Full text data of LNPEP
LNPEP
(OTASE)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Leucyl-cystinyl aminopeptidase; Cystinyl aminopeptidase; 3.4.11.3 (Insulin-regulated membrane aminopeptidase; Insulin-responsive aminopeptidase; IRAP; Oxytocinase; OTase; Placental leucine aminopeptidase; P-LAP; Leucyl-cystinyl aminopeptidase, pregnancy serum form)
Leucyl-cystinyl aminopeptidase; Cystinyl aminopeptidase; 3.4.11.3 (Insulin-regulated membrane aminopeptidase; Insulin-responsive aminopeptidase; IRAP; Oxytocinase; OTase; Placental leucine aminopeptidase; P-LAP; Leucyl-cystinyl aminopeptidase, pregnancy serum form)
UniProt
Q9UIQ6
ID LCAP_HUMAN Reviewed; 1025 AA.
AC Q9UIQ6; O00769; Q15145; Q59H76; Q9TNQ2; Q9TNQ3; Q9UIQ7;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-APR-2007, sequence version 3.
DT 22-JAN-2014, entry version 136.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 160-168; 319-332;
RP 615-624; 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
RT type 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.,
RA Moestrup S.K., 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.,
RA Carrion A.G., Kristensen T.;
RT "Structure of the human oxytocinase/insulin-regulated aminopeptidase
RT gene 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.,
RA Mizutani S., Tsujimoto M.;
RT "Expression of placental leucine aminopeptidase/oxytocinase in
RT neuronal 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
RT detailed peptide motifs, constraints of processing, and general
RT 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.,
RA Tomoda Y.;
RT "Identification of human placental leucine aminopeptidase as
RT 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.,
RA Mustafa T., Lee J., Mendelsohn F.A., Simpson R.J., Connolly L.M.,
RA Chai S.Y.;
RT "Evidence that the angiotensin IV (AT(4)) receptor is the enzyme
RT insulin-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, AND MASS SPECTROMETRY.
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-
RT linked 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.,
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Release of an N-terminal amino acid, cleaves before
CC cysteine, leucine as well as other amino acids. Degrades peptide
CC hormones such as oxytocin, vasopressin and angiotensin III, and
CC plays a role in maintaining homeostasis during pregnancy. May be
CC involved in the inactivation of neuronal peptides in the brain.
CC Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may
CC be the angiotensin IV receptor in the brain.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid, Cys-|-
CC Xaa-, in which the half-cystine residue is involved in a disulfide
CC loop, notably in oxytocin or vasopressin. Hydrolysis rates on a
CC range of aminoacyl arylamides exceed that for the cystinyl
CC derivative, however.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- SUBUNIT: Homodimer. Binds tankyrases 1 and 2.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Note=In brain only the membrane-bound form is found. The
CC protein resides in intracellular vesicles together with GLUT4 and
CC can then translocate to the cell surface in response to insulin
CC and/or oxytocin. Localization may be determined by dileucine
CC internalization motifs, and/or by interaction with tankyrases.
CC -!- SUBCELLULAR LOCATION: Leucyl-cystinyl aminopeptidase, pregnancy
CC serum form: Secreted. Note=During pregnancy serum levels are low
CC in the first trimester, rise progressively during the second and
CC third 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
CC 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
CC and small intestine. Detected at lower levels in neuronal cells in
CC the brain, in skeletal muscle, spleen, liver, testes and colon.
CC -!- PTM: The pregnancy serum form is derived from the membrane-bound
CC form by proteolytic processing.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09436.1; Type=Erroneous initiation;
CC Sequence=BAD92120.1; Type=Frameshift; Positions=405;
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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 PIR; A59383; A59383.
DR PIR; A59384; A59384.
DR RefSeq; NP_005566.2; NM_005575.2.
DR RefSeq; NP_787116.2; NM_175920.3.
DR UniGene; Hs.527199; -.
DR UniGene; Hs.656905; -.
DR ProteinModelPortal; Q9UIQ6; -.
DR SMR; Q9UIQ6; 161-1025.
DR IntAct; Q9UIQ6; 4.
DR STRING; 9606.ENSP00000231368; -.
