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Database: UniProt
Entry: Q9NZ08
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Original site: Q9NZ08 
ID   ERAP1_HUMAN             Reviewed;         941 AA.
AC   Q9NZ08; O60278; Q6UWY6; Q8NEL4; Q8TAD0; Q9UHF8; Q9UKY2;
DT   05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   24-JUL-2007, sequence version 3.
DT   17-JUN-2020, entry version 189.
DE   RecName: Full=Endoplasmic reticulum aminopeptidase 1;
DE            EC=3.4.11.-;
DE   AltName: Full=ARTS-1;
DE   AltName: Full=Adipocyte-derived leucine aminopeptidase;
DE            Short=A-LAP;
DE   AltName: Full=Aminopeptidase PILS;
DE   AltName: Full=Puromycin-insensitive leucyl-specific aminopeptidase;
DE            Short=PILS-AP;
DE   AltName: Full=Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator;
GN   Name=ERAP1; Synonyms=APPILS, ARTS1, KIAA0525; ORFNames=UNQ584/PRO1154;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-127.
RC   TISSUE=White adipose tissue;
RX   PubMed=10220586; DOI=10.1093/oxfordjournals.jbchem.a022371;
RA   Hattori A., Matsumoto H., Mizutani S., Tsujimoto M.;
RT   "Molecular cloning of adipocyte-derived leucine aminopeptidase highly
RT   related to placental leucine aminopeptidase/oxytocinase.";
RL   J. Biochem. 125:931-938(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS PRO-127;
RP   VAL-349; ARG-528; ASN-575; GLN-725 AND GLU-730.
RC   TISSUE=Leukocyte;
RX   PubMed=11481040; DOI=10.1093/oxfordjournals.jbchem.a002977;
RA   Hattori A., Matsumoto K., Mizutani S., Tsujimoto M.;
RT   "Genomic organization of the human adipocyte-derived leucine aminopeptidase
RT   gene and its relationship to the placental leucine
RT   aminopeptidase/oxytocinase gene.";
RL   J. Biochem. 130:235-241(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASP-346; ARG-528 AND
RP   GLU-730.
RA   Schomburg L.;
RT   "Molecular characterization of human aminopeptidase PILS.";
RL   Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Cui X., Alsaaty S., Lawrence M., Combs C.A., Rouhani F.N., Levine S.J.;
RT   "Identification of an aminopeptidase regulator of type I tumor necrosis
RT   factor receptor shedding.";
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS PRO-127;
RP   VAL-349; ARG-528; ASN-575; GLN-725 AND GLU-730.
RC   TISSUE=Brain;
RX   PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA   Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA   Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. IX. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:31-39(1998).
RN   [6]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PRO-127;
RP   VAL-349; ARG-528; ASN-575; GLN-725 AND GLU-730.
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   PROTEIN SEQUENCE OF 37-49, AND CHARACTERIZATION.
RX   PubMed=11056387; DOI=10.1093/oxfordjournals.jbchem.a022812;
RA   Hattori A., Kitatani K., Matsumoto H., Miyazawa S., Rogi T., Tsuruoka N.,
RA   Mizutani S., Natori Y., Tsujimoto M.;
RT   "Characterization of recombinant human adipocyte-derived leucine
RT   aminopeptidase expressed in Chinese hamster ovary cells.";
RL   J. Biochem. 128:755-762(2000).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INDUCTION BY IFNG.
RX   PubMed=15908954; DOI=10.1038/ni1208;
RA   Saveanu L., Carroll O., Lindo V., Del Val M., Lopez D., Lepelletier Y.,
RA   Greer F., Schomburg L., Fruci D., Niedermann G., van Endert P.M.;
RT   "Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase
RT   complexes in the endoplasmic reticulum.";
RL   Nat. Immunol. 6:689-697(2005).
RN   [11]
RP   FUNCTION.
RX   PubMed=16286653; DOI=10.1073/pnas.0500721102;
RA   Chang S.-C., Momburg F., Bhutani N., Goldberg A.L.;
RT   "The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I
RT   peptides by a 'molecular ruler' mechanism.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:17107-17112(2005).
