ID ERAP1_HUMAN Reviewed; 941 AA.
AC Q9NZ08; O60278; Q6UWY6; Q8NEL4; Q8TAD0; Q9UHF8; Q9UKY2;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 3.
DT 27-MAR-2024, entry version 208.
DE RecName: Full=Endoplasmic reticulum aminopeptidase 1;
DE EC=3.4.11.-;
DE AltName: Full=ARTS-1;
DE AltName: Full=Adipocyte-derived leucine aminopeptidase;
DE Short=A-LAP;
DE AltName: Full=Aminopeptidase PILS;
DE AltName: Full=Puromycin-insensitive leucyl-specific aminopeptidase;
DE Short=PILS-AP;
DE AltName: Full=Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator;
GN Name=ERAP1; Synonyms=APPILS, ARTS1, KIAA0525; ORFNames=UNQ584/PRO1154;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-127.
RC TISSUE=White adipose tissue;
RX PubMed=10220586; DOI=10.1093/oxfordjournals.jbchem.a022371;
RA Hattori A., Matsumoto H., Mizutani S., Tsujimoto M.;
RT "Molecular cloning of adipocyte-derived leucine aminopeptidase highly
RT related to placental leucine aminopeptidase/oxytocinase.";
RL J. Biochem. 125:931-938(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS PRO-127;
RP VAL-349; ARG-528; ASN-575; GLN-725 AND GLU-730.
RC TISSUE=Leukocyte;
RX PubMed=11481040; DOI=10.1093/oxfordjournals.jbchem.a002977;
RA Hattori A., Matsumoto K., Mizutani S., Tsujimoto M.;
RT "Genomic organization of the human adipocyte-derived leucine aminopeptidase
RT gene and its relationship to the placental leucine
RT aminopeptidase/oxytocinase gene.";
RL J. Biochem. 130:235-241(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASP-346; ARG-528 AND
RP GLU-730.
RA Schomburg L.;
RT "Molecular characterization of human aminopeptidase PILS.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Cui X., Alsaaty S., Lawrence M., Combs C.A., Rouhani F.N., Levine S.J.;
RT "Identification of an aminopeptidase regulator of type I tumor necrosis
RT factor receptor shedding.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS PRO-127;
RP VAL-349; ARG-528; ASN-575; GLN-725 AND GLU-730.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [6]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PRO-127;
RP VAL-349; ARG-528; ASN-575; GLN-725 AND GLU-730.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 37-49, AND CHARACTERIZATION.
RX PubMed=11056387; DOI=10.1093/oxfordjournals.jbchem.a022812;
RA Hattori A., Kitatani K., Matsumoto H., Miyazawa S., Rogi T., Tsuruoka N.,
RA Mizutani S., Natori Y., Tsujimoto M.;
RT "Characterization of recombinant human adipocyte-derived leucine
RT aminopeptidase expressed in Chinese hamster ovary cells.";
RL J. Biochem. 128:755-762(2000).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INDUCTION BY IFNG.
RX PubMed=15908954; DOI=10.1038/ni1208;
RA Saveanu L., Carroll O., Lindo V., Del Val M., Lopez D., Lepelletier Y.,
RA Greer F., Schomburg L., Fruci D., Niedermann G., van Endert P.M.;
RT "Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase
RT complexes in the endoplasmic reticulum.";
RL Nat. Immunol. 6:689-697(2005).
RN [11]
RP FUNCTION.
RX PubMed=16286653; DOI=10.1073/pnas.0500721102;
RA Chang S.-C., Momburg F., Bhutani N., Goldberg A.L.;
RT "The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I
RT peptides by a 'molecular ruler' mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17107-17112(2005).
RN [12]
RP INTERACTION WITH RBMX.
RX PubMed=18445477; DOI=10.1016/j.bbrc.2008.04.103;
RA Adamik B., Islam A., Rouhani F.N., Hawari F.I., Zhang J., Levine S.J.;
RT "An association between RBMX, a heterogeneous nuclear ribonucleoprotein,
RT and ARTS-1 regulates extracellular TNFR1 release.";
RL Biochem. Biophys. Res. Commun. 371:505-509(2008).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-414.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-940 IN COMPLEX WITH ZINC IONS,
RP DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-70; ASN-154 AND ASN-414.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the soluble domain of human endoplasmic reticulum
RT aminopeptidase 1 ERAP1.";
RL Submitted (MAY-2010) to the PDB data bank.
