Genetic associations and functional characterization of M1 aminopeptidases and immune-mediated diseases

Endosplasmic reticulum aminopeptidase 1 ( ERAP1 ), endoplasmic reticulum aminopeptidase 2 ( ERAP2 ) and puromycin-sensitive aminopeptidase ( NPEPPS ) are key zinc metallopeptidases that belong to the oxytocinase subfamily of M1 aminopeptidase family. NPEPPS catalyzes the processing of proteosome-der...

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Bibliographic Details
Published inGenes and immunity Vol. 15; no. 8; pp. 521 - 527
Main Authors Agrawal, N, Brown, M A
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.12.2014
Nature Publishing Group
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Summary:Endosplasmic reticulum aminopeptidase 1 ( ERAP1 ), endoplasmic reticulum aminopeptidase 2 ( ERAP2 ) and puromycin-sensitive aminopeptidase ( NPEPPS ) are key zinc metallopeptidases that belong to the oxytocinase subfamily of M1 aminopeptidase family. NPEPPS catalyzes the processing of proteosome-derived peptide repertoire followed by trimming of antigenic peptides by ERAP1 and ERAP2 for presentation on major histocompatibility complex (MHC) Class I molecules. A series of genome-wide association studies have demonstrated associations of these aminopeptidases with a range of immune-mediated diseases such as ankylosing spondylitis, psoriasis, Behçet’s disease, inflammatory bowel disease and type I diabetes, and significantly, genetic interaction between some aminopeptidases and HLA Class I loci with which these diseases are strongly associated. In this review, we highlight the current state of understanding of the genetic associations of this class of genes, their functional role in disease, and potential as therapeutic targets.
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ISSN:1466-4879
1476-5470
DOI:10.1038/gene.2014.46