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Gene Review

ERAP1  -  endoplasmic reticulum aminopeptidase 1

Homo sapiens

Synonyms: A-LAP, ALAP, APPILS, ARTS-1, ARTS1, ...
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Disease relevance of ARTS-1


Psychiatry related information on ARTS-1

  • In September 2001, the author was invited by Dr. Wendy Makin (Macmillan Consultant in Palliative Care) and Andrea Sarginson (Volunteer Arts Worker) to introduce art therapy to the Christie Hospital as part of a postgraduate training course at the University of Sheffield [5].
  • After the war, interest in Reflexology and Pavlov's theories slowly rose again, first through psychosomatic medicine and then in the 60's because of the works of such authors as Monserrat-Esteve, Rof Carballo and Colodrón. The progressive inclusion of psychology in the Schools of Philosophy and Arts after 1968 marked the beginning of a new era [6].

High impact information on ARTS-1

  • ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum [7].
  • Here we identify ERAAP, the aminopeptidase associated with antigen processing in the ER [7].
  • Reducing the expression of ERAAP through RNA interference prevents the trimming of peptides for MHC class I molecules in the ER and greatly reduces the expression of MHC class I molecules on the cell surface [7].
  • Furthermore, ERAAP-deficient cells presented many unstable and structurally unique peptide-MHC complexes, which elicited potent CD8(+) T cell and B cell responses [8].
  • We show here that one of these, ERAP1, was unable to remove several N-terminal amino acids that were trimmed efficiently by the second enzyme, ERAP2 [9].

Chemical compound and disease context of ARTS-1


Biological context of ARTS-1


Anatomical context of ARTS-1


Associations of ARTS-1 with chemical compounds

  • ARTS-1 expression also enhances ionomycin-induced IL-1RII shedding [17].
  • ERAP1 is inhibited by agents that block precursor trimming in ER vesicles and although it trimmed NH2-extended precursors, it spared presented peptides of 8 amino acid and less [18].
  • Enzymatically, P-LAP degrades oxytocin, vasopressin, and angiotensin III, while A-LAP degrades angiotensin II and kallidin [1].
  • Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure [2].
  • Exploratory analysis of global power (sites F3, Fz, F4, C3, Cz, C4, P3, Pz, and P4) revealed that ERAP increased during SH from time 1 to time 3 at all sites except Fz and Pz, whereas only one site (C4) revealed an increase during BL [19].

Physical interactions of ARTS-1

  • We propose that formation of a TNFR1-ARTS-1 molecular complex represents a novel mechanism by which TNFR1 shedding is regulated [16].

Regulatory relationships of ARTS-1

  • These data indicate that ARTS-1 is a multifunctional ectoprotein capable of binding to and promoting TNFR1 shedding [16].
  • We conclude that the ability of ARTS-1 to enhance IL-1RII shedding represents a new mechanism by which IL-1-induced cellular events can be modulated [17].
  • Overexpression of A-LAP attenuated Ang II-induced VEGF expression in HEC-1A cells [4].
  • This study provides the first evidence showing that ERAP1 is localized in the ER of trophoblasts and is involved in regulating cell surface HLA-G expression in the presence of LIF [20].

Other interactions of ARTS-1


Analytical, diagnostic and therapeutic context of ARTS-1

  • Reciprocal co-immunoprecipitation experiments identified that membrane-associated ARTS-1 directly binds to a 55-kDa IL-6Ralpha, a size consistent with soluble IL-6Ralpha generated by ectodomain cleavage of the membrane-bound receptor [21].
  • Northern blot analysis revealed that A-LAP was expressed in all the tissues tested, some of which expressed at least three forms of mRNA, suggesting that the regulation of the gene expression is complex [15].
  • Immunohistochemistry showed strong ERAP1 expression in cultured EVTs [20].
  • Flow cytometry with HLA-G antibody to monitor the supply of antigenic peptides presenting to HLA-G in the ER showed that reducing ERAP1 transcripts by RNA interference did not affect cell surface expression of membrane HLA-G1 (mHLA-G1) in JEG-3 cells under basal conditions [20].
  • In this study, the role of Lys528 in the enzymatic activity of human A-LAP was examined by site-directed mutagenesis [22].