DR BindingDB; Q9UIQ6; -.
DR ChEMBL; CHEMBL2693; -.
DR MEROPS; M01.011; -.
DR PhosphoSite; Q9UIQ6; -.
DR DMDM; 145559489; -.
DR PaxDb; Q9UIQ6; -.
DR PeptideAtlas; Q9UIQ6; -.
DR PRIDE; Q9UIQ6; -.
DR DNASU; 4012; -.
DR Ensembl; ENST00000231368; ENSP00000231368; ENSG00000113441.
DR Ensembl; ENST00000395770; ENSP00000379117; ENSG00000113441.
DR GeneID; 4012; -.
DR KEGG; hsa:4012; -.
DR UCSC; uc003kmv.1; human.
DR CTD; 4012; -.
DR GeneCards; GC05P096272; -.
DR H-InvDB; HIX0005054; -.
DR HGNC; HGNC:6656; LNPEP.
DR HPA; HPA043642; -.
DR MIM; 151300; gene.
DR neXtProt; NX_Q9UIQ6; -.
DR PharmGKB; PA30418; -.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG108296; -.
DR InParanoid; Q9UIQ6; -.
DR KO; K01257; -.
DR OMA; EIQPSDA; -.
DR OrthoDB; EOG754HNR; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_6900; Immune System.
DR SABIO-RK; Q9UIQ6; -.
DR GeneWiki; Cystinyl_aminopeptidase; -.
DR GenomeRNAi; 4012; -.
DR NextBio; 15736; -.
DR PMAP-CutDB; Q9UIQ6; -.
DR PRO; PR:Q9UIQ6; -.
DR Bgee; Q9UIQ6; -.
DR CleanEx; HS_LNPEP; -.
DR Genevestigator; Q9UIQ6; -.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
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 to plasma membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:HGNC.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
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:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
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 Acetylation; Alternative splicing; Aminopeptidase; Cell membrane;
KW Complete proteome; Direct protein sequencing; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Polymorphism; Protease; Reference proteome; Secreted; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1 1025 Leucyl-cystinyl aminopeptidase.
FT /FTId=PRO_0000095114.
FT CHAIN 155 1025 Leucyl-cystinyl aminopeptidase, pregnancy
FT serum form.
FT /FTId=PRO_0000292264.
FT TOPO_DOM 1 110 Cytoplasmic (Potential).
FT TRANSMEM 111 131 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 132 1025 Extracellular (Potential).
FT REGION 96 101 Tankyrase binding.
FT REGION 428 432 Substrate binding (By similarity).
FT MOTIF 53 54 Dileucine internalization motif
FT (Potential).
FT MOTIF 76 77 Dileucine internalization motif
FT (Potential).
FT ACT_SITE 465 465 Proton acceptor (By similarity).
FT METAL 464 464 Zinc; catalytic (By similarity).
FT METAL 468 468 Zinc; catalytic (By similarity).
FT METAL 487 487 Zinc; catalytic (By similarity).
FT BINDING 295 295 Substrate (By similarity).
FT SITE 154 155 Cleavage; to produce pregnancy serum
FT form.
FT SITE 549 549 Transition state stabilizer (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 70 70 Phosphotyrosine (By similarity).
FT MOD_RES 80 80 Phosphoserine (By similarity).
FT MOD_RES 91 91 Phosphoserine (By similarity).
FT CARBOHYD 145 145 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 184 184 N-linked (GlcNAc...).
FT CARBOHYD 215 215 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 256 256 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 266 266 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 368 368 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 374 374 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 448 448 N-linked (GlcNAc...).
FT CARBOHYD 525 525 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 578 578 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 598 598 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 664 664 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 682 682 N-linked (GlcNAc...).
FT CARBOHYD 760 760 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 834 834 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 850 850 N-linked (GlcNAc...).
FT CARBOHYD 989 989 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 19 Missing (in isoform 3).
FT /FTId=VSP_005449.
FT VAR_SEQ 1 14 Missing (in isoform 2).
FT /FTId=VSP_005448.
FT VARIANT 86 86 S -> P (in dbSNP:rs3797799).
FT /FTId=VAR_031616.
