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Information on EC 3.4.24.61 - nardilysin and Organism(s) Homo sapiens and UniProt Accession O43847
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3.4.24.61 nardilysinSpecify your search results
Word Map
- 3.4.24.61
- metalloendopeptidase
- ectodomain
-
heparin-binding
- pitrilysins
- adam17
- hb-egf
- insulysin
- insulinase
-
hxxeh
- dynorphins
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hydrolysis of polypeptides, preferably at -Xaa-/-Arg-Lys-, and less commonly at -Arg-/-Arg-Xaa-, in which Xaa is not Arg or Lys
Synonyms
nardilysin, nrd convertase, n-arginine dibasic convertase, nardilysin convertase, n-arginine dibasic (nrd) convertase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
N-Arginine dibasic convertase
NRD convertase
-
-
-
-
NRD-convertase
-
-
-
-
N-Arginine dibasic convertase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
157906-54-2
-
292850-69-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
heparin-binding epidermal growth factor-like growth factor + H2O
?
substrate is synthesized as a transmembrane protein. Enzyme enhances ectodomain shedding of substrate in coperation with tumor necrosis factor-alpha-converting enzyme. Metalloendopeptidase activity of enzyme is not required for enhancement of shedding
-
-
?
PRAME190-198 + H2O
?
-
nardilysin produces precursors of tumor-associated protein PRAME(190-198) by producing cleavage after Lys200, Arg201 and Lys202 but does not excise precisely at the C terminus (Lys198)
-
-
?
additional information
?
-
NRDc interacts with the NCoR/SMRT corepressor complex
-
-
?
additional information
?
-
NRDc is identifiend as a H3K4me2-binding protein. The H3K4me2-binding activity resides in the N-terminal region of NRDc
-
-
?
additional information
?
-
-
enhancement of alpha-secretase cleavage of amyloid precursor protein by a metalloendopeptidase nardilysin, resulting in down-regulation of beta-amyloid protein, overview, the enzyme also enhances ectodomain shedding of heparin-binding epidermal growth factor-like growth factor through activation of ADAM17, NRDc is regulatorally involved in the metabolism
-
-
?
additional information
?
-
-
expression of nardilysin synergistically enhances TNF-alpha-converting enzyme-induced TNF-alpha ectodomain-shedding via activation of ADAM proteases ADAM9 and ADAM10, activation is independent of protein kinase C, overview
-
-
?
additional information
?
-
-
the enzyme interacts with the brain-specific protein p42IP4/centaurin-alpha1, the interactionis regulated by phosphatidylinositol 3,4,5-triphosphate and inositol-1,3,4,5-tetrakisphophate, nardilysin might play a role in brain development, overview
-
-
?
additional information
?
-
-
the metalloendopeptidase cleaves N-terminal Arg or Lys residues of peptides
-
-
?
additional information
?
-
-
tubulin enhances the binding of NRD to functionally p42IP4
-
-
?
additional information
?
-
-
nardilysin can generate both N termini and C termini of CTL epitopes
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
heparin-binding epidermal growth factor-like growth factor + H2O
?
substrate is synthesized as a transmembrane protein. Enzyme enhances ectodomain shedding of substrate in coperation with tumor necrosis factor-alpha-converting enzyme. Metalloendopeptidase activity of enzyme is not required for enhancement of shedding
-
-
?
additional information
?
-
NRDc interacts with the NCoR/SMRT corepressor complex
-
-
?
additional information
?
-
NRDc is identifiend as a H3K4me2-binding protein. The H3K4me2-binding activity resides in the N-terminal region of NRDc
-
-
?
additional information
?
-
-
enhancement of alpha-secretase cleavage of amyloid precursor protein by a metalloendopeptidase nardilysin, resulting in down-regulation of beta-amyloid protein, overview, the enzyme also enhances ectodomain shedding of heparin-binding epidermal growth factor-like growth factor through activation of ADAM17, NRDc is regulatorally involved in the metabolism
-
-
?
additional information
?
