ID   ERAP1_MOUSE             Reviewed;         930 AA.
AC   Q9EQH2; Q6GTP5; Q9ET63;
DT   05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 179.
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=VEGF-induced aminopeptidase;
GN   Name=Erap1; Synonyms=Appils, Arts1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Hattori A., Kitatani K., Matsumoto H., Mizutani S., Tsujimoto M.;
RT   "Molecular cloning of murine adipocyte-derived leucine aminopeptidase and
RT   its expression in adipocyte cell line, 3T3-L1 cells.";
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11964289; DOI=10.1182/blood.v99.9.3241;
RA   Miyashita H., Yamazaki T., Akada T., Niizeki O., Ogawa M., Nishikawa S.,
RA   Sato Y.;
RT   "A mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase
RT   is expressed in endothelial cells and plays an important role in
RT   angiogenesis.";
RL   Blood 99:3241-3249(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon;
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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBUNIT: Monomer. May also exist as a heterodimer; with ERAP2.
CC       Interacts with RBMX (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC       Single-pass type II membrane protein {ECO:0000250}.
CC   -!- PTM: N-glycosylated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR   EMBL; AF227511; AAG44260.1; -; mRNA.
DR   EMBL; AB047552; BAB11982.1; -; mRNA.
DR   EMBL; AK030329; BAC26904.1; -; mRNA.
DR   EMBL; CH466563; EDL37102.1; -; Genomic_DNA.
DR   EMBL; BC046610; AAH46610.1; -; mRNA.
DR   CCDS; CCDS26647.1; -.
DR   RefSeq; NP_109636.1; NM_030711.4.
DR   RefSeq; XP_006517539.1; XM_006517476.3.
DR   AlphaFoldDB; Q9EQH2; -.
DR   SMR; Q9EQH2; -.
DR   BioGRID; 219837; 7.
DR   IntAct; Q9EQH2; 1.
DR   MINT; Q9EQH2; -.
DR   STRING; 10090.ENSMUSP00000133166; -.
DR   ChEMBL; CHEMBL3414412; -.
DR   MEROPS; M01.018; -.
DR   GlyConnect; 2283; 2 N-Linked glycans (1 site).
DR   GlyCosmos; Q9EQH2; 6 sites, 2 glycans.
DR   GlyGen; Q9EQH2; 6 sites, 2 N-linked glycans (1 site).
DR   iPTMnet; Q9EQH2; -.
DR   PhosphoSitePlus; Q9EQH2; -.
DR   SwissPalm; Q9EQH2; -.
DR   CPTAC; non-CPTAC-3804; -.
DR   EPD; Q9EQH2; -.
DR   jPOST; Q9EQH2; -.
DR   MaxQB; Q9EQH2; -.
DR   PaxDb; 10090-ENSMUSP00000133166; -.
DR   PeptideAtlas; Q9EQH2; -.
DR   ProteomicsDB; 275671; -.
DR   Pumba; Q9EQH2; -.
DR   Antibodypedia; 25075; 436 antibodies from 36 providers.
DR   DNASU; 80898; -.
DR   Ensembl; ENSMUST00000169114.3; ENSMUSP00000133166.2; ENSMUSG00000021583.8.
DR   GeneID; 80898; -.
DR   KEGG; mmu:80898; -.
DR   UCSC; uc007rfi.1; mouse.
DR   AGR; MGI:1933403; -.
DR   CTD; 51752; -.
DR   MGI; MGI:1933403; Erap1.
DR   VEuPathDB; HostDB:ENSMUSG00000021583; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   GeneTree; ENSGT00940000159086; -.
DR   HOGENOM; CLU_003705_0_1_1; -.
DR   InParanoid; Q9EQH2; -.
DR   OMA; MENWGVV; -.
DR   OrthoDB; 3085317at2759; -.
DR   PhylomeDB; Q9EQH2; -.
DR   TreeFam; TF300395; -.
