binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0046872">metal ion binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0042277">peptide binding</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0070006">metalloaminopeptidase activity</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0004175">endopeptidase activity</a></li></ul> </div></td></tr><tr><td style="background-color:#c3fdb8;font-weight:bold">Cellular component</td><td style="background-color:#eee"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016021">integral component of membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005788">endoplasmic reticulum lumen</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005789">endoplasmic reticulum membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0016020">membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005783">endoplasmic reticulum</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005886">plasma membrane</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0005737">cytoplasm</a></li></ul> </div></td></tr><tr><td style="background-color:#c3fdb8;font-weight:bold">Biological process</td><td style="background-color:#eee"><div class="plainlinks"> <ul><li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0002376">immune system process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0002250">adaptive immune response</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0006508">proteolysis</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0008217">regulation of blood pressure</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0002474">antigen processing and presentation of peptide antigen via MHC class I</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0043171">peptide catabolic process</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0019885">antigen processing and presentation of endogenous peptide antigen via MHC class I</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007165">signal transduction</a></li> <li><a rel="nofollow" class="external text" href="http://amigo.geneontology.org/amigo/term/GO:0007267">cell-cell signaling</a></li></ul> </div></td></tr><tr><td colspan="4" style="background-color:#eee;text-align:center">Sources:<a rel="nofollow" class="external text" href="http://amigo.geneontology.org/">Amigo</a> / <a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/QuickGO/">QuickGO</a></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table class="collapsible" style="padding:0;border:none;margin:0;width:100%;text-align:left"><tbody><tr><th colspan="4" style="text-align:center;background-color:#ddd"><a href="/wiki/Orthologs" class="mw-redirect" title="Orthologs">Orthologs</a></th></tr><tr><th scope="row" style="background-color:#c3fdb8">Species</th><td><b>Human</b></td><td><b>Mouse</b></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/Entrez" title="Entrez">Entrez</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=64167&rn=1">64167</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks">n/a</p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/Ensembl" class="mw-redirect" title="Ensembl">Ensembl</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000164308;db=core">ENSG00000164308</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks">n/a</p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/UniProt" title="UniProt">UniProt</a></th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks"><a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprot/Q6P179">Q6P179</a></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1"><span class="plainlinks"></span></th></tr><tr><td colspan="1"><p class="plainlinks">n/a</p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8">RefSeq (mRNA)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001130140">NM_001130140</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_022350">NM_022350</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001329229">NM_001329229</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001329233">NM_001329233</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks">n/a</span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8">RefSeq (protein)</th><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001123612">NP_001123612</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001316158">NP_001316158</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001316162">NP_001316162</a><br /><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_071745">NP_071745</a></span></p></td></tr></tbody></table></td><td><table class="none" style="padding:0;border:none;margin:0;width:100%;text-align:right"><tbody><tr><th colspan="1" class="plainlinks"></th></tr><tr><td colspan="1"><p><span class="plainlinks">n/a</span></p></td></tr></tbody></table></td></tr><tr><th scope="row" style="background-color:#c3fdb8">Location (UCSC)</th><td><span class="plainlinks"><a rel="nofollow" class="external text" href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&position=chr5:96875986-96919703">Chr 5: 96.88 – 96.92 Mb</a></span></td><td><span class="plainlinks">n/a</span></td></tr><tr><th scope="row" style="background-color:#c3fdb8"><a href="/wiki/PubMed" title="PubMed">PubMed</a> search</th><td><span class="plainlinks"><sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></span></td><td><span class="plainlinks">n/a</span></td></tr></tbody></table></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><a href="/wiki/Wikidata" title="Wikidata">Wikidata</a></td></tr><tr><td colspan="4" style="text-align:center;background-color:#eee"><table style="padding:0;border:none;margin:0;width:100%;text-align:center"><tbody><tr><td colspan="4" style="background-color:#eee;text-align:center"><a href="https://www.wikidata.org/wiki/Q18045592" class="extiw" title="d:Q18045592">View/Edit Human</a></td><td colspan="0" style="background-color:#eee;text-align:center"></td></tr></tbody></table></td></tr></tbody></table> <p class="mw-empty-elt"> </p><p>Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a <a href="/wiki/Protein" title="Protein">protein</a> that in humans is encoded by the <i>ERAP2</i> <a href="/wiki/Gene" title="Gene">gene</a>. ERAP2 is part of the M1 <a href="/wiki/Aminopeptidase" title="Aminopeptidase">aminopeptidase</a> family. It is expressed along with <a href="/wiki/ERAP1" title="ERAP1">ERAP1</a> in the <a href="/wiki/Endoplasmic_reticulum" title="Endoplasmic reticulum">endoplasmic reticulum</a> (ER). In the ER, both enzymes help process and present <a href="/wiki/Antigen" title="Antigen">antigens</a> by trimming the ends of precursor peptides. This creates the optimal pieces for display by <a href="/wiki/MHC_class_I" title="MHC class I">Major Histocompatibility Complex (MHC) class I molecules</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Biology_/_Functions"><span id="Biology_.2F_Functions"></span>Biology / Functions</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=1" title="Edit section: Biology / Functions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Expression">Expression</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=2" title="Edit section: Expression"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>ERAP2 expression is regulated by <a href="/wiki/Interferon_gamma" title="Interferon gamma">interferon gamma</a> signalling. While ERAP2 and homologous enzyme ERAP1 are both expressed in <a href="/wiki/White_blood_cell" title="White blood cell">immune cells</a>, the expression of the enzymes is independently regulated in other tissues without significant correlation of expression levels. However, coordinated expression patterns have also been observed, in which ERAP2 downregulation is counterbalanced by an increase in ERAP1 expression.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Overexpression of ERAP2 in various cancer types, including <a href="/wiki/Melanoma" title="Melanoma">melanomas</a> and different <a href="/wiki/Adenocarcinoma" title="Adenocarcinoma">adenocarcinomas</a>, has been suggested to modulate the presentation of cancer antigens on MHC-I, which may affect cancer invasion by immune cells.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> ERAP2 is not expressed in mice making it more difficult to study. </p> <div class="mw-heading mw-heading3"><h3 id="Antigen_presentation">Antigen presentation</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=3" title="Edit section: Antigen presentation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Unlike ERAP1, ERAP2 can trim efficiently peptides that already have optimal length for MHC class I presentation. Thus ERAP2 has been shown to shorten peptides of 9 or fewer amino acids, thereby destroying antigenic peptides in some cases.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> ERAP2 displays a preference for peptide substrates that carry N-terminal basic residues (arginine, lysine).<sup id="cite_ref-:0_7-0" class="reference"><a href="#cite_note-:0-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> A fraction of ERAP2 is reported to form complexes with ERAP1, as seen in co-precipitation experiments.<sup id="cite_ref-:0_7-1" class="reference"><a href="#cite_note-:0-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Heterodimer formation improves peptide-trimming efficiency, resulting in an expanded antigenic repertoire and a more diverse <a href="/wiki/Immune_response" title="Immune response">immune response</a>.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> The ERAP1-ERAP2 complex can trim free peptides in the ER and may also be able to trim MHC I-bound precursor peptides, according to some authors.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Individuals homozygous for ERAP2 haplotype B lack ERAP2 protein expression and have significantly lower MHC class I levels on the surface of <a href="/wiki/B_cell" title="B cell">B cells</a>. This may result in an altered presentation of antigens and resulting immune responses.