LCAP_HUMAN
ID LCAP_HUMAN Reviewed; 1025 AA.
AC Q9UIQ6; O00769; Q15145; Q59H76; Q9TNQ2; Q9TNQ3; Q9UIQ7;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Leucyl-cystinyl aminopeptidase;
DE Short=Cystinyl aminopeptidase;
DE EC=3.4.11.3;
DE AltName: Full=Insulin-regulated membrane aminopeptidase;
DE AltName: Full=Insulin-responsive aminopeptidase;
DE Short=IRAP;
DE AltName: Full=Oxytocinase;
DE Short=OTase;
DE AltName: Full=Placental leucine aminopeptidase;
DE Short=P-LAP;
DE Contains:
DE RecName: Full=Leucyl-cystinyl aminopeptidase, pregnancy serum form;
GN Name=LNPEP; Synonyms=OTASE;
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], PROTEIN SEQUENCE OF 160-168; 319-332; 615-624;
RP 635-647; 798-814 AND 870-880, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=8550619; DOI=10.1074/jbc.271.1.56;
RA Rogi T., Tsujimoto M., Nakazato H., Mizutani S., Tomoda Y.;
RT "Human placental leucine aminopeptidase/oxytocinase. A new member of type
RT II membrane-spanning zinc metallopeptidase family.";
RL J. Biol. Chem. 271:56-61(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=9177475; DOI=10.1016/s0167-4781(97)00036-5;
RA Laustsen P.G., Rasmussen T.E., Petersen K., Pedraza-Diaz S., Moestrup S.K.,
RA Gliemann J., Sottrup-Jensen L., Kristensen T.;
RT "The complete amino acid sequence of human placental oxytocinase.";
RL Biochim. Biophys. Acta 1352:1-7(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
RX PubMed=10759854; DOI=10.1046/j.1432-1327.2000.01234.x;
RA Rasmussen T.E., Pedraza-Diaz S., Hardre R., Laustsen P.G., Carrion A.G.,
RA Kristensen T.;
RT "Structure of the human oxytocinase/insulin-regulated aminopeptidase gene
RT and localization to chromosome 5q21.";
RL Eur. J. Biochem. 267:2297-2306(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11389728; DOI=10.1046/j.1432-1327.2001.02221.x;
RA Matsumoto H., Nagasaka T., Hattori A., Rogi T., Tsuruoka N., Mizutani S.,
RA Tsujimoto M.;
RT "Expression of placental leucine aminopeptidase/oxytocinase in neuronal
RT cells and its action on neuronal peptides.";
RL Eur. J. Biochem. 268:3259-3266(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 206-1025.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 285-301 AND 710-724.
RX PubMed=8119729; DOI=10.1007/bf00188785;
RA Falk K., Roetzschke O., Stevanovic S., Jung G., Rammensee H.G.;
RT "Pool sequencing of natural HLA-DR, DQ, and DP ligands reveals detailed
RT peptide motifs, constraints of processing, and general rules.";
RL Immunogenetics 39:230-242(1994).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1731608; DOI=10.1016/0003-9861(92)90007-j;
RA Tsujimoto M., Mizutani S., Adachi H., Kimura M., Nakazato H., Tomoda Y.;
RT "Identification of human placental leucine aminopeptidase as oxytocinase.";
RL Arch. Biochem. Biophys. 292:388-392(1992).
RN [8]
RP FUNCTION.
RX PubMed=11707427; DOI=10.1074/jbc.c100512200;
RA Albiston A.L., McDowall S.G., Matsacos D., Sim P., Clune E., Mustafa T.,
RA Lee J., Mendelsohn F.A., Simpson R.J., Connolly L.M., Chai S.Y.;
RT "Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-
RT regulated aminopeptidase.";
RL J. Biol. Chem. 276:48623-48626(2001).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184; ASN-448; ASN-682 AND
RP ASN-850.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-91, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91, AND IDENTIFICATION BY
RP 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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Release of an N-terminal amino acid, cleaves before cysteine,
CC leucine as well as other amino acids. Degrades peptide hormones such as
CC oxytocin, vasopressin and angiotensin III, and plays a role in
CC maintaining homeostasis during pregnancy. May be involved in the
CC inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin
CC and dynorphin. Binds angiotensin IV and may be the angiotensin IV
CC receptor in the brain. {ECO:0000269|PubMed:11389728,
CC ECO:0000269|PubMed:11707427, ECO:0000269|PubMed:1731608}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal amino acid, Cys-|-Xaa-, in which the
CC half-cystine residue is involved in a disulfide loop, notably in
CC oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl
CC arylamides exceed that for the cystinyl derivative, however.;
CC EC=3.4.11.3; Evidence={ECO:0000269|PubMed:11389728,
CC ECO:0000269|PubMed:1731608};
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: Homodimer. Binds tankyrases 1 and 2.