RN   [12]
RP   INTERACTION WITH RBMX.
RX   PubMed=18445477; DOI=10.1016/j.bbrc.2008.04.103;
RA   Adamik B., Islam A., Rouhani F.N., Hawari F.I., Zhang J., Levine S.J.;
RT   "An association between RBMX, a heterogeneous nuclear ribonucleoprotein,
RT   and ARTS-1 regulates extracellular TNFR1 release.";
RL   Biochem. Biophys. Res. Commun. 371:505-509(2008).
RN   [13]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-414.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-940 IN COMPLEX WITH ZINC IONS,
RP   DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-70; ASN-154 AND ASN-414.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of the soluble domain of human endoplasmic reticulum
RT   aminopeptidase 1 ERAP1.";
RL   Submitted (MAY-2010) to the PDB data bank.
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 37-939 IN COMPLEX WITH ZINC IONS
RP   AND BESTATIN, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-70; ASN-154
RP   AND ASN-760, ACTIVE SITE, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF
RP   TYR-438.
RX   PubMed=21478864; DOI=10.1038/nsmb.2021;
RA   Nguyen T.T., Chang S.C., Evnouchidou I., York I.A., Zikos C., Rock K.L.,
RA   Goldberg A.L., Stratikos E., Stern L.J.;
RT   "Structural basis for antigenic peptide precursor processing by the
RT   endoplasmic reticulum aminopeptidase ERAP1.";
RL   Nat. Struct. Mol. Biol. 18:604-613(2011).
CC   -!- FUNCTION: Aminopeptidase that plays a central role in peptide trimming,
CC       a step required for the generation of most HLA class I-binding
CC       peptides. Peptide trimming is essential to customize longer precursor
CC       peptides to fit them to the correct length required for presentation on
CC       MHC class I molecules. Strongly prefers substrates 9-16 residues long.
CC       Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially
CC       hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus,
CC       while it has weak activity toward peptides with charged C-terminus. May
CC       play a role in the inactivation of peptide hormones. May be involved in
CC       the regulation of blood pressure through the inactivation of
CC       angiotensin II and/or the generation of bradykinin in the kidney.
CC       {ECO:0000269|PubMed:15908954, ECO:0000269|PubMed:16286653,
CC       ECO:0000269|PubMed:21478864}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 1 zinc ion per subunit.;
CC   -!- SUBUNIT: Monomer. May also exist as a heterodimer; with ERAP2.
CC       Interacts with RBMX. {ECO:0000269|PubMed:15908954,
CC       ECO:0000269|PubMed:18445477, ECO:0000269|PubMed:21478864,
CC       ECO:0000269|Ref.16}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:15908954}; Single-pass type II membrane protein
CC       {ECO:0000305|PubMed:15908954}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NZ08-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NZ08-2; Sequence=VSP_005450;
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- INDUCTION: By IFNG/IFN-gamma. {ECO:0000269|PubMed:15908954}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19159218,
CC       ECO:0000269|PubMed:21478864, ECO:0000269|Ref.16}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-13 is the initiator.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA25451.2; Type=Erroneous initiation; Evidence={ECO:0000305};
DR   EMBL; AF106037; AAF07395.1; -; mRNA.
DR   EMBL; AY028806; AAK37777.1; -; mRNA.
DR   EMBL; AY028807; AAK37778.1; -; mRNA.
DR   EMBL; AF183569; AAF20384.1; -; mRNA.
DR   EMBL; AF222340; AAF34664.1; -; mRNA.
DR   EMBL; AB011097; BAA25451.2; ALT_INIT; mRNA.
DR   EMBL; AY358590; AAQ88953.1; -; mRNA.
DR   EMBL; BC030775; AAH30775.1; -; mRNA.
