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Protein

Leucyl-cystinyl aminopeptidase

Gene

Lnpep

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Release of an N-terminal amino acid, cleave before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain (By similarity).By similarity

Catalytic activityi

Release of an N-terminal amino acid, Cys-|-Xaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei295 – 2951SubstrateBy similarity
Metal bindingi464 – 4641Zinc; catalyticPROSITE-ProRule annotation
Active sitei465 – 4651Proton acceptorPROSITE-ProRule annotation
Metal bindingi468 – 4681Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi487 – 4871Zinc; catalyticPROSITE-ProRule annotation
Sitei549 – 5491Transition state stabilizerBy similarity

GO - Molecular functioni

  • aminopeptidase activity Source: RGD
  • angiotensin receptor activity Source: RGD
  • metallopeptidase activity Source: UniProtKB-KW
  • peptide hormone binding Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • angiotensin-activated signaling pathway Source: GOC
  • neuropeptide catabolic process Source: RGD
  • peptide catabolic process Source: RGD
  • positive regulation of blood pressure Source: RGD
  • regulation of long-term neuronal synaptic plasticity Source: RGD
  • response to hormone Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_312094. Antigen processing: Ubiquitination & Proteasome degradation.
REACT_323565. Endosomal/Vacuolar pathway.
REACT_347820. Translocation of GLUT4 to the plasma membrane.

Protein family/group databases

MEROPSiM01.011.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucyl-cystinyl aminopeptidase (EC:3.4.11.3)
Short name:
Cystinyl aminopeptidase
Alternative name(s):
GP160
Insulin-regulated membrane aminopeptidase
Insulin-responsive aminopeptidase
Short name:
IRAP
Oxytocinase
Short name:
OTase
Placental leucine aminopeptidase
Short name:
P-LAP
Vesicle protein of 165 kDa
Short name:
Vp165
Gene namesi
Name:Lnpep
Synonyms:Irap, Otase
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi621752. Lnpep.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 109109CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei110 – 13122Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini132 – 1025894ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • insulin-responsive compartment Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • intracellular membrane-bounded organelle Source: RGD
  • intracellular organelle Source: RGD
  • neuronal cell body Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • plasma membrane Source: RGD
  • vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10251025Leucyl-cystinyl aminopeptidasePRO_0000095115Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei70 – 701PhosphotyrosineBy similarity
Modified residuei80 – 801Phosphoserine; by PKC/PRKCZ; in vitro1 Publication
Modified residuei91 – 911Phosphoserine; by PKC/PRKCZ; in vitro1 Publication
Glycosylationi145 – 1451N-linked (GlcNAc...)Sequence Analysis
Glycosylationi184 – 1841N-linked (GlcNAc...)Sequence Analysis
Glycosylationi215 – 2151N-linked (GlcNAc...)Sequence Analysis
Glycosylationi256 – 2561N-linked (GlcNAc...)Sequence Analysis
Glycosylationi266 – 2661N-linked (GlcNAc...)Sequence Analysis
Glycosylationi368 – 3681N-linked (GlcNAc...)Sequence Analysis
Glycosylationi374 – 3741N-linked (GlcNAc...)Sequence Analysis
Glycosylationi447 – 4471N-linked (GlcNAc...)Sequence Analysis
Glycosylationi525 – 5251N-linked (GlcNAc...)Sequence Analysis
Glycosylationi578 – 5781N-linked (GlcNAc...)Sequence Analysis
Glycosylationi664 – 6641N-linked (GlcNAc...)Sequence Analysis
Glycosylationi682 – 6821N-linked (GlcNAc...)Sequence Analysis
Glycosylationi695 – 6951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi758 – 7581N-linked (GlcNAc...)Sequence Analysis
Glycosylationi834 – 8341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi850 – 8501N-linked (GlcNAc...)Sequence Analysis
Glycosylationi989 – 9891N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP97629.
PRIDEiP97629.