CC -!- INTERACTION:
CC Q9UIQ6; Q969F0: FATE1; NbExp=3; IntAct=EBI-2805360, EBI-743099;
CC Q9UIQ6; Q04864: REL; NbExp=3; IntAct=EBI-2805360, EBI-307352;
CC Q9UIQ6; P15884: TCF4; NbExp=3; IntAct=EBI-2805360, EBI-533224;
CC Q9UIQ6; Q9H2K2: TNKS2; NbExp=3; IntAct=EBI-2805360, EBI-4398527;
CC Q9UIQ6-2; Q13520: AQP6; NbExp=3; IntAct=EBI-12133176, EBI-13059134;
CC Q9UIQ6-2; P07307-3: ASGR2; NbExp=3; IntAct=EBI-12133176, EBI-12808270;
CC Q9UIQ6-2; Q99675: CGRRF1; NbExp=3; IntAct=EBI-12133176, EBI-2130213;
CC Q9UIQ6-2; P78358: CTAG1B; NbExp=3; IntAct=EBI-12133176, EBI-1188472;
CC Q9UIQ6-2; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-12133176, EBI-18938272;
CC Q9UIQ6-2; Q969F0: FATE1; NbExp=3; IntAct=EBI-12133176, EBI-743099;
CC Q9UIQ6-2; Q9UJ14: GGT7; NbExp=3; IntAct=EBI-12133176, EBI-1058791;
CC Q9UIQ6-2; O15529: GPR42; NbExp=3; IntAct=EBI-12133176, EBI-18076404;
CC Q9UIQ6-2; Q8TED1: GPX8; NbExp=3; IntAct=EBI-12133176, EBI-11721746;
CC Q9UIQ6-2; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-12133176, EBI-1052304;
CC Q9UIQ6-2; P80188: LCN2; NbExp=3; IntAct=EBI-12133176, EBI-11911016;
CC Q9UIQ6-2; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-12133176, EBI-2820517;
CC Q9UIQ6-2; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-12133176, EBI-6163737;
CC Q9UIQ6-2; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-12133176, EBI-7545592;
CC Q9UIQ6-2; Q7Z769: SLC35E3; NbExp=3; IntAct=EBI-12133176, EBI-13389236;
CC Q9UIQ6-2; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-12133176, EBI-2823239;
CC Q9UIQ6-2; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-12133176, EBI-17280858;
CC Q9UIQ6-2; P27105: STOM; NbExp=3; IntAct=EBI-12133176, EBI-1211440;
CC Q9UIQ6-2; P59542: TAS2R19; NbExp=3; IntAct=EBI-12133176, EBI-12847034;
CC Q9UIQ6-2; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-12133176, EBI-12947623;
CC Q9UIQ6-2; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-12133176, EBI-11722971;
CC Q9UIQ6-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-12133176, EBI-741480;
CC Q9UIQ6-2; Q86WB7-2: UNC93A; NbExp=3; IntAct=EBI-12133176, EBI-13356252;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11389728};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:11389728}.
CC Note=In brain only the membrane-bound form is found. The protein
CC resides in intracellular vesicles together with GLUT4 and can then
CC translocate to the cell surface in response to insulin and/or oxytocin.
CC Localization may be determined by dileucine internalization motifs,
CC and/or by interaction with tankyrases.
CC -!- SUBCELLULAR LOCATION: [Leucyl-cystinyl aminopeptidase, pregnancy serum
CC form]: Secreted. Note=During pregnancy serum levels are low in the
CC first trimester, rise progressively during the second and third
CC trimester and decrease rapidly after parturition.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q9UIQ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UIQ6-2; Sequence=VSP_005448;
CC Name=3;
CC IsoId=Q9UIQ6-3; Sequence=VSP_005449;
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, heart, kidney and
CC small intestine. Detected at lower levels in neuronal cells in the
CC brain, in skeletal muscle, spleen, liver, testes and colon.