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 37-939 IN COMPLEX WITH ZINC IONS
RP AND BESTATIN, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-70; ASN-154
RP AND ASN-760, ACTIVE SITE, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF
RP TYR-438.
RX PubMed=21478864; DOI=10.1038/nsmb.2021;
RA Nguyen T.T., Chang S.C., Evnouchidou I., York I.A., Zikos C., Rock K.L.,
RA Goldberg A.L., Stratikos E., Stern L.J.;
RT "Structural basis for antigenic peptide precursor processing by the
RT endoplasmic reticulum aminopeptidase ERAP1.";
RL Nat. Struct. Mol. Biol. 18:604-613(2011).
CC -!- FUNCTION: Aminopeptidase that plays a central role in peptide trimming,
CC a step required for the generation of most HLA class I-binding
CC peptides. Peptide trimming is essential to customize longer precursor
CC peptides to fit them to the correct length required for presentation on
CC MHC class I molecules. Strongly prefers substrates 9-16 residues long.
CC Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially
CC hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus,
CC while it has weak activity toward peptides with charged C-terminus. May
CC play a role in the inactivation of peptide hormones. May be involved in
CC the regulation of blood pressure through the inactivation of
CC angiotensin II and/or the generation of bradykinin in the kidney.
CC {ECO:0000269|PubMed:15908954, ECO:0000269|PubMed:16286653,
CC ECO:0000269|PubMed:21478864}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- SUBUNIT: Monomer. May also exist as a heterodimer; with ERAP2.
CC Interacts with RBMX. {ECO:0000269|PubMed:15908954,
CC ECO:0000269|PubMed:18445477, ECO:0000269|PubMed:21478864,
CC ECO:0000269|Ref.16}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:15908954}; Single-pass type II membrane protein
CC {ECO:0000305|PubMed:15908954}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NZ08-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZ08-2; Sequence=VSP_005450;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: By IFNG/IFN-gamma. {ECO:0000269|PubMed:15908954}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:21478864, ECO:0000269|Ref.16}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-13 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25451.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF106037; AAF07395.1; -; mRNA.
DR EMBL; AY028806; AAK37777.1; -; mRNA.
DR EMBL; AY028807; AAK37778.1; -; mRNA.
DR EMBL; AF183569; AAF20384.1; -; mRNA.
DR EMBL; AF222340; AAF34664.1; -; mRNA.
DR EMBL; AB011097; BAA25451.2; ALT_INIT; mRNA.
DR EMBL; AY358590; AAQ88953.1; -; mRNA.
DR EMBL; BC030775; AAH30775.1; -; mRNA.
DR CCDS; CCDS4085.1; -. [Q9NZ08-2]
DR CCDS; CCDS47250.1; -. [Q9NZ08-1]
DR RefSeq; NP_001035548.1; NM_001040458.1. [Q9NZ08-1]
DR RefSeq; NP_001185470.1; NM_001198541.1. [Q9NZ08-1]
DR RefSeq; NP_057526.3; NM_016442.3. [Q9NZ08-2]
DR RefSeq; XP_011541788.1; XM_011543486.2. [Q9NZ08-1]
DR RefSeq; XP_016865071.1; XM_017009582.1.
DR PDB; 2YD0; X-ray; 2.70 A; A=46-940.
DR PDB; 3MDJ; X-ray; 2.95 A; A/B/C=37-939.
DR PDB; 3QNF; X-ray; 3.00 A; A/B/C=1-941.
DR PDB; 3RJO; X-ray; 2.30 A; A=529-941.
DR PDB; 5J5E; X-ray; 2.80 A; A=529-941.
DR PDB; 6M8P; X-ray; 3.31 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=33-485, A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=514-940.
DR PDB; 6MGQ; X-ray; 2.92 A; A/B/C=33-939.
DR PDB; 6Q4R; X-ray; 1.60 A; A=1-485, A=514-937.
DR PDB; 6RQX; X-ray; 1.68 A; A=1-938.
DR PDB; 6RYF; X-ray; 1.72 A; A=46-938.