  1. Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells. Ino, K., Kikkawa, F., Suzuki, T., Kajiyama, H., Shibata, K., Nomura, S., Itakura, A., Ito, M., Nagasaka, T., Hattori, A., Tsujimoto, M., Mizutani, S. Lab. Invest. (2003) [Pubmed]
  2. Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension. Yamamoto, N., Nakayama, J., Yamakawa-Kobayashi, K., Hamaguchi, H., Miyazaki, R., Arinami, T. Hum. Mutat. (2002) [Pubmed]
  3. The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. Firat, E., Saveanu, L., Aichele, P., Staeheli, P., Huai, J., Gaedicke, S., Nil, A., Besin, G., Kanzler, B., van Endert, P., Niedermann, G. J. Immunol. (2007) [Pubmed]
  4. Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system. Watanabe, Y., Shibata, K., Kikkawa, F., Kajiyama, H., Ino, K., Hattori, A., Tsujimoto, M., Mizutani, S. Clin. Cancer Res. (2003) [Pubmed]
  5. Introducing art therapy into the Christie Hospital, Manchester, UK, 2001-2002. Heywood, K. Complementary therapies in nursing & midwifery. (2003) [Pubmed]
  6. Pavlov in Spain. Bandrés, J., Llavona, R. The Spanish journal of psychology. (2003) [Pubmed]
  7. ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Serwold, T., Gonzalez, F., Kim, J., Jacob, R., Shastri, N. Nature (2002) [Pubmed]
  8. In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Hammer, G.E., Gonzalez, F., James, E., Nolla, H., Shastri, N. Nat. Immunol. (2007) [Pubmed]
  9. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Saveanu, L., Carroll, O., Lindo, V., Del Val, M., Lopez, D., Lepelletier, Y., Greer, F., Schomburg, L., Fruci, D., Niedermann, G., van Endert, P.M. Nat. Immunol. (2005) [Pubmed]
  10. Possible involvement of adipocyte-derived leucine aminopeptidase via angiotensin II in endometrial carcinoma. Shibata, K., Kikkawa, F., Mizokami, Y., Kajiyama, H., Ino, K., Nomura, S., Mizutani, S. Tumour Biol. (2005) [Pubmed]
  11. Who was...Almroth Wright? Diggins, F. Biologist (London, England) (2002) [Pubmed]
  12. Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy. Hallberg, P., Lind, L., Michaëlsson, K., Kurland, L., Kahan, T., Malmqvist, K., Ohman, K.P., Nyström, F., Liljedahl, U., Syvänen, A.C., Melhus, H. BMC cardiovascular disorders [electronic resource]. (2003) [Pubmed]
  13. Extracellular TNFR1 release requires the calcium-dependent formation of a nucleobindin 2-ARTS-1 complex. Islam, A., Adamik, B., Hawari, F.I., Ma, G., Rouhani, F.N., Zhang, J., Levine, S.J. J. Biol. Chem. (2006) [Pubmed]
  14. Distribution of adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase (ERAP)-1 in human uterine endometrium. Shibata, D., Ando, H., Iwase, A., Nagasaka, T., Hattori, A., Tsujimoto, M., Mizutani, S. J. Histochem. Cytochem. (2004) [Pubmed]
  15. Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase. Hattori, A., Matsumoto, H., Mizutani, S., Tsujimoto, M. J. Biochem. (1999) [Pubmed]
  16. Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. Cui, X., Hawari, F., Alsaaty, S., Lawrence, M., Combs, C.A., Geng, W., Rouhani, F.N., Miskinis, D., Levine, S.J. J. Clin. Invest. (2002) [Pubmed]
  17. Shedding of the type II IL-1 decoy receptor requires a multifunctional aminopeptidase, aminopeptidase regulator of TNF receptor type 1 shedding. Cui, X., Rouhani, F.N., Hawari, F., Levine, S.J. J. Immunol. (2003) [Pubmed]
  18. An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Saric, T., Chang, S.C., Hattori, A., York, I.A., Markant, S., Rock, K.L., Tsujimoto, M., Goldberg, A.L. Nat. Immunol. (2002) [Pubmed]
  19. Cerebral cortical adaptations associated with visuomotor practice. Kerick, S.E., Douglass, L.W., Hatfield, B.D. Medicine and science in sports and exercise. (2004) [Pubmed]
  20. Endoplasmic reticulum aminopeptidase-1 mediates leukemia inhibitory factor-induced cell surface human leukocyte antigen-G expression in JEG-3 choriocarcinoma cells. Shido, F., Ito, T., Nomura, S., Yamamoto, E., Sumigama, S., Ino, K., Itakura, A., Hattori, A., Tsujimoto, M., Mizutani, S., Kikkawa, F. Endocrinology (2006) [Pubmed]
  21. An aminopeptidase, ARTS-1, is required for interleukin-6 receptor shedding. Cui, X., Rouhani, F.N., Hawari, F., Levine, S.J. J. Biol. Chem. (2003) [Pubmed]
  22. Reduced activity of the hypertension-associated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-1. Goto, Y., Hattori, A., Ishii, Y., Tsujimoto, M. FEBS Lett. (2006) [Pubmed]
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