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http://purl.uniprot.org/citations/28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28446606http://www.w3.org/2000/01/rdf-schema#comment"A low-activity variant of endoplasmic reticulum aminopeptidase 1 (ERAP1), Hap10, is associated with the autoinflammatory disorder Behçet's disease (BD) in epistasis with HLA-B*51, which is the main risk factor for this disorder. The role of Hap10 in BD pathogenesis is unknown. We sought to define the effects of Hap10 on the HLA-B*51 peptidome and to distinguish these effects from those due to HLA-B*51 polymorphisms unrelated to disease. The peptidome of the BD-associated HLA-B*51:08 subtype expressed in a Hap10-positive cell line was isolated, characterized by mass spectrometry, and compared with the HLA-B*51:01 peptidome from cells expressing more active ERAP1 allotypes. We additionally performed synthetic peptide digestions with recombinant ERAP1 variants and estimated peptide-binding affinity with standard algorithms. In the BD-associated ERAP1 context of B*51:08, longer peptides were generated; of the two major HLA-B*51 subpeptidomes with Pro-2 and Ala-2, the former one was significantly reduced, and the latter was increased and showed more ERAP1-susceptible N-terminal residues. These effects were readily explained by the low activity of Hap10 and the differential susceptibility of X-Pro and X-Ala bonds to ERAP1 trimming and together resulted in a significantly altered peptidome with lower affinity. The differences due to ERAP1 were clearly distinguished from those due to HLA-B*51 subtype polymorphism, which affected residue frequencies at internal positions of the peptide ligands. The alterations in the nature and affinity of HLA-B*51·peptide complexes probably affect T-cell and natural killer cell recognition, providing a sound basis for the joint association of ERAP1 and HLA-B*51 with BD."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m117.789180"xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Admon A."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Gonzalez-Escribano M.F."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Jimenez-Reinoso A."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Regueiro J.R."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Lopez de Castro J.A."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Barnea E."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/author"Guasp P."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/pages"9680-9689"xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/title"The Behcet's disease-associated variant of the aminopeptidase ERAP1 shapes a low-affinity HLA-B*51 peptidome by differential subpeptidome processing."xsd:string
http://purl.uniprot.org/citations/28446606http://purl.uniprot.org/core/volume"292"xsd:string
http://purl.uniprot.org/citations/28446606http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28446606
http://purl.uniprot.org/citations/28446606http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/28446606
http://purl.uniprot.org/uniprot/#_A0A0A7C552-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A0E3DC98-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A0E3DCA0-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A0E3DCA1-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A068B107-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A068B112-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A068B116-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606
http://purl.uniprot.org/uniprot/#_A0A068B2J5-mappedCitation-28446606http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28446606