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 27-MAR-2024, entry version 216. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7ZYF; X-ray; 2.81 A; A/B=155-1025. DR PDBsum; 4P8Q; -. DR PDBsum; 4PJ6; -. DR PDBsum; 4Z7I; -. DR PDBsum; 5C97; -. DR PDBsum; 5JHQ; -. DR PDBsum; 5MJ6; -. DR PDBsum; 7ZYF; -. DR AlphaFoldDB; Q9UIQ6; -. DR SMR; Q9UIQ6; -. DR BioGRID; 110196; 209. DR ELM; Q9UIQ6; -. DR IntAct; Q9UIQ6; 81. 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 GlyCosmos; Q9UIQ6; 17 sites, 10 glycans. DR GlyGen; Q9UIQ6; 20 sites, 10 N-linked glycans (2 sites), 2 O-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; 9606-ENSP00000231368; -. DR PeptideAtlas; Q9UIQ6; -. DR ProteomicsDB; 84551; -. [Q9UIQ6-1] DR ProteomicsDB; 84552; -. [Q9UIQ6-2] DR ProteomicsDB; 84553; -. [Q9UIQ6-3] DR Pumba; Q9UIQ6; -. DR Antibodypedia; 25094; 167 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 AGR; HGNC:6656; -. 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; ERFFLSM; -. DR OrthoDB; 3085317at2759; -. 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; 12 hits in 1164 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 198 other cell types or tissues. 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: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; IDA:HGNC-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 CDD; cd09601; M1_APN-Q_like; 1. DR Gene3D; 1.25.50.20; -; 1. DR Gene3D; 2.60.40.1910; -; 1. DR Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1. DR Gene3D; 2.60.40.1730; tricorn interacting facor f3 domain; 1. DR InterPro; IPR045357; Aminopeptidase_N-like_N. DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf. 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; LEUCYL-CYSTINYL AMINOPEPTIDASE; 1. DR PANTHER; PTHR11533; PROTEASE M1 ZINC METALLOPROTEASE; 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; Leukotriene A4 hydrolase N-terminal domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; Q9UIQ6; HS. 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:7ZYF" 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 //