ERAP1_RAT
ID ERAP1_RAT Reviewed; 930 AA.
AC Q9JJ22; Q9JJ23;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 144.
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;
GN Name=Erap1; Synonyms=Appils, Arts1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Pineal gland;
RX PubMed=10824104; DOI=10.1046/j.1432-1327.2000.01348.x;
RA Schomburg L., Kollmus H., Friedrichsen S., Bauer K.;
RT "Molecular characterization of a puromycin-insensitive leucyl-specific
RT aminopeptidase, PILS-AP.";
RL Eur. J. Biochem. 267:3198-3207(2000).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JJ22-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JJ22-2; Sequence=VSP_005451, VSP_005452;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10824104}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; AF148323; AAF73106.1; -; mRNA.
DR EMBL; AF148324; AAF73107.1; -; mRNA.
DR RefSeq; NP_110463.1; NM_030836.1. [Q9JJ22-2]
DR AlphaFoldDB; Q9JJ22; -.
DR SMR; Q9JJ22; -.
DR STRING; 10116.ENSRNOP00000013625; -.
DR MEROPS; M01.018; -.
DR GlyGen; Q9JJ22; 6 sites.
DR iPTMnet; Q9JJ22; -.
DR PhosphoSitePlus; Q9JJ22; -.
DR jPOST; Q9JJ22; -.
DR PaxDb; Q9JJ22; -.
DR PeptideAtlas; Q9JJ22; -.
DR PRIDE; Q9JJ22; -.
DR GeneID; 80897; -.
DR KEGG; rno:80897; -.
DR UCSC; RGD:708542; rat. [Q9JJ22-1]
DR CTD; 51752; -.
DR RGD; 708542; Erap1.
DR eggNOG; KOG1046; Eukaryota.
DR InParanoid; Q9JJ22; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; Q9JJ22; -.
DR Reactome; R-RNO-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR PRO; PR:Q9JJ22; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; IMP:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:RGD.
DR GO; GO:0008270; F:zinc ion binding; IMP:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019882; P:antigen processing and presentation; TAS:RGD.
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; ISO:RGD.
DR GO; GO:0030163; P:protein catabolic process; IMP:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
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 2: Evidence at transcript level;
KW Adaptive immunity; Alternative splicing; Aminopeptidase; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Immunity; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..930
FT /note="Endoplasmic reticulum aminopeptidase 1"
FT /id="PRO_0000026753"
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 /note="Proton acceptor"
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 VAR_SEQ 883..884
FT /note="FF -> CM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10824104"
FT /id="VSP_005451"
FT VAR_SEQ 885..930
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10824104"
FT /id="VSP_005452"
SQ SEQUENCE 930 AA; 106419 MW; 928E7143CBD0EE7F CRC64;
MPSLLSLVLT FLAVSSPSCC QNSDTASPKA SNGASFPWNN MRLPEYITPI HYDLMIHANL
STLTFWGKTE VEITVSQPTS TIIMHSHQLQ ISKATLRRGA EEMLPEEPLK LMEYSAHEQV
ALLTAQPLLA GSVYTVIITY AANLSENFHG FYKSTYRTQE GERRILAATQ FEPTAARMAF
PCFDEPALKA SFSIKIKRDP RHLAISNMPL VKSVTVAEGL IEDHFDITVK MSTYLVAFII
SDFKSVSKMT KSGVKVSVYA VPDKINQADY ALDAAVTLLE FYEDYFSIPY PLPKQDLAAI
PDFQSGAMEN WGLTTYRESA LLYDKEKSSA SSKLGITMTV SHELAHQWFG NLVTMEWWND
LWLNEGFAKF MEFVSVTVTH PELKVEEYFF GKCFNAMEVD ALNSSHPVST PVENPAQIRE
MFDEVSYEKG ACILNMLRDY LSADTFKRGI VQYLQKYSYK NTKNEDLWNS MMHICPTDGT
QTMDGFCSRN QHSSSTSHWR QEVIDIKSMM NTWTLQKGFP LITITVRGRN VHLKQEHYMK
GSECFPETGS LWHVPLTFIT SKSDSVQRFL LKTKTDVIIL PEAVEWIKFN VGMNGYYIVH
YGDDGWASLN GLLKEAHTTI SSNDRASLIN NAFQLVSIGK LSIEKALDLI LYLKNETEIM
PIFQGLNELI PMYKLMEKRD MVEVETQFKD FLLRLLKDLI NKQTWTDEGS VSERMLRSQL
LLLACVHRYQ LCVQRAERYF REWKASNGNM SLPIDVTLAV FAVGAQNTEG WDFLYSKYQS
SLSSTEKSQI EFSLCISQDP EKLQWLLDQS FKGEIIKTQE FPHILTLIGR NPVGYPLAWK
FLKENWNKIV QKFELGSSSI AHMVMGTTNQ FSTRARLEEV KGFFSSLKKN GSQLRCVQQT
IETIEENIRW MDKNFDKIRL WLQKERQELL
