Full text data of ERAP1
ERAP1
(APPILS, ARTS1, KIAA0525)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Endoplasmic reticulum aminopeptidase 1; 3.4.11.- (ARTS-1; Adipocyte-derived leucine aminopeptidase; A-LAP; Aminopeptidase PILS; Puromycin-insensitive leucyl-specific aminopeptidase; PILS-AP; Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator)
Endoplasmic reticulum aminopeptidase 1; 3.4.11.- (ARTS-1; Adipocyte-derived leucine aminopeptidase; A-LAP; Aminopeptidase PILS; Puromycin-insensitive leucyl-specific aminopeptidase; PILS-AP; Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator)
Comments
Isoform Q9NZ08-2 was detected.
Isoform Q9NZ08-2 was detected.
UniProt
Q9NZ08
ID ERAP1_HUMAN Reviewed; 941 AA.
AC Q9NZ08; O60278; Q6UWY6; Q8NEL4; Q8TAD0; Q9UHF8; Q9UKY2;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 24-JUL-2007, sequence version 3.
DT 22-JAN-2014, entry version 132.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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;
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;
RA Hattori A., Matsumoto K., Mizutani S., Tsujimoto M.;
RT "Genomic organization of the human adipocyte-derived leucine
RT aminopeptidase 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
RP AND 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.,
RA Levine S.J.;
RT "Identification of an aminopeptidase regulator of type I tumor
RT necrosis 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
RP PRO-127; 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.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for 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
RP PRO-127; 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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics 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
RT project: 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;
RA Hattori A., Kitatani K., Matsumoto H., Miyazawa S., Rogi T.,
RA Tsuruoka N., 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.,
RA Lepelletier Y., Greer F., Schomburg L., Fruci D., Niedermann G.,
RA 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
RT class I 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
RT ribonucleoprotein, 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, AND MASS
RP SPECTROMETRY.
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
RT multiple 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-940 IN COMPLEX WITH ZINC
RP IONS, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-70; ASN-154 AND
RP ASN-414.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the soluble domain of human endoplasmic
RT reticulum aminopeptidase 1 ERAP1.";
RL Submitted (MAY-2010) to the PDB data bank.
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 37-939 IN COMPLEX WITH ZINC
RP IONS AND BESTATIN, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-70;
RP ASN-154 AND ASN-760, ACTIVE SITE, CATALYTIC ACTIVITY, SUBUNIT, AND
RP MUTAGENESIS OF TYR-438.
RX PubMed=21478864; DOI=10.1038/nsmb.2021;
RA Nguyen T.T., Chang S.C., Evnouchidou I., York I.A., Zikos C.,
RA Rock K.L., 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
CC trimming, a step required for the generation of most HLA class I-
CC binding peptides. Peptide trimming is essential to customize
CC longer precursor peptides to fit them to the correct length
CC required for presentation on MHC class I molecules. Strongly
CC prefers substrates 9-16 residues long. Rapidly degrades 13-mer to
CC a 9-mer and then stops. Preferentially hydrolyzes the residue Leu
CC and peptides with a hydrophobic C-terminus, while it has weak
CC activity toward peptides with charged C-terminus. May play a role
CC in the inactivation of peptide hormones. May be involved in the
CC regulation of blood pressure through the inactivation of
CC angiotensin II and/or the generation of bradykinin in the kidney.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid, Xaa-|-
CC Xbb-, in which Xaa is preferably Leu, but may be other amino acids
CC including Met, Cys and Phe.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Monomer. May also exist as a heterodimer; with ERAP2.
CC Interacts with RBMX.
CC -!- INTERACTION:
CC P08887:IL6R; NbExp=1; IntAct=EBI-299412, EBI-299383;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type II membrane protein (Probable).
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.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-13 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25451.2; Type=Erroneous initiation;
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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 RefSeq; NP_001035548.1; NM_001040458.1.
DR RefSeq; NP_001185470.1; NM_001198541.1.
DR RefSeq; NP_057526.3; NM_016442.3.
DR UniGene; Hs.666524; -.
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 PDBsum; 2YD0; -.
DR PDBsum; 3MDJ; -.
DR PDBsum; 3QNF; -.
DR PDBsum; 3RJO; -.
DR ProteinModelPortal; Q9NZ08; -.
DR SMR; Q9NZ08; 46-941.
DR IntAct; Q9NZ08; 3.
DR STRING; 9606.ENSP00000296754; -.
DR ChEMBL; CHEMBL5939; -.
DR MEROPS; M01.018; -.
DR PhosphoSite; Q9NZ08; -.
DR DMDM; 158937334; -.
DR PaxDb; Q9NZ08; -.
DR PRIDE; Q9NZ08; -.
DR Ensembl; ENST00000296754; ENSP00000296754; ENSG00000164307.
DR Ensembl; ENST00000443439; ENSP00000406304; ENSG00000164307.
DR GeneID; 51752; -.
DR KEGG; hsa:51752; -.
DR UCSC; uc003kmm.3; human.
DR CTD; 51752; -.
DR GeneCards; GC05M096124; -.
DR H-InvDB; HIX0164377; -.
DR HGNC; HGNC:18173; ERAP1.
DR HPA; CAB025095; -.
DR MIM; 606832; gene.
DR neXtProt; NX_Q9NZ08; -.
DR PharmGKB; PA162385163; -.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG108296; -.
DR InParanoid; Q9NZ08; -.
DR KO; K09604; -.
DR OMA; LIHANLT; -.
DR OrthoDB; EOG754HNR; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; Q9NZ08; -.
DR GeneWiki; ARTS-1; -.
DR GenomeRNAi; 51752; -.
DR NextBio; 55845; -.
DR PRO; PR:Q9NZ08; -.
DR ArrayExpress; Q9NZ08; -.
DR Bgee; Q9NZ08; -.
DR CleanEx; HS_ERAP1; -.
DR Genevestigator; Q9NZ08; -.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:HGNC.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; NAS:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0005151; F:interleukin-1, Type II receptor binding; TAS:HGNC.
