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ENPEP glutamyl aminopeptidase [ Homo sapiens (human) ]

Gene ID: 2028, updated on 2-Nov-2024

Summary

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Official Symbol
ENPEPprovided by HGNC
Official Full Name
glutamyl aminopeptidaseprovided by HGNC
Primary source
HGNC:HGNC:3355
See related
Ensembl:ENSG00000138792 MIM:138297; AllianceGenome:HGNC:3355
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
APA; CD249; gp160
Summary
The ENPEP gene encodes glutamyl aminopeptidase, a type II integral membrane protein with an extracellular zinc-binding domain. This protein can upregulate blood pressure by cleaving the N-terminal aspartate from angiotensin II, and can regulate blood vessel formation and enhance tumorigenesis in some tissues. Along with ANPEP and DPP4, ENPEP was found to be a candidate co-receptor for the coronavirus SARS-CoV-2, which causes COVID-19. [provided by RefSeq, Apr 2020]
Expression
Biased expression in small intestine (RPKM 132.9), kidney (RPKM 71.6) and 5 other tissues See more
Orthologs
mouse all
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Genomic context

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See ENPEP in Genome Data Viewer
Location:
4q25
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (110476155..110565285)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (113778214..113867343)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (111397311..111486441)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene zinc finger protein 969, pseudogene Neighboring gene small nucleolar RNA U2-19 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:111393905-111394607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21817 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_72001 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_72004 Neighboring gene Sharpr-MPRA regulatory region 9284 Neighboring gene uncharacterized LOC105377363 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:111537217-111537875 Neighboring gene PITX2 adjacent non-coding RNA Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111540229-111540882 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111540883-111541534 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111542189-111542841 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15630 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111547605-111548106 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111548107-111548606 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr4:111549504-111550355 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111553473-111553985 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr4:111562143-111562646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111560253-111560848 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111559017-111559517 Neighboring gene paired like homeodomain 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta. Ito N, et al. Early Hum Dev, 2003 Feb. PMID 12614948
  2. Aminopeptidase A contributes to the N-terminal truncation of amyloid beta-peptide. Sevalle J, et al. J Neurochem, 2009 Apr. PMID 19187443
  3. Human brain aminopeptidase A: biochemical properties and distribution in brain nuclei. de Mota N, et al. J Neurochem, 2008 Jul. PMID 18410507
  4. Functional genetic variation in aminopeptidase A (ENPEP): lack of clear association with focal and segmental glomerulosclerosis (FSGS). Tonna S, et al. Gene, 2008 Feb 29. PMID 18206321, Free PMC Article
  5. New insights into the importance of aminopeptidase A in hypertension. Mizutani S, et al. Heart Fail Rev, 2008 Sep. PMID 17990103, Free PMC Article

See all (51) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Uncovering the role of TET2-mediated ENPEP activation in trophoblast cell fate determination.
    Title: Uncovering the role of TET2-mediated ENPEP activation in trophoblast cell fate determination.
  2. Aminopeptidase A contributes to biochemical, anatomical and cognitive defects in Alzheimer's disease (AD) mouse model and is increased at early stage in sporadic AD brain.
    Title: Aminopeptidase A contributes to biochemical, anatomical and cognitive defects in Alzheimer's disease (AD) mouse model and is increased at early stage in sporadic AD brain.
  3. Aminopeptidase A (ENPEP) gene polymorphisms and preeclampsia: Descriptive analysis.
    Title: Aminopeptidase A (ENPEP) gene polymorphisms and preeclampsia: Descriptive analysis.
  4. We suggest that APA enzymatic activity affects tumor initiation and cancer malignancy in a TWIST-dependent manner
    Title: Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer.
  5. 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.
  6. This study suggests a role for GAP in the neoplastic development of renal tumours and provides additional data for considering the activity and expression of this enzyme of interest in the diagnosis and prognosis of renal neoplasms.
    Title: Altered glutamyl-aminopeptidase activity and expression in renal neoplasms.
  7. miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-alpha, CCNJ, and MEGF9.
    Title: miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-α, CCNJ, and MEGF9.
  8. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation
    Title: Structural insights into central hypertension regulation by human aminopeptidase A.
  9. There was no significant alteration in plasma APA activity in the patients with Chagas disease or dilated cardiomyopathies, as compared with that in health controls
    Title: Does the aminopeptidase A have prognostic and diagnostic value in Chagas disease and other dilated cardiomyopathies?
  10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Submit: New GeneRIF Correction See all GeneRIFs (21)

