| Primary Identifier | IPR033520 | Type | Family |
| Short Name | ERAP1 |
| description | Endoplasmic reticulum aminopeptidase 1 (ERAP1 or PILS; MEROPS identifier M01.018) is an aminopeptidase with a preference to release Leu or Met from the N terminus of a peptide, but can hydrolyze Phe, Tyr, Ile or Cys bonds but poorly [, ]. The aminopeptidase is insensitive to inhibition by puromycin (which inhibits cytosol alanyl aminopeptidase and dipeptidyl-peptidases II and IV) and is also known as puromycin-insensitive leucyl-specific aminopeptidase or PILS-AP [, ]. In humans, ERAP1 associates with another aminopeptidase, ERAP2, in the endoplasmic reticulum and both participate in the processing of MHC-presented peptides []. Peptides generated by degradation of proteins by the proteasome bind to a transporter associated with antigen presentation (TAP) and are exported across the plasma membrane from the cytoplasm to the endoplasmic reticulum where they are trimmed by the ERAP aminopeptidases and cystinyl aminopeptidase to be 8-11 amino acids in length which then associate with the MHC complex and beta2-microglobulin []. ERAP1 is most active with peptides 9-16 residues long, but activity drops once a peptide optimal for antigen presentation is achieved. This molecular ruler effect is achieved by binding the C terminus of the substrate peptide close to the active site []. ERAP1 may also function in blood pressure regulation because it cleaves angiotensin II to the tripeptide His-Pro-Phe via angiotensin II and IV intermediates, and converts kallidin to bradykinin []. ERAP1 has been associated with several human diseases, including ankylosing spondylitis [], psoriasis [], type 1 diabetes []and osteoporsis []. |
