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NRDC nardilysin convertase [ Homo sapiens (human) ]

Gene ID: 4898, updated on 11-Apr-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
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Genomic context

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Location:
1p32.3
Exon count:
34
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (51789210..51878727, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (51669503..51759610, complement)
105.20220307 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
  • 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. 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
  2. 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
  3. Nardilysin in human brain diseases: both friend and foe. Bernstein HG, et al. Amino Acids, 2013 Aug. PMID 23604405
  4. 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
  5. Histochemical evidence for wide expression of the metalloendopeptidase nardilysin in human brain neurons. Bernstein HG, et al. Neuroscience, 2007 Jun 8. PMID 17442499

See all (78) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. NRD1 interacts with p53 mutant R273H
    Title: Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion.
  10. These results demonstrate that gastric cancer cell growth is maintained by autonomous TNF-alpha-NF-kappaB and IL-6-STAT3 signalling, and that NRDc and ADAM proteases turn on these signalling cascades by stimulating ectodomain shedding of TNF-alpha.
    Title: Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-α.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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 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
  
located_in mitochondrion 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_2023_10

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

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