DR   BRENDA; 3.4.11.22; 3474.
DR   Reactome; R-MMU-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR   BioGRID-ORCS; 80898; 13 hits in 80 CRISPR screens.
DR   ChiTaRS; Erap1; mouse.
DR   PRO; PR:Q9EQH2; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; Q9EQH2; Protein.
DR   Bgee; ENSMUSG00000021583; Expressed in duodenum and 165 other cell types or tissues.
DR   ExpressionAtlas; Q9EQH2; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR   GO; GO:0004177; F:aminopeptidase activity; IDA:MGI.
DR   GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR   GO; GO:0005138; F:interleukin-6 receptor binding; ISS:UniProtKB.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008235; F:metalloexopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0008233; F:peptidase activity; IMP:MGI.
DR   GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR   GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IMP:MGI.
DR   GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; IDA:MGI.
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.
DR   Genevisible; Q9EQH2; MM.
PE   1: Evidence at protein level;
KW   Adaptive immunity; Aminopeptidase; 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..930
FT                   /note="Endoplasmic reticulum aminopeptidase 1"
FT                   /id="PRO_0000026752"
FT   TOPO_DOM        1..2
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3..23
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        24..930
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        343
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         172
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         306..310
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         342
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         346
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         365
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   SITE            427
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        59
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        655
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        749
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        890
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        393..432
FT                   /evidence="ECO:0000250"
FT   DISULFID        725..732
FT                   /evidence="ECO:0000250"
FT   CONFLICT        540..541
FT                   /note="KG -> NA (in Ref. 1; AAG44260)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   930 AA;  106599 MW;  B5F542EBB30D16EB CRC64;
     MPSLLPLVLT FLSVSSPSWC QNSDIESLKA SNGDSFPWNN MRLPEYMTPI HYDLMIHANL
     STLTFWGKTE VEIIASRPTS TIIMHSHHLQ ISKATLRRGA GEMLSEEPLK VLEYPAHEQV
     ALLAAQPLLA GSLYTVIIDY AANLSESFHG FYKSTYRTQE GEMRILAATQ FEPTAARMAF
     PCFDEPALKA SFSIKIKRDP RHLAISNMPL VKSVNVAEGL IEDHFDITVK MSTYLVAFII
     SDFKSVSKMT KSGVKVSVYA VPDKINQADY ALDAAVTLLE FYEDYFNIPY PLPKQDLAAI
     PDFQSGAMEN WGLTTYRESS LLYDKEKSSA SSKLGITMIV SHELAHQWFG NLVTMEWWND
     LWLNEGFAKF MEFVSVTVTH PELKVEDYFF GKCFNAMEVD ALNSSHPVST PVENPAQIRE
     MFDDVSYEKG ACILNMLRDY LSADTFKRGI VQYLQKYSYK NTKNEDLWNS MMHICPTDGT
     QTMDGFCSRS QHSSSTSHWR QEVVDVKTMM NTWTLQKGFP LITITVSGRN VHMKQEHYMK
     GSERFPETGY LWHVPLTFIT SKSDSVQRFL LKTKTDVLIL PEAVQWIKFN VGMNGYYIVH
     YADDGWASLS GLLKEAHTTI SSNDRASLIN NAFQLVSIEK LSIEKALDLT LYLKNETEIM
     PIFQALNELI PMYKLMEKRD MIEVETQFKD FLLKLLKDLI DKQTWTDEGS VSERMLRSQL
     LLLACVRNYQ PCVQRAERYF REWKSSNGNM SIPIDVTLAV FAVGAQNTEG WDFLYSKYQS
     SLSSTEKSQI EFSLCTSKDP EKLQWLLDQS FKGEIIKTQE FPHILTLIGR NPVGYPLAWK
     FLRENWNKLV QKFELGSSSI AHMVMGTTDQ FSTRARLEEV KGFFSSLKEN GSQLRCVQQT
     IETIEENIRW MDKNFDKIRL WLQKEKPELL
//