DR GO; GO:0008235; F:metalloexopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; TAS:HGNC.
DR GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; NAS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; NAS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; NAS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; NAS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:BHF-UCL.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Aminopeptidase;
KW Complete proteome; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Immunity; Membrane;
KW Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1 941 Endoplasmic reticulum aminopeptidase 1.
FT /FTId=PRO_0000026751.
FT TOPO_DOM 1 1 Cytoplasmic (Potential).
FT TRANSMEM 2 21 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 22 941 Lumenal (Potential).
FT REGION 317 321 Substrate binding (By similarity).
FT ACT_SITE 354 354 Proton acceptor (By similarity).
FT METAL 353 353 Zinc; catalytic.
FT METAL 357 357 Zinc; catalytic.
FT METAL 376 376 Zinc; catalytic.
FT BINDING 183 183 Substrate (By similarity).
FT SITE 438 438 Transition state stabilizer (By
FT similarity).
FT CARBOHYD 70 70 N-linked (GlcNAc...).
FT CARBOHYD 154 154 N-linked (GlcNAc...).
FT CARBOHYD 414 414 N-linked (GlcNAc...).
FT CARBOHYD 760 760 N-linked (GlcNAc...).
FT CARBOHYD 901 901 N-linked (GlcNAc...) (Potential).
FT DISULFID 404 443
FT DISULFID 736 743
FT VAR_SEQ 940 941 RM -> HDPEADATG (in isoform 2).
FT /FTId=VSP_005450.
FT VARIANT 56 56 E -> K (in dbSNP:rs3734016).
FT /FTId=VAR_046681.
FT VARIANT 127 127 R -> P (in dbSNP:rs26653).
FT /FTId=VAR_012779.
FT VARIANT 276 276 I -> M (in dbSNP:rs26618).
FT /FTId=VAR_012780.
FT VARIANT 346 346 G -> D (in dbSNP:rs27895).
FT /FTId=VAR_012781.
FT VARIANT 349 349 M -> V (in dbSNP:rs2287987).
FT /FTId=VAR_012782.
FT VARIANT 528 528 K -> R (in dbSNP:rs30187).
FT /FTId=VAR_012783.
FT VARIANT 575 575 D -> G (in dbSNP:rs6863093).
FT /FTId=VAR_046682.
FT VARIANT 575 575 D -> N (in dbSNP:rs10050860).
FT /FTId=VAR_021555.
FT VARIANT 725 725 R -> Q (in dbSNP:rs17482078).
FT /FTId=VAR_021556.
FT VARIANT 730 730 Q -> E (in dbSNP:rs27044).
FT /FTId=VAR_012784.
FT MUTAGEN 438 438 Y->F: Loss of enzyme activity.
FT CONFLICT 12 12 T -> I (in Ref. 1; AAF07395 and 2;
FT AAK37777/AAK37778).
FT CONFLICT 514 514 G -> R (in Ref. 3; AAF20384).
FT STRAND 56 70
FT TURN 71 74
FT STRAND 75 88
FT STRAND 90 96
FT STRAND 101 109
FT STRAND 116 119
FT STRAND 121 125
FT TURN 126 129
FT STRAND 130 139
FT STRAND 145 154
FT STRAND 156 168
FT STRAND 174 181
FT TURN 183 186
FT HELIX 187 190
FT STRAND 201 209
FT STRAND 214 219
FT STRAND 221 228
FT STRAND 231 236
FT HELIX 244 246
FT STRAND 249 252
FT STRAND 255 260
FT STRAND 266 271
FT TURN 273 275
FT HELIX 276 278
FT HELIX 280 296
FT STRAND 303 313
FT STRAND 315 319
FT STRAND 324 328
FT HELIX 329 331
FT TURN 336 338
FT HELIX 341 356
FT TURN 357 359
FT TURN 361 363
FT STRAND 364 368
FT HELIX 369 372
FT HELIX 373 390
FT HELIX 392 394
FT HELIX 396 399
FT HELIX 400 411
FT HELIX 426 431
FT HELIX 435 451
FT HELIX 454 468
FT STRAND 471 473
FT HELIX 475 483
FT HELIX 517 525
FT STRAND 530 538
FT STRAND 541 549
FT STRAND 565 573
FT STRAND 578 582
FT STRAND 584 590
FT STRAND 598 606
FT STRAND 609 611
FT HELIX 613 627
FT HELIX 628 630
FT HELIX 633 648
FT HELIX 654 661
FT HELIX 662 666
FT HELIX 670 687
FT HELIX 693 713
FT STRAND 716 718
FT HELIX 722 737
FT HELIX 741 756
FT TURN 757 759
FT HELIX 765 767
FT HELIX 768 775
FT HELIX 779 791
FT HELIX 795 805
FT HELIX 811 823
FT STRAND 824 827
FT HELIX 829 831
FT HELIX 832 840
FT TURN 843 845
FT HELIX 846 864
FT HELIX 869 877
FT TURN 878 881
FT HELIX 885 896
FT TURN 897 900
FT TURN 902 904
FT HELIX 906 941
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
//
ID ERAP1_HUMAN Reviewed; 941 AA.
AC Q9NZ08; O60278; Q6UWY6; Q8NEL4; Q8TAD0; Q9UHF8; Q9UKY2;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 24-JUL-2007, sequence version 3.
DT 22-JAN-2014, entry version 132.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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;
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;
RA Hattori A., Matsumoto K., Mizutani S., Tsujimoto M.;
RT "Genomic organization of the human adipocyte-derived leucine
RT aminopeptidase 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
RP AND 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.,
RA Levine S.J.;
RT "Identification of an aminopeptidase regulator of type I tumor
RT necrosis 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
RP PRO-127; 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.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for 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
RP PRO-127; 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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics 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
RT project: 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;
RA Hattori A., Kitatani K., Matsumoto H., Miyazawa S., Rogi T.,
RA Tsuruoka N., 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.,
RA Lepelletier Y., Greer F., Schomburg L., Fruci D., Niedermann G.,
RA 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
RT class I 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
RT ribonucleoprotein, 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, AND MASS
RP SPECTROMETRY.