FT VARIANT 594 594 N -> I (in dbSNP:rs12520455).
FT /FTId=VAR_051567.
FT VARIANT 763 763 A -> T (in dbSNP:rs2303138).
FT /FTId=VAR_012812.
FT VARIANT 913 913 S -> T (in dbSNP:rs17087233).
FT /FTId=VAR_051568.
FT VARIANT 963 963 I -> V (in dbSNP:rs11746232).
FT /FTId=VAR_031617.
FT CONFLICT 66 66 D -> V (in Ref. 3; CAB61646/CAB94753).
FT CONFLICT 301 301 S -> L (in Ref. 6; AA sequence).
FT CONFLICT 386 386 K -> N (in Ref. 2; AAB66672/AAB66673 and
FT 3; CAB61646/CAB94753).
FT CONFLICT 892 892 K -> Q (in Ref. 1; BAA09436).
FT CONFLICT 944 944 F -> L (in Ref. 1; BAA09436).
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
//
ID LCAP_HUMAN Reviewed; 1025 AA.
AC Q9UIQ6; O00769; Q15145; Q59H76; Q9TNQ2; Q9TNQ3; Q9UIQ7;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-APR-2007, sequence version 3.
DT 22-JAN-2014, entry version 136.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 160-168; 319-332;
RP 615-624; 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
RT type 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.,
RA Moestrup S.K., 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.,
RA Carrion A.G., Kristensen T.;
RT "Structure of the human oxytocinase/insulin-regulated aminopeptidase
RT gene 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.,
RA Mizutani S., Tsujimoto M.;
RT "Expression of placental leucine aminopeptidase/oxytocinase in
RT neuronal 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
RT detailed peptide motifs, constraints of processing, and general
RT 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.,
RA Tomoda Y.;
RT "Identification of human placental leucine aminopeptidase as
RT 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.,
RA Mustafa T., Lee J., Mendelsohn F.A., Simpson R.J., Connolly L.M.,
RA Chai S.Y.;
RT "Evidence that the angiotensin IV (AT(4)) receptor is the enzyme
RT insulin-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, AND MASS SPECTROMETRY.
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-
RT linked 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.,
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Release of an N-terminal amino acid, cleaves before
CC cysteine, leucine as well as other amino acids. Degrades peptide
CC hormones such as oxytocin, vasopressin and angiotensin III, and
CC plays a role in maintaining homeostasis during pregnancy. May be
CC involved in the inactivation of neuronal peptides in the brain.
CC Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may
CC be the angiotensin IV receptor in the brain.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid, Cys-|-
CC Xaa-, in which the half-cystine residue is involved in a disulfide
CC loop, notably in oxytocin or vasopressin. Hydrolysis rates on a
CC range of aminoacyl arylamides exceed that for the cystinyl
CC derivative, however.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- SUBUNIT: Homodimer. Binds tankyrases 1 and 2.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Note=In brain only the membrane-bound form is found. The
CC protein resides in intracellular vesicles together with GLUT4 and
CC can then translocate to the cell surface in response to insulin
CC and/or oxytocin. Localization may be determined by dileucine
CC internalization motifs, and/or by interaction with tankyrases.
CC -!- SUBCELLULAR LOCATION: Leucyl-cystinyl aminopeptidase, pregnancy
CC serum form: Secreted. Note=During pregnancy serum levels are low
CC in the first trimester, rise progressively during the second and
CC third 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
CC 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
CC and small intestine. Detected at lower levels in neuronal cells in
CC the brain, in skeletal muscle, spleen, liver, testes and colon.
CC -!- PTM: The pregnancy serum form is derived from the membrane-bound
CC form by proteolytic processing.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09436.1; Type=Erroneous initiation;
CC Sequence=BAD92120.1; Type=Frameshift; Positions=405;
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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 PIR; A59383; A59383.
DR PIR; A59384; A59384.
DR RefSeq; NP_005566.2; NM_005575.2.
DR RefSeq; NP_787116.2; NM_175920.3.
DR UniGene; Hs.527199; -.
DR UniGene; Hs.656905; -.
DR ProteinModelPortal; Q9UIQ6; -.
DR SMR; Q9UIQ6; 161-1025.