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Other_functions">Other functions</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=4" title="Edit section: Other functions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>ERAP2 can modulate the <a href="/wiki/Renin%E2%80%93angiotensin_system" title="Renin–angiotensin system">renin-angiotensin system (RAS)</a> in blood pressure homeostasis through angiotensin cleavage. In concert with ERAP1, ERAP2 counteracts angiotensin II activity, inducing vasodilation and hypertension reduction.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> Blood pressure modulation by ERAP2 is supported by the association of ERAP2 with blood pressure progression and hypertension incidence.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Its link to pre-eclampsia in multiple populations shows further support for the role of ERAP2 in blood pressure homeostasis.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Genetics_/_clinical_significance"><span id="Genetics_.2F_clinical_significance"></span>Genetics / clinical significance</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=5" title="Edit section: Genetics / clinical significance"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Gene_/_location"><span id="Gene_.2F_location"></span>Gene / location</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=6" title="Edit section: Gene / location"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><i>ERAP2</i> gene is located on human chromosome 5 in between the <i>ERAP1</i> and <i><a href="/wiki/Leucyl/cystinyl_aminopeptidase" class="mw-redirect" title="Leucyl/cystinyl aminopeptidase">LNPEP</a></i> genes encoding the other two family members of the M1 aminopeptidases. It has 41,438 base pair length and consists of 19 exons.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="SNPs_and_disease_association">SNPs and disease association</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=7" title="Edit section: SNPs and disease association"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The <i>ERAP2</i> gene is highly polymorphic and contains many common <a href="/wiki/Single-nucleotide_polymorphism" title="Single-nucleotide polymorphism">single nucleotide variants</a> (SNVs) that are in strong linkage disequilibrium and are maintained at intermediate frequencies through balancing selection.<sup id="cite_ref-Andrés_2010_16-0" class="reference"><a href="#cite_note-Andrés_2010-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> There are two common SNVs in <i>ERAP2</i> that facilitate the alternative splicing of three haplotypes by altering splice motifs.<sup id="cite_ref-Andrés_2010_16-1" class="reference"><a href="#cite_note-Andrés_2010-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> The A allele of splice variant rs2248374 tags haplotype A, which results in the full-length 960 amino acid long <i>ERAP2</i> protein being produced.<sup id="cite_ref-Andrés_2010_16-2" class="reference"><a href="#cite_note-Andrés_2010-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> However, the G allele of rs2248374 (i.e., haplotype B) disrupts splicing at exon 10, introducing downstream premature stop codons.<sup id="cite_ref-Andrés_2010_16-3" class="reference"><a href="#cite_note-Andrés_2010-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> Under steady state conditions, the truncated mRNA is destroyed by nonsense mediated decay (NMD), but during influenza infections it is translated to two truncated isoforms.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> Accordingly, 25% of the general population (haplotype B homozygotes) are deficient in full-length <i>ERAP2</i> protein. The G allele of SNV rs17486481 activates a cryptic splice site upstream of exon 12 that also introduces premature stop codons and makes the transcript likely vulnerable to NMD (haplotype C). Different <i>ERAP2</i> protein haplotypes (or allotypes) have been detected among the major continental populations based on common <a href="/wiki/Missense_mutation" title="Missense mutation">missense variants</a> in <i>ERAP2</i>.<sup id="cite_ref-Andrés_2010_16-4" class="reference"><a href="#cite_note-Andrés_2010-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> <i>ERAP2</i> haplotypes are associated with severe inflammatory conditions (e.g., <a href="/wiki/Birdshot_chorioretinopathy" title="Birdshot chorioretinopathy">birdshot chorioretinopathy</a>, <a href="/wiki/Crohn%27s_disease" title="Crohn's disease">Crohn's disease</a>, <a href="/wiki/Ankylosing_spondylitis" title="Ankylosing spondylitis">ankylosing spondylitis</a>, <a href="/wiki/Psoriasis" title="Psoriasis">psoriasis</a>) and cancer treatment responses.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Interestingly, the alleles from SNVs that strongly predispose to autoimmune conditions (i.e., A allele of rs2248374 and other SNVs in haplotype A) display natural selection in recent human history, which has been suggested to provide higher resistance against severe respiratory illnesses, including the <a href="/wiki/Bubonic_plague" title="Bubonic plague">bubonic plague</a> ("Black Death"), <a href="/wiki/Pneumonia" title="Pneumonia">pneumonia</a> and <a href="/wiki/COVID-19" title="COVID-19">COVID-19</a>.