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Q9UIQ6 (LCAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leucyl-cystinyl aminopeptidase

Short name=Cystinyl aminopeptidase
EC=3.4.11.3
Alternative name(s):
Insulin-regulated membrane aminopeptidase
Insulin-responsive aminopeptidase
Short name=IRAP
Oxytocinase
Short name=OTase
Placental leucine aminopeptidase
Short name=P-LAP
Gene names
Name:LNPEP
Synonyms:OTASE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1025 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Release of an N-terminal amino acid, cleaves 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. Ref.4 Ref.7 Ref.8

Catalytic activity

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. Ref.4 Ref.7

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Homodimer. Binds tankyrases 1 and 2.

Subcellular location

Cell membrane; Single-pass type II membrane protein. Note: In brain only the membrane-bound form is found. The protein resides in intracellular vesicles together with GLUT4 and can then translocate to the cell surface in response to insulin and/or oxytocin. Localization may be determined by dileucine internalization motifs, and/or by interaction with tankyrases. Ref.4

Leucyl-cystinyl aminopeptidase, pregnancy serum form: Secreted. Note: During pregnancy serum levels are low in the first trimester, rise progressively during the second and third trimester and decrease rapidly after parturition. Ref.4

Tissue specificity

Highly expressed in placenta, heart, kidney and small intestine. Detected at lower levels in neuronal cells in the brain, in skeletal muscle, spleen, liver, testes and colon. Ref.1 Ref.2 Ref.4

Post-translational modification

The pregnancy serum form is derived from the membrane-bound form by proteolytic processing.

N-glycosylated.

Sequence similarities

Belongs to the peptidase M1 family.

Sequence caution

The sequence BAA09436.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAD92120.1 differs from that shown. Reason: Frameshift at position 405.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionAminopeptidase
Hydrolase
Metalloprotease
Protease
   PTMAcetylation
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class I

Traceable author statement. Source: Reactome

antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent

Traceable author statement. Source: Reactome

antigen processing and presentation of peptide antigen via MHC class I

Traceable author statement. Source: Reactome

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

female pregnancy

Traceable author statement Ref.1. Source: ProtInc

membrane organization

Traceable author statement. Source: Reactome

protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein polyubiquitination

Traceable author statement. Source: Reactome

proteolysis

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytoplasmic vesicle membrane

Traceable author statement. Source: Reactome

cytosol

Traceable author statement. Source: Reactome

early endosome lumen

Traceable author statement. Source: Reactome

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement Ref.2. Source: ProtInc

intracellular

Inferred from direct assay PubMed 15691326. Source: HGNC

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement Ref.2. Source: ProtInc

   Molecular_functionaminopeptidase activity

Traceable author statement PubMed 15691326. Source: HGNC

metallopeptidase activity

Traceable author statement Ref.2. Source: ProtInc

zinc ion binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9UIQ6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9UIQ6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
Isoform 3 (identifier: Q9UIQ6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10251025Leucyl-cystinyl aminopeptidase
PRO_0000095114
Chain155 – 1025871Leucyl-cystinyl aminopeptidase, pregnancy serum form
PRO_0000292264

Regions

Topological domain1 – 110110Cytoplasmic Potential
Transmembrane111 – 13121Helical; Signal-anchor for type II membrane protein; Potential
Topological domain132 – 1025894Extracellular Potential
Region96 – 1016Tankyrase binding
Region428 – 4325Substrate binding By similarity
Motif53 – 542Dileucine internalization motif Potential
Motif76 – 772Dileucine internalization motif Potential

