2019
DOI: 10.1016/j.humimm.2018.11.002
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The genetics, structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease

Abstract: The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their funct… Show more

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Cited by 19 publications
(22 citation statements)
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“…38) Overall, we postulated that ERAP1 is primarily secreted into the extracellular milieu; however, can be retained in the ER-lumen in the presence of putative binding proteins. 6,11) Further, we depleted the exon 10 coding sequence, and observed that the mutant enzyme was no longer retained in the ER-lumen and was constitutively secreted into the culture medium; thereby, supporting our hypothesis. 13) It is plausible that saturation with putative binding protein resulted in free residual ERAP1 in the ER-lumen, which was then secreted into the extracellular milieu.…”
Section: Secretion Of Erap1supporting
confidence: 77%
See 1 more Smart Citation
“…38) Overall, we postulated that ERAP1 is primarily secreted into the extracellular milieu; however, can be retained in the ER-lumen in the presence of putative binding proteins. 6,11) Further, we depleted the exon 10 coding sequence, and observed that the mutant enzyme was no longer retained in the ER-lumen and was constitutively secreted into the culture medium; thereby, supporting our hypothesis. 13) It is plausible that saturation with putative binding protein resulted in free residual ERAP1 in the ER-lumen, which was then secreted into the extracellular milieu.…”
Section: Secretion Of Erap1supporting
confidence: 77%
“…4) It is now well recognized that ERAP1 is primarily an antigenic peptide-processing enzyme located in the lumen of endoplasmic reticulum (ER-lumen), and involved in several autoimmune and inflammatory diseases. [5][6][7][8] However, there are additional activities of ERAP1 that have not been well documented to date. Here, we summarize multiple functions of ERAP1 enzyme outside ER-lumen.…”
Section: Introductionmentioning
confidence: 99%
“…Given that ERAP1 and ERAP2 have similar contribution to the field and a high sequence homology (22) that allows them to function both as homodimers and heterodimers (2, 23), we decided to clarify the following questions regarding ERAP2: (1) can ERAP2 be secreted by immune-competent activated cells? (2) If this is the case, does secreted ERAP2 retain its anti-HIV-1 properties?…”
Section: Introductionmentioning
confidence: 99%
“…Beside the proteasome, ~20 proteases act in the MHC-I presentation pathway and can alter presented peptides (Lázaro et al, 2015). ERAP1 is probably the most relevant example here since this aminopeptidase plays a major role in antigen processing through N-terminal peptide trimming into the endoplasmic reticulum and is associated with a number of different autoimmune diseases (Hanson et al, 2018;Serwold et al, 2002). Other aminopeptidases such as methionine aminopeptidase 2 (METAP2), leucine aminopeptidase 3 (LAP3), peptidase D (PEPD) and dipeptidyl peptidase 4 (DPP4) were showcased in this study, the latter also known to be involved in TCR-MHC signaling (Ghersi et al, 2006;Wagner et al, 2016).…”
Section: Discussionmentioning
confidence: 99%