ArticleFrontiers in immunology2020
The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Extracellular vesicles derived from induced pluripotent stem cells mediate anti-inflammatory effects in primary human macrophages.Scientific reports · 2026Article
- Rare and common variants in ERAP1 and ERAP2 selected for in response to Yersinia pestis infection contribute to autoimmune disease including inflammatory bowel disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Population-scale sequencing resolves correlates and determinants of latent Epstein-Barr Virus infection.bioRxiv : the preprint server for biology · 2025Article
- A systematic strategy for identifying causal single nucleotide polymorphisms and their target genes on Juvenile arthritis risk haplotypes.BMC medical genomics · 2024Article
- Exploring the Pathogenesis of Spondylarthritis beyond HLA-B27: A Descriptive Review.International journal of molecular sciences · 2024Review
- The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.Human genetics · 2024Article
- The Role of Aminopeptidase ERAP1 in Human Pathology-A Review.Current issues in molecular biology · 2024Review
- Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).Genes and immunity · 2023Review
- Review
- Article
- Mutation screening of AOPEP variants in a large dystonia cohort.Journal of neurology · 2023Article
- Discovery of Biomarkers for Amyotrophic Lateral Sclerosis from Human Cerebrospinal Fluid Using Mass-Spectrometry-Based Proteomics.Biomedicines · 2023Article
- Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease.Human molecular genetics · 2023Article
- Circular RNA Expression Signatures Provide Promising Diagnostic and Therapeutic Biomarkers for Chronic Lymphocytic Leukemia.Cancers · 2023Article
- Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates.Pharmacogenomics and personalized medicine · 2023Article
- Sex differences in the genetics of sarcoidosis across European and African ancestry populations.Frontiers in medicine · 2023Article
- Phenylsulfamoyl Benzoic Acid Inhibitor of ERAP2 with a Novel Mode of Inhibition.ACS chemical biology · 2022Article
- A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation.International journal of molecular sciences · 2022Article
- NK-cell dysfunction of acute myeloid leukemia in relation to the renin-angiotensin system and neurotransmitter genes.Open medicine (Warsaw, Poland) · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the human genome, the aminopeptidases ERAP1, ERAP2 and LNPEP lie contiguously on chromosome 5. They share sequence homology, functions and associations with immune-mediated diseases. By analyzing their multifaceted activities as well as their expression in the zoological scale, we suggest here that the progenitor of the three aminopeptidases might be LNPEP from which the other two aminopeptidases could have derived by gene duplications. We also propose that their functions are partially redundant. More precisely, the evolutionary story of the three aminopeptidases might have been dictated by their role in regulating the renin-angiotensin system, which requires their controlled and coordinated expression. This hypothesis is supported by the many species that lack one or the other gene as well as by the lack of ERAP2 in rodents and a null expression in 25% of humans. Finally, we speculate that their role in antigen presentation has been acquired later on during evolution. They have therefore been diversified between those residing in the ER, ERAP1 and ERAP2, whose role is to refine the MHC-I peptidomes, and LNPEP, mostly present in the endosomal vesicles where it can contribute to antigen cross-presentation or move to the cell membrane as receptor for angiotensin IV. Their association with autoinflammatory/autoimmune diseases can therefore be two-fold: as "contributors" to the shaping of the immune-peptidomes as well as to the regulation of the vascular response.
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