LCAP_RAT
ID LCAP_RAT Reviewed; 1025 AA.
AC P97629; Q11009;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Leucyl-cystinyl aminopeptidase;
DE Short=Cystinyl aminopeptidase;
DE EC=3.4.11.3;
DE AltName: Full=GP160;
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 AltName: Full=Vesicle protein of 165 kDa;
DE Short=Vp165;
GN Name=Lnpep; Synonyms=Irap, Otase;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC STRAIN=Sprague-Dawley; TISSUE=Adipocyte;
RX PubMed=7559527; DOI=10.1074/jbc.270.40.23612;
RA Keller S.R., Scott H.M., Mastick C.C., Aebersold R., Lienhard G.E.;
RT "Cloning and characterization of a novel insulin-regulated membrane
RT aminopeptidase from Glut4 vesicles.";
RL J. Biol. Chem. 270:23612-23618(1995).
RN [2]
RP PROTEIN SEQUENCE OF 168-176; 387-399; 731-740 AND 893-905.
RX PubMed=8119954; DOI=10.1016/s0021-9258(17)37573-7;
RA Mastick C.C., Aebersold R., Lienhard G.E.;
RT "Characterization of a major protein in GLUT4 vesicles. Concentration in
RT the vesicles and insulin-stimulated translocation to the plasma membrane.";
RL J. Biol. Chem. 269:6089-6092(1994).
RN [3]
RP PHOSPHORYLATION AT SER-80 AND SER-91, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12061804; DOI=10.1016/s0003-9861(02)00261-8;
RA Ryu J., Hah J.S., Park J.S.S., Lee W., Rampal A.L., Jung C.Y.;
RT "Protein kinase C-zeta phosphorylates insulin-responsive aminopeptidase in
RT vitro at Ser-80 and Ser-91.";
RL Arch. Biochem. Biophys. 403:71-82(2002).
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; Single-pass type II membrane
CC protein. Endomembrane system; Single-pass type II membrane protein.
CC Note=Localized mainly in intracellular vesicles together with GLUT4.
CC Relocalizes to the plasma membrane in response to insulin. The
CC dileucine internalization motif and/or the interaction with tankyrases
CC may be involved in intracellular sequestration.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, brain, spleen, lung,
CC kidney and white adipose tissue. Detected at lower levels in skeletal
CC muscle and liver.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; U76997; AAB19066.1; -; mRNA.
DR EMBL; U32990; AAB38021.1; -; mRNA.
DR PIR; I55441; I55441.
DR RefSeq; NP_001106874.1; NM_001113403.1.
DR RefSeq; NP_598258.1; NM_133574.1.
DR RefSeq; XP_008757040.1; XM_008758818.2.
DR RefSeq; XP_017443357.1; XM_017587868.1.
DR AlphaFoldDB; P97629; -.
DR SMR; P97629; -.
DR IntAct; P97629; 2.
DR BindingDB; P97629; -.
DR ChEMBL; CHEMBL3712; -.
DR DrugCentral; P97629; -.
DR MEROPS; M01.011; -.
DR GlyGen; P97629; 17 sites.
DR iPTMnet; P97629; -.
DR PhosphoSitePlus; P97629; -.
DR jPOST; P97629; -.
DR PaxDb; P97629; -.
DR PRIDE; P97629; -.
DR Ensembl; ENSRNOT00000017718; ENSRNOP00000017718; ENSRNOG00000055229.
DR GeneID; 171105; -.
DR KEGG; rno:171105; -.
DR UCSC; RGD:621752; rat.
DR CTD; 4012; -.
DR RGD; 621752; Lnpep.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000157902; -.
DR HOGENOM; CLU_003705_2_2_1; -.
DR InParanoid; P97629; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; P97629; -.
DR BRENDA; 3.4.11.3; 5301.
DR Reactome; R-RNO-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:P97629; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Genevisible; P97629; RN.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISO:RGD.
DR GO; GO:0032593; C:insulin-responsive compartment; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0043229; C:intracellular organelle; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:RGD.
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; ISS:YuBioLab.
DR GO; GO:0010813; P:neuropeptide catabolic process; IMP:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IDA:RGD.
DR GO; GO:0045777; P:positive regulation of blood pressure; IMP:RGD.
DR GO; GO:0030163; P:protein catabolic process; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
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; Direct protein sequencing;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..1025
FT /note="Leucyl-cystinyl aminopeptidase"
FT /id="PRO_0000095115"
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:0000250|UniProtKB:Q8C129"
FT MOD_RES 80
FT /note="Phosphoserine; by PKC/PRKCZ; in vitro"
FT /evidence="ECO:0000269|PubMed:12061804"
FT MOD_RES 91
FT /note="Phosphoserine; by PKC/PRKCZ; in vitro"
FT /evidence="ECO:0000269|PubMed:12061804"
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:0000255"
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:0000255"
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"
FT CONFLICT 909..916
FT /note="LMKSSLDG -> YGTTQRAW (in Ref. 1; AAB38021)"
FT /evidence="ECO:0000305"
FT CONFLICT 916..1025
FT /note="Missing (in Ref. 1; AAB38021)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1025 AA; 117201 MW; 8AD3BA3A446FB5EF CRC64;
METFTNDRLQ LPRNMIENSM FEEEPDVVDL AKEPCLHPLE PDEVEYEPRG SRLLVRGLGE
HEMDEDEEDY ESSAKLLGMS FMNRSSGLRN SATGYRQSPD GTCSVPSART LVICVFVIVV
AVSVIMVIYL LPRCTFTKEG CHKTNQSAEL IQPIATNGKV FPWAQIRLPT AIIPQRYELS
LHPNLTSMTF RGSVTISLQA LQDTRDIILH STGHNISSVT FMSAVSSQEK QVEILEYPYH
EQIAVVAPES LLTGHNYTLK IEYSANISNS YYGFYGITYT DKSNEKKNFA ATQFEPLAAR
SAFPCFDEPA FKATFIIKIT RDEHHTALSN MPKKSSVPTE EGLIQDEFSE SVKMSTYLVA
FIVGEMRNLS QDVNGTLVSV YAVPEKIDQV YHALDTTVKL LEFYQNYFEI QYPLKKLDLV
AIPDFEAGAM ENWGLLTFRE ETLLYDNATS SVADRKLVTK IIAHELAHQW FGNLVTMQWW
NDLWLNEGFA TFMEYFSVEK IFKELNSYED FLDARFKTMR KDSLNSSHPI SSSVQSSEQI
EEMFDSLSYF KGASLLLMLK SYLSEDVFQH AIILYLHNHS YAAIQSDDLW DSFNEVTGKT
LDVKKMMKTW TLQKGFPLVT VQRKGTELLL QQERFFPSMQ PEIQDSDTSH LWHIPISYVT
DGRNYSEYRS VSLLDKKSDV INLTEQVQWV KVNTNMTGYY IVHYAHDGWA ALINQLKRNP
YVLSDKDRAN LINNIFELAG LGKVPLQMAF DLIDYLRNET HTAPITEALF QTDLIYNLLE
KLGHMDLSSR LVTRVHKLLQ NQIQQQTWTD EGTPSMRELR SALLEFACAH SLENCTTMAT
KLFDGWMASN GTQSLPTDVM TTVFKVGART EKGWLFLFSM YSSMGSEAEK DKILEALASS
ADAHKLYWLM KSSLDGDIIR TQKLSLIIRT VGRQFPGHLL AWDFVKENWN KLVHKFHLGS
YTIQSIVAGS THLFSTKTHL SEVQEFFENQ SEATLQLRCV QEAFEVIELN IQWMARNLKT
LTLWL
