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    ERAP1 Gene

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    Submitted by: Vivi Li
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    Endoplasmic reticulum aminopeptidase 1

    1. Normal Function

    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.

    2. Health Conditions Related to Genetic Changes

    2.1 Ankylosing Spondylitis

    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.

    3. Other 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

    The entry is from https://medlineplus.gov/genetics/gene/erap1

    References

    1. Brionez TF, Reveille JD. The contribution of genes outside the majorhistocompatibility complex to susceptibility to ankylosing spondylitis. Curr OpinRheumatol. 2008 Jul;20(4):384-91. doi: 10.1097/BOR.0b013e32830460fe. Review.
    2. Brown MA. Breakthroughs in genetic studies of ankylosing spondylitis.Rheumatology (Oxford). 2008 Feb;47(2):132-7.
    3. 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.
    4. Hammer GE, Gonzalez F, Champsaur M, Cado D, Shastri N. The aminopeptidaseERAAP shapes the peptide repertoire displayed by major histocompatibility complexclass I molecules. Nat Immunol. 2006 Jan;7(1):103-12.
    5. 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, trimsprecursors to MHC class I-presented peptides. Nat Immunol. 2002Dec;3(12):1169-76.
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    7. York IA, Brehm MA, Zendzian S, Towne CF, Rock KL. Endoplasmic reticulumaminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and playsan important role in immunodominance. Proc Natl Acad Sci U S A. 2006 Jun13;103(24):9202-7.
    8. 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 epitopesto 8-9 residues. Nat Immunol. 2002 Dec;3(12):1177-84.
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