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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.

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