ID   LCAP_MOUSE              Reviewed;        1025 AA.
AC   Q8C129;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=Leucyl-cystinyl aminopeptidase;
DE            Short=Cystinyl aminopeptidase;
DE            EC=3.4.11.3;
DE   AltName: Full=Oxytocinase;
DE            Short=OTase;
GN   Name=Lnpep;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Skin;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-70; SER-80 AND SER-91, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [4]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-447 AND ASN-682.
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   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Release of an N-terminal amino acid, cleave 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 (By similarity). {ECO:0000250}.
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;
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 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC       membrane protein {ECO:0000250}. Endomembrane system {ECO:0000250};
CC       Single-pass type II membrane protein {ECO:0000250}. Note=Localized
CC       mainly in intracellular vesicles together with GLUT4. Relocalizes to
CC       the plasma membrane in response to insulin. The dileucine
CC       internalization motif and/or the interaction with tankyrases may be
CC       involved in intracellular sequestration (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR   EMBL; AK029094; BAC26293.1; -; mRNA.
DR   EMBL; BC120925; AAI20926.1; -; mRNA.
DR   EMBL; BC120926; AAI20927.1; -; mRNA.
DR   CCDS; CCDS37457.1; -.
DR   RefSeq; NP_766415.1; NM_172827.3.
DR   AlphaFoldDB; Q8C129; -.
DR   SMR; Q8C129; -.
DR   BioGRID; 232146; 12.
DR   STRING; 10090.ENSMUSP00000036998; -.
DR   ChEMBL; CHEMBL4105715; -.
DR   MEROPS; M01.011; -.
DR   GlyConnect; 2477; 16 N-Linked glycans (6 sites).
DR   GlyCosmos; Q8C129; 17 sites, 16 glycans.
DR   GlyGen; Q8C129; 18 sites, 16 N-linked glycans (6 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; Q8C129; -.
DR   PhosphoSitePlus; Q8C129; -.
DR   SwissPalm; Q8C129; -.
DR   EPD; Q8C129; -.
DR   jPOST; Q8C129; -.
DR   MaxQB; Q8C129; -.
DR   PaxDb; 10090-ENSMUSP00000036998; -.
DR   PeptideAtlas; Q8C129; -.
DR   ProteomicsDB; 286179; -.
DR   Pumba; Q8C129; -.
DR   Antibodypedia; 25094; 167 antibodies from 31 providers.
DR   DNASU; 240028; -.
DR   Ensembl; ENSMUST00000041047.4; ENSMUSP00000036998.3; ENSMUSG00000023845.8.
DR   GeneID; 240028; -.
DR   KEGG; mmu:240028; -.
DR   UCSC; uc008apk.1; mouse.
DR   AGR; MGI:2387123; -.
DR   CTD; 4012; -.
DR   MGI; MGI:2387123; Lnpep.
DR   VEuPathDB; HostDB:ENSMUSG00000023845; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   GeneTree; ENSGT00940000157902; -.
DR   HOGENOM; CLU_003705_2_2_1; -.
DR   InParanoid; Q8C129; -.
DR   OMA; ERFFLSM; -.
DR   OrthoDB; 3085317at2759; -.
DR   PhylomeDB; Q8C129; -.
DR   TreeFam; TF300395; -.
DR   BRENDA; 3.4.11.3; 3474.
DR   Reactome; R-MMU-1236977; Endosomal/Vacuolar pathway.
DR   Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   BioGRID-ORCS; 240028; 4 hits in 81 CRISPR screens.
DR   ChiTaRS; Lnpep; mouse.
DR   PRO; PR:Q8C129; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; Q8C129; Protein.
DR   Bgee; ENSMUSG00000023845; Expressed in ascending aorta and 216 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:MGI.
DR   GO; GO:0032593; C:insulin-responsive compartment; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IMP:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0031982; C:vesicle; ISO:MGI.
DR   GO; GO:0004177; F:aminopeptidase activity; IMP:MGI.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR   GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR   GO; GO:0010813; P:neuropeptide catabolic process; ISO:MGI.
DR   GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR   GO; GO:0045777; P:positive regulation of blood pressure; ISO:MGI.
DR   GO; GO:0030163; P:protein catabolic process; IMP:MGI.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0008217; P:regulation of blood pressure; IBA:GO_Central.
DR   GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISO:MGI.
DR   GO; GO:0009725; P:response to hormone; ISO:MGI.
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; Q8C129; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Aminopeptidase; Cell membrane; Glycoprotein; Hydrolase;
KW   Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW   Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW   Zinc.
FT   CHAIN           1..1025
FT                   /note="Leucyl-cystinyl aminopeptidase"
FT                   /id="PRO_0000278198"
FT   TOPO_DOM        1..109
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        110..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                   /evidence="ECO:0000250"
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            549
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UIQ6"
FT   MOD_RES         70
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:19144319"
FT   MOD_RES         80
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         91
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319"
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:0000255"
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        447
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        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        695
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        758
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:0000255"
FT   CARBOHYD        989
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1025 AA;  117304 MW;  AD6F98196EBA683B CRC64;
     MESFTNDRLQ LPRNMIENSM FEEEPDVVDL AKEPCLHPLE PDEVEYEPRG SRLLVRGLGE
     HEMDEDEEDY ESSAKLLGMS FMNRSSGLRN SAAGYRQSPD GTCSLPSART LVICVFVIVV
     AVSVIMVIYL LPRCTFTKEG CHKTNQSAEL IQPVATNGKV FPWAQIRLPT AIIPLCYELS
     LHPNLTSMTF RGSVTISLQA LQDTRDIILH STGHNISRVT FMSAVSSQEK QVEILEYPYH
     EQIAVVAPEP LLTGHNYTLK IEYSANISNS YYGFYGITYT DKSNEKKYFA ATQFEPLAAR
     SAFPCFDEPA FKATFIIKIT RNEHHTALSN MPKKSSVPAE EGLIQDEFSE SVKMSTYLVA
     FIVGEMRNLS QDVNGTLVSV YAVPEKIGQV HHALDTTIKL LEFYQTYFEI QYPLKKLDLV
     AIPDFEAGAM ENWGLLTFRE ETLLYDNATS SVADRKLVTK IIAHELAHQW FGNLVTMQWW
     NDLWLNEGFA TFMEYFSVEK IFKELNSYED FLDARFKTMR KDSLNSSHPI SSSVQSSEQI
     EEMFDSLSYF KGASLLLMLK SYLSEDVFRH AVILYLHNHS YAAIQSDDLW DSFNEVTDKT
     LDVKKMMKTW TLQKGFPLVT VQRKGTELLL QQERFFLRMQ PESQPSDTSH LWHIPISYVT
     DGRNYSEYRS VSLLDKKSDV INLTEQVQWV KVNSNMTGYY IVHYAHDDWT ALINQLKRNP
     YVLSDKDRAN LINNIFELAG LGKVPLRMAF DLIDYLKNET HTAPITEALF QTNLIYNLLE
     KLGHMDLSSR LVARVHKLLQ NQIQQQTWTD EGTPSMRELR SALLEFACAH SLENCTTMAT
     NLFDSWMASN GTQSLPTDVM VTVFKVGART EKGWLFLFSM YSSMGSEAEK NKILEALASS
     EDVHKLYWLM KSSLDGDIIR TQKLSLIIRT VGRHFPGHLL AWDFVKENWN KLVHKFHLGS
     YTIQSIVAGS THLFSTKTHL SEVQAFFENQ SEATLKLRCV QEALEVIQLN IQWMVRNLKT
     LSQWL
//