DR PDB; 6T6R; X-ray; 1.67 A; A=1-941.
DR PDB; 7MWB; X-ray; 3.20 A; A/B/C/D=529-941.
DR PDB; 7MWC; X-ray; 3.00 A; A/B/C/D=529-941.
DR PDB; 7Z28; X-ray; 1.55 A; A=45-936.
DR PDBsum; 2YD0; -.
DR PDBsum; 3MDJ; -.
DR PDBsum; 3QNF; -.
DR PDBsum; 3RJO; -.
DR PDBsum; 5J5E; -.
DR PDBsum; 6M8P; -.
DR PDBsum; 6MGQ; -.
DR PDBsum; 6Q4R; -.
DR PDBsum; 6RQX; -.
DR PDBsum; 6RYF; -.
DR PDBsum; 6T6R; -.
DR PDBsum; 7MWB; -.
DR PDBsum; 7MWC; -.
DR PDBsum; 7Z28; -.
DR AlphaFoldDB; Q9NZ08; -.
DR SMR; Q9NZ08; -.
DR BioGRID; 119713; 83.
DR CORUM; Q9NZ08; -.
DR IntAct; Q9NZ08; 18.
DR MINT; Q9NZ08; -.
DR STRING; 9606.ENSP00000296754; -.
DR BindingDB; Q9NZ08; -.
DR ChEMBL; CHEMBL5939; -.
DR GuidetoPHARMACOLOGY; 1566; -.
DR MEROPS; M01.018; -.
DR GlyConnect; 1203; 2 N-Linked glycans (1 site).
DR GlyCosmos; Q9NZ08; 5 sites, 2 glycans.
DR GlyGen; Q9NZ08; 6 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9NZ08; -.
DR MetOSite; Q9NZ08; -.
DR PhosphoSitePlus; Q9NZ08; -.
DR SwissPalm; Q9NZ08; -.
DR BioMuta; ERAP1; -.
DR DMDM; 158937334; -.
DR EPD; Q9NZ08; -.
DR jPOST; Q9NZ08; -.
DR MassIVE; Q9NZ08; -.
DR MaxQB; Q9NZ08; -.
DR PaxDb; 9606-ENSP00000296754; -.
DR PeptideAtlas; Q9NZ08; -.
DR ProteomicsDB; 83312; -. [Q9NZ08-1]
DR ProteomicsDB; 83313; -. [Q9NZ08-2]
DR Pumba; Q9NZ08; -.
DR Antibodypedia; 25075; 436 antibodies from 36 providers.
DR DNASU; 51752; -.
DR Ensembl; ENST00000296754.7; ENSP00000296754.3; ENSG00000164307.13. [Q9NZ08-2]
DR Ensembl; ENST00000443439.7; ENSP00000406304.2; ENSG00000164307.13. [Q9NZ08-1]
DR GeneID; 51752; -.
DR KEGG; hsa:51752; -.
DR MANE-Select; ENST00000443439.7; ENSP00000406304.2; NM_001040458.3; NP_001035548.1.
DR UCSC; uc003kml.4; human. [Q9NZ08-1]
DR AGR; HGNC:18173; -.
DR CTD; 51752; -.
DR DisGeNET; 51752; -.
DR GeneCards; ERAP1; -.
DR HGNC; HGNC:18173; ERAP1.
DR HPA; ENSG00000164307; Low tissue specificity.
DR MalaCards; ERAP1; -.
DR MIM; 606832; gene.
DR neXtProt; NX_Q9NZ08; -.
DR OpenTargets; ENSG00000164307; -.
DR Orphanet; 117; Behcet disease.
DR PharmGKB; PA162385163; -.
DR VEuPathDB; HostDB:ENSG00000164307; -.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000159086; -.
DR HOGENOM; CLU_003705_2_1_1; -.
DR InParanoid; Q9NZ08; -.
DR OMA; MENWGVV; -.
DR OrthoDB; 3085317at2759; -.
DR PhylomeDB; Q9NZ08; -.
DR TreeFam; TF300395; -.
DR BRENDA; 3.4.11.1; 2681.
DR BRENDA; 3.4.11.22; 2681.
DR PathwayCommons; Q9NZ08; -.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; Q9NZ08; -.