DR IntAct; Q9UIQ6; 4.
DR STRING; 9606.ENSP00000231368; -.
DR BindingDB; Q9UIQ6; -.
DR ChEMBL; CHEMBL2693; -.
DR MEROPS; M01.011; -.
DR PhosphoSite; Q9UIQ6; -.
DR DMDM; 145559489; -.
DR PaxDb; Q9UIQ6; -.
DR PeptideAtlas; Q9UIQ6; -.
DR PRIDE; Q9UIQ6; -.
DR DNASU; 4012; -.
DR Ensembl; ENST00000231368; ENSP00000231368; ENSG00000113441.
DR Ensembl; ENST00000395770; ENSP00000379117; ENSG00000113441.
DR GeneID; 4012; -.
DR KEGG; hsa:4012; -.
DR UCSC; uc003kmv.1; human.
DR CTD; 4012; -.
DR GeneCards; GC05P096272; -.
DR H-InvDB; HIX0005054; -.
DR HGNC; HGNC:6656; LNPEP.
DR HPA; HPA043642; -.
DR MIM; 151300; gene.
DR neXtProt; NX_Q9UIQ6; -.
DR PharmGKB; PA30418; -.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG108296; -.
DR InParanoid; Q9UIQ6; -.
DR KO; K01257; -.
DR OMA; EIQPSDA; -.
DR OrthoDB; EOG754HNR; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_6900; Immune System.
DR SABIO-RK; Q9UIQ6; -.
DR GeneWiki; Cystinyl_aminopeptidase; -.
DR GenomeRNAi; 4012; -.
DR NextBio; 15736; -.
DR PMAP-CutDB; Q9UIQ6; -.
DR PRO; PR:Q9UIQ6; -.
DR Bgee; Q9UIQ6; -.
DR CleanEx; HS_LNPEP; -.
DR Genevestigator; Q9UIQ6; -.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
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 to plasma membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:HGNC.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
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:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
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 Acetylation; Alternative splicing; Aminopeptidase; Cell membrane;
KW Complete proteome; Direct protein sequencing; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Polymorphism; Protease; Reference proteome; Secreted; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1 1025 Leucyl-cystinyl aminopeptidase.
FT /FTId=PRO_0000095114.
FT CHAIN 155 1025 Leucyl-cystinyl aminopeptidase, pregnancy
FT serum form.
FT /FTId=PRO_0000292264.
FT TOPO_DOM 1 110 Cytoplasmic (Potential).
FT TRANSMEM 111 131 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 132 1025 Extracellular (Potential).
FT REGION 96 101 Tankyrase binding.
FT REGION 428 432 Substrate binding (By similarity).
FT MOTIF 53 54 Dileucine internalization motif
FT (Potential).
FT MOTIF 76 77 Dileucine internalization motif
FT (Potential).
FT ACT_SITE 465 465 Proton acceptor (By similarity).
FT METAL 464 464 Zinc; catalytic (By similarity).
FT METAL 468 468 Zinc; catalytic (By similarity).
FT METAL 487 487 Zinc; catalytic (By similarity).
FT BINDING 295 295 Substrate (By similarity).
FT SITE 154 155 Cleavage; to produce pregnancy serum
FT form.
FT SITE 549 549 Transition state stabilizer (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 70 70 Phosphotyrosine (By similarity).
FT MOD_RES 80 80 Phosphoserine (By similarity).
FT MOD_RES 91 91 Phosphoserine (By similarity).
FT CARBOHYD 145 145 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 184 184 N-linked (GlcNAc...).
FT CARBOHYD 215 215 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 256 256 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 266 266 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 368 368 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 374 374 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 448 448 N-linked (GlcNAc...).
FT CARBOHYD 525 525 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 578 578 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 598 598 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 664 664 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 682 682 N-linked (GlcNAc...).
FT CARBOHYD 760 760 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 834 834 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 850 850 N-linked (GlcNAc...).
FT CARBOHYD 989 989 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 19 Missing (in isoform 3).
FT /FTId=VSP_005449.
FT VAR_SEQ 1 14 Missing (in isoform 2).
FT /FTId=VSP_005448.