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
RT multiple 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-940 IN COMPLEX WITH ZINC
RP IONS, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-70; ASN-154 AND
RP ASN-414.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the soluble domain of human endoplasmic
RT reticulum aminopeptidase 1 ERAP1.";
RL Submitted (MAY-2010) to the PDB data bank.
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 37-939 IN COMPLEX WITH ZINC
RP IONS AND BESTATIN, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-70;
RP ASN-154 AND ASN-760, ACTIVE SITE, CATALYTIC ACTIVITY, SUBUNIT, AND
RP MUTAGENESIS OF TYR-438.
RX PubMed=21478864; DOI=10.1038/nsmb.2021;
RA Nguyen T.T., Chang S.C., Evnouchidou I., York I.A., Zikos C.,
RA Rock K.L., 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
CC trimming, a step required for the generation of most HLA class I-
CC binding peptides. Peptide trimming is essential to customize
CC longer precursor peptides to fit them to the correct length
CC required for presentation on MHC class I molecules. Strongly
CC prefers substrates 9-16 residues long. Rapidly degrades 13-mer to
CC a 9-mer and then stops. Preferentially hydrolyzes the residue Leu
CC and peptides with a hydrophobic C-terminus, while it has weak
CC activity toward peptides with charged C-terminus. May play a role
CC in the inactivation of peptide hormones. May be involved in the
CC regulation of blood pressure through the inactivation of
CC angiotensin II and/or the generation of bradykinin in the kidney.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid, Xaa-|-
CC Xbb-, in which Xaa is preferably Leu, but may be other amino acids
CC including Met, Cys and Phe.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Monomer. May also exist as a heterodimer; with ERAP2.
CC Interacts with RBMX.
CC -!- INTERACTION:
CC P08887:IL6R; NbExp=1; IntAct=EBI-299412, EBI-299383;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type II membrane protein (Probable).
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.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-13 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25451.2; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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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 RefSeq; NP_001035548.1; NM_001040458.1.
DR RefSeq; NP_001185470.1; NM_001198541.1.
DR RefSeq; NP_057526.3; NM_016442.3.
DR UniGene; Hs.666524; -.
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 PDBsum; 2YD0; -.
DR PDBsum; 3MDJ; -.
DR PDBsum; 3QNF; -.
DR PDBsum; 3RJO; -.
DR ProteinModelPortal; Q9NZ08; -.
DR SMR; Q9NZ08; 46-941.
DR IntAct; Q9NZ08; 3.
DR STRING; 9606.ENSP00000296754; -.
DR ChEMBL; CHEMBL5939; -.
DR MEROPS; M01.018; -.
DR PhosphoSite; Q9NZ08; -.
DR DMDM; 158937334; -.
DR PaxDb; Q9NZ08; -.
DR PRIDE; Q9NZ08; -.
DR Ensembl; ENST00000296754; ENSP00000296754; ENSG00000164307.
DR Ensembl; ENST00000443439; ENSP00000406304; ENSG00000164307.
DR GeneID; 51752; -.
DR KEGG; hsa:51752; -.
DR UCSC; uc003kmm.3; human.
DR CTD; 51752; -.
DR GeneCards; GC05M096124; -.
DR H-InvDB; HIX0164377; -.
DR HGNC; HGNC:18173; ERAP1.
DR HPA; CAB025095; -.
DR MIM; 606832; gene.
DR neXtProt; NX_Q9NZ08; -.
DR PharmGKB; PA162385163; -.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG108296; -.
DR InParanoid; Q9NZ08; -.
DR KO; K09604; -.
DR OMA; LIHANLT; -.
DR OrthoDB; EOG754HNR; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; Q9NZ08; -.
DR GeneWiki; ARTS-1; -.
DR GenomeRNAi; 51752; -.
DR NextBio; 55845; -.
DR PRO; PR:Q9NZ08; -.
DR ArrayExpress; Q9NZ08; -.
DR Bgee; Q9NZ08; -.
DR CleanEx; HS_ERAP1; -.
DR Genevestigator; Q9NZ08; -.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:HGNC.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; NAS:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0005151; F:interleukin-1, Type II receptor binding; TAS:HGNC.
DR GO; GO:0008235; F:metalloexopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; TAS:HGNC.
DR GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; NAS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; NAS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; NAS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; NAS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:BHF-UCL.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Aminopeptidase;
KW Complete proteome; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Immunity; Membrane;
KW Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1 941 Endoplasmic reticulum aminopeptidase 1.
FT /FTId=PRO_0000026751.
FT TOPO_DOM 1 1 Cytoplasmic (Potential).
FT TRANSMEM 2 21 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 22 941 Lumenal (Potential).
FT REGION 317 321 Substrate binding (By similarity).
FT ACT_SITE 354 354 Proton acceptor (By similarity).
FT METAL 353 353 Zinc; catalytic.
FT METAL 357 357 Zinc; catalytic.
FT METAL 376 376 Zinc; catalytic.
FT BINDING 183 183 Substrate (By similarity).
FT SITE 438 438 Transition state stabilizer (By
FT similarity).
FT CARBOHYD 70 70 N-linked (GlcNAc...).
FT CARBOHYD 154 154 N-linked (GlcNAc...).
FT CARBOHYD 414 414 N-linked (GlcNAc...).
FT CARBOHYD 760 760 N-linked (GlcNAc...).
FT CARBOHYD 901 901 N-linked (GlcNAc...) (Potential).
FT DISULFID 404 443
FT DISULFID 736 743
FT VAR_SEQ 940 941 RM -> HDPEADATG (in isoform 2).
FT /FTId=VSP_005450.
FT VARIANT 56 56 E -> K (in dbSNP:rs3734016).
