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.
Division of Rheumatology, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
Nigil
N
Haroon
Robert D
RD
Inman
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