PTM databases

PhosphoSiteiP97629.

Expressioni

Tissue specificityi

Highly expressed in heart, brain, spleen, lung, kidney and white adipose tissue. Detected at lower levels in skeletal muscle and liver.

Gene expression databases

GenevisibleiP97629. RN.

Interactioni

Subunit structurei

Homodimer. Binds tankyrases 1 and 2 (By similarity).By similarity

Protein-protein interaction databases

IntActiP97629. 1 interaction.
STRINGi10116.ENSRNOP00000017718.

Structurei

3D structure databases

ProteinModelPortaliP97629.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni96 – 1016Tankyrase bindingBy similarity
Regioni428 – 4325Substrate bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi53 – 542Dileucine internalization motifSequence Analysis
Motifi76 – 772Dileucine internalization motifSequence Analysis

Sequence similaritiesi

Belongs to the peptidase M1 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0308.
HOGENOMiHOG000106482.
HOVERGENiHBG108296.
InParanoidiP97629.
KOiK01257.
OMAiQALQATW.
OrthoDBiEOG754HNR.
PhylomeDBiP97629.

Family and domain databases

InterProiIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P97629-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METFTNDRLQ LPRNMIENSM FEEEPDVVDL AKEPCLHPLE PDEVEYEPRG
60 70 80 90 100
SRLLVRGLGE HEMDEDEEDY ESSAKLLGMS FMNRSSGLRN SATGYRQSPD
110 120 130 140 150
GTCSVPSART LVICVFVIVV AVSVIMVIYL LPRCTFTKEG CHKTNQSAEL
160 170 180 190 200
IQPIATNGKV FPWAQIRLPT AIIPQRYELS LHPNLTSMTF RGSVTISLQA
210 220 230 240 250
LQDTRDIILH STGHNISSVT FMSAVSSQEK QVEILEYPYH EQIAVVAPES
260 270 280 290 300
LLTGHNYTLK IEYSANISNS YYGFYGITYT DKSNEKKNFA ATQFEPLAAR
310 320 330 340 350
SAFPCFDEPA FKATFIIKIT RDEHHTALSN MPKKSSVPTE EGLIQDEFSE
360 370 380 390 400
SVKMSTYLVA FIVGEMRNLS QDVNGTLVSV YAVPEKIDQV YHALDTTVKL
410 420 430 440 450
LEFYQNYFEI QYPLKKLDLV AIPDFEAGAM ENWGLLTFRE ETLLYDNATS
460 470 480 490 500
SVADRKLVTK IIAHELAHQW FGNLVTMQWW NDLWLNEGFA TFMEYFSVEK
510 520 530 540 550
IFKELNSYED FLDARFKTMR KDSLNSSHPI SSSVQSSEQI EEMFDSLSYF
560 570 580 590 600
KGASLLLMLK SYLSEDVFQH AIILYLHNHS YAAIQSDDLW DSFNEVTGKT
610 620 630 640 650
LDVKKMMKTW TLQKGFPLVT VQRKGTELLL QQERFFPSMQ PEIQDSDTSH
660 670 680 690 700
LWHIPISYVT DGRNYSEYRS VSLLDKKSDV INLTEQVQWV KVNTNMTGYY
710 720 730 740 750
IVHYAHDGWA ALINQLKRNP YVLSDKDRAN LINNIFELAG LGKVPLQMAF
760 770 780 790 800
DLIDYLRNET HTAPITEALF QTDLIYNLLE KLGHMDLSSR LVTRVHKLLQ
810 820 830 840 850
NQIQQQTWTD EGTPSMRELR SALLEFACAH SLENCTTMAT KLFDGWMASN
860 870 880 890 900
GTQSLPTDVM TTVFKVGART EKGWLFLFSM YSSMGSEAEK DKILEALASS
910 920 930 940 950
ADAHKLYWLM KSSLDGDIIR TQKLSLIIRT VGRQFPGHLL AWDFVKENWN
960 970 980 990 1000
KLVHKFHLGS YTIQSIVAGS THLFSTKTHL SEVQEFFENQ SEATLQLRCV
1010 1020
QEAFEVIELN IQWMARNLKT LTLWL
Length:1,025
Mass (Da):117,201
Last modified:May 1, 1997 - v1
Checksum:i8AD3BA3A446FB5EF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti909 – 9168LMKSSLDG → YGTTQRAW in AAB38021 (PubMed:7559527).Curated
Sequence conflicti916 – 1025110Missing in AAB38021 (PubMed:7559527).CuratedAdd
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76997 mRNA. Translation: AAB19066.1.
U32990 mRNA. Translation: AAB38021.1.
PIRiI55441.
RefSeqiNP_001106874.1. NM_001113403.1.
NP_598258.1. NM_133574.1.
XP_003748754.1. XM_003748706.3.
XP_008757040.1. XM_008758818.1.
UniGeneiRn.10614.

