ERAP1_MOUSE
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 03-AUG-2022, entry version 171.
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, Pancreas,
RC 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; 6.
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 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; Q9EQH2; -.
DR PeptideAtlas; Q9EQH2; -.
DR PRIDE; Q9EQH2; -.
DR ProteomicsDB; 275671; -.
DR Antibodypedia; 25075; 375 antibodies from 36 providers.
DR DNASU; 80898; -.
DR Ensembl; ENSMUST00000169114; ENSMUSP00000133166; ENSMUSG00000021583.
DR GeneID; 80898; -.
DR KEGG; mmu:80898; -.
DR UCSC; uc007rfi.1; mouse.
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; QFSTRTW; -.
DR OrthoDB; 110058at2759; -.
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 75 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 163 other tissues.
DR ExpressionAtlas; Q9EQH2; baseline and differential.
DR Genevisible; Q9EQH2; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; IEA:InterPro.
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 GO; GO:0008217; P:regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR033520; ERAP1.
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; PTHR11533:SF156; 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; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
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