FT /FTId=VAR_046681.
FT VARIANT 127 127 R -> P (in dbSNP:rs26653).
FT /FTId=VAR_012779.
FT VARIANT 276 276 I -> M (in dbSNP:rs26618).
FT /FTId=VAR_012780.
FT VARIANT 346 346 G -> D (in dbSNP:rs27895).
FT /FTId=VAR_012781.
FT VARIANT 349 349 M -> V (in dbSNP:rs2287987).
FT /FTId=VAR_012782.
FT VARIANT 528 528 K -> R (in dbSNP:rs30187).
FT /FTId=VAR_012783.
FT VARIANT 575 575 D -> G (in dbSNP:rs6863093).
FT /FTId=VAR_046682.
FT VARIANT 575 575 D -> N (in dbSNP:rs10050860).
FT /FTId=VAR_021555.
FT VARIANT 725 725 R -> Q (in dbSNP:rs17482078).
FT /FTId=VAR_021556.
FT VARIANT 730 730 Q -> E (in dbSNP:rs27044).
FT /FTId=VAR_012784.
FT MUTAGEN 438 438 Y->F: Loss of enzyme activity.
FT CONFLICT 12 12 T -> I (in Ref. 1; AAF07395 and 2;
FT AAK37777/AAK37778).
FT CONFLICT 514 514 G -> R (in Ref. 3; AAF20384).
FT STRAND 56 70
FT TURN 71 74
FT STRAND 75 88
FT STRAND 90 96
FT STRAND 101 109
FT STRAND 116 119
FT STRAND 121 125
FT TURN 126 129
FT STRAND 130 139
FT STRAND 145 154
FT STRAND 156 168
FT STRAND 174 181
FT TURN 183 186
FT HELIX 187 190
FT STRAND 201 209
FT STRAND 214 219
FT STRAND 221 228
FT STRAND 231 236
FT HELIX 244 246
FT STRAND 249 252
FT STRAND 255 260
FT STRAND 266 271
FT TURN 273 275
FT HELIX 276 278
FT HELIX 280 296
FT STRAND 303 313
FT STRAND 315 319
FT STRAND 324 328
FT HELIX 329 331
FT TURN 336 338
FT HELIX 341 356
FT TURN 357 359
FT TURN 361 363
FT STRAND 364 368
FT HELIX 369 372
FT HELIX 373 390
FT HELIX 392 394
FT HELIX 396 399
FT HELIX 400 411
FT HELIX 426 431
FT HELIX 435 451
FT HELIX 454 468
FT STRAND 471 473
FT HELIX 475 483
FT HELIX 517 525
FT STRAND 530 538
FT STRAND 541 549
FT STRAND 565 573
FT STRAND 578 582
FT STRAND 584 590
FT STRAND 598 606
FT STRAND 609 611
FT HELIX 613 627
FT HELIX 628 630
FT HELIX 633 648
FT HELIX 654 661
FT HELIX 662 666
FT HELIX 670 687
FT HELIX 693 713
FT STRAND 716 718
FT HELIX 722 737
FT HELIX 741 756
FT TURN 757 759
FT HELIX 765 767
FT HELIX 768 775
FT HELIX 779 791
FT HELIX 795 805
FT HELIX 811 823
FT STRAND 824 827
FT HELIX 829 831
FT HELIX 832 840
FT TURN 843 845
FT HELIX 846 864
FT HELIX 869 877
FT TURN 878 881
FT HELIX 885 896
FT TURN 897 900
FT TURN 902 904
FT HELIX 906 941
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
//
MIM
606832
*RECORD*
*FIELD* NO
606832
*FIELD* TI
*606832 ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1; ERAP1
;;ADIPOCYTE-DERIVED LEUCINE AMINOPEPTIDASE; ALAP;;
read moreAMINOPEPTIDASE REGULATOR OF TNFR1 SHEDDING 1; ARTS1;;
PUROMYCIN-INSENSITIVE LEUCYL-SPECIFIC AMINOPEPTIDASE; PILSAP;;
ENDOPLASMIC RETICULUM AMINOPEPTIDASE ASSOCIATED WITH ANTIGEN PROCESSING;
ERAAP;;
KIAA0525
*FIELD* TX
DESCRIPTION
Aminopeptidases play a role in the metabolism of several peptides that
may be involved in blood pressure and the pathogenesis of essential
hypertension (145500). Adipocyte-derived leucine aminopeptidase (ALAP)
is a member of the M1 family of zinc metallopeptidases.
CLONING
By searching for cDNAs with the potential to encode large proteins
expressed in brain, Nagase et al. (1998) identified a partial cDNA
encoding ERAP1, which they called KIAA0525. The 875-amino acid protein
was predicted to be 44% identical to ALPP (171800) over 428 amino acids.
RT-PCR analysis detected highest expression in placenta, ovary, kidney,
and thymus.
By searching an EST database for sequences similar to ALPP, Hattori et
al. (1999) obtained a full-length cDNA encoding ALAP. The deduced
941-amino acid protein contains an N-terminal signal peptide, 5
potential N-glycosylation sites, a potential membrane-spanning domain,
and a zinc-binding motif. Northern blot analysis revealed expression of
3.6- and 5.1-kb transcripts in all tissues tested except brain, where
only the 5.1-kb mRNA was expressed. An additional 5.6-kb transcript was
expressed in spleen and ovary. Hattori et al. (1999) identified an ALAP
splice variant encoding a protein with 948 residues. Western blot
analysis showed expression of an approximately 100-kD cytoplasmic
protein, close to the predicted size. Functional analysis indicated a
preference for leucine substrates.
By expressing recombinant ALAP in Chinese hamster ovary cells, Hattori
et al. (2000) showed that ALAP is a monomeric protein with a molecular
mass of 120 kD that hydrolyzes a variety of bioactive peptides,
including angiotensin II (see 106150). ALAP was expressed widely in
human tissues, including the cortex of the kidney, where tissue
kallikrein (147910) is localized. The authors suggested that ALAP plays
a role in the regulation of blood pressure through inactivation of
angiotensin II and/or generation of bradykinin (see 113503) in the
kidney.