-
-
expression of nardilysin synergistically enhances TNF-alpha-converting enzyme-induced TNF-alpha ectodomain-shedding via activation of ADAM proteases ADAM9 and ADAM10, activation is independent of protein kinase C, overview
-
-
?
additional information
?
-
-
the enzyme interacts with the brain-specific protein p42IP4/centaurin-alpha1, the interactionis regulated by phosphatidylinositol 3,4,5-triphosphate and inositol-1,3,4,5-tetrakisphophate, nardilysin might play a role in brain development, overview
-
-
?
additional information
?
-
-
tubulin enhances the binding of NRD to functionally p42IP4
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
p42IP4
-
p42IP4 (centaurin alpha1) enhances the enzymatic activity of NRD 3-4 times.
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in cortical neurons the enzyme is partially co-localized with parvalbumin, but not with calretinin
-
NRD is expressed in the neurites of RA-stimulated SHSY5Y cells, and localized in vesicular structures
-
NRDc is expressed almost exclusively in cortical neurons, particularly in large neurons, not in glial cells
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immunolocalisation of nardilysin. In Alzheimer's disease and in Down syndrome brains there is a decreased cellular expression of nardilysin
-
reduced neuronal co-localisation of nardilysin and the putative alpha-secretases ADAM10 and ADAM17 in Alzheimers disease and Down syndrome brains
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
although NRDc can also be detected in the cytoplasm, it is enriched in the nucleus in both HeLa and NIH3T3 cells
-
p42IP4 (centaurin-alpha), nardilysin and tubulin are found in the cytosol and at the plasma membrane of SH-SY5Y neuroblastoma cells
-
p42IP4 (centaurin-alpha), nardilysin and tubulin are found in the cytosol and at the plasma membrane of SH-SY5Y neuroblastoma cells
although NRDc can also be detected in the cytoplasm, it is enriched in the nucleus in both HeLa and NIH3T3 cells
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
knockdown of enzyme expression attenuates gastric cancer cell growth in vitro
physiological function
physiological function
physiological function
NRDc is physically associated with and recruits the NCoR complex to some of the repressed genes and this association correlates with binding of H3K4me2
physiological function
nardilysin promotes gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of tumor necrosis factor-alpha
physiological function
the interaction between the enzyme and centaurin-1alpha contribute to brain structural damage observed in Alzheimer's disease
physiological function
the enzyme controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation
physiological function
-
nardilysin is involved in degradation of neuropeptides and limited intracellular proteolysis. It might play a role in human brain pathology of in Alzheimer's disease and in Down syndrome that nardilysin enhances the activity of alpha-secretases ADAM10 and ADAM17. Alzheimer's disease and in Down syndrome brains show decreased cellular expression of all three antigens, and a reduction in the number of those neurons that co-express nardilysin with ADAM10 or with ADAM17
physiological function
-
nardilysin and thimet oligopeptidase (TOP) are required, either together or alone, for the generation of a tumor-specific CTL epitope from PRAME, an immunodominant CTL epitope from Epstein-Barr virus protein EBNA3C, and a clinically important epitope from the melanoma protein MART-1
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NRDC_HUMAN
1151
0
131701
Swiss-Prot
Mitochondrion (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
interaction of enzyme with tumor necrosis factor-alpha-converting enzyme
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C948A
-
the mutation of a highly conserved cysteine residue in NRD to Ala abolishes the potentiation by tubulin
additional information
additional information
-
detection and reconstruction of the naturally occurring mutation APP770, overview
additional information
-
NRD lacking the characteristic acidic domain is able to bind p42IP4 but addition of tubulin does not significantly potentiate the binding of this deletion mutant to p42IP4. A function-abolishing mutation of the Zn2+-binding motif of NRD does not affect the potentiation by tubulin
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the wild-type enzyme and the mutant E235A in COS-7 or HEK-293T cells, co-expression with ADAM17
-
heterologous expression of hNRDc1 by both human myometrial smooth muscle cells and ltk- mouse fibroblasts. Analysation of the regulatory function of hNRDc1 regarding mK44 (a splice variant of maxi-K chanel). Data indicate that hNRDc1 is involved in regulating the excitation of smooth muscle cells.