DR   CCDS; CCDS4085.1; -. [Q9NZ08-2]
DR   CCDS; CCDS47250.1; -. [Q9NZ08-1]
DR   RefSeq; NP_001035548.1; NM_001040458.1. [Q9NZ08-1]
DR   RefSeq; NP_001185470.1; NM_001198541.1. [Q9NZ08-1]
DR   RefSeq; NP_057526.3; NM_016442.3. [Q9NZ08-2]
DR   RefSeq; XP_011541788.1; XM_011543486.2. [Q9NZ08-1]
DR   RefSeq; XP_016865071.1; XM_017009582.1.
DR   PDB; 2YD0; X-ray; 2.70 A; A=46-940.
DR   PDB; 3MDJ; X-ray; 2.95 A; A/B/C=37-939.
DR   PDB; 3QNF; X-ray; 3.00 A; A/B/C=1-941.
DR   PDB; 3RJO; X-ray; 2.30 A; A=529-941.
DR   PDB; 5J5E; X-ray; 2.80 A; A=529-941.
DR   PDB; 6M8P; X-ray; 3.31 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=33-485, A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=514-940.
DR   PDB; 6MGQ; X-ray; 2.92 A; A/B/C=33-939.
DR   PDB; 6Q4R; X-ray; 1.60 A; A=1-485, A=514-937.
DR   PDB; 6RQX; X-ray; 1.68 A; A=1-938.
DR   PDB; 6RYF; X-ray; 1.72 A; A=46-938.
DR   PDB; 6T6R; X-ray; 1.67 A; A=1-941.
DR   PDBsum; 2YD0; -.
DR   PDBsum; 3MDJ; -.
DR   PDBsum; 3QNF; -.
DR   PDBsum; 3RJO; -.
DR   PDBsum; 5J5E; -.
DR   PDBsum; 6M8P; -.
DR   PDBsum; 6MGQ; -.
DR   PDBsum; 6Q4R; -.
DR   PDBsum; 6RQX; -.
DR   PDBsum; 6RYF; -.
DR   PDBsum; 6T6R; -.
DR   SMR; Q9NZ08; -.
DR   BioGRID; 119713; 26.
DR   CORUM; Q9NZ08; -.
DR   IntAct; Q9NZ08; 15.
DR   STRING; 9606.ENSP00000296754; -.
DR   BindingDB; Q9NZ08; -.
DR   ChEMBL; CHEMBL5939; -.
DR   GuidetoPHARMACOLOGY; 1566; -.
DR   MEROPS; M01.018; -.
DR   GlyConnect; 1203; -.
DR   iPTMnet; Q9NZ08; -.
DR   MetOSite; Q9NZ08; -.
DR   PhosphoSitePlus; Q9NZ08; -.
DR   SwissPalm; Q9NZ08; -.
DR   BioMuta; ERAP1; -.
DR   DMDM; 158937334; -.
DR   EPD; Q9NZ08; -.
DR   jPOST; Q9NZ08; -.
DR   MassIVE; Q9NZ08; -.
DR   MaxQB; Q9NZ08; -.
DR   PaxDb; Q9NZ08; -.
DR   PeptideAtlas; Q9NZ08; -.
DR   PRIDE; Q9NZ08; -.
DR   ProteomicsDB; 83312; -. [Q9NZ08-1]
DR   ProteomicsDB; 83313; -. [Q9NZ08-2]
DR   Antibodypedia; 25075; 333 antibodies.
DR   Ensembl; ENST00000296754; ENSP00000296754; ENSG00000164307. [Q9NZ08-2]
DR   Ensembl; ENST00000443439; ENSP00000406304; ENSG00000164307. [Q9NZ08-1]
DR   GeneID; 51752; -.
DR   KEGG; hsa:51752; -.
DR   UCSC; uc003kml.4; human. [Q9NZ08-1]
DR   CTD; 51752; -.
DR   DisGeNET; 51752; -.
DR   EuPathDB; HostDB:ENSG00000164307.12; -.
DR   GeneCards; ERAP1; -.
DR   HGNC; HGNC:18173; ERAP1.
DR   HPA; ENSG00000164307; Low tissue specificity.
DR   MalaCards; ERAP1; -.
DR   MIM; 606832; gene.
DR   neXtProt; NX_Q9NZ08; -.
DR   OpenTargets; ENSG00000164307; -.
