NRDC (nardilysin convertase)

Gene

• Entrez ID: 4898
• Gene name: Nardilysin convertase
• Gene symbol: NRDC
• Synonyms (NCBI Gene): NRD1, hNRD1, hNRD2
• Chromosome: 1
• Chromosome location: 1p32.3
• 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

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0004222	Function	Metalloendopeptidase activity	NAS	9581555
GO:0005515	Function	Protein binding	IPI	18355445, 22653443
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IDA	28017472
GO:0005829	Component	Cytosol	TAS	12463163
GO:0006508	Process	Proteolysis	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0009986	Component	Cell surface	TAS	12463163
GO:0016787	Function	Hydrolase activity	IEA
GO:0030425	Component	Dendrite	IEA
GO:0031643	Process	Positive regulation of myelination	ISS
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IDA	18355445
GO:0042995	Component	Cell projection	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048408	Function	Epidermal growth factor binding	TAS	12463163
GO:0050772	Process	Positive regulation of axonogenesis	ISS
GO:0051044	Process	Positive regulation of membrane protein ectodomain proteolysis	IDA	18355445
GO:0061133	Function	Endopeptidase activator activity	IDA	18355445
GO:0120163	Process	Negative regulation of cold-induced thermogenesis	ISS	24492630
GO:1903265	Process	Positive regulation of tumor necrosis factor-mediated signaling pathway	IDA	18355445

Other IDs

• MIM: 602651
• HGNC: 7995
• e!Ensembl: ENSG00000078618

Protein

• UniProt ID: O43847
• Protein name: Nardilysin (EC 3.4.24.61) (N-arginine dibasic convertase) (NRD convertase) (NRD-C) (Nardilysin convertase)
• Protein function: Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs. Is a critical activator of BACE1- and ADAM17-mediated pro-neuregulin ectodomain shedding, involved in the positive regulation of axonal maturation and myelinatio
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00675	Peptidase_M16	199 → 337	Insulinase (Peptidase family M16)	Family
  PF05193	Peptidase_M16_C	362 → 548	Peptidase M16 inactive domain	Domain
  PF16187	Peptidase_M16_M	553 → 834	Middle or third domain of peptidase_M16	Family
  PF05193	Peptidase_M16_C	838 → 1021	Peptidase M16 inactive domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Primarily in adult heart, skeletal muscle, and testis and at much lower levels in other tissues.
• Sequence:

  MLRRVTVAAVCATRRKLCEAGRELAALWGIETRGRCEDSAAARPFPILAMPGRNKAKSTC
  SCPDLQPNGQDLGENSRVARLGADESEEEGRRGSLSNAGDPEIVKSPSDPKQYRYIKLQN
  GLQALLISDLSNMEGKTGNTTDDEEEEEVEEEEEDDDEDSGAEIEDDDEEGFDDEDEFDD
  EHDDDLDTEDNELEELEERAEARKKTTEKQSAAALCVGVGSFADPDDLPGLAHFLEHMVF
  MGSLKYPDENGFDAFLKKHGGSDNASTDCERTVFQFDVQRKYFKEALDRWAQFFIHPLMI
  RDAIDREVEAVDSEYQLARPSDANRKEMLFGSLARPGHPMGKFFWGNAETLKHEPRKNNI
  DTHARLREFWMRYYSSHYMTLVVQSKETLDTLEKWVTEIFSQIPNNGLPRPNFGHLTDPF
  DTPAFNKLYRVVPIRKIHALTITWALPPQQQHYRVKPLHYISWLVGHEGKGSILSFLRKK
  CWALALFGGNGETGFEQNSTYSVFSISITLTDEGYEHFYEVAYTVFQYLKMLQKLGPEKR
  IFEEIRKIEDNEFHYQEQTDPVEYVENMCENMQLYPLQDILTGDQLLFEYKPEVIGEALN
  QLVPQKANLVLLSGANEGKCDLKEKWFGTQYSIEDIENSWAELWNSNFELNPDLHLPAEN
  KYIATDFTLKAFDCPETEYPVKIVNTPQGCLWYKKDNKFKIPKAYIRFHLISPLIQKSAA
  NVVLFDIFVNILTHNLAEPAYEADVAQLEYKLVAGEHGLIIRVKGFNHKLPLLFQLIIDY
  LAEFNSTPAVFTMITEQLKKTYFNILIKPETLAKDVRLLILEYARWSMIDKYQALMDGLS
  LESLLSFVKEFKSQLFVEGLVQGNVTSTESMDFLKYVVDKLNFKPLEQEMPVQFQVVELP
  SGHHLCKVKALNKGDANSEVTVYYQSGTRSLREYTLMELLVMHMEEPCFDFLRTKQTLGY
  HVYPTCRNTSGILGFSVTVGTQATKYNSEVVDKKIEEFLSSFEEKIENLTEEAFNTQVTA
  LIKLKECEDTHLGEEVDRNWNEVVTQQYLFDRLAHEIEALKSFSKSDLVNWFKAHRGPGS
  KMLSVHVVGYGKYELEEDGTPSSEDSNSSCEVMQLTYLPTSPLLADCIIPITDIRAFTTT
  LNLLPYHKIVK

• Sequence length: 1151

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Esophageal Neoplasms	Associate	24168165	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Stimulate	24168165	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Associate	22351606	★☆☆☆☆ Found in Text Mining only