Endoplasmic reticulum aminopeptidase 1
Also known as: APPILS, ARTS1, ERAP1, KIAA0525
Function
Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney.
Classification
- Family (Pfam)
- PF11838 ERAP1_C, PF01433 Peptidase_M1, PF17900 Peptidase_M1_N
- InterPro
- Aminopeptidase_N-like_N, Aminopeptidase_N-like_N_sf, ERAP1-like_C_dom, M1_APN-typ, Peptidase_M1, Peptidase_M1_aminopeptidases, Peptidase_M1_dom, Peptidase_M4/M1_CTD_sf
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 18
- 2YD0 X-ray 2.70A
- 3MDJ X-ray 2.95A
- 3QNF X-ray 3.00A
- 3RJO X-ray 2.30A
- 5J5E X-ray 2.80A
- 6M8P X-ray 3.31A
- 6MGQ X-ray 2.92A
- 6Q4R X-ray 1.60A
- 6RQX X-ray 1.68A
- 6RYF X-ray 1.72A
- 6T6R X-ray 1.67A
- 7MWB X-ray 3.20A
- … and 6 more
A predicted model is available from AlphaFold.
Gene Ontology · 26
- GO:0005829 cytosol
- GO:0005783 endoplasmic reticulum
- GO:0005788 endoplasmic reticulum lumen
- GO:0005789 endoplasmic reticulum membrane
- GO:0070062 extracellular exosome
- GO:0005576 extracellular region
- GO:0005615 extracellular space
- GO:0016020 membrane
- GO:0004177 aminopeptidase activity
- GO:0004175 endopeptidase activity
- GO:0005151 interleukin-1, type II receptor binding
- GO:0005138 interleukin-6 receptor binding
- GO:0070006 metalloaminopeptidase activity
- GO:0008235 metalloexopeptidase activity
- GO:0008270 zinc ion binding
- GO:0002250 adaptive immune response
- GO:0001525 angiogenesis
- GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I
- GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
- GO:0045444 fat cell differentiation
- GO:0006509 membrane protein ectodomain proteolysis
- GO:0043171 peptide catabolic process
- GO:0006508 proteolysis
- GO:0008217 regulation of blood pressure
- GO:0045088 regulation of innate immune response
- GO:0009617 response to bacterium
Drugs targeting this protein · 1
- TOSEDOSTAT inhibitor
Related proteins · sequence + function similarity
- Endoplasmic reticulum aminopeptidase 1 0.97
- Endoplasmic reticulum aminopeptidase 1 0.97
- Endoplasmic reticulum aminopeptidase 2 0.95
- Endoplasmic reticulum aminopeptidase 2 0.95
- Endoplasmic reticulum aminopeptidase 2 0.94
- Leucyl-cystinyl aminopeptidase 0.92
- Leucyl-cystinyl aminopeptidase 0.92
- Leucyl-cystinyl aminopeptidase 0.91
- Glutamyl aminopeptidase 0.91
- Glutamyl aminopeptidase 0.89
- Glutamyl aminopeptidase 0.89
- Glutamyl aminopeptidase 0.88
Co-cited proteins · studied together in the literature
- Endoplasmic reticulum aminopeptidase 2 2 shared papers
- RNA-binding motif protein, X chromosome 1 shared papers
Literature · 14 cited papers
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat. Struct. Mol. Biol. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J. Proteome Res. · 2009
- An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release. Biochem. Biophys. Res. Commun. · 2008
- 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
- Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat. Immunol. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. · 2003
- Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. · 2002
- Genomic organization of the human adipocyte-derived leucine aminopeptidase gene and its relationship to the placental leucine aminopeptidase/oxytocinase gene. J. Biochem. · 2001
- Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells. J. Biochem. · 2000
- … and 2 more in the literature graph