CC {ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:8550619,
CC ECO:0000269|PubMed:9177475}.
CC -!- PTM: The pregnancy serum form is derived from the membrane-bound form
CC by proteolytic processing.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19349973}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09436.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAD92120.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D50810; BAA09436.1; ALT_INIT; mRNA.
DR EMBL; U62768; AAB66672.1; -; mRNA.
DR EMBL; U62769; AAB66673.1; -; mRNA.
DR EMBL; AJ131023; CAB61646.1; -; Genomic_DNA.
DR EMBL; AJ131025; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131026; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131027; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131028; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131029; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131030; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131031; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131032; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131033; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131034; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131035; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131036; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131037; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131038; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131039; CAB61646.1; JOINED; Genomic_DNA.
DR EMBL; AJ131025; CAB94753.1; -; Genomic_DNA.
DR EMBL; AJ131026; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131027; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131028; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131029; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131030; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131031; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131032; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131033; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131034; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131035; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131036; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131037; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131038; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AJ131039; CAB94753.1; JOINED; Genomic_DNA.
DR EMBL; AB208883; BAD92120.1; ALT_FRAME; mRNA.
DR CCDS; CCDS4087.1; -. [Q9UIQ6-1]
DR CCDS; CCDS43346.1; -. [Q9UIQ6-2]
DR PIR; A59383; A59383.
DR PIR; A59384; A59384.
DR RefSeq; NP_005566.2; NM_005575.2. [Q9UIQ6-1]
DR RefSeq; NP_787116.2; NM_175920.3. [Q9UIQ6-2]
DR PDB; 4P8Q; X-ray; 3.02 A; A/B=155-1025.
DR PDB; 4PJ6; X-ray; 2.96 A; A/B=155-1025.
DR PDB; 4Z7I; X-ray; 3.31 A; A/B=155-1025.
DR PDB; 5C97; X-ray; 3.37 A; A/B=155-1025.
DR PDB; 5JHQ; X-ray; 3.20 A; E/F/G/H/I/J/K/L=92-107.
DR PDB; 5MJ6; X-ray; 2.53 A; A/B=155-1025.
DR PDBsum; 4P8Q; -.
DR PDBsum; 4PJ6; -.
DR PDBsum; 4Z7I; -.
DR PDBsum; 5C97; -.
DR PDBsum; 5JHQ; -.
DR PDBsum; 5MJ6; -.
DR AlphaFoldDB; Q9UIQ6; -.
DR SMR; Q9UIQ6; -.
DR BioGRID; 110196; 200.
DR ELM; Q9UIQ6; -.
DR IntAct; Q9UIQ6; 75.
DR MINT; Q9UIQ6; -.
DR STRING; 9606.ENSP00000231368; -.
DR BindingDB; Q9UIQ6; -.
DR ChEMBL; CHEMBL2693; -.
DR DrugBank; DB00107; Oxytocin.
DR GuidetoPHARMACOLOGY; 1570; -.
DR MEROPS; M01.011; -.
DR GlyConnect; 1455; 10 N-Linked glycans (2 sites).
DR GlyGen; Q9UIQ6; 18 sites, 10 N-linked glycans (2 sites).
DR iPTMnet; Q9UIQ6; -.
DR PhosphoSitePlus; Q9UIQ6; -.
DR SwissPalm; Q9UIQ6; -.
DR BioMuta; LNPEP; -.
DR DMDM; 145559489; -.
DR EPD; Q9UIQ6; -.
DR jPOST; Q9UIQ6; -.
DR MassIVE; Q9UIQ6; -.
DR MaxQB; Q9UIQ6; -.
DR PaxDb; Q9UIQ6; -.
DR PeptideAtlas; Q9UIQ6; -.
DR PRIDE; Q9UIQ6; -.
DR ProteomicsDB; 84551; -. [Q9UIQ6-1]
DR ProteomicsDB; 84552; -. [Q9UIQ6-2]
DR ProteomicsDB; 84553; -. [Q9UIQ6-3]
DR Antibodypedia; 25094; 144 antibodies from 31 providers.
DR DNASU; 4012; -.
DR Ensembl; ENST00000231368.10; ENSP00000231368.5; ENSG00000113441.16. [Q9UIQ6-1]
DR Ensembl; ENST00000395770.3; ENSP00000379117.3; ENSG00000113441.16. [Q9UIQ6-2]
DR GeneID; 4012; -.