FT VARIANT 86 86 S -> P (in dbSNP:rs3797799).
FT /FTId=VAR_031616.
FT VARIANT 594 594 N -> I (in dbSNP:rs12520455).
FT /FTId=VAR_051567.
FT VARIANT 763 763 A -> T (in dbSNP:rs2303138).
FT /FTId=VAR_012812.
FT VARIANT 913 913 S -> T (in dbSNP:rs17087233).
FT /FTId=VAR_051568.
FT VARIANT 963 963 I -> V (in dbSNP:rs11746232).
FT /FTId=VAR_031617.
FT CONFLICT 66 66 D -> V (in Ref. 3; CAB61646/CAB94753).
FT CONFLICT 301 301 S -> L (in Ref. 6; AA sequence).
FT CONFLICT 386 386 K -> N (in Ref. 2; AAB66672/AAB66673 and
FT 3; CAB61646/CAB94753).
FT CONFLICT 892 892 K -> Q (in Ref. 1; BAA09436).
FT CONFLICT 944 944 F -> L (in Ref. 1; BAA09436).
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
//
MIM
151300
*RECORD*
*FIELD* NO
151300
*FIELD* TI
*151300 LEUCYL-CYSTINYL AMINOPEPTIDASE; LNPEP
;;LEUCINE AMINOPEPTIDASE OF PLACENTA;;
read moreOXYTOCINASE;;
INSULIN-RESPONSIVE AMINOPEPTIDASE, MOUSE, HOMOLOG OF; IRAP
*FIELD* TX
CLONING
Beckman et al. (1966) found 3 placental leucine aminopeptidase (LAP)
types. (LAP enzymes in the serum of pregnant women probably are not
derived from placenta.) Beckman et al. (1969) stated a preference for
the designation amino acid naphthylamidase. The serum level of placental
LAP increases during pregnancy and degrades several peptide hormones
such as oxytocin (167050) and vasopressin (192340).
Rogi et al. (1996) cloned a human placenta cDNA encoding leucyl-cystinyl
aminopeptidase, which they symbolized PLAP. The deduced 944-amino acid
polypeptide contains the HEXXH consensus sequence of zinc
metallopeptidases as well as an N-terminal hydrophobic region that
resembles a transmembrane domain. Northern blot analysis detected
expression of 3.6-kb and 10.5-kb transcripts in placenta, heart, and
skeletal muscle, and a 10.5-kb transcript in brain. Using
immunohistochemistry, Nagasaka et al. (1997) localized LNPEP to
syncytiotrophoblasts in placenta as well as in fetal and adult vascular
endothelial cells, the epithelial lining of several organs, neurons, and
sweat gland cells; adult seminal vesicles and prostate; and fetal
adipocytes and skeletal muscle.
GENE FUNCTION
In muscle and fat cells, insulin (INS; 176730) stimulation activates a
signaling cascade that causes intracellular vesicles containing glucose
transporter-4 (GLUT4, or SLC2A4; 138190) to translocate to and fuse with
the plasma membrane. Using mass spectrometry, Larance et al. (2005)
identified Irap as a major membrane protein associated with Glut4
vesicles in cultured mouse adipocytes. The Rab GTPase-activating protein
As160 (TBC1D4; 612465), another major constituent of Glut4 vesicles,
interacted directly with the cytoplasmic tail of Irap in vitro and in
vivo. Since As160 dissociated from Glut4 vesicles upon insulin
stimulation, Larance et al. (2005) concluded that interaction between
AS160 and IRAP mediates association of AS160 with GLUT4 vesicles.
Major histocompatibility complex (MHC) class I molecules present
peptides, produced through cytosolic proteasomal degradation of cellular
proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides
can also be derived from internalized antigens through a process known
as crosspresentation. Saveanu et al. (2009) identified a role for
peptide trimming by IRAP in crosspresentation. In human dendritic cells,
IRAP was localized to a Rab14+ endosomal storage compartment in which it
interacted with MHC class I molecules. IRAP deficiency compromised
crosspresentation in vitro and in vivo but did not affect endogenous
presentation. Saveanu et al. (2009) proposed the existence of 2 pathways
for proteasome-dependent crosspresentation in which final peptide
trimming involves IRAP in endosomes and involves the related
aminopeptidases in the endoplasmic reticulum.
