LCAP_MOUSE
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 03-AUG-2022, entry version 150.
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, Pancreas,
RC 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 GlyGen; Q8C129; 17 sites, 16 N-linked glycans (6 sites).
DR iPTMnet; Q8C129; -.
DR PhosphoSitePlus; Q8C129; -.
DR SwissPalm; Q8C129; -.
DR EPD; Q8C129; -.
DR jPOST; Q8C129; -.
DR MaxQB; Q8C129; -.
DR PaxDb; Q8C129; -.
DR PeptideAtlas; Q8C129; -.
DR PRIDE; Q8C129; -.
DR ProteomicsDB; 286179; -.
DR Antibodypedia; 25094; 144 antibodies from 31 providers.
DR DNASU; 240028; -.
DR Ensembl; ENSMUST00000041047; ENSMUSP00000036998; ENSMUSG00000023845.
DR GeneID; 240028; -.
DR KEGG; mmu:240028; -.
DR UCSC; uc008apk.1; mouse.
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; TSMTFKG; -.
DR OrthoDB; 110058at2759; -.
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 76 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 214 other tissues.
DR Genevisible; Q8C129; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:MGI.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IMP:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA: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:0043171; P:peptide catabolic process; IBA:GO_Central.
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:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:MGI.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR034017; Cystinyl_aminopeptidase.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR034016; M1_APN-typ.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR PANTHER; PTHR11533:SF42; PTHR11533:SF42; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 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