Sites

Active site4651Proton acceptor By similarity
Metal binding4641Zinc; catalytic By similarity
Metal binding4681Zinc; catalytic By similarity
Metal binding4871Zinc; catalytic By similarity
Binding site2951Substrate By similarity
Site154 – 1552Cleavage; to produce pregnancy serum form
Site5491Transition state stabilizer By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.12
Modified residue701Phosphotyrosine By similarity
Modified residue801Phosphoserine By similarity
Modified residue911Phosphoserine By similarity
Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) Ref.10
Glycosylation2151N-linked (GlcNAc...) Potential
Glycosylation2561N-linked (GlcNAc...) Potential
Glycosylation2661N-linked (GlcNAc...) Potential
Glycosylation3681N-linked (GlcNAc...) Potential
Glycosylation3741N-linked (GlcNAc...) Potential
Glycosylation4481N-linked (GlcNAc...) Ref.10
Glycosylation5251N-linked (GlcNAc...) Potential
Glycosylation5781N-linked (GlcNAc...) Potential
Glycosylation5981N-linked (GlcNAc...) Potential
Glycosylation6641N-linked (GlcNAc...) Potential
Glycosylation6821N-linked (GlcNAc...) Ref.10
Glycosylation7601N-linked (GlcNAc...) Potential
Glycosylation8341N-linked (GlcNAc...) Potential
Glycosylation8501N-linked (GlcNAc...) Ref.10
Glycosylation9891N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 1919Missing in isoform 3.
VSP_005449
Alternative sequence1 – 1414Missing in isoform 2.
VSP_005448
Natural variant861S → P.
Corresponds to variant rs3797799 [ dbSNP | Ensembl ].
VAR_031616
Natural variant5941N → I.
Corresponds to variant rs12520455 [ dbSNP | Ensembl ].
VAR_051567
Natural variant7631A → T.
Corresponds to variant rs2303138 [ dbSNP | Ensembl ].
VAR_012812
Natural variant9131S → T.
Corresponds to variant rs17087233 [ dbSNP | Ensembl ].
VAR_051568
Natural variant9631I → V.
Corresponds to variant rs11746232 [ dbSNP | Ensembl ].
VAR_031617

Experimental info

Sequence conflict661D → V in CAB61646. Ref.3
Sequence conflict661D → V in CAB94753. Ref.3
Sequence conflict3011S → L AA sequence Ref.6
Sequence conflict3861K → N in AAB66672. Ref.2
Sequence conflict3861K → N in AAB66673. Ref.2
Sequence conflict3861K → N in CAB61646. Ref.3
Sequence conflict3861K → N in CAB94753. Ref.3
Sequence conflict8921K → Q in BAA09436. Ref.1
Sequence conflict9441F → L in BAA09436. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 17, 2007. Version 3.
Checksum: F84C0EA9D48DC2C0

FASTA1,025117,349
        10         20         30         40         50         60 
MEPFTNDRLQ LPRNMIENSM FEEEPDVVDL AKEPCLHPLE PDEVEYEPRG SRLLVRGLGE 

        70         80         90        100        110        120 
HEMEEDEEDY ESSAKLLGMS FMNRSSGLRN SATGYRQSPD GACSVPSART MVVCAFVIVV 

       130        140        150        160        170        180 
AVSVIMVIYL LPRCTFTKEG CHKKNQSIGL IQPFATNGKL FPWAQIRLPT AVVPLRYELS 

       190        200        210        220        230        240 
LHPNLTSMTF RGSVTISVQA LQVTWNIILH STGHNISRVT FMSAVSSQEK QAEILEYAYH 

       250        260        270        280        290        300 
GQIAIVAPEA LLAGHNYTLK IEYSANISSS YYGFYGFSYT DESNEKKYFA ATQFEPLAAR 

       310        320        330        340        350        360 
SAFPCFDEPA FKATFIIKII RDEQYTALSN MPKKSSVVLD DGLVQDEFSE SVKMSTYLVA 

       370        380        390        400        410        420 
FIVGEMKNLS QDVNGTLVSI YAVPEKIGQV HYALETTVKL LEFFQNYFEI QYPLKKLDLV 

       430        440        450        460        470        480 
AIPDFEAGAM ENWGLLTFRE ETLLYDSNTS SMADRKLVTK IIAHELAHQW FGNLVTMKWW 