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
Human metabolic individuality in biomedical and pharmaceutical research.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians.
EBI GWAS Catalog
Variants conferring risk of atrial fibrillation on chromosome 4q25.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aminopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metalloaminopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metalloaminopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metalloaminopeptidase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables peptide binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables zinc ion binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in angiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in angiotensin maturation NAS
Non-traceable Author Statement
more info
 PubMed 
acts_upstream_of_or_within cell migration IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell-cell signaling NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in glomerulus development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in peptide catabolic process IBA
Inferred from Biological aspect of Ancestor
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
  
involved_in regulation of systemic arterial blood pressure by renin-angiotensin IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of systemic arterial blood pressure by renin-angiotensin NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in apical part of cell ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in apical plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in brush border ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasmic vesicle ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in external side of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lysosomal membrane HDA PubMed 
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 NAS
Non-traceable Author Statement
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
glutamyl aminopeptidase
Names
AP-A
EAP
aminopeptidase A
differentiation antigen gp160
NP_001366540.1
NP_001366541.1
NP_001366542.1
NP_001968.3
XP_016863366.1
XP_054205159.1

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)

  1. NM_001379611.1 → NP_001366540.1  glutamyl aminopeptidase isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC017068, AC098798
    UniProtKB/TrEMBL
    B0BCZ6, B0BCZ7
    Conserved Domains (2) summary
    cd09601
    Location:100 → 540
    M1_APN-Q_like; Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), aminopeptidase Q (APQ), tricorn interacting factor F3, and endoplasmic reticulum aminopeptidase 1 (ERAP1)
    pfam11838
    Location:616 → 908
    ERAP1_C; ERAP1-like C-terminal domain

  2. NM_001379612.1 → NP_001366541.1  glutamyl aminopeptidase isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC017068, AC098798
    UniProtKB/TrEMBL
    B0BCZ6, B0BCZ7
    Conserved Domains (2) summary
    cd09601
    Location:100 → 540
    M1_APN-Q_like; Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), aminopeptidase Q (APQ), tricorn interacting factor F3, and endoplasmic reticulum aminopeptidase 1 (ERAP1)
    pfam11838
    Location:616 → 880
    ERAP1_C; ERAP1-like C-terminal domain

  3. NM_001379613.1 → NP_001366542.1  glutamyl aminopeptidase isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC017068, AC098798
    UniProtKB/TrEMBL
    B0BCZ3, B0BCZ4, B0BCZ5
    Conserved Domains (2) summary
    cd09601
    Location:100 → 540
    M1_APN-Q_like; Peptidase M1 aminopeptidase N catalytic domain family which includes aminopeptidase N (APN), aminopeptidase Q (APQ), tricorn interacting factor F3, and endoplasmic reticulum aminopeptidase 1 (ERAP1)
    pfam11838
    Location:616 → 859
    ERAP1_C; ERAP1-like C-terminal domain

  4. NM_001977.4 → NP_001968.3  glutamyl aminopeptidase isoform 1

    See identical proteins and their annotated locations for NP_001968.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC017068, AC098798, AI640493, AL568777, BC094770, BG400415
    Consensus CDS
    CCDS3691.1
    UniProtKB/Swiss-Prot
    Q07075, Q504U2
    UniProtKB/TrEMBL
    B0BCY7, B0BCY8, B0BCY9, B0BCZ0, B0BCZ1, B0BCZ2, B0BCZ3, B0BCZ4, B0BCZ5, B0BCZ6, B0BCZ7
    Related
    ENSP00000265162.5, ENST00000265162.10
    Conserved Domains (3) summary
    cd09601
    Location:100 → 545
    M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)
    pfam01433
    Location:92 → 482
    Peptidase_M1; Peptidase family M1
    pfam11838
    Location:617 → 931
    ERAP1_C; ERAP1-like C-terminal domain

RNA

  1. NR_166842.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC017068, AC098798

  2. NR_166844.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC017068, AC098798

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    110476155..110565285
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017007877.2 → XP_016863366.1  glutamyl aminopeptidase isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    113778214..113867343
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054349184.1 → XP_054205159.1  glutamyl aminopeptidase isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q07075.3 GenPept UniProtKB/Swiss-Prot:Q07075

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
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