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid38190099_22-0" class="reference"><a href="#cite_note-pmid38190099-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> Klunk et al. found that individuals with the protective allele (dominant in the present European population) had a fivefold increase in ERAP2 expression in macrophages resulting in reduced replication of <i>Y. pestis.</i> </p> <div class="mw-heading mw-heading2"><h2 id="Structure_/_Mechanism"><span id="Structure_.2F_Mechanism"></span>Structure / Mechanism</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=8" title="Edit section: Structure / Mechanism"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Structure">Structure</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=9" title="Edit section: Structure"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>ERAP2 is composed of 4 structural units (I-IV), with the HEXXHX<sub>18</sub>E zinc-binding motif and the known GAMEN aminopeptidase motif located in domain II, similarly to its closely related enzyme ERAP1. The catalytic site features a single Zn(II) ion and is coordinated by two histidine residues (H370, H374) and a glutamate residue (E393). Domains II and IV, which are linked by domain III, form a large internal cavity close to the catalytic site and exclude the external solvent, in accordance with the “closed” conformation obtained for ERAP1.<sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Mechanism">Mechanism</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=10" title="Edit section: Mechanism"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>ERAP2 selects substrates by sequestering them in its internal cavity and allowing interactions to determine trimming rates, thus combining substrate permissiveness with sequence bias.<sup id="cite_ref-Mpakali_2015_25-0" class="reference"><a href="#cite_note-Mpakali_2015-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> A crystal structure of ERAP2 with a peptide product located in this cavity has revealed lack of deep specificity pockets and lack of a cavity that interacts with the peptide C- terminus, which justify the limited selectivity of this enzyme and the differences in length selection compared to ERAP1 (ERAP2 can effectively trim 8-mer peptides, while it is less active with longer substrates<sup id="cite_ref-Mpakali_2015_25-1" class="reference"><a href="#cite_note-Mpakali_2015-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Saveanu_2005_26-0" class="reference"><a href="#cite_note-Saveanu_2005-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup>). Interactions between side-chains of a 10-mer phosphinic analogue and residues of the interior of the cavity also appear shallow and opportunistic, further confirming its ability to process a variety of peptide substrates<sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup>.  In terms of N-terminal residue specificity, ERAP2 prefers basic amino acids, such as arginine.<sup id="cite_ref-Saveanu_2005_26-1" class="reference"><a href="#cite_note-Saveanu_2005-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Interactions">Interactions</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=11" title="Edit section: Interactions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Some experimental evidence has suggested the formation of a heterodimer between ERAP2 and the homologous enzyme ERAP1. Formation of leucine zipper-fused heterodimers of ERAP1 and ERAP2 produces mature epitopes more efficiently than a dilute mixture of the two enzymes. The interaction of ERAP2 with ERAP1 changes basic enzymatic parameters of the latter and improves its substrate-binding affinity.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> A possible dimerization between ERAP1/ERAP2 could be the basis for enhanced synergism between these two enzymes which helps define the human immunopeptidome.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Therapeutic_approaches_and_pharmacology">Therapeutic approaches and pharmacology</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=12" title="Edit section: Therapeutic approaches and pharmacology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Therapeutic approaches for ERAP2 regulation rely mostly on the development of small molecule inhibitors. The most explored classes of inhibitors for ERAP2 are the allosteric site ones. </p> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Figure_1._(A)_Crystal_structure_of_ERAP2_co-crystallized_with_hydroxamic_acid_triazole_in_the_active_site._Adapted_and_recreated_from_PDB_code_7NSK29._(B)_2D_chemical_structure_of_co-crystallized_compound..png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/d/de/Figure_1._%28A%29_Crystal_structure_of_ERAP2_co-crystallized_with_hydroxamic_acid_triazole_in_the_active_site._Adapted_and_recreated_from_PDB_code_7NSK29._%28B%29_2D_chemical_structure_of_co-crystallized_compound..png/487px-thumbnail.png" decoding="async" width="487" height="224" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/de/Figure_1._%28A%29_Crystal_structure_of_ERAP2_co-crystallized_with_hydroxamic_acid_triazole_in_the_active_site._Adapted_and_recreated_from_PDB_code_7NSK29._%28B%29_2D_chemical_structure_of_co-crystallized_compound..png/731px-thumbnail.