N-methylated ERAP1substrate – Growth Factors and Cytokines

Non-hydrolysable ERAP1 substrate. An optimized ERAP1 substrate with N-methylation of the first amide bond to prevent its degradation by ERAP1. Endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) are ER-resident, interferon-γ inducible, metalloaminopeptidase which critically shape the major histocompatibility complex I (MHC I) immunopeptidome. The ERAPs remove N-terminal residues from antigenic precursor peptides and generate optimal-length peptides (i.e. 8-10-mers) to fit into the MHC class I groove. The immune recognition of surface MHC I/peptide complexes initiates activation of CD8+ T cells as a critical step in the elimination of pathogens. ERAP1 has unique substrate preferences, trimming long peptides while sparing shorter ones as well as sequence preferences. ERAP1 and ERAP2 can form a heterodimer (ERAP1/ERAP2) with distinct functional properties. Allelic variants of ERAP1 have been linked to a number of human diseases, including the autoimmune disease ankylosing spondylitis (AS), diabetes, some forms of cervical cancer, and hypertension.