DR   Orphanet; 117; Behcet disease.
DR   PharmGKB; PA162385163; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   eggNOG; COG0308; LUCA.
DR   GeneTree; ENSGT00940000159086; -.
DR   HOGENOM; CLU_003705_2_1_1; -.
DR   InParanoid; Q9NZ08; -.
DR   KO; K09604; -.
DR   OMA; QFSTRTW; -.
DR   OrthoDB; 110058at2759; -.
DR   PhylomeDB; Q9NZ08; -.
DR   TreeFam; TF300395; -.
DR   Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR   BioGRID-ORCS; 51752; 3 hits in 786 CRISPR screens.
DR   ChiTaRS; ERAP1; human.
DR   EvolutionaryTrace; Q9NZ08; -.
DR   GeneWiki; ARTS-1; -.
DR   GenomeRNAi; 51752; -.
DR   Pharos; Q9NZ08; Tchem.
DR   PRO; PR:Q9NZ08; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q9NZ08; protein.
DR   Bgee; ENSG00000164307; Expressed in intestine and 219 other tissues.
DR   ExpressionAtlas; Q9NZ08; baseline and differential.
DR   Genevisible; Q9NZ08; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:HGNC-UCL.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0005151; F:interleukin-1, type II receptor binding; TAS:HGNC-UCL.
DR   GO; GO:0005138; F:interleukin-6 receptor binding; IPI:UniProtKB.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008235; F:metalloexopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0001525; P:angiogenesis; TAS:HGNC-UCL.
DR   GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; TAS:HGNC-UCL.
DR   GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR   GO; GO:0045444; P:fat cell differentiation; NAS:UniProtKB.
DR   GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR   GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0008217; P:regulation of blood pressure; TAS:HGNC-UCL.
DR   GO; GO:0045088; P:regulation of innate immune response; NAS:UniProtKB.
DR   GO; GO:0009617; P:response to bacterium; NAS:BHF-UCL.
DR   CDD; cd09601; M1_APN-Q_like; 1.
DR   Gene3D; 2.60.40.1730; -; 1.
DR   InterPro; IPR042097; Aminopeptidase_N-like_N.
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   PANTHER; PTHR11533:SF156; PTHR11533:SF156; 1.
DR   Pfam; PF11838; ERAP1_C; 1.
DR   Pfam; PF01433; Peptidase_M1; 1.
DR   PRINTS; PR00756; ALADIPTASE.
DR   SUPFAM; SSF63737; SSF63737; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Adaptive immunity; Alternative splicing; Aminopeptidase;
KW   Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW   Glycoprotein; Hydrolase; Immunity; Membrane; Metal-binding;
KW   Metalloprotease; Polymorphism; Protease; Reference proteome; Signal-anchor;
KW   Transmembrane; Transmembrane helix; Zinc.
FT   CHAIN           1..941
FT                   /note="Endoplasmic reticulum aminopeptidase 1"
FT                   /id="PRO_0000026751"
FT   TOPO_DOM        1
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2..21
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        22..941
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   REGION          317..321
FT                   /note="Substrate binding"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        354
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   METAL           353
FT                   /note="Zinc; catalytic"
FT   METAL           357
FT                   /note="Zinc; catalytic"
FT   METAL           376
FT                   /note="Zinc; catalytic"
FT   BINDING         183
FT                   /note="Substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            438
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        70
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:21478864, ECO:0000269|Ref.16"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:21478864, ECO:0000269|Ref.16"
FT   CARBOHYD        414
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218, ECO:0000269|Ref.16"
FT   CARBOHYD        760
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:21478864"
FT   CARBOHYD        901
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        404..443
FT   DISULFID        736..743
FT   VAR_SEQ         940..941
FT                   /note="RM -> HDPEADATG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11481040,
FT                   ECO:0000303|PubMed:9628581"
FT                   /id="VSP_005450"
FT   VARIANT         56
FT                   /note="E -> K (in dbSNP:rs3734016)"
FT                   /id="VAR_046681"
FT   VARIANT         127
FT                   /note="R -> P (in dbSNP:rs26653)"
FT                   /evidence="ECO:0000269|PubMed:10220586,
FT                   ECO:0000269|PubMed:11481040, ECO:0000269|PubMed:12975309,
FT                   ECO:0000269|PubMed:9628581"
FT                   /id="VAR_012779"
FT   VARIANT         276
FT                   /note="I -> M (in dbSNP:rs26618)"
FT                   /id="VAR_012780"
FT   VARIANT         346
FT                   /note="G -> D (in dbSNP:rs27895)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_012781"
FT   VARIANT         349
FT                   /note="M -> V (in dbSNP:rs2287987)"
FT                   /evidence="ECO:0000269|PubMed:11481040,
FT                   ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581"
FT                   /id="VAR_012782"
FT   VARIANT         528
FT                   /note="K -> R (in dbSNP:rs30187)"
FT                   /evidence="ECO:0000269|PubMed:11481040,
FT                   ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581,
FT                   ECO:0000269|Ref.3"
FT                   /id="VAR_012783"
FT   VARIANT         575
FT                   /note="D -> G (in dbSNP:rs6863093)"
FT                   /id="VAR_046682"
FT   VARIANT         575
FT                   /note="D -> N (in dbSNP:rs10050860)"
FT                   /evidence="ECO:0000269|PubMed:11481040,
FT                   ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581"
FT                   /id="VAR_021555"
FT   VARIANT         725
FT                   /note="R -> Q (in dbSNP:rs17482078)"
FT                   /evidence="ECO:0000269|PubMed:11481040,
FT                   ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581"
FT                   /id="VAR_021556"
FT   VARIANT         730
FT                   /note="Q -> E (in dbSNP:rs27044)"
FT                   /evidence="ECO:0000269|PubMed:11481040,
FT                   ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:9628581,
FT                   ECO:0000269|Ref.3"
FT                   /id="VAR_012784"
FT   MUTAGEN         438
FT                   /note="Y->F: Loss of enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:21478864"
FT   CONFLICT        12