DR SIGNOR; Q9NZ08; -.
DR BioGRID-ORCS; 51752; 17 hits in 1152 CRISPR screens.
DR ChiTaRS; ERAP1; human.
DR EvolutionaryTrace; Q9NZ08; -.
DR GeneWiki; ARTS-1; -.
DR GenomeRNAi; 51752; -.
DR Pharos; Q9NZ08; Tchem.
DR PRO; PR:Q9NZ08; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9NZ08; Protein.
DR Bgee; ENSG00000164307; Expressed in jejunal mucosa and 208 other cell types or tissues.
DR ExpressionAtlas; Q9NZ08; baseline and differential.
DR Genevisible; Q9NZ08; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:HGNC-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; EXP:Reactome.
DR GO; GO:0005151; F:interleukin-1, type II receptor binding; TAS:HGNC-UCL.
DR GO; GO:0005138; F:interleukin-6 receptor binding; IPI:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0008235; F:metalloexopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; TAS:HGNC-UCL.
DR GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; TAS:HGNC-UCL.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0045444; P:fat cell differentiation; NAS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; TAS:HGNC-UCL.
DR GO; GO:0045088; P:regulation of innate immune response; NAS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; NAS:BHF-UCL.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.25.50.20; -; 1.
DR Gene3D; 2.60.40.1910; -; 1.
DR Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1.
DR Gene3D; 2.60.40.1730; tricorn interacting facor f3 domain; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR034016; M1_APN-typ.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR PANTHER; PTHR11533:SF156; ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1; 1.
DR PANTHER; PTHR11533; PROTEASE M1 ZINC METALLOPROTEASE; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; Leukotriene A4 hydrolase N-terminal domain; 1.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Aminopeptidase;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Hydrolase; Immunity; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..941
FT /note="Endoplasmic reticulum aminopeptidase 1"
FT /id="PRO_0000026751"
FT TOPO_DOM 1
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2..21
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 22..941
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 183
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 317..321
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 357
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT SITE 438
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21478864, ECO:0000269|Ref.16"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21478864, ECO:0000269|Ref.16"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218, ECO:0000269|Ref.16"
FT CARBOHYD 760
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21478864"
FT CARBOHYD 901
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 404..443
FT DISULFID 736..743
FT VAR_SEQ 940..941
FT /note="RM -> HDPEADATG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11481040,
FT ECO:0000303|PubMed:9628581"
FT /id="VSP_005450"
FT VARIANT 56
FT /note="E -> K (in dbSNP:rs3734016)"
FT /id="VAR_046681"
FT VARIANT 127
FT /note="R -> P (in dbSNP:rs26653)"
FT /evidence="ECO:0000269|PubMed:10220586,
FT ECO:0000269|PubMed:11481040, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:9628581"
FT /id="VAR_012779"
FT VARIANT 276
FT /note="I -> M (in dbSNP:rs26618)"
FT /id="VAR_012780"
FT VARIANT 346
FT /note="G -> D (in dbSNP:rs27895)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_012781"
FT VARIANT 349
FT /note="M -> V (in dbSNP:rs2287987)"
FT /evidence="ECO:0000269|PubMed:11481040,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581"
FT /id="VAR_012782"
FT VARIANT 528
FT /note="K -> R (in dbSNP:rs30187)"
FT /evidence="ECO:0000269|PubMed:11481040,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581,
FT ECO:0000269|Ref.3"
FT /id="VAR_012783"
FT VARIANT 575
FT /note="D -> G (in dbSNP:rs6863093)"
FT /id="VAR_046682"
FT VARIANT 575
FT /note="D -> N (in dbSNP:rs10050860)"
FT /evidence="ECO:0000269|PubMed:11481040,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581"
FT /id="VAR_021555"
FT VARIANT 725
FT /note="R -> Q (in dbSNP:rs17482078)"
FT /evidence="ECO:0000269|PubMed:11481040,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581"
FT /id="VAR_021556"
FT VARIANT 730
FT /note="Q -> E (in dbSNP:rs27044)"
FT /evidence="ECO:0000269|PubMed:11481040,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581,
FT ECO:0000269|Ref.3"
FT /id="VAR_012784"
FT MUTAGEN 438
FT /note="Y->F: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:21478864"
FT CONFLICT 12
FT /note="T -> I (in Ref. 1; AAF07395 and 2; AAK37777/
FT AAK37778)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="G -> R (in Ref. 3; AAF20384)"
FT /evidence="ECO:0000305"
FT STRAND 56..70
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 75..88
