The ERAP1 gene (also known as ERAAP and ARTS1) 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, endoplasmic reticulum aminopeptidase 1 cleaves several 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.
Health Conditions Related to Genetic Changes
Several variations (polymorphisms) in the ERAP1 gene have been found to influence the risk of ankylosing spondylitis. Each of these variations changes a single protein building block (amino acid) in endoplasmic reticulum aminopeptidase 1. Little is known about the effects of these variations, although researchers believe that changes in the protein's structure could alter either of its two major functions. It is unclear how these changes contribute to a person's risk of ankylosing spondylitis. Other genetic and environmental factors, many of which are unknown, also affect the chance of developing this condition.More About This Health Condition
Other Names for This Gene
- adipocyte-derived leucine aminopeptidase
- aminopeptidase PILS
- aminopeptidase regulator of TNFR1 shedding
- 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
- Brionez TF, Reveille JD. The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis. Curr Opin Rheumatol. 2008 Jul;20(4):384-91. doi: 10.1097/BOR.0b013e32830460fe. Review. Citation on PubMed
- Brown MA. Breakthroughs in genetic studies of ankylosing spondylitis. Rheumatology (Oxford). 2008 Feb;47(2):132-7. Epub 2007 Nov 22. Review. 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. Epub 2005 Nov 14. Citation on PubMed or Free article on PubMed Central
- Hammer GE, Gonzalez F, Champsaur M, Cado D, Shastri N. The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules. Nat Immunol. 2006 Jan;7(1):103-12. Epub 2005 Nov 20. Citation on PubMed
- Saric T, Chang SC, Hattori A, York IA, Markant S, Rock KL, Tsujimoto M, Goldberg AL. An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Nat Immunol. 2002 Dec;3(12):1169-76. Epub 2002 Nov 18. Citation on PubMed
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- 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. Epub 2006 Jun 5. Citation on PubMed or Free article on PubMed Central
- York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, Rock KL. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nat Immunol. 2002 Dec;3(12):1177-84. Epub 2002 Nov 18. Citation on PubMed