Human Gene LNPEP (uc003kmw.1)
  Description: Homo sapiens leucyl/cystinyl aminopeptidase (LNPEP), transcript variant 2, mRNA.
RefSeq Summary (NM_175920): This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr5:96,294,156-96,365,115 Size: 70,960 Total Exon Count: 18 Strand: +
Coding Region
   Position: hg19 chr5:96,314,865-96,364,237 Size: 49,373 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:96,294,156-96,365,115)mRNA (may differ from genome)Protein (1011 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeTreefamUniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: LCAP_HUMAN
DESCRIPTION: RecName: Full=Leucyl-cystinyl aminopeptidase; Short=Cystinyl aminopeptidase; EC=3.4.11.3; AltName: Full=Insulin-regulated membrane aminopeptidase; AltName: Full=Insulin-responsive aminopeptidase; Short=IRAP; AltName: Full=Oxytocinase; Short=OTase; AltName: Full=Placental leucine aminopeptidase; Short=P-LAP; Contains: RecName: Full=Leucyl-cystinyl aminopeptidase, pregnancy serum form;
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.
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.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBUNIT: 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.
SUBCELLULAR LOCATION: 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.
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.
PTM: The pregnancy serum form is derived from the membrane-bound form by proteolytic processing.
PTM: N-glycosylated.
SIMILARITY: Belongs to the peptidase M1 family.
SEQUENCE CAUTION: Sequence=BAA09436.1; Type=Erroneous initiation; Sequence=BAD92120.1; Type=Frameshift; Positions=405;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LNPEP
CDC HuGE Published Literature: LNPEP

-  MalaCards Disease Associations
  MalaCards Gene Search: LNPEP
Diseases sorted by gene-association score: gestational diabetes insipidus (18), trophoblastic neoplasm (16), placental site trophoblastic tumor (13), choriocarcinoma (12), dysgerminoma of ovary (11), birdshot chorioretinopathy (9), diabetes insipidus, neurohypophyseal (7), endometrial adenocarcinoma (6), mild pre-eclampsia (5), diabetes insipidus, nephrogenic (5), preeclampsia/eclampsia 1 (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.62 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 299.22 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -105.42348-0.303 Picture PostScript Text
3' UTR -220.17878-0.251 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR024571 - DUF3358
IPR001930 - Peptidase_M1
IPR014782 - Peptidase_M1_N

Pfam Domains:
PF01433 - Peptidase family M1 domain
PF11838 - ERAP1-like C-terminal domain

SCOP Domains:
63737 - Leukotriene A4 hydrolase N-terminal domain
55486 - Metalloproteases ("zincins"), catalytic domain

ModBase Predicted Comparative 3D Structure on Q9UIQ6
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologGenome BrowserNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
 Protein SequenceProtein Sequence Protein Sequence 
 AlignmentAlignment Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004177 aminopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0042277 peptide binding
GO:0046872 metal ion binding
GO:0070006 metalloaminopeptidase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0002480 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
GO:0006508 proteolysis
GO:0007165 signal transduction
GO:0007267 cell-cell signaling
GO:0007565 female pregnancy
GO:0008217 regulation of blood pressure
GO:0030163 protein catabolic process
GO:0043171 peptide catabolic process
GO:0060395 SMAD protein signal transduction

Cellular Component:
GO:0005576 extracellular region
GO:0005622 intracellular
GO:0005765 lysosomal membrane
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030659 cytoplasmic vesicle membrane
GO:0031905 early endosome lumen
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  D50810 - Homo sapiens mRNA for placental leucine aminopeptidase, complete cds.
U62768 - Human oxytocinase splice variant 1 mRNA, complete cds.
AK314226 - Homo sapiens cDNA, FLJ94965, highly similar to Homo sapiens leucyl/cystinyl aminopeptidase (LNPEP), mRNA.
BC111718 - Homo sapiens cDNA clone IMAGE:40008834, containing frame-shift errors.
BC113117 - Homo sapiens cDNA clone IMAGE:40008839, containing frame-shift errors.
BC028692 - Homo sapiens leucyl/cystinyl aminopeptidase, mRNA (cDNA clone IMAGE:4827653), containing frame-shift errors.
BC160010 - Synthetic construct Homo sapiens clone IMAGE:100063946, MGC:193125 leucyl/cystinyl aminopeptidase (LNPEP) mRNA, encodes complete protein.
U62769 - Human oxytocinase variant 2 mRNA, complete cds.
KJ897140 - Synthetic construct Homo sapiens clone ccsbBroadEn_06534 LNPEP-like gene, encodes complete protein.
AB208883 - Homo sapiens mRNA for leucyl/cystinyl aminopeptidase variant protein.
JD302479 - Sequence 283503 from Patent EP1572962.
JD080133 - Sequence 61157 from Patent EP1572962.
JD477261 - Sequence 458285 from Patent EP1572962.
JD193626 - Sequence 174650 from Patent EP1572962.
JD500670 - Sequence 481694 from Patent EP1572962.
JD069249 - Sequence 50273 from Patent EP1572962.
JD437472 - Sequence 418496 from Patent EP1572962.
AK023633 - Homo sapiens cDNA FLJ13571 fis, clone PLACE1008405.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04614 - Renin-angiotensin system

Reactome (by CSHL, EBI, and GO)

Protein Q9UIQ6 (Reactome details) participates in the following event(s):

R-HSA-1445149 14-3-3 binds p-5S,T642-AS160 (TBC1D4)
R-HSA-1236954 Trimming of peptides by IRAP in endocytic vesicles
R-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1236977 Endosomal/Vacuolar pathway
R-HSA-199991 Membrane Trafficking
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-1236975 Antigen processing-Cross presentation
R-HSA-5653656 Vesicle-mediated transport
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: LCAP_HUMAN, NM_175920, NP_787116, O00769, OTASE, Q15145, Q59H76, Q9TNQ2, Q9TNQ3, Q9UIQ6, Q9UIQ7
UCSC ID: uc003kmw.1
RefSeq Accession: NM_175920
Protein: Q9UIQ6 (aka LCAP_HUMAN)
CCDS: CCDS43346.1, CCDS4087.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_175920.3
exon count: 18CDS single in 3' UTR: no RNA size: 4262
ORF size: 3036CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6196.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.