Schomburg et al. (2000) cloned rat Alap, which they termed
puromycin-insensitive, leucyl-specific aminopeptidase, or Pilsap. Pilsap
is a 930-amino acid protein, and its hydrolytic activity appeared to be
restricted to leucine and, to a lesser extent, methionine.
Serwold et al. (2002) biochemically purified and cloned the 930-amino
acid mouse aminopeptidase, which they termed Eraap. Western blot and
immunofluorescence microscopy showed that the approximately 106-kD
glycosylated protein, which is upregulatable by gamma-interferon (IFNG;
147570), trims N-terminal lysine, leucine, tyrosine, and asparagine
residues when they are not followed by proline in the endoplasmic
reticulum (ER) to yield the optimal octamer, primarily, and nonamer
peptides for antigen presentation by major histocompatibility complex
(MHC) molecules. Serwold et al. (2002) concluded that cytoplasmic
proteolysis generates only the C terminus of antigenic peptides. After
transport by TAP (170260), N-terminally extended peptides bind to MHC in
the ER and are then trimmed by Eraap to acquire the optimal length
before export from the ER, explaining why peptides presented by MHC
class I have precise lengths.
GENE STRUCTURE
By genomic sequence analysis, Hattori et al. (2001) determined that the
ERAP1 gene contains 20 exons and spans approximately 47 kb. Primer
extension analysis revealed 2 transcriptional initiation sites but no
TATA or CAAT boxes. Luciferase reporter assays revealed a functional
promoter activity in the 5-prime-flanking region of the gene and
suggested that the activity is regulated in a cell type-specific manner.
MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the ERAP1 gene
to chromosome 5. By genomic sequence analysis, Hattori et al. (2001)
mapped the ERAP1 gene to chromosome 5q15 close to the leucyl-cystinyl
aminopeptidase gene (LNPEP; 151300), suggesting a recent gene
duplication.
GENE FUNCTION
By yeast 2-hybrid analysis and by coimmunoprecipitation experiments, Cui
et al. (2002) found that human ARTS1 bound to the extracellular domain
of TNFR1 (191190). Overexpression of ARTS1 resulted in increased TNFR1
shedding and decreased membrane-associated TNFR1. Reducing the membrane
levels of ARTS1 by expression of antisense ARTS1 mRNA had the opposite
effect. Recombinant ARTS1 demonstrated selective aminopeptidase activity
toward nonpolar amino acids, but it had no activity against TNFR1 and
was not the TNFR1 sheddase. ARTS1 neither bound to TNFR2 (191191) nor
altered its shedding, suggesting specificity for TNFR1. Cui et al.
(2002) concluded that formation of the TNFR1-ARTS1 molecular complex
represents a novel mechanism by which TNFR1 shedding is regulated.
Saric et al. (2002) and York et al. (2002) determined that purified
ERAP1 trims peptides greater than 10 residues in length, but it spares
and enhances the production of 8-residue peptides generated either in
the ER or cytosol. ERAP1 was also found to trim nearly half of 9-residue
peptides, thereby reducing the supply of antigenic peptides in the
absence of IFNG expression, which induces ERAP1 expression and instead
causes proteasomes to produce more N-terminally extended antigenic
precursors and 9-residue peptides.
Using fractionated ER contents to test for aminopeptidase activity,
Saveanu et al. (2005) found that ERAP1 and ERAP2 (609497) copurified.
Confocal microscopy confirmed colocalization of ERAP1 and ERAP2 in the
ER. Immunoprecipitation experiments suggested that ERAP1 and ERAP2 form
heterodimers. Enzymatic analysis showed that ERAP2 preferentially
hydrolyzed the basic residues arg and lys, whereas ERAP1 acted on leu.
Trimming did not continue after production of minimal nonamer epitopes.
Saveanu et al. (2005) concluded that ERAP1 and ERAP2 function in a
complementary manner on peptides with 9 or more residues.
Using synthetic peptides and natural antigenic precursors, Chang et al.
(2005) showed that ERAP1 preferred substrates of the same lengths (9 to
16 residues) as those transported by TAP. Like most MHC class I
molecules, ERAP1 preferred peptides with hydrophobic C-terminal amino
acids. Chang et al. (2005) concluded that these properties, particularly
its 'molecular ruler' mechanism of binding hydrophobic C termini 9 to 16
residues from the active site, distinguish ERAP1 from other
aminopeptidases. They proposed that ERAP1 evolved to facilitate antigen
presentation.
MOLECULAR GENETICS
Hypothesizing that genomic variants of the ALAP gene may be associated
with hypertension or individual variations in blood pressure, Yamamoto
et al. (2002) screened the ALAP gene for mutations in 488 unrelated
Japanese individuals. They identified 33 polymorphisms, including 15
novel polymorphisms. One, lys528 to arg, showed an association with
essential hypertension. The estimated odds ratio for essential
hypertension was 2.3 for presence of the arg allele at codon 528, in
comparison with presence of the lys/lys genotype (P of 0.004). The lys
at codon 528 is conserved in ALAP, LNPEP, rat Pils, and mouse VEGF
(192240)-induced aminopeptidase.
For discussion of a possible association between variation in the ERAP1
gene and ankylosing spondylitis, see SPDA1 (106300).
ANIMAL MODEL
York et al. (2006) generated fertile, healthy mice lacking Erap1. MHC
class I levels were reduced in Erap1 -/- splenocytes, but not
fibroblasts, and peptide trimming in Erap1 -/- fibroblasts was reduced.
The immune response in Erap1 -/- mice to some viral peptides was altered
due to lack of the trimming enzyme.
*FIELD* RF
1. Chang, S.-C.; Momburg, F.; Bhutani, N.; Goldberg, A. L.: The ER
aminopeptidase, ERAP1, trims precursors to lengths of MHC class I
peptides by a "molecular ruler" mechanism. Proc. Nat. Acad. Sci. 102:
17107-17112, 2005.
