ARTS-1
Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as ARTS-1, is a protein which in humans is encoded by the ARTS-1 gene.[2]
ARTS1 is also known as:
- ER aminopeptidase 1 (ERAP1)
- ER aminopeptidase associated with antigen processing (ERAAP)
- Adipocyte-derived leucine aminopeptidase (ALAP)
- Puromycin-insensitive leucine aminopeptidase (PILS-AP)
Endoplasmic reticulum aminopeptidase 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 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.[3]
Function
ARTS-1 is a member of the M1 family of zinc metallopeptidases which acts as a 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.[2]
ARTS-1 is a transmembrane protein that is localized to the endoplasmic reticulum. It has been implicated in the following functions:
Clinical significance
Aminopeptidases play a role in the metabolism of several peptides that may be involved in blood pressure and the pathogenesis of essential hypertension.[2] Mutations in the ARTS-1 have been linked to an increased risk of ankylosing spondylitis.[4]
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.[2]
References
Further reading
- 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. PMID 12168954.
- Tsujimoto, M; Hattori, A (2005). "The oxytocinase subfamily of M1 aminopeptidases". Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics 1751: 9–18. doi:10.1016/j.bbapap.2004.09.011. PMID 16054015.
- Kazuo, M; Sumio, 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. PMID 8125298.
- 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. PMID 9373149.
- 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. PMID 9628581.
- 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. PMID 10220586.
- Hattori, A; Kitatani, K; Matsumoto, H; Miyazawa, S; Rogi, T; Tsuruoka, N; Mizutani, S; Natori, Y et al. (2000). "Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells". Journal of biochemistry 128 (5): 755–62. PMID 11056387.
- 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. PMID 11481040.
- Yamamoto, Nao; Nakayama, Junko; Yamakawa-Kobayashi, Kimiko; Hamaguchi, Hideo; Miyazaki, Ryunosuke; Arinami, Tadao (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. PMID 11857741.
- Cui, Xinle; Hawari, Feras; Alsaaty, Sura; Lawrence, Marion; Combs, Christian A.; Geng, Weidong; Rouhani, Farshid N.; Miskinis, Dianne et al. (2002). "Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding". Journal of Clinical Investigation 110 (4): 515–26. doi:10.1172/JCI13847. PMC 150410. PMID 12189246. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=150410.
- Serwold, Thomas; Gonzalez, Federico; Kim, Jennifer; Jacob, Richard; Shastri, Nilabh (2002). "ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum". Nature 419 (6906): 480–3. doi:10.1038/nature01074. PMID 12368856.
- Saric, Tomo; Chang, Shih-Chung; Hattori, Akira; York, Ian A.; Markant, Shirley; Rock, Kenneth L.; Tsujimoto, Masafumi; Goldberg, Alfred L. (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. PMID 12436109.
- York, Ian A.; Chang, Shih-Chung; Saric, Tomo; Keys, Jennifer A.; Favreau, Janice M.; Goldberg, Alfred L.; Rock, Kenneth L. (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. PMID 12436110.
- Mammalian Gene Collection Program Team* (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- 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. PMID 12748171.
- Clark, H. F.; Gurney, AL; Abaya, E; Baker, K; Baldwin, D; Brush, J; Chen, J; Chow, B et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Research 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=403697.
- Cui, Xinle; Rouhani, Farshid N.; Hawari, Feras; Levine, Stewart J. (2003). "Shedding of the Type II IL-1 Decoy Receptor Requires a Multifunctional Aminopeptidase, Aminopeptidase Regulator of TNF Receptor Type 1 Shedding". The Journal of Immunology 171 (12): 6814–9. PMID 14662887. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=14662887.
- 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. PMID 15314084.
- Gerhard, DS; Wagner, L; Feingold, EA; Shenmen, CM; Grouse, LH; Schuler, G; Klein, SL; Old, S et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Research 14 (10b): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.