GENE STRUCTURE
Horio et al. (1999) isolated and sequenced genomic clones containing the
upstream region of LNPEP and identified 4 GC-rich sequences, a TATA box,
and 3 half palindromic estrogen-responsive element (ERE)-like motifs.
MAPPING
By FISH, Horio et al. (1999) mapped the LNPEP gene to chromosome
5q14.2-q15.
ANIMAL MODEL
Mouse Irap, a zinc-dependent membrane aminopeptidase, is the homolog of
human LNPEP. Keller et al. (2002) characterized Irap-null mice with
regard to glucose homeostasis and regulation of the insulin-responsive
glucose transporter Glut4 (138190). Irap-null mice maintained normal
glucose homeostasis despite decreased glucose uptake into muscle and fat
cells. The absence of Irap did not affect the subcellular distribution
of Glut4 in adipocytes, but it led to a substantial decrease in Glut4
expression.
*FIELD* SA
Scandalios (1967)
*FIELD* RF
1. Beckman, L.; Beckman, G.; Mi, M. P.; De Simone, J.: The human
placental amino acid naphthylamidases: their molecular interrelations
and correlations with perinatal factors. Hum. Hered. 19: 249-257,
1969.
2. Beckman, L.; Bjorling, G.; Christodoulou, C.: Pregnancy enzymes
and placental polymorphism. II. Leucine aminopeptidase. Acta Genet.
Statist. Med. 16: 122-131, 1966.
3. Horio, J.; Nomura, S.; Okada, M.; Katsumata, Y.; Nakanishi, Y.;
Kumano, Y.; Takami, S.; Kinoshita, M.; Tsujimoto, M.; Nakazato, H.;
Mizutani, S.: Structural organization of the 5-prime-end and chromosomal
assignment of human placental leucine aminopeptidase/insulin-regulated
membrane aminopeptidase gene. Biochem. Biophys. Res. Commun. 262:
269-274, 1999.
4. Keller, S. R.; Davis, A. C.; Clairmont, K. B.: Mice deficient
in the insulin-regulated membrane aminopeptidase show substantial
decreases in glucose transporter GLUT4 levels but maintain normal
glucose homeostasis. J. Biol. Chem. 277: 17677-17686, 2002.
5. Larance, M.; Ramm, G.; Stockli, J.; van Dam, E. M.; Winata, S.;
Wasinger, V.; Simpson, F.; Graham, M.; Junutula, J. R.; Guilhaus,
M.; James, D. E.: Characterization of the role of the Rab GTPase-activating
protein AS160 in insulin-regulated GLUT4 trafficking. J. Biol. Chem. 280:
37803-37813, 2005.
6. Nagasaka, T.; Nomura, S.; Okamura, M.; Tsujimoto, M.; Nakazato,
H.; Oiso, Y.; Nakashima, N.; Mizutani, S.: Immunohistochemical localization
of placental leucine aminopeptidase/oxytocinase in normal human placental,
fetal and adult tissues. Reprod. Fertil. Dev. 9: 747-753, 1997.
7. Rogi, T.; Tsujimoto, M.; Nakazato, H.; Mizutani, S.; Tomoda, Y.
: Human placental leucine aminopeptidase/oxytocinase: a new member
of type II membrane-spanning zinc metallopeptidase family. J. Biol.
Chem. 271: 56-61, 1996.
8. Saveanu, L.; Carroll, O.; Weimershaus, M.; Guermonprez, P.; Firat,
E.; Lindo, V.; Greer, F.; Davoust, J.; Kratzer, R.; Keller, S. R.;
Niedermann, G.; van Endert, P.: IRAP identifies an endosomal compartment
required for MHC class I cross-presentation. Science 325: 213-217,
2009.
9. Scandalios, J. G.: Human serum leucine aminopeptidase: variation
in pregnancy and in disease states. J. Hered. 58: 153-156, 1967.
