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Information on EC 2.7.1.173 - nicotinate riboside kinase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
The enzyme from yeast and human also has the activity of EC 2.7.1.22 (ribosylnicotinamide kinase).
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This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
nr kinase, nicotinate riboside kinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nicotinamide riboside kinase
nicotinamide riboside kinase 1
-
nicotinamide riboside kinase 2
-
nicotinic acid riboside kinase
-
-
-
-
nicotinic acid riboside kinase 1
-
NR kinase
-
-
ribosylnicotinic acid kinase
-
-
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + beta-D-ribosylnicotinate = ADP + nicotinate beta-D-ribonucleotide
show the reaction diagram
catalytic mechanism, overview
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:beta-D-ribosylnicotinate 5-phosphotransferase
The enzyme from yeast and human also has the activity of EC 2.7.1.22 (ribosylnicotinamide kinase).
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
show the reaction diagram
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
show the reaction diagram
ATP + cytidine
ADP + CMP
show the reaction diagram
ATP + nicotinamide mononucleotide
ADP + nicotinamide mononucleotide phosphate
show the reaction diagram
ATP + tiazofurin
ADP + ?
show the reaction diagram
ATP + uridine
ADP + UMP
show the reaction diagram
GTP + beta-D-ribosylnicotinate
GDP + nicotinate beta-D-ribonucleotide
show the reaction diagram
nicotinic acid riboside is a specific substrate of human Nrk enzymes
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + beta-D-ribosylnicotinamide
ADP + nicotinamide beta-D-ribonucleotide
show the reaction diagram
-
-
-
?
ATP + beta-D-ribosylnicotinate
ADP + nicotinate beta-D-ribonucleotide
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
GTP
active with Nrk1
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.051 - 0.063
beta-D-ribosylnicotinamide
0.051 - 30
beta-D-ribosylnicotinate
15 - 30
cytidine
0.11 - 0.27
tiazofurin
1.3 - 17
uridine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.21 - 0.34
beta-D-ribosylnicotinamide
0.21 - 1.7
beta-D-ribosylnicotinate
0.48 - 0.82
cytidine
0.35 - 0.49
tiazofurin
0.21 - 1.1
uridine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.1 - 5.4
beta-D-ribosylnicotinamide
0.057 - 6.8
beta-D-ribosylnicotinate
0.016 - 0.055
cytidine
1.3 - 4.5
tiazofurin
0.012 - 0.85
uridine
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.9
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
additional information
-
ubiquitous expression of nicotinamide riboside kinase in tissues and cell lines
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme is structurally similar to Rossmann fold metabolite kinases
malfunction
in NRK1-silenced cells, both nicotinamide riboside- and NMN-mediated rescue from FK866-induced NAD+ depletion and cell death are potently and significantly reduced, overview
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NRK2_HUMAN
230
0
26046
Swiss-Prot
other Location (Reliability: 3)
NRK1_HUMAN
199
0
23193
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Nrk1 bound to nucleoside and nucleotide substrates and products, i.e. nicotinamide mononucleotide, ADP, tiazofurin, beta-D-ribosylnicotinate with AppNHp, and beta-D-ribosylnicotinate alone, addition of 10 mM ligand and 20 mM MgCl2, overview. Usage of different crystallization solutions depending on the ligand, containing PEG 2000 mono-methylether or PEG 3350 or PEG 4000 at 15-35%, at pH 5.0-8.0, with 0.2 M NaH2PO4, and different buffers, X-ray diffraction structure determination and analysis at 1.32-1.95 A resolution, molecular replacement
NRK1 in complex with the reaction product nicotinamide mononucleotide, and NRK1 in a ternary complex with ADP and the anticancer drug tiazofurin, sitting-drop vapor-diffusion method, 22°C, mixing of protein solution containing 20 mg/ml protein, 2 mM ligand, 20 mM Tris, pH 7.5-7.8, 200 mM NaCl, 5 mM DTT, with reservoir solution containing 28% w/v PEG 3350, 200 mM NH4Cl, 5 mM DTT, and 5 mM Na2HPO4, X-ray diffraction structure determination and analysis at 1.5 A and 2.7 A resolution, respectively, modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D35A
site-directed mutagenesis of Nrk2
D36A
site-directed mutagenesis of Nrk1
E100A
site-directed mutagenesis of Nrk2, mutant activity in ATP-dependent phosphorylation is below the level of detection
E174R
site-directed mutagenesis of Nrk2
E98A
site-directed mutagenesis of Nrk1, mutant activity in ATP-dependent phosphorylation is below the level of detection
additional information
enzyme NRK1 specific silencing in human ovarian carcinoma cell line OVCAR-3 by NRK1-specific siRNA
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged NRK1 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant Nrk1 and Nrk2 from Escherichia coli by metal chelate affinity chromatography
recombinant Nrk2 from Escherichia coli by metal chelate affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NRK1, quantitative real-time PCR enzyme expression analysis
His-tagged wild-type Nrk1 expression in Escherichia coli, expression of wild-type and mutant Nrk1 from the GAL1 promoter on a LEU2 plasmid in Saccharomyces cerevisiae strain BY278
His-tagged wild-type Nrk2 expression in Escherichia coli, expression of wild-type and mutant Nrk2 from the GAL1 promoter on a LEU2 plasmid in Saccharomyces cerevisiae strain BY278
overexpression of His-tagged NRK1 in Escherichia coli strain BL21(DE3)
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Nmrk2 mRNA expression is substantially induced (over 80fold) in models of lethal cardiomyopathy
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
screening of tumors for NRK activity is necessary for the design of efficient NamPRT-targeted antitumor therapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Khan, J.A.; Xiang, S.; Tong, L.
Crystal structure of human nicotinamide riboside kinase
Structure
15
1005-1013
2007
Homo sapiens (Q9NWW6)
Manually annotated by BRENDA team
Tempel, W.; Rabeh, W.M.; Bogan, K.L.; Belenky, P.; Wojcik, M.; Seidle, H.F.; Nedyalkova, L.; Yang, T.; Sauve, A.A.; Park, H.W.; Brenner, C.
Nicotinamide riboside kinase structures reveal new pathways to NAD+
PLoS Biol.
5
e263
2007
Homo sapiens (Q9NPI5), Homo sapiens (Q9NWW6)
Manually annotated by BRENDA team
Zamporlini, F.; Ruggieri, S.; Mazzola, F.; Amici, A.; Orsomando, G.; Raffaelli, N.
Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD+ biosynthetic machinery in mammalian cells
FEBS J.
281
5104-5119
2014
Homo sapiens
Manually annotated by BRENDA team
Sociali, G.; Raffaghello, L.; Magnone, M.; Zamporlini, F.; Emionite, E.; Sturla, L.; Bianchi, G.; Vigliarolo, T.; Nahimana, A.; Nencioni, A.; Raffaelli, N.; Bruzzone, S
Antitumor effect of combined NAMPT and CD73 inhibition in an ovarian cancer model
Oncotarget
7
2968-2984
2016
Homo sapiens (Q9NWW6)
Manually annotated by BRENDA team
Fletcher, R.S.; Lavery, G.G.
The emergence of the nicotinamide riboside kinases in the regulation of NAD+ metabolism
J. Mol. Endocrinol.
61
R107-R121
2018
Homo sapiens (Q9NPI5), Homo sapiens (Q9NWW6)
Manually annotated by BRENDA team