LNPEP leucyl and cystinyl aminopeptidase [Homo sapiens (human)] - Gene

Summary

Official Symbol: LNPEPprovided by HGNC
Official Full Name: leucyl and cystinyl aminopeptidaseprovided by HGNC
Primary source: HGNC:HGNC:6656
See related: Ensembl:ENSG00000113441 MIM:151300; AllianceGenome:HGNC:6656
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CAP; IRAP; PLAP; P-LAP
Summary: 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]
Expression: Ubiquitous expression in lymph node (RPKM 8.2), appendix (RPKM 6.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q15

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (96936080..97037513)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (97435206..97538276)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (96271784..96373217)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
Title: Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
The role of LNPEP and ANPEP gene polymorphisms in the pathogenesis of pre-eclampsia.
Title: The role of LNPEP and ANPEP gene polymorphisms in the pathogenesis of pre-eclampsia.
LNPEP expression in the left atrium in mitral regurgitation patients significantly differed from those in aortic valve disease patients and normal controls.
Title: Differential Gene Expression Profile of Renin-Angiotensin System in the Left Atrium in Mitral Regurgitation Patients.
This study shown that the schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia.
Title: Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.
Vasopressinase might be a potential early biomarker for acute kidney injury after cardiopulmonary bypass.
Title: Vasopressinase Activity: A Potential Early Biomarker for Detecting Cardiopulmonary Bypass-Associated Acute Kidney Injury?
Structural and biological characterization of three low molecular weight aryl sulfonamides: binding modes to human IRAP were explored by docking calculations combined with molecular dynamics simulations and binding affinity estimations using the linear interaction energy method. Two of these drug-like IRAP inhibitors can alter dendritic spine morphology and increase spine density in primary cultures of hippocampal neurons
Title: Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine Density in Primary Hippocampal Neuron Cultures.
The PCR-RFLP is a simple and reliable method that allows a quick genotyping for the rs4869317 SNP of LNPEP gene.
Title: A PCR-RFLP method for detection of the LNPEP encoding human insulin-regulated aminopeptidase (IRAP) rs4869317 polymorphism.
This study describes a crystal structure of insulin-regulated aminopeptidase in complex with a recently developed bioactive and selective inhibitor at 2.53 A resolution.
Title: Ligand-Induced Conformational Change of Insulin-Regulated Aminopeptidase: Insights on Catalytic Mechanism and Active Site Plasticity.
The substrate Angiotensin II, the enzymes aminopeptidases-A, B, M as well as IRAP were detected in the jejunal mucosa.
Title: Local expression of AP/AngIV/IRAP and effect of AngIV on glucose-induced epithelial transport in human jejunal mucosa.
Determined is the crystal structure of human IRAP revealing a closed, four domain arrangement with a large, mostly buried cavity abutting the active site.
Title: Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH123520 (e-PCR)
- UniSTS:135938

G60101 (e-PCR)
- UniSTS:137229

WI-11346 (e-PCR)
- UniSTS:17423

SGC38194 (e-PCR)
- UniSTS:72216

RH98440 (e-PCR)
- UniSTS:87843

WI-14824 (e-PCR)
- UniSTS:16431

NoName (e-PCR)
- UniSTS:484431

SHGC-36280 (e-PCR)
- UniSTS:81283

RH93950 (e-PCR)
- UniSTS:92547

SHGC-82127 (e-PCR)
- UniSTS:103047

D5S2387 (e-PCR)
- UniSTS:55989

G63141 (e-PCR)
- UniSTS:140258

RH102413 (e-PCR)
- UniSTS:96747

D5S1849 (e-PCR)
- UniSTS:20972

D5S1627E (e-PCR)
- UniSTS:151037

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables aminopeptidase activity	EXP Inferred from Experiment more info	PubMed
enables aminopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables metalloaminopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metallopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables peptide binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent	TAS Traceable Author Statement more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in female pregnancy	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in peptide catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein polyubiquitination	TAS Traceable Author Statement more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of blood pressure	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic vesicle membrane	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in early endosome lumen	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: leucyl-cystinyl aminopeptidase

Names: AT (4) receptor; angiotensin IV receptor; cystinyl aminopeptidase; insulin-regulated aminopeptidase; insulin-regulated membrane aminopeptidase; insulin-responsive aminopeptidase; otase; oxytocinase; placental leucine aminopeptidase; vasopressinase

NP_005566.2

EC 3.4.11.3

NP_787116.2

EC 3.4.11.3

XP_047273133.1

EC 3.4.11.3

XP_054208557.1

EC 3.4.11.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_005575.3 → NP_005566.2 leucyl-cystinyl aminopeptidase isoform 1

See identical proteins and their annotated locations for NP_005566.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC008850, AC008865, BC028692, BG622952, BQ923659, U62768

Consensus CDS

CCDS4087.1

UniProtKB/Swiss-Prot

O00769, Q15145, Q59H76, Q9TNQ2, Q9TNQ3, Q9UIQ6, Q9UIQ7

UniProtKB/TrEMBL

B2RAK1

Related

ENSP00000231368.5, ENST00000231368.10

Conserved Domains (2) summary

cd09601
Location:175 → 617

M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)

pfam11838
Location:689 → 1009

ERAP1_C; ERAP1-like C-terminal domain
NM_175920.4 → NP_787116.2 leucyl-cystinyl aminopeptidase isoform 2

See identical proteins and their annotated locations for NP_787116.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' exon, which results in a distinct 5' UTR and use of a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus when compared to isoform 1.

Source sequence(s)

AC008850, AC008865, BC028692, BG622952, BQ923659, U62768, U62769

Consensus CDS

CCDS43346.1

UniProtKB/TrEMBL

B2RAK1

Related

ENSP00000379117.3, ENST00000395770.3

Conserved Domains (3) summary

cd09601
Location:161 → 603

M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)

pfam01433
Location:153 → 538

Peptidase_M1; Peptidase family M1

pfam11838
Location:676 → 991

ERAP1_C; ERAP1-like C-terminal domain