*FIELD* CN
Ada Hamosh - updated: 8/14/2009
Patricia A. Hartz - updated: 2/27/2009
Patricia A. Hartz - updated: 5/4/2004
Patricia A. Hartz - updated: 4/4/2002
Mark H. Paalman - updated: 5/8/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 08/18/2009
terry: 8/14/2009
mgross: 3/18/2009
terry: 2/27/2009
terry: 3/16/2005
mgross: 5/4/2004
mgross: 8/21/2002
carol: 4/4/2002
mark: 8/20/1997
mark: 5/8/1997
alopez: 5/8/1997
mark: 5/1/1997
jenny: 4/21/1997
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 6/2/1986
*RECORD*
*FIELD* NO
151300
*FIELD* TI
*151300 LEUCYL-CYSTINYL AMINOPEPTIDASE; LNPEP
;;LEUCINE AMINOPEPTIDASE OF PLACENTA;;
read moreOXYTOCINASE;;
INSULIN-RESPONSIVE AMINOPEPTIDASE, MOUSE, HOMOLOG OF; IRAP
*FIELD* TX
CLONING
Beckman et al. (1966) found 3 placental leucine aminopeptidase (LAP)
types. (LAP enzymes in the serum of pregnant women probably are not
derived from placenta.) Beckman et al. (1969) stated a preference for
the designation amino acid naphthylamidase. The serum level of placental
LAP increases during pregnancy and degrades several peptide hormones
such as oxytocin (167050) and vasopressin (192340).
Rogi et al. (1996) cloned a human placenta cDNA encoding leucyl-cystinyl
aminopeptidase, which they symbolized PLAP. The deduced 944-amino acid
polypeptide contains the HEXXH consensus sequence of zinc
metallopeptidases as well as an N-terminal hydrophobic region that
resembles a transmembrane domain. Northern blot analysis detected
expression of 3.6-kb and 10.5-kb transcripts in placenta, heart, and
skeletal muscle, and a 10.5-kb transcript in brain. Using
immunohistochemistry, Nagasaka et al. (1997) localized LNPEP to
syncytiotrophoblasts in placenta as well as in fetal and adult vascular
endothelial cells, the epithelial lining of several organs, neurons, and
sweat gland cells; adult seminal vesicles and prostate; and fetal
adipocytes and skeletal muscle.
GENE FUNCTION
In muscle and fat cells, insulin (INS; 176730) stimulation activates a
signaling cascade that causes intracellular vesicles containing glucose
transporter-4 (GLUT4, or SLC2A4; 138190) to translocate to and fuse with
the plasma membrane. Using mass spectrometry, Larance et al. (2005)
identified Irap as a major membrane protein associated with Glut4
vesicles in cultured mouse adipocytes. The Rab GTPase-activating protein
As160 (TBC1D4; 612465), another major constituent of Glut4 vesicles,
interacted directly with the cytoplasmic tail of Irap in vitro and in
vivo. Since As160 dissociated from Glut4 vesicles upon insulin
stimulation, Larance et al. (2005) concluded that interaction between
AS160 and IRAP mediates association of AS160 with GLUT4 vesicles.
Major histocompatibility complex (MHC) class I molecules present
peptides, produced through cytosolic proteasomal degradation of cellular
proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides
can also be derived from internalized antigens through a process known
as crosspresentation. Saveanu et al. (2009) identified a role for
peptide trimming by IRAP in crosspresentation. In human dendritic cells,
IRAP was localized to a Rab14+ endosomal storage compartment in which it
interacted with MHC class I molecules. IRAP deficiency compromised
crosspresentation in vitro and in vivo but did not affect endogenous
presentation. Saveanu et al. (2009) proposed the existence of 2 pathways
for proteasome-dependent crosspresentation in which final peptide
trimming involves IRAP in endosomes and involves the related
aminopeptidases in the endoplasmic reticulum.
GENE STRUCTURE
Horio et al. (1999) isolated and sequenced genomic clones containing the
upstream region of LNPEP and identified 4 GC-rich sequences, a TATA box,
and 3 half palindromic estrogen-responsive element (ERE)-like motifs.
MAPPING
By FISH, Horio et al. (1999) mapped the LNPEP gene to chromosome
5q14.2-q15.