-
overexpression of V5-tagged NRDc from a a lentivirus vector in TACE-deficient fibroblasts, co-expression of NRDc with ADAM10, recombinant wild-type NRDc and mutant E235A are synthesized using a Bac-to-Bac baculovirus expression system, co-expression of the C-terminally V5-tagged wild-type enzyme with the TNF-alpha-converting enzyme in COS-7 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
protein expression is frequently elevated both in the serum and cancer epithelium of gastric cancer patients
there is strongly decreased neuronal enzyme expression in Down syndrome. The enzyme is down-regulated (about 1.21fold) in brains of individuals with bipolar disorder
differentiation of SH-SY5Y cells by stimulation with 10 microM retinoic acid (RA) results in upregulation of NRD protein levels, with a 6fold rise after 15 days
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
rising serum nardilysin concentrations following malignant cerebral infarction are strongly related to stroke severity, inflammatory extent and a higher risk of mortality, substantializing serum nardilysin is a potential prognostic biomarker for malignant cerebral infarction
medicine
serum nardilysin has potential as a novel prognostic biomarker for intrahepatic cholangiocarcinoma, which may reflect epithelial-mesenchymal transition features in primary tumor regions. It is proposed that the preoperative evaluation of serum nardilysin is a potential clinical tool for predicting tumor recurrence in and the overall prognosis of patients after curative-intent surgery
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nishi, E.; Hiraoka, Y.; Yoshida, K.; Okawa, K.; Kita, T.
Nardilysin enhances ectodomain shedding of heparin-binding epidermal growth factor-like growth factor through activation of tumor necrosis factor-alpha-converting enzyme
J. Biol. Chem.
281
31164-31172
2006
Homo sapiens (O43847)
Hiraoka, Y.; Yoshida, K.; Ohno, M.; Matsuoka, T.; Kita, T.; Nishi, E.
Ectodomain shedding of TNF-alpha is enhanced by nardilysin via activation of ADAM proteases
Biochem. Biophys. Res. Commun.
370
154-158
2008
Homo sapiens
Hiraoka, Y.; Ohno, M.; Yoshida, K.; Okawa, K.; Tomimoto, H.; Kita, T.; Nishi, E.
Enhancement of alpha-secretase cleavage of amyloid precursor protein by a metalloendopeptidase nardilysin
J. Neurochem.
102
1595-1605
2007
Homo sapiens
Bernstein, H.; Stricker, R.; Dobrowolny, H.; Truebner, K.; Bogerts, B.; Reiser, G.
Histochemical evidence for wide expression of the metalloendopeptidase nardilysin in human brain neurons
Neuroscience
146
1513-1523
2007
Homo sapiens
Bernstein, H.G.; Stricker, R.; Lendeckel, U.; Bertram, I.; Dobrowolny, H.; Steiner, J.; Bogerts, B.; Reiser, G.
Reduced neuronal co-localisation of nardilysin and the putative alpha-secretases ADAM10 and ADAM17 in Alzheimers disease and Down syndrome brains
Age (Dordr. )
31
11-25
2009
Homo sapiens
Korovkina, V.P.; Stamnes, S.J.; Brainard, A.M.; England, S.K.
Nardilysin convertase regulates the function of the maxi-K channel isoform mK44 in human myometrium
Am. J. Physiol. Cell Physiol.