DR KEGG; hsa:4012; -.
DR MANE-Select; ENST00000231368.10; ENSP00000231368.5; NM_005575.3; NP_005566.2.
DR UCSC; uc003kmv.2; human. [Q9UIQ6-1]
DR CTD; 4012; -.
DR DisGeNET; 4012; -.
DR GeneCards; LNPEP; -.
DR HGNC; HGNC:6656; LNPEP.
DR HPA; ENSG00000113441; Low tissue specificity.
DR MIM; 151300; gene.
DR neXtProt; NX_Q9UIQ6; -.
DR OpenTargets; ENSG00000113441; -.
DR PharmGKB; PA30418; -.
DR VEuPathDB; HostDB:ENSG00000113441; -.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000157902; -.
DR HOGENOM; CLU_003705_2_2_1; -.
DR InParanoid; Q9UIQ6; -.
DR OMA; TSMTFKG; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; Q9UIQ6; -.
DR TreeFam; TF300395; -.
DR BRENDA; 3.4.11.3; 2681.
DR PathwayCommons; Q9UIQ6; -.
DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SABIO-RK; Q9UIQ6; -.
DR SignaLink; Q9UIQ6; -.
DR SIGNOR; Q9UIQ6; -.
DR BioGRID-ORCS; 4012; 10 hits in 1084 CRISPR screens.
DR ChiTaRS; LNPEP; human.
DR GeneWiki; Cystinyl_aminopeptidase; -.
DR GenomeRNAi; 4012; -.
DR Pharos; Q9UIQ6; Tchem.
DR PRO; PR:Q9UIQ6; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9UIQ6; protein.
DR Bgee; ENSG00000113441; Expressed in visceral pleura and 196 other tissues.
DR Genevisible; Q9UIQ6; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031905; C:early endosome lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0004177; F:aminopeptidase activity; EXP:Reactome.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0002480; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent; TAS:Reactome.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
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; IPR034017; Cystinyl_aminopeptidase.
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:SF42; PTHR11533:SF42; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Aminopeptidase;
KW Cell membrane; Direct protein sequencing; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..1025
FT /note="Leucyl-cystinyl aminopeptidase"
FT /id="PRO_0000095114"
FT CHAIN 155..1025
FT /note="Leucyl-cystinyl aminopeptidase, pregnancy serum
FT form"
FT /id="PRO_0000292264"
FT TOPO_DOM 1..110
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..1025
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 96..101
FT /note="Tankyrase binding"
FT MOTIF 53..54
FT /note="Dileucine internalization motif"
FT /evidence="ECO:0000255"
FT MOTIF 76..77
FT /note="Dileucine internalization motif"
FT /evidence="ECO:0000255"
FT ACT_SITE 465
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 295
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 428..432
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 464
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 468
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 487
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 154..155
FT /note="Cleavage; to produce pregnancy serum form"
FT SITE 549
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 70
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8C129"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 525
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 578
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 598
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 664
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 682
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 760
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 834
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 850
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..19
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11389728"
FT /id="VSP_005449"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11389728,
FT ECO:0000303|PubMed:9177475"
FT /id="VSP_005448"
FT VARIANT 86
FT /note="S -> P (in dbSNP:rs3797799)"
FT /id="VAR_031616"
FT VARIANT 594
FT /note="N -> I (in dbSNP:rs12520455)"
FT /id="VAR_051567"
FT VARIANT 763
FT /note="A -> T (in dbSNP:rs2303138)"
FT /id="VAR_012812"
FT VARIANT 913
FT /note="S -> T (in dbSNP:rs17087233)"
FT /id="VAR_051568"
FT VARIANT 963
FT /note="I -> V (in dbSNP:rs11746232)"
FT /id="VAR_031617"
FT CONFLICT 66
FT /note="D -> V (in Ref. 3; CAB61646/CAB94753)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="S -> L (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="K -> N (in Ref. 2; AAB66672/AAB66673 and 3;
FT CAB61646/CAB94753)"
FT /evidence="ECO:0000305"
FT CONFLICT 892
FT /note="K -> Q (in Ref. 1; BAA09436)"
FT /evidence="ECO:0000305"
FT CONFLICT 944
FT /note="F -> L (in Ref. 1; BAA09436)"
FT /evidence="ECO:0000305"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 170..184
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 189..202
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 204..210
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 215..223
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 256..266
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 268..280
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:5C97"
FT STRAND 286..293
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 295..298