ANIMAL MODEL
Mouse Irap, a zinc-dependent membrane aminopeptidase, is the homolog of
human LNPEP. Keller et al. (2002) characterized Irap-null mice with
regard to glucose homeostasis and regulation of the insulin-responsive
glucose transporter Glut4 (138190). Irap-null mice maintained normal
glucose homeostasis despite decreased glucose uptake into muscle and fat
cells. The absence of Irap did not affect the subcellular distribution
of Glut4 in adipocytes, but it led to a substantial decrease in Glut4
expression.
*FIELD* SA
Scandalios (1967)
*FIELD* RF
1. Beckman, L.; Beckman, G.; Mi, M. P.; De Simone, J.: The human
placental amino acid naphthylamidases: their molecular interrelations
and correlations with perinatal factors. Hum. Hered. 19: 249-257,
1969.
2. Beckman, L.; Bjorling, G.; Christodoulou, C.: Pregnancy enzymes
and placental polymorphism. II. Leucine aminopeptidase. Acta Genet.
Statist. Med. 16: 122-131, 1966.
3. Horio, J.; Nomura, S.; Okada, M.; Katsumata, Y.; Nakanishi, Y.;
Kumano, Y.; Takami, S.; Kinoshita, M.; Tsujimoto, M.; Nakazato, H.;
Mizutani, S.: Structural organization of the 5-prime-end and chromosomal
assignment of human placental leucine aminopeptidase/insulin-regulated
membrane aminopeptidase gene. Biochem. Biophys. Res. Commun. 262:
269-274, 1999.
4. Keller, S. R.; Davis, A. C.; Clairmont, K. B.: Mice deficient
in the insulin-regulated membrane aminopeptidase show substantial
decreases in glucose transporter GLUT4 levels but maintain normal
glucose homeostasis. J. Biol. Chem. 277: 17677-17686, 2002.
5. Larance, M.; Ramm, G.; Stockli, J.; van Dam, E. M.; Winata, S.;
Wasinger, V.; Simpson, F.; Graham, M.; Junutula, J. R.; Guilhaus,
M.; James, D. E.: Characterization of the role of the Rab GTPase-activating
protein AS160 in insulin-regulated GLUT4 trafficking. J. Biol. Chem. 280:
37803-37813, 2005.
6. Nagasaka, T.; Nomura, S.; Okamura, M.; Tsujimoto, M.; Nakazato,
H.; Oiso, Y.; Nakashima, N.; Mizutani, S.: Immunohistochemical localization
of placental leucine aminopeptidase/oxytocinase in normal human placental,
fetal and adult tissues. Reprod. Fertil. Dev. 9: 747-753, 1997.
7. Rogi, T.; Tsujimoto, M.; Nakazato, H.; Mizutani, S.; Tomoda, Y.
: Human placental leucine aminopeptidase/oxytocinase: a new member
of type II membrane-spanning zinc metallopeptidase family. J. Biol.
Chem. 271: 56-61, 1996.
8. Saveanu, L.; Carroll, O.; Weimershaus, M.; Guermonprez, P.; Firat,
E.; Lindo, V.; Greer, F.; Davoust, J.; Kratzer, R.; Keller, S. R.;
Niedermann, G.; van Endert, P.: IRAP identifies an endosomal compartment
required for MHC class I cross-presentation. Science 325: 213-217,
2009.
9. Scandalios, J. G.: Human serum leucine aminopeptidase: variation
in pregnancy and in disease states. J. Hered. 58: 153-156, 1967.
*FIELD* CN
Ada Hamosh - updated: 8/14/2009
Patricia A. Hartz - updated: 2/27/2009
Patricia A. Hartz - updated: 5/4/2004
Patricia A. Hartz - updated: 4/4/2002
Mark H. Paalman - updated: 5/8/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 08/18/2009
terry: 8/14/2009
mgross: 3/18/2009
terry: 2/27/2009
terry: 3/16/2005
mgross: 5/4/2004
mgross: 8/21/2002
carol: 4/4/2002
mark: 8/20/1997
mark: 5/8/1997
alopez: 5/8/1997
mark: 5/1/1997
jenny: 4/21/1997
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 6/2/1986