       490        500        510        520        530        540 
NDLWLNEGFA TFMEYFSLEK IFKELSSYED FLDARFKTMK KDSLNSSHPI SSSVQSSEQI 

       550        560        570        580        590        600 
EEMFDSLSYF KGSSLLLMLK TYLSEDVFQH AVVLYLHNHS YASIQSDDLW DSFNEVTNQT 

       610        620        630        640        650        660 
LDVKRMMKTW TLQKGFPLVT VQKKGKELFI QQERFFLNMK PEIQPSDTSY LWHIPLSYVT 

       670        680        690        700        710        720 
EGRNYSKYQS VSLLDKKSGV INLTEEVLWV KVNINMNGYY IVHYADDDWE ALIHQLKINP 

       730        740        750        760        770        780 
YVLSDKDRAN LINNIFELAG LGKVPLKRAF DLINYLGNEN HTAPITEALF QTDLIYNLLE 

       790        800        810        820        830        840 
KLGYMDLASR LVTRVFKLLQ NQIQQQTWTD EGTPSMRELR SALLEFACTH NLGNCSTTAM 

       850        860        870        880        890        900 
KLFDDWMASN GTQSLPTDVM TTVFKVGAKT DKGWSFLLGK YISIGSEAEK NKILEALASS 

       910        920        930        940        950        960 
EDVRKLYWLM KSSLNGDNFR TQKLSFIIRT VGRHFPGHLL AWDFVKENWN KLVQKFPLGS 

       970        980        990       1000       1010       1020 
YTIQNIVAGS TYLFSTKTHL SEVQAFFENQ SEATFRLRCV QEALEVIQLN IQWMEKNLKS 


LTWWL 

« Hide

Isoform 2 [UniParc].

Checksum: FBB54EFECFBA8FD9
Show »

FASTA1,011115,636
Isoform 3 [UniParc].

Checksum: F57E71F1AA3C28E3
Show »

FASTA1,006115,062

References

« Hide 'large scale' references
[1]"Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family."
Rogi T., Tsujimoto M., Nakazato H., Mizutani S., Tomoda Y.
J. Biol. Chem. 271:56-61(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 160-168; 319-332; 615-624; 635-647; 798-814 AND 870-880, TISSUE SPECIFICITY.
Tissue: Placenta.
[2]"The complete amino acid sequence of human placental oxytocinase."
Laustsen P.G., Rasmussen T.E., Petersen K., Pedraza-Diaz S., Moestrup S.K., Gliemann J., Sottrup-Jensen L., Kristensen T.
Biochim. Biophys. Acta 1352:1-7(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Tissue: Placenta.
[3]"Structure of the human oxytocinase/insulin-regulated aminopeptidase gene and localization to chromosome 5q21."
Rasmussen T.E., Pedraza-Diaz S., Hardre R., Laustsen P.G., Carrion A.G., Kristensen T.
Eur. J. Biochem. 267:2297-2306(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
[4]"Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides."
Matsumoto H., Nagasaka T., Hattori A., Rogi T., Tsuruoka N., Mizutani S., Tsujimoto M.
Eur. J. Biochem. 268:3259-3266(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 206-1025.
Tissue: Brain.
[6]"Pool sequencing of natural HLA-DR, DQ, and DP ligands reveals detailed peptide motifs, constraints of processing, and general rules."
Falk K., Roetzschke O., Stevanovic S., Jung G., Rammensee H.G.
Immunogenetics 39:230-242(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 285-301 AND 710-724.
[7]"Identification of human placental leucine aminopeptidase as oxytocinase."
Tsujimoto M., Mizutani S., Adachi H., Kimura M., Nakazato H., Tomoda Y.
Arch. Biochem. Biophys. 292:388-392(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[8]"Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase."
Albiston A.L., McDowall S.G., Matsacos D., Sim P., Clune E., Mustafa T., Lee J., Mendelsohn F.A., Simpson R.J., Connolly L.M., Chai S.Y.
J. Biol. Chem. 276:48623-48626(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184; ASN-448; ASN-682 AND ASN-850.
Tissue: Leukemic T-cell.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D50810 mRNA. Translation: BAA09436.1. Different initiation.
U62768 mRNA. Translation: AAB66672.1.
U62769 mRNA. Translation: AAB66673.1.
AJ131023 expand/collapse EMBL AC list , AJ131025, AJ131026, AJ131027, AJ131028, AJ131029, AJ131030, AJ131031, AJ131032, AJ131033, AJ131034, AJ131035, AJ131036, AJ131037, AJ131038, AJ131039 Genomic DNA. Translation: CAB61646.1.
AJ131025 expand/collapse EMBL AC list , AJ131026, AJ131027, AJ131028, AJ131029, AJ131030, AJ131031, AJ131032, AJ131033, AJ131034, AJ131035, AJ131036, AJ131037, AJ131038, AJ131039 Genomic DNA. Translation: CAB94753.1.
AB208883 mRNA. Translation: BAD92120.1. Frameshift.
CCDSCCDS4087.1. [Q9UIQ6-1]
CCDS43346.1. [Q9UIQ6-2]
PIRA59383.
A59384.
RefSeqNP_005566.2. NM_005575.2. [Q9UIQ6-1]
NP_787116.2. NM_175920.3. [Q9UIQ6-2]
UniGeneHs.527199.
Hs.656905.