2. Cui, X.; Hawari, F.; Alsaaty, S.; Lawrence, M.; Combs, C. A.; Geng,
W.; Rouhani, F. N.; Miskinis, D.; Levine, S. J.: Identification of
ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain
shedding. J. Clin. Invest. 110: 515-526, 2002.
3. Hattori, A.; Kitatani, K.; Matsumoto, H.; Miyazawa, S.; Rogi, T.;
Tsuruoka, N.; Mizutani, S.; Natori, Y.; Tsujimoto, M.: Characterization
of recombinant human adipocyte-derived leucine aminopeptidase expressed
in Chinese hamster ovary cells. J. Biochem. 128: 755-762, 2000.
4. Hattori, A.; Matsumoto, H.; Mizutani, S.; Tsujimoto, M.: Molecular
cloning of adipocyte-derived leucine aminopeptidase highly related
to placental leucine aminopeptidase/oxytocinase. J. Biochem. 125:
931-938, 1999.
5. Hattori, A.; Matsumoto, K.; Mizutani, S.; Tsujimoto, M.: Genomic
organization of the human adipocyte-derived leucine aminopeptidase
gene and its relationship to the placental leucine aminopeptidase/oxytocinase
gene. J. Biochem. 130: 235-241, 2001.
6. Nagase, T.; Ishikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: Prediction of the coding sequences of unidentified
human genes. IX. The complete sequences of 100 new cDNA clones from
brain which can code for large proteins in vitro. DNA Res. 5: 31-39,
1998.
7. Saric, T.; Chang, S.-C.; Hattori, A.; York, I. A.; Markant, S.;
Rock, K. L.; Tsujimoto, M.; Goldberg, A. L.: An IFN-gamma-induced
aminopeptidase in the ER, ERAPI, trims precursors to MHC class I-presented
peptides. Nature Immun. 3: 1169-1176, 2002.
8. Saveanu, L.; Carroll, O.; Lindo, V.; Del Val, M.; Lopez, D.; Lepelletier,
Y.; Greer, F.; Schomburg, L.; Fruci, D.; Niedermann, G.; van Endert,
P. M.: Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase
complexes in the endoplasmic reticulum. Nature Immun. 6: 689-697,
2005.
9. Schomburg, L.; Kollmus, H.; Friedrichsen, S.; Bauer, K.: Molecular
characterization of a puromycin-insensitive leucyl-specific aminopeptidase,
PILS-AP. Europ. J. Biochem. 267: 3198-3207, 2000.
10. Serwold, T.; Gonzalez, F.; Kim, J.; Jacob, R.; Shastri, N.: ERAAP
customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 419:
480-483, 2002.
11. Yamamoto, N.; Nakayama, J.; Yamakawa-Kobayashi, K.; Hamaguchi,
H.; Miyazaki, R.; Arinami, T.: Identification of 33 polymorphisms
in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible
association with hypertension. Hum. Mutat. 19: 251-257, 2002.
12. York, I. A.; Brehm, M. A.; Zendzian, S.; Towne, C. F.; Rock, K.
L.: Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class
I-presented peptides in vivo and plays an important role in immunodominance. Proc.
Nat. Acad. Sci. 103: 9202-9207, 2006.
13. York, I. A.; Chang, S.-C.; Saric, T.; Keys, J. A.; Favreau, J.
M.; Goldberg, A. L.; Rock, K. L.: The ER aminopeptidase ERAPI enhances
or limits antigen presentation by trimming epitopes to 8-9 residues. Nature
Immun. 3: 1177-1184, 2002.
*FIELD* CN
Marla J. F. O'Neill - updated: 1/29/2010
Paul J. Converse - updated: 3/2/2007
Paul J. Converse - updated: 7/28/2006
Paul J. Converse - updated: 7/25/2005
Paul J. Converse - updated: 12/20/2002
Patricia A. Hartz - updated: 12/17/2002
Paul J. Converse - updated: 10/2/2002
Paul J. Converse - updated: 5/24/2002
Paul J. Converse - updated: 5/10/2002
*FIELD* CD
Victor A. McKusick: 4/5/2002
*FIELD* ED
wwang: 01/29/2010
terry: 1/29/2010
wwang: 10/14/2008
carol: 5/16/2008
mgross: 3/9/2007
terry: 3/2/2007
mgross: 9/25/2006
terry: 7/28/2006
mgross: 7/25/2005
alopez: 1/2/2003
mgross: 12/20/2002
mgross: 12/18/2002
terry: 12/17/2002
mgross: 10/2/2002
mgross: 5/24/2002
mgross: 5/10/2002
mgross: 4/5/2002
*RECORD*
*FIELD* NO
606832
*FIELD* TI
*606832 ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1; ERAP1
;;ADIPOCYTE-DERIVED LEUCINE AMINOPEPTIDASE; ALAP;;
read moreAMINOPEPTIDASE REGULATOR OF TNFR1 SHEDDING 1; ARTS1;;
PUROMYCIN-INSENSITIVE LEUCYL-SPECIFIC AMINOPEPTIDASE; PILSAP;;
ENDOPLASMIC RETICULUM AMINOPEPTIDASE ASSOCIATED WITH ANTIGEN PROCESSING;
ERAAP;;
KIAA0525
*FIELD* TX
DESCRIPTION
Aminopeptidases play a role in the metabolism of several peptides that
may be involved in blood pressure and the pathogenesis of essential
hypertension (145500). Adipocyte-derived leucine aminopeptidase (ALAP)
is a member of the M1 family of zinc metallopeptidases.
CLONING
By searching for cDNAs with the potential to encode large proteins
expressed in brain, Nagase et al. (1998) identified a partial cDNA
encoding ERAP1, which they called KIAA0525. The 875-amino acid protein
was predicted to be 44% identical to ALPP (171800) over 428 amino acids.