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 101..114
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 145..154
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 156..168
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 174..181
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 201..209
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 221..228
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 273..278
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 280..297
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 303..313
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 329..332
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 341..356
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 364..368
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 369..372
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 373..390
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 396..400
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 401..411
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:6MGQ"
FT HELIX 426..431
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 435..452
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 454..467
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 468..470
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 475..482
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 518..525
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 529..538
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 541..549
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 565..571
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 574..582
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 584..590
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 598..601
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 602..604
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 609..612
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 613..615
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 616..627
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 633..648
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 650..652
FT /evidence="ECO:0007829|PDB:7MWC"
FT HELIX 654..661
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 662..666
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 670..687
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 688..691
FT /evidence="ECO:0007829|PDB:5J5E"
FT HELIX 693..713
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 716..718
FT /evidence="ECO:0007829|PDB:6Q4R"
FT HELIX 722..737
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 741..756
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 757..761
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 765..775
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 779..789
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 795..805
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 811..823
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 825..827
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 829..831
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 832..840
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 843..845
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 846..855
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 857..864
FT /evidence="ECO:0007829|PDB:7Z28"
FT STRAND 866..868
FT /evidence="ECO:0007829|PDB:5J5E"
FT HELIX 869..879
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 885..896
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 897..901
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 902..904
FT /evidence="ECO:0007829|PDB:7Z28"
FT HELIX 906..935
FT /evidence="ECO:0007829|PDB:7Z28"
FT TURN 936..939
FT /evidence="ECO:0007829|PDB:2YD0"
SQ SEQUENCE 941 AA; 107235 MW; 22A0795C90155F04 CRC64;
MVFLPLKWSL ATMSFLLSSL LALLTVSTPS WCQSTEASPK RSDGTPFPWN KIRLPEYVIP
VHYDLLIHAN LTTLTFWGTT KVEITASQPT STIILHSHHL QISRATLRKG AGERLSEEPL
QVLEHPRQEQ IALLAPEPLL VGLPYTVVIH YAGNLSETFH GFYKSTYRTK EGELRILAST
QFEPTAARMA FPCFDEPAFK ASFSIKIRRE PRHLAISNMP LVKSVTVAEG LIEDHFDVTV
KMSTYLVAFI ISDFESVSKI TKSGVKVSVY AVPDKINQAD YALDAAVTLL EFYEDYFSIP
YPLPKQDLAA IPDFQSGAME NWGLTTYRES ALLFDAEKSS ASSKLGITMT VAHELAHQWF
GNLVTMEWWN DLWLNEGFAK FMEFVSVSVT HPELKVGDYF FGKCFDAMEV DALNSSHPVS
TPVENPAQIR EMFDDVSYDK GACILNMLRE YLSADAFKSG IVQYLQKHSY KNTKNEDLWD
SMASICPTDG VKGMDGFCSR SQHSSSSSHW HQEGVDVKTM MNTWTLQKGF PLITITVRGR
NVHMKQEHYM KGSDGAPDTG YLWHVPLTFI TSKSDMVHRF LLKTKTDVLI LPEEVEWIKF
NVGMNGYYIV HYEDDGWDSL TGLLKGTHTA VSSNDRASLI NNAFQLVSIG KLSIEKALDL
SLYLKHETEI MPVFQGLNEL IPMYKLMEKR DMNEVETQFK AFLIRLLRDL IDKQTWTDEG
SVSERMLRSQ LLLLACVHNY QPCVQRAEGY FRKWKESNGN LSLPVDVTLA VFAVGAQSTE
GWDFLYSKYQ FSLSSTEKSQ IEFALCRTQN KEKLQWLLDE SFKGDKIKTQ EFPQILTLIG
RNPVGYPLAW QFLRKNWNKL VQKFELGSSS IAHMVMGTTN QFSTRTRLEE VKGFFSSLKE
NGSQLRCVQQ TIETIEENIG WMDKNFDKIR VWLQSEKLER M
//