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 299..302
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:4PJ6"
FT STRAND 313..322
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 343..348
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:4PJ6"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 367..373
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 376..382
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 384..390
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 391..408
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 415..424
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 426..430
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 435..439
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 452..468
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 472..474
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 475..479
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 480..483
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 484..501
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 503..505
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 508..522
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 523..526
FT /evidence="ECO:0007829|PDB:4Z7I"
FT HELIX 537..542
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 546..562
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 565..579
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 586..597
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 600..602
FT /evidence="ECO:0007829|PDB:4P8Q"
FT HELIX 603..612
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 613..615
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 617..624
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 627..634
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 654..662
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 663..665
FT /evidence="ECO:0007829|PDB:4PJ6"
FT STRAND 667..674
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 676..682
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 687..693
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 694..696
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 698..704
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 706..718
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 720..722
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 725..741
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 742..744
FT /evidence="ECO:0007829|PDB:5C97"
FT HELIX 746..753
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 754..758
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 762..782
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 785..804
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 808..810
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 814..829
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 835..847
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 848..850
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 857..859
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 860..867
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 871..881
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 887..897
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 903..915
FT /evidence="ECO:0007829|PDB:5MJ6"
FT STRAND 917..919
FT /evidence="ECO:0007829|PDB:4PJ6"
FT HELIX 921..923
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 924..933
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 935..947
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 949..955
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 961..969
FT /evidence="ECO:0007829|PDB:5MJ6"
FT TURN 970..973
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 977..988
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 992..995
FT /evidence="ECO:0007829|PDB:5MJ6"
FT HELIX 998..1024
FT /evidence="ECO:0007829|PDB:5MJ6"
SQ SEQUENCE 1025 AA; 117349 MW; F84C0EA9D48DC2C0 CRC64;
MEPFTNDRLQ LPRNMIENSM FEEEPDVVDL AKEPCLHPLE PDEVEYEPRG SRLLVRGLGE
HEMEEDEEDY ESSAKLLGMS FMNRSSGLRN SATGYRQSPD GACSVPSART MVVCAFVIVV
AVSVIMVIYL LPRCTFTKEG CHKKNQSIGL IQPFATNGKL FPWAQIRLPT AVVPLRYELS
LHPNLTSMTF RGSVTISVQA LQVTWNIILH STGHNISRVT FMSAVSSQEK QAEILEYAYH
GQIAIVAPEA LLAGHNYTLK IEYSANISSS YYGFYGFSYT DESNEKKYFA ATQFEPLAAR
SAFPCFDEPA FKATFIIKII RDEQYTALSN MPKKSSVVLD DGLVQDEFSE SVKMSTYLVA
FIVGEMKNLS QDVNGTLVSI YAVPEKIGQV HYALETTVKL LEFFQNYFEI QYPLKKLDLV
AIPDFEAGAM ENWGLLTFRE ETLLYDSNTS SMADRKLVTK IIAHELAHQW FGNLVTMKWW
NDLWLNEGFA TFMEYFSLEK IFKELSSYED FLDARFKTMK KDSLNSSHPI SSSVQSSEQI
EEMFDSLSYF KGSSLLLMLK TYLSEDVFQH AVVLYLHNHS YASIQSDDLW DSFNEVTNQT
LDVKRMMKTW TLQKGFPLVT VQKKGKELFI QQERFFLNMK PEIQPSDTSY LWHIPLSYVT
EGRNYSKYQS VSLLDKKSGV INLTEEVLWV KVNINMNGYY IVHYADDDWE ALIHQLKINP
YVLSDKDRAN LINNIFELAG LGKVPLKRAF DLINYLGNEN HTAPITEALF QTDLIYNLLE
KLGYMDLASR LVTRVFKLLQ NQIQQQTWTD EGTPSMRELR SALLEFACTH NLGNCSTTAM
KLFDDWMASN GTQSLPTDVM TTVFKVGAKT DKGWSFLLGK YISIGSEAEK NKILEALASS
EDVRKLYWLM KSSLNGDNFR TQKLSFIIRT VGRHFPGHLL AWDFVKENWN KLVQKFPLGS
YTIQNIVAGS TYLFSTKTHL SEVQAFFENQ SEATFRLRCV QEALEVIQLN IQWMEKNLKS
LTWWL