RT-PCR analysis detected highest expression in placenta, ovary, kidney,
and thymus.
By searching an EST database for sequences similar to ALPP, Hattori et
al. (1999) obtained a full-length cDNA encoding ALAP. The deduced
941-amino acid protein contains an N-terminal signal peptide, 5
potential N-glycosylation sites, a potential membrane-spanning domain,
and a zinc-binding motif. Northern blot analysis revealed expression of
3.6- and 5.1-kb transcripts in all tissues tested except brain, where
only the 5.1-kb mRNA was expressed. An additional 5.6-kb transcript was
expressed in spleen and ovary. Hattori et al. (1999) identified an ALAP
splice variant encoding a protein with 948 residues. Western blot
analysis showed expression of an approximately 100-kD cytoplasmic
protein, close to the predicted size. Functional analysis indicated a
preference for leucine substrates.
By expressing recombinant ALAP in Chinese hamster ovary cells, Hattori
et al. (2000) showed that ALAP is a monomeric protein with a molecular
mass of 120 kD that hydrolyzes a variety of bioactive peptides,
including angiotensin II (see 106150). ALAP was expressed widely in
human tissues, including the cortex of the kidney, where tissue
kallikrein (147910) is localized. The authors suggested that ALAP plays
a role in the regulation of blood pressure through inactivation of
angiotensin II and/or generation of bradykinin (see 113503) in the
kidney.
Schomburg et al. (2000) cloned rat Alap, which they termed
puromycin-insensitive, leucyl-specific aminopeptidase, or Pilsap. Pilsap
is a 930-amino acid protein, and its hydrolytic activity appeared to be
restricted to leucine and, to a lesser extent, methionine.
Serwold et al. (2002) biochemically purified and cloned the 930-amino
acid mouse aminopeptidase, which they termed Eraap. Western blot and
immunofluorescence microscopy showed that the approximately 106-kD
glycosylated protein, which is upregulatable by gamma-interferon (IFNG;
147570), trims N-terminal lysine, leucine, tyrosine, and asparagine
residues when they are not followed by proline in the endoplasmic
reticulum (ER) to yield the optimal octamer, primarily, and nonamer
peptides for antigen presentation by major histocompatibility complex
(MHC) molecules. Serwold et al. (2002) concluded that cytoplasmic
proteolysis generates only the C terminus of antigenic peptides. After
transport by TAP (170260), N-terminally extended peptides bind to MHC in
the ER and are then trimmed by Eraap to acquire the optimal length
before export from the ER, explaining why peptides presented by MHC
class I have precise lengths.
GENE STRUCTURE
By genomic sequence analysis, Hattori et al. (2001) determined that the
ERAP1 gene contains 20 exons and spans approximately 47 kb. Primer
extension analysis revealed 2 transcriptional initiation sites but no
TATA or CAAT boxes. Luciferase reporter assays revealed a functional
promoter activity in the 5-prime-flanking region of the gene and
suggested that the activity is regulated in a cell type-specific manner.
MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the ERAP1 gene
to chromosome 5. By genomic sequence analysis, Hattori et al. (2001)
mapped the ERAP1 gene to chromosome 5q15 close to the leucyl-cystinyl
aminopeptidase gene (LNPEP; 151300), suggesting a recent gene
duplication.
GENE FUNCTION
By yeast 2-hybrid analysis and by coimmunoprecipitation experiments, Cui
et al. (2002) found that human ARTS1 bound to the extracellular domain
of TNFR1 (191190). Overexpression of ARTS1 resulted in increased TNFR1
shedding and decreased membrane-associated TNFR1. Reducing the membrane
levels of ARTS1 by expression of antisense ARTS1 mRNA had the opposite
effect. Recombinant ARTS1 demonstrated selective aminopeptidase activity
toward nonpolar amino acids, but it had no activity against TNFR1 and
was not the TNFR1 sheddase. ARTS1 neither bound to TNFR2 (191191) nor
altered its shedding, suggesting specificity for TNFR1. Cui et al.
(2002) concluded that formation of the TNFR1-ARTS1 molecular complex
represents a novel mechanism by which TNFR1 shedding is regulated.
Saric et al. (2002) and York et al. (2002) determined that purified
ERAP1 trims peptides greater than 10 residues in length, but it spares
and enhances the production of 8-residue peptides generated either in
the ER or cytosol. ERAP1 was also found to trim nearly half of 9-residue
peptides, thereby reducing the supply of antigenic peptides in the
absence of IFNG expression, which induces ERAP1 expression and instead
causes proteasomes to produce more N-terminally extended antigenic
precursors and 9-residue peptides.
Using fractionated ER contents to test for aminopeptidase activity,
Saveanu et al. (2005) found that ERAP1 and ERAP2 (609497) copurified.
Confocal microscopy confirmed colocalization of ERAP1 and ERAP2 in the
ER. Immunoprecipitation experiments suggested that ERAP1 and ERAP2 form
heterodimers. Enzymatic analysis showed that ERAP2 preferentially
hydrolyzed the basic residues arg and lys, whereas ERAP1 acted on leu.
Trimming did not continue after production of minimal nonamer epitopes.
Saveanu et al. (2005) concluded that ERAP1 and ERAP2 function in a
complementary manner on peptides with 9 or more residues.
Using synthetic peptides and natural antigenic precursors, Chang et al.
(2005) showed that ERAP1 preferred substrates of the same lengths (9 to
16 residues) as those transported by TAP. Like most MHC class I
molecules, ERAP1 preferred peptides with hydrophobic C-terminal amino
acids. Chang et al. (2005) concluded that these properties, particularly
its 'molecular ruler' mechanism of binding hydrophobic C termini 9 to 16
residues from the active site, distinguish ERAP1 from other
aminopeptidases. They proposed that ERAP1 evolved to facilitate antigen
presentation.
