Endoplasmic reticulum aminopeptidases: Biology and pathogenic potential.
Endoplasmic reticulum aminopeptidase 1 (ERAP1) and the closely related ERAP2 are involved in the final trimming of peptides within the endoplasmic reticulum for presentation by major histocompatibility complex (MHC) class I molecules. ERAP1 was found to be associated with ankylosing spondylitis (AS) in a genome-wide association study of nonsynonymous single nucleotide polymorphisms, and this association has been confirmed in several studies. An ERAP1/ERAP2 haplotype has also been reported to be associated with familial AS. ERAP1 and ERAP2 could carry out several potential roles in the pathogenesis of AS. ERAP1-deficient mice show a considerable alteration in the level and repertoire of peptides presented by MHC class I molecules. Furthermore, ERAP1 has been shown to be involved in shedding cytokine receptors. Both of these functions require further analysis to better understand the exact role of ERAP1 in AS.
Haroon
Nigil
N
Division of Rheumatology, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
Inman
Robert D
RD
D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000378:metabolism
D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human