FT                   /note="T -> I (in Ref. 1; AAF07395 and 2; AAK37777/
FT                   AAK37778)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        514
FT                   /note="G -> R (in Ref. 3; AAF20384)"
FT                   /evidence="ECO:0000305"
FT   STRAND          56..70
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            71..74
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          75..88
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          91..96
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          101..109
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            112..114
FT                   /evidence="ECO:0000244|PDB:6RQX"
FT   STRAND          116..119
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          121..125
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            126..129
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          130..134
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          145..154
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          156..168
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          174..181
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            183..186
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           187..189
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          201..209
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          214..219
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          221..228
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          231..236
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           244..246
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          249..252
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          255..260
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          266..271
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           273..278
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           280..297
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          303..313
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          315..319
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          324..328
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           329..331
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            336..338
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           341..357
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            361..363
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          364..368
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           369..372
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           373..390
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           392..394
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           396..400
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           401..411
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          413..415
FT                   /evidence="ECO:0000244|PDB:6MGQ"
FT   HELIX           426..431
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           435..452
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           454..467
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            468..470
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          471..473
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           475..483
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           517..525
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          526..529
FT                   /evidence="ECO:0000244|PDB:6MGQ"
FT   STRAND          531..538
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          541..548
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          565..571
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          574..582
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          584..590
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          598..601
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           602..604
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          609..612
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            613..615
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           616..626
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           628..630
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           633..648
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           654..661
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           662..666
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           670..688
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           693..713
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          716..718
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           722..737
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           741..756
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            757..759
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           765..775
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           779..789
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           795..805
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           811..823
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          825..827
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           829..831
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           832..841
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            843..845
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           846..855
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           857..864
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   STRAND          866..868
FT                   /evidence="ECO:0000244|PDB:5J5E"
FT   HELIX           869..879
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           885..896
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           897..901
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   TURN            902..904
FT                   /evidence="ECO:0000244|PDB:6Q4R"
FT   HELIX           906..936
FT                   /evidence="ECO:0000244|PDB:6Q4R"
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
//
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