Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the ARTS-1gene.[1]
Endoplasmic reticulum amino peptidase 1 is active in the endoplasmic reticulum, which is involved in protein processing and transport. This protein is an aminopeptidase, which is an enzyme that cleaves other proteins into smaller fragments called peptides.
ERAP1 has two major functions in the immune system:
First, ERAP1 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, ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto major histocompatibility complex (MHC) class I. These peptides are attached to MHC class I in the endoplasmic reticulum and exported to the cell surface, where they are displayed 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.[3]
ARTS-1 is a member of the M1 family of zinc metallopeptidases which acts as an aminopeptidase that degrades oligopeptides by cleavage starting at the amino terminus. One of the functions of aminopeptidases is to degrade potentially toxic peptides in the cytosol.[1]
ARTS-1 is a transmembrane protein that is localized to the endoplasmic reticulum. It has been implicated in the following functions:
The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[1]
↑Brionez TF, Reveille JD (2008). "The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis". Current Opinion in Rheumatology. 20 (4): 384–91. doi:10.1097/BOR.0b013e32830460fe. PMID18525349.
Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (2002). "Construction of Expression-ready cDNA Clones for KIAA Genes: Manual Curation of 330 KIAA cDNA Clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID12168954.
Tsujimoto M, Hattori A (2005). "The oxytocinase subfamily of M1 aminopeptidases". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1751: 9–18. doi:10.1016/j.bbapap.2004.09.011. PMID16054015.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (1998). "Prediction of the Coding Sequences of Unidentified Human Genes. IX. The Complete Sequences of 100 New cDNA Clones from Brain Which Can Code for Large Proteins in vitro". DNA Research. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID9628581.
Hattori A, Matsumoto H, Mizutani S, Tsujimoto M (1999). "Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase". Journal of Biochemistry. 125 (5): 931–8. doi:10.1093/oxfordjournals.jbchem.a022371. PMID10220586.
Hattori A, Kitatani K, Matsumoto H, Miyazawa S, Rogi T, Tsuruoka N, Mizutani S, Natori Y, Tsujimoto M (2000). "Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells". Journal of Biochemistry. 128 (5): 755–62. doi:10.1093/oxfordjournals.jbchem.a022812. PMID11056387.
Hattori A, Matsumoto K, Mizutani S, Tsujimoto M (2001). "Genomic organization of the human adipocyte-derived leucine aminopeptidase gene and its relationship to the placental leucine aminopeptidase/oxytocinase gene". Journal of Biochemistry. 130 (2): 235–41. doi:10.1093/oxfordjournals.jbchem.a002977. PMID11481040.
Yamamoto N, Nakayama J, Yamakawa-Kobayashi K, Hamaguchi H, Miyazaki R, Arinami T (2002). "Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension". Human Mutation. 19 (3): 251–7. doi:10.1002/humu.10047. PMID11857741.
Serwold T, Gonzalez F, Kim J, Jacob R, Shastri N (2002). "ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum". Nature. 419 (6906): 480–3. doi:10.1038/nature01074. PMID12368856.
Saric T, Chang SC, Hattori A, York IA, Markant S, Rock KL, Tsujimoto M, Goldberg AL (2002). "An IFN-γ–induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I–presented peptides". Nature Immunology. 3 (12): 1169–76. doi:10.1038/ni859. PMID12436109.
York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, Rock KL (2002). "The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8–9 residues". Nature Immunology. 3 (12): 1177–84. doi:10.1038/ni860. PMID12436110.
Cui X, Rouhani FN, Hawari F, Levine SJ (2003). "An Aminopeptidase, ARTS-1, Is Required for Interleukin-6 Receptor Shedding". Journal of Biological Chemistry. 278 (31): 28677–85. doi:10.1074/jbc.M300456200. PMID12748171.
Shibata D, Ando H, Iwase A, Nagasaka T, Hattori A, Tsujimoto M, Mizutani S (2004). "Distribution of Adipocyte-derived Leucine Aminopeptidase (A-LAP)/ER-aminopeptidase (ERAP)-1 in Human Uterine Endometrium". Journal of Histochemistry and Cytochemistry. 52 (9): 1169–75. doi:10.1369/jhc.3A6216.2004. PMID15314084.