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Normal Function
The ERAP1 gene provides instructions for making a protein called endoplasmic reticulum aminopeptidase 1. As its name suggests, this protein is active in a cellular structure called the endoplasmic reticulum, which is involved in protein processing and transport. This protein is an aminopeptidase, which is an enzyme that cuts (cleaves) other proteins into smaller fragments called peptides.
Endoplasmic reticulum aminopeptidase 1 has two major functions, both of which are important for normal immune system function. First, the protein cleaves several other proteins called cytokine receptors on the surface of cells. Cleaving these receptors reduces their ability to transmit chemical signals into the cell, which affects the process of inflammation.
Second, endoplasmic reticulum aminopeptidase 1 cleaves many types of proteins into small peptides that can be recognized by the immune system. These peptides are exported to the cell surface, where they attach to major histocompatibility complex (MHC) class I proteins. MHC class I proteins display the peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.
While the protein is involved in the normal functioning of the immune system, it plays a particular role in protecting the body against the development of autoimmune disorders and cancer.
Health Conditions Related to Genetic Changes
Ankylosing spondylitis
Variations (polymorphisms) in the ERAP1 gene have been found to influence the risk of ankylosing spondylitis. This condition is a form of painful, ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine. Each of the ERAP1 gene variants changes a single protein building block (amino acid) in endoplasmic reticulum aminopeptidase 1. Individuals with an ERAP1 polymorphism who go on to develop ankylosing spondylitis tend to also have a variant in the HLA-B gene (specifically, the HLA-B27 variant).
Researchers believe that changes in the structure of endoplasmic reticulum aminopeptidase 1 could alter either of its two major functions. Other genetic and environmental factors, many of which are unknown, also affect the chance of developing ankylosing spondylitis.
More About This Health ConditionOther Names for This Gene
- A-LAP
- adipocyte-derived leucine aminopeptidase
- ALAP
- aminopeptidase PILS
- aminopeptidase regulator of TNFR1 shedding
- APPILS
- ARTS-1
- ARTS1
- ERAAP
- ERAAP1
- ERAP1_HUMAN
- KIAA0525
- PILS-AP
- PILSAP
- puromycin-insensitive leucyl-specific aminopeptidase
- type 1 tumor necrosis factor receptor shedding aminopeptidase regulator
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis--insights into pathogenesis. Nat Rev Rheumatol. 2016 Feb;12(2):81-91. doi: 10.1038/nrrheum.2015.133. Epub 2015 Oct 6. Citation on PubMed
- Chang SC, Momburg F, Bhutani N, Goldberg AL. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17107-12. doi: 10.1073/pnas.0500721102. Epub 2005 Nov 14. Citation on PubMed or Free article on PubMed Central
- Hanson AL, Cuddihy T, Haynes K, Loo D, Morton CJ, Oppermann U, Leo P, Thomas GP, Le Cao KA, Kenna TJ, Brown MA. Genetic Variants in ERAP1 and ERAP2 Associated With Immune-Mediated Diseases Influence Protein Expression and the Isoform Profile. Arthritis Rheumatol. 2018 Feb;70(2):255-265. doi: 10.1002/art.40369. Epub 2017 Dec 29. Citation on PubMed
- Haroon N, Tsui FW, Uchanska-Ziegler B, Ziegler A, Inman RD. Endoplasmic reticulum aminopeptidase 1 (ERAP1) exhibits functionally significant interaction with HLA-B27 and relates to subtype specificity in ankylosing spondylitis. Ann Rheum Dis. 2012 Apr;71(4):589-95. doi: 10.1136/annrheumdis-2011-200347. Epub 2012 Feb 21. Erratum In: Ann Rheum Dis. 2012 Jul;71(7):1264. Citation on PubMed
- Roberts AR, Appleton LH, Cortes A, Vecellio M, Lau J, Watts L, Brown MA, Wordsworth P. ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations. Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):558-561. doi: 10.1073/pnas.1618856114. Epub 2017 Jan 3. Citation on PubMed
- Saulle I, Vicentini C, Clerici M, Biasin M. An Overview on ERAP Roles in Infectious Diseases. Cells. 2020 Mar 14;9(3):720. doi: 10.3390/cells9030720. Citation on PubMed
- Vitulano C, Tedeschi V, Paladini F, Sorrentino R, Fiorillo MT. The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis. Clin Exp Immunol. 2017 Dec;190(3):281-290. doi: 10.1111/cei.13020. Epub 2017 Aug 30. Citation on PubMed
- Yao Y, Liu N, Zhou Z, Shi L. Influence of ERAP1 and ERAP2 gene polymorphisms on disease susceptibility in different populations. Hum Immunol. 2019 May;80(5):325-334. doi: 10.1016/j.humimm.2019.02.011. Epub 2019 Feb 21. Citation on PubMed
- York IA, Brehm MA, Zendzian S, Towne CF, Rock KL. Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9202-7. doi: 10.1073/pnas.0603095103. Epub 2006 Jun 5. Citation on PubMed or Free article on PubMed Central
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