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/de/Figure_1._%28A%29_Crystal_structure_of_ERAP2_co-crystallized_with_hydroxamic_acid_triazole_in_the_active_site._Adapted_and_recreated_from_PDB_code_7NSK29._%28B%29_2D_chemical_structure_of_co-crystallized_compound..png/974px-thumbnail.png 2x" data-file-width="1626" data-file-height="748" /></a><figcaption><b>Figure 1. A.</b> Crystal structure of ERAP2 co-crystallized with hydroxamic acid triazole in the active site. Adapted and recreated from PDB code 7NSK.<sup id="cite_ref-Camberlein_2022_30-0" class="reference"><a href="#cite_note-Camberlein_2022-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> <b>B.</b> 2D chemical structure of co-crystallized compound.</figcaption></figure> <div class="mw-heading mw-heading3"><h3 id="ERAP2_catalytic_site_inhibitors">ERAP2 catalytic site inhibitors</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=13" title="Edit section: ERAP2 catalytic site inhibitors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li>Phosphinic derivatives</li></ul> <p>Although most of the phosphinic pseudopeptide analogs disclosed by Kokkala <i>et al.</i> in 2016 were non-selective ERAP inhibitors, compound 1 displayed nanomolar potency towards ERAP2 (IC<sub>50</sub> = 129 nM) with a highly improved selectivity against ERAP1, and was active in modulating the immunopeptidome of cancer cells.<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> </p> <ul><li>Hydroxamic acid triazoles</li></ul> <p>In 2022, the first nanomolar selective ERAP2 inhibitors were discovered by kinetic-target guided synthesis (KTGS). A central core structure of hydroxamic acid triazoles targets the zinc ion in the catalytic site. Further investigations to optimize the activity led to nanomolar inhibitor BDM88952 (IC<sub>50</sub> = 3.9 nM) with the relative protein-ligand interactions studied by ERAP2 X-ray co-crystallography (Figure 1).<sup id="cite_ref-Camberlein_2022_30-1" class="reference"><a href="#cite_note-Camberlein_2022-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> </p> <ul><li>Carboxylic acids</li></ul> <p>Two hits of carboxylic acid derivatives were identified via <a href="/wiki/High-throughput_screening" title="High-throughput screening">high-throughput screening</a> (HTS) against ERAP2, from an in-house library of 1920 compounds. Compound 3 was amongst those selected for their potency (ERAP2, IC<sub>50</sub> = 22 nM) and selectivity. Docking studies revealed that the carboxylic acid is predicted to coordinate the catalytic zinc ion within ERAP2. Several analogues were designed and synthesized.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="ERAP2_allosteric_site_inhibitors">ERAP2 allosteric site inhibitors</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=14" title="Edit section: ERAP2 allosteric site inhibitors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li>Sulfonamides</li></ul> <p>Sulfonamide compound <b>4</b> was identified as a potential allosteric inhibitor against ERAP2 in 2022 by Arya <i>et al.</i>.<sup id="cite_ref-Arya_2022_34-0" class="reference"><a href="#cite_note-Arya_2022-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> This compound targets ERAP2 through an uncompetitive manner (IC<sub>50</sub> = 44 μM) by inhibiting the hydrolysis of peptide substrates. At the same time it acts as a competitive inhibitor against ERAP1 (IC<sub>50</sub> = 73 μM).<sup id="cite_ref-Arya_2022_34-1" class="reference"><a href="#cite_note-Arya_2022-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p> <figure class="mw-halign-center" typeof="mw:File/Thumb"><a href="/wiki/File:Table1Representative_examples_of_reported_ERAP2_inhibitors..png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/8/8c/Table1Representative_examples_of_reported_ERAP2_inhibitors..png/758px-Table1Representative_examples_of_reported_ERAP2_inhibitors..png" decoding="async" width="758" height="517" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/8/8c/Table1Representative_examples_of_reported_ERAP2_inhibitors..png/1137px-Table1Representative_examples_of_reported_ERAP2_inhibitors..png 1.5x, //upload.wikimedia.org/wikipedia/commons/8/8c/Table1Representative_examples_of_reported_ERAP2_inhibitors..png 2x" data-file-width="1328" data-file-height="906" /></a><figcaption><b>Table 1.</b> Representative examples of reported ERAP2 inhibitors. *IC<sub>50</sub> value measured on long-peptide assay.</figcaption></figure><div style="clear:both;" class=""></div> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=ERAP2&action=edit&section=15" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output 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