MOLECULAR GENETICS
Hypothesizing that genomic variants of the ALAP gene may be associated
with hypertension or individual variations in blood pressure, Yamamoto
et al. (2002) screened the ALAP gene for mutations in 488 unrelated
Japanese individuals. They identified 33 polymorphisms, including 15
novel polymorphisms. One, lys528 to arg, showed an association with
essential hypertension. The estimated odds ratio for essential
hypertension was 2.3 for presence of the arg allele at codon 528, in
comparison with presence of the lys/lys genotype (P of 0.004). The lys
at codon 528 is conserved in ALAP, LNPEP, rat Pils, and mouse VEGF
(192240)-induced aminopeptidase.
For discussion of a possible association between variation in the ERAP1
gene and ankylosing spondylitis, see SPDA1 (106300).
ANIMAL MODEL
York et al. (2006) generated fertile, healthy mice lacking Erap1. MHC
class I levels were reduced in Erap1 -/- splenocytes, but not
fibroblasts, and peptide trimming in Erap1 -/- fibroblasts was reduced.
The immune response in Erap1 -/- mice to some viral peptides was altered
due to lack of the trimming enzyme.
*FIELD* RF
1. Chang, S.-C.; Momburg, F.; Bhutani, N.; Goldberg, A. L.: The ER
aminopeptidase, ERAP1, trims precursors to lengths of MHC class I
peptides by a "molecular ruler" mechanism. Proc. Nat. Acad. Sci. 102:
17107-17112, 2005.
2. Cui, X.; Hawari, F.; Alsaaty, S.; Lawrence, M.; Combs, C. A.; Geng,
W.; Rouhani, F. N.; Miskinis, D.; Levine, S. J.: Identification of
ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain
shedding. J. Clin. Invest. 110: 515-526, 2002.
3. Hattori, A.; Kitatani, K.; Matsumoto, H.; Miyazawa, S.; Rogi, T.;
Tsuruoka, N.; Mizutani, S.; Natori, Y.; Tsujimoto, M.: Characterization
of recombinant human adipocyte-derived leucine aminopeptidase expressed
in Chinese hamster ovary cells. J. Biochem. 128: 755-762, 2000.
4. Hattori, A.; Matsumoto, H.; Mizutani, S.; Tsujimoto, M.: Molecular
cloning of adipocyte-derived leucine aminopeptidase highly related
to placental leucine aminopeptidase/oxytocinase. J. Biochem. 125:
931-938, 1999.
5. Hattori, A.; Matsumoto, K.; Mizutani, S.; Tsujimoto, M.: Genomic
organization of the human adipocyte-derived leucine aminopeptidase
gene and its relationship to the placental leucine aminopeptidase/oxytocinase
gene. J. Biochem. 130: 235-241, 2001.
6. Nagase, T.; Ishikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: Prediction of the coding sequences of unidentified
human genes. IX. The complete sequences of 100 new cDNA clones from
brain which can code for large proteins in vitro. DNA Res. 5: 31-39,
1998.
7. Saric, T.; Chang, S.-C.; Hattori, A.; York, I. A.; Markant, S.;
Rock, K. L.; Tsujimoto, M.; Goldberg, A. L.: An IFN-gamma-induced
aminopeptidase in the ER, ERAPI, trims precursors to MHC class I-presented
peptides. Nature Immun. 3: 1169-1176, 2002.
8. Saveanu, L.; Carroll, O.; Lindo, V.; Del Val, M.; Lopez, D.; Lepelletier,
Y.; Greer, F.; Schomburg, L.; Fruci, D.; Niedermann, G.; van Endert,
P. M.: Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase
complexes in the endoplasmic reticulum. Nature Immun. 6: 689-697,
2005.
9. Schomburg, L.; Kollmus, H.; Friedrichsen, S.; Bauer, K.: Molecular
characterization of a puromycin-insensitive leucyl-specific aminopeptidase,
PILS-AP. Europ. J. Biochem. 267: 3198-3207, 2000.
10. Serwold, T.; Gonzalez, F.; Kim, J.; Jacob, R.; Shastri, N.: ERAAP
customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 419:
480-483, 2002.
11. Yamamoto, N.; Nakayama, J.; Yamakawa-Kobayashi, K.; Hamaguchi,
H.; Miyazaki, R.; Arinami, T.: Identification of 33 polymorphisms
in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible
association with hypertension. Hum. Mutat. 19: 251-257, 2002.
12. York, I. A.; Brehm, M. A.; Zendzian, S.; Towne, C. F.; Rock, K.
L.: Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class
I-presented peptides in vivo and plays an important role in immunodominance. Proc.
Nat. Acad. Sci. 103: 9202-9207, 2006.
13. York, I. A.; Chang, S.-C.; Saric, T.; Keys, J. A.; Favreau, J.
M.; Goldberg, A. L.; Rock, K. L.: The ER aminopeptidase ERAPI enhances
or limits antigen presentation by trimming epitopes to 8-9 residues. Nature
Immun. 3: 1177-1184, 2002.
*FIELD* CN
Marla J. F. O'Neill - updated: 1/29/2010
Paul J. Converse - updated: 3/2/2007
Paul J. Converse - updated: 7/28/2006
Paul J. Converse - updated: 7/25/2005
Paul J. Converse - updated: 12/20/2002
Patricia A. Hartz - updated: 12/17/2002
Paul J. Converse - updated: 10/2/2002
Paul J. Converse - updated: 5/24/2002
Paul J. Converse - updated: 5/10/2002
*FIELD* CD
Victor A. McKusick: 4/5/2002
*FIELD* ED
wwang: 01/29/2010
terry: 1/29/2010
wwang: 10/14/2008
carol: 5/16/2008
mgross: 3/9/2007
terry: 3/2/2007
mgross: 9/25/2006
terry: 7/28/2006
mgross: 7/25/2005
alopez: 1/2/2003
mgross: 12/20/2002
mgross: 12/18/2002
terry: 12/17/2002
mgross: 10/2/2002
mgross: 5/24/2002
mgross: 5/10/2002
mgross: 4/5/2002