Genome annotation databases

GeneIDi100912445.
171105.
KEGGirno:100912445.
rno:171105.
UCSCiRGD:621752. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76997 mRNA. Translation: AAB19066.1.
U32990 mRNA. Translation: AAB38021.1.
PIRiI55441.
RefSeqiNP_001106874.1. NM_001113403.1.
NP_598258.1. NM_133574.1.
XP_003748754.1. XM_003748706.3.
XP_008757040.1. XM_008758818.1.
UniGeneiRn.10614.

3D structure databases

ProteinModelPortaliP97629.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP97629. 1 interaction.
STRINGi10116.ENSRNOP00000017718.

Chemistry

BindingDBiP97629.
ChEMBLiCHEMBL3712.

Protein family/group databases

MEROPSiM01.011.

PTM databases

PhosphoSiteiP97629.

Proteomic databases

PaxDbiP97629.
PRIDEiP97629.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100912445.
171105.
KEGGirno:100912445.
rno:171105.
UCSCiRGD:621752. rat.

Organism-specific databases

CTDi4012.
RGDi621752. Lnpep.

Phylogenomic databases

eggNOGiCOG0308.
HOGENOMiHOG000106482.
HOVERGENiHBG108296.
InParanoidiP97629.
KOiK01257.
OMAiQALQATW.
OrthoDBiEOG754HNR.
PhylomeDBiP97629.

Enzyme and pathway databases

ReactomeiREACT_312094. Antigen processing: Ubiquitination & Proteasome degradation.
REACT_323565. Endosomal/Vacuolar pathway.
REACT_347820. Translocation of GLUT4 to the plasma membrane.

Miscellaneous databases

NextBioi621794.
PROiP97629.

Gene expression databases

GenevisibleiP97629. RN.

Family and domain databases

InterProiIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles."
    Keller S.R., Scott H.M., Mastick C.C., Aebersold R., Lienhard G.E.
    J. Biol. Chem. 270:23612-23618(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
    Strain: Sprague-Dawley.
    Tissue: Adipocyte.
  2. "Characterization of a major protein in GLUT4 vesicles. Concentration in the vesicles and insulin-stimulated translocation to the plasma membrane."
    Mastick C.C., Aebersold R., Lienhard G.E.
    J. Biol. Chem. 269:6089-6092(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 168-176; 387-399; 731-740 AND 893-905.
  3. "Protein kinase C-zeta phosphorylates insulin-responsive aminopeptidase in vitro at Ser-80 and Ser-91."
    Ryu J., Hah J.S., Park J.S.S., Lee W., Rampal A.L., Jung C.Y.
    Arch. Biochem. Biophys. 403:71-82(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-80 AND SER-91, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiLCAP_RAT
AccessioniPrimary (citable) accession number: P97629
Secondary accession number(s): Q11009
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: May 1, 1997
Last modified: July 22, 2015
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.