3D structure databases

ProteinModelPortalQ9UIQ6.
SMRQ9UIQ6. Positions 161-1025.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110196. 7 interactions.
IntActQ9UIQ6. 4 interactions.
STRING9606.ENSP00000231368.

Chemistry

BindingDBQ9UIQ6.
ChEMBLCHEMBL2693.

Protein family/group databases

MEROPSM01.011.

PTM databases

PhosphoSiteQ9UIQ6.

Polymorphism databases

DMDM145559489.

Proteomic databases

MaxQBQ9UIQ6.
PaxDbQ9UIQ6.
PeptideAtlasQ9UIQ6.
PRIDEQ9UIQ6.

Protocols and materials databases

DNASU4012.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000231368; ENSP00000231368; ENSG00000113441. [Q9UIQ6-1]
ENST00000395770; ENSP00000379117; ENSG00000113441. [Q9UIQ6-2]
GeneID4012.
KEGGhsa:4012.
UCSCuc003kmv.1. human. [Q9UIQ6-1]

Organism-specific databases

CTD4012.
GeneCardsGC05P096272.
H-InvDBHIX0005054.
HGNCHGNC:6656. LNPEP.
HPAHPA043642.
MIM151300. gene.
neXtProtNX_Q9UIQ6.
PharmGKBPA30418.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0308.
HOVERGENHBG108296.
InParanoidQ9UIQ6.
KOK01257.
OMAMEPFTND.
OrthoDBEOG754HNR.
PhylomeDBQ9UIQ6.
TreeFamTF300395.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.
REACT_6900. Immune System.
SABIO-RKQ9UIQ6.

Gene expression databases

BgeeQ9UIQ6.
CleanExHS_LNPEP.
GenevestigatorQ9UIQ6.

Family and domain databases

InterProIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERPTHR11533. PTHR11533. 1 hit.
PfamPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSPR00756. ALADIPTASE.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCystinyl_aminopeptidase.
GenomeRNAi4012.
NextBio15736.
PMAP-CutDBQ9UIQ6.
PROQ9UIQ6.
SOURCESearch...

Entry information

Entry nameLCAP_HUMAN
AccessionPrimary (citable) accession number: Q9UIQ6
Secondary accession number(s): O00769 expand/collapse secondary AC list , Q15145, Q59H76, Q9TNQ2, Q9TNQ3, Q9UIQ7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: April 17, 2007
Last modified: July 9, 2014
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM