Exon 10 Coding Sequence Is Important for Endoplasmic Reticulum Retention of Endoplasmic Reticulum Aminopeptidase 1

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a final trimming enzyme of N-extended antigenic peptides bound to major histocompatibility complex class 1 molecules in the endoplasmic reticulum (ER). In our previous work, we found that ERAP1 is secreted from macrophages in response to activation by lipopolysaccharide and interferon-gamma. In this paper, we searched for the amino acid sequence of ERAP1 protein important for ER retention by constructing chimeric proteins and found that the sequence between 485 and 615 was significant. Moreover, by comparing the genomic organizations of oxytocinase subfamily members, the exon 10 coding sequence, which might be inserted into the common ancestral gene of the oxytocinase subfamily enzymes during evolution, was found to be important for ER retention of ERAP1. Taken together, our data indicate that ERAP1 contains amino acid sequence important for ER retention.