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    NRDC nardilysin convertase [ Homo sapiens (human) ]

    Gene ID: 4898, updated on 2-Nov-2024

    Summary

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    Official Symbol
    NRDCprovided by HGNC
    Official Full Name
    nardilysin convertaseprovided by HGNC
    Primary source
    HGNC:HGNC:7995
    See related
    Ensembl:ENSG00000078618 MIM:602651; AllianceGenome:HGNC:7995
    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
    NRD1; hNRD1; hNRD2
    Summary
    This gene encodes a zinc-dependent endopeptidase that cleaves peptide substrates at the N-terminus of arginine residues in dibasic moieties and is a member of the peptidase M16 family. This protein interacts with heparin-binding EGF-like growth factor and plays a role in cell migration and proliferation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]
    Expression
    Ubiquitous expression in testis (RPKM 55.2), skin (RPKM 27.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NRDC in Genome Data Viewer
    Location:
    1p32.3
    Exon count:
    34
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (51789210..51878727, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (51669503..51759610, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (52254882..52344399, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene oxysterol binding protein like 9 Neighboring gene small nucleolar RNA SNORA26 Neighboring gene solute carrier family 25 member 6 pseudogene 3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:52195252-52195772 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 881 Neighboring gene Sharpr-MPRA regulatory region 3774 Neighboring gene MPRA-validated peak222 silencer Neighboring gene MPRA-validated peak223 silencer Neighboring gene microRNA 761 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:52342189-52342720 Neighboring gene Sharpr-MPRA regulatory region 5937 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:52345137-52345690 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:52346444-52346641 Neighboring gene MPRA-validated peak224 silencer Neighboring gene tRNA splicing endonuclease subunit 15 pseudogene 2 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:52362999-52364198 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1029 Neighboring gene RAB3B, member RAS oncogene family Neighboring gene RNA, 5S ribosomal pseudogene 48 Neighboring gene ribosomal protein S26 pseudogene 14

    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. Histochemical evidence for wide expression of the metalloendopeptidase nardilysin in human brain neurons. Bernstein HG, et al. Neuroscience, 2007 Jun 8. PMID 17442499
    2. Increased serum nardilysin is associated with worse long-term outcome of ST-elevation myocardial infarction. Miao CQ, et al. Eur Rev Med Pharmacol Sci, 2018 Nov. PMID 30536341
    3. Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome. Chen PM, et al. Int J Cardiol, 2017 Sep 15. PMID 28747015
    4. Nardilysin in human brain diseases: both friend and foe. Bernstein HG, et al. Amino Acids, 2013 Aug. PMID 23604405
    5. Decreased expression of nardilysin in SH-SY5Y cells under ethanol stress and reduced density of nardilysin-expressing neurons in brains of alcoholics. Bernstein HG, et al. J Psychiatr Res, 2013 Mar. PMID 23219461