296
C433-C440
2009
Homo sapiens
Kessler, J.H.; Khan, S.; Seifert, U.; Le Gall, S.; Chow, K.M.; Paschen, A.; Bres-Vloemans, S.A.; de Ru, A.; van Montfoort, N.; Franken, K.L.; Benckhuijsen, W.E.; Brooks, J.M.; van Hall, T.; Ray, K.; Mulder, A.; Doxiadis, I.I.; van Swieten, P.F.; Overkleeft, H.S.; Prat, A.; Tomkinson, B.; Neefjes, J.; Klo, K.l.o.e.
Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
Nat. Immunol.
12
45-53
2011
Homo sapiens
Borrmann, C.; Stricker, R.; Reiser, G.
Tubulin potentiates the interaction of the metalloendopeptidase nardilysin with the neuronal scaffold protein p42IP4/centaurin-alpha1 (ADAP1)
Cell Tissue Res.
346
89-98
2011
Homo sapiens
Li, J.; Chu, M.; Wang, S.; Chan, D.; Qi, S.; Wu, M.; Zhou, Z.; Li, J.; Nishi, E.; Qin, J.; Wong, J.
Identification and Characteriation of Nardilysin as a Novel Dimethyl H3K4 Binding Protein Involved in Transcriptional Regulation
J. Biol. Chem.
287
10089-10098
2012
Homo sapiens (O43847)
Borrmann, C.; Stricker, R.; Reiser, G.
Retinoic acid-induced upregulation of the metalloendopeptidase nardilysin is accelerated by co-expression of the brain-specific protein p42(IP4) (centaurin alpha1; ADAP1) in neuroblastoma cells
Neurochem. Int.
59
936-944
2011
Homo sapiens
Bernstein, H.; Stricker, R.; Dobrowolny, H.; Steiner, J.; Bogerts, B.; Trbner, K.; Reiser, G.
Nardilysin in human brain diseases: both friend and foe
Amino Acids
45
269-278
2013
Homo sapiens (O43847), Homo sapiens
Kanda, K.; Komekado, H.; Sawabu, T.; Ishizu, S.; Nakanishi, Y.; Nakatsuji, M.; Akitake-Kawano, R.; Ohno, M.; Hiraoka, Y.; Kawada, M.; Kawada, K.; Sakai, Y.; Matsumoto, K.; Kunichika, M.; Kimura, T.; Seno, H.; Nishi, E.; Chiba, T.
Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-alpha
EMBO Mol. Med.
4
396-411
2012
Homo sapiens (O43847), Homo sapiens
Yoh, T.; Hatano, E.; Kasai, Y.; Fuji, H.; Nishi, K.; Toriguchi, K.; Sueoka, H.; Ohno, M.; Seo, S.; Iwaisako, K.; Taura, K.; Yamaguchi, R.; Kurokawa, M.; Fujimoto, J.; Kimura, T.; Uemoto, S.; Nishi, E.
Serum nardilysin, a surrogate marker for epithelial-mesenchymal transition, predicts prognosis of intrahepatic cholangiocarcinoma after surgical resection
Clin. Cancer Res.
25
619-628
2019
Homo sapiens (O43847), Homo sapiens
Chen, F.H.; Wang, Y.; Jiang, Y.X.; Zhang, G.H.; Wang, Z.M.; Yang, H.
Clinical determination of serum nardilysin levels in predicting 30-day mortality among adults with malignant cerebral infarction
Clin. Chim. Acta
494
8-13
2019
Homo sapiens (O43847), Homo sapiens
Kanda, K.; Sakamoto, J.; Matsumoto, Y.; Ikuta, K.; Goto, N.; Morita, Y.; Ohno, M.; Nishi, K.; Eto, K.; Kimura, Y.; Nakanishi, Y.; Ikegami, K.; Yoshikawa, T.; Fukuda, A.; Kawada, K.; Sakai, Y.; Ito, A.; Yoshida, M.; Kimura, T.; Chiba, T.; Nishi, E.; Seno, H.
Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation
JCI Insight
3
91316
2018
Homo sapiens (O43847), Homo sapiens, Mus musculus (Q8BHG1)
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