    See all (83) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CircNRD1 elevates THAP domain containing 11 through sequestering microRNA-421 to inhibit gastric cancer growth and tumorigenesis.
      Title: CircNRD1 elevates THAP domain containing 11 through sequestering microRNA-421 to inhibit gastric cancer growth and tumorigenesis.
    2. Altered Levels of Negative Costimulatory Molecule V-Set Domain-Containing T-Cell Activation Inhibitor-1 (VTCN1) and Metalloprotease Nardilysin (NRD1) are Associated with Generalized Active Vitiligo.
      Title: Altered Levels of Negative Costimulatory Molecule V-Set Domain-Containing T-Cell Activation Inhibitor-1 (VTCN1) and Metalloprotease Nardilysin (NRD1) are Associated with Generalized Active Vitiligo.
    3. Increased serum nardilysin at admission is associated with a higher risk of all-cause mortality for ST-elevation myocardial infarction patients.
      Title: Increased serum nardilysin is associated with worse long-term outcome of ST-elevation myocardial infarction.
    4. NRDC expression was reduced in infarcted regions in autopsy samples from acute myocardial ischemia patients.
      Title: Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome.
    5. Gene expression level of NRD1 is significantly higher in AD patients when compared to normal controls.
      Title: Association of gene expression and methylation of UQCRC1 to the predisposition of Alzheimer's disease in a Chinese population.
    6. MRNA expression of NRD1 was upregulated in 56% of ESCC tissue samples.
      Title: NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression.
    7. This study demonistrated that alcohol-dependent reduction of nardilysin in cell culture and nervous tissue points to an implication of the enzyme in the pathophysiology of alcoholism.
      Title: Decreased expression of nardilysin in SH-SY5Y cells under ethanol stress and reduced density of nardilysin-expressing neurons in brains of alcoholics.
    8. possible roles of nardilysin in Alzheimer disease, Down syndrome, schizophrenia, mood disorders, alcohol abuse, heroin addiction and cancer; show that nardilysin is a Janus-faced enzyme with regard to brain pathology-- probably neuropathogenic in some diseases, but neuroprotective in others [review]
      Title: Nardilysin in human brain diseases: both friend and foe.
    9. SH-SY5Y cells, stably transfected with green fluorescent protein-tagged-p42(IP4) show enhanced NRD protein expression already at an earlier time point after retinoic acid stimulation.
      Title: Retinoic acid-induced upregulation of the metalloendopeptidase nardilysin is accelerated by co-expression of the brain-specific protein p42(IP4) (centaurin α 1; ADAP1) in neuroblastoma cells.
    10. NRD1 interacts with p53 mutant R273H
      Title: Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, nardilysin (N-arginine dibasic convertase) (NRD1), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with NRD1 is decreased by RRE PubMed
    Vif vif HIV-1 Vif interacts with NRDC; interaction predicted to be relevant to proteolysis PubMed

    Go to the HIV-1, Human Interaction Database

    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 epidermal growth factor binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of axonogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of membrane protein ectodomain proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of myelination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell surface TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in dendrite IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    nardilysin
    Names
    NRD convertase
    nardilysin (N-arginine dibasic convertase)
    NP_001095132.1
    NP_001229290.1
    NP_002516.2

    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.

    Genomic

    1. NG_029171.2 RefSeqGene

      Range
      5211..94728
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001101662.2 → NP_001095132.1  nardilysin isoform b precursor

      See identical proteins and their annotated locations for NP_001095132.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks alternate in-frame exons, compared to variant 1, resulting in a shorter protein (isoform b), compared to isoform a.
      Source sequence(s)
      AY360265, BC008775, DA245717, X93209
      Consensus CDS
      CCDS41335.1
      UniProtKB/Swiss-Prot
      A6NI41, O15241, O15242, O43847, Q5VUL0, Q96HB2, Q9NU57
      UniProtKB/TrEMBL
      B4DRI0
      Related
      ENSP00000262679.8, ENST00000352171.12
      Conserved Domains (1) summary
      cl25708
      Location:103 → 1089
      Peptidase_M16; Insulinase (Peptidase family M16)

    2. NM_001242361.2 → NP_001229290.1  nardilysin isoform c

      See identical proteins and their annotated locations for NP_001229290.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AY360265, BC008775, DB084774
      Consensus CDS
      CCDS55599.1
      UniProtKB/TrEMBL
      G3V1R5, Q6UUU9
      Related
      ENSP00000444416.1, ENST00000539524.5
      Conserved Domains (1) summary
      cl25708
      Location:147 → 1025
      Peptidase_M16; Insulinase (Peptidase family M16)

    3. NM_002525.3 → NP_002516.2  nardilysin isoform a

      See identical proteins and their annotated locations for NP_002516.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AY360265, BC008775, DA245717, X93207
      Consensus CDS
      CCDS559.1
      UniProtKB/TrEMBL
      Q6UUU9
      Related
      ENSP00000346890.7, ENST00000354831.11
      Conserved Domains (4) summary
      COG1025
      Location:279 → 1157
      Ptr; Secreted/periplasmic Zn-dependent peptidases, insulinase-like [Posttranslational modification, protein turnover, chaperones]
      pfam00675
      Location:279 → 405
      Peptidase_M16; Insulinase (Peptidase family M16)
      pfam05193
      Location:430 → 616
      Peptidase_M16_C; Peptidase M16 inactive domain
      pfam16187
      Location:621 → 902
      Peptidase_M16_M; Middle or third domain of peptidase_M16

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      51789210..51878727 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      51669503..51759610 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43847.3 GenPept UniProtKB/Swiss-Prot:O43847

    Gene LinkOut

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

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