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Literature summary for 2.7.1.22 extracted from

  • Fletcher, R.S.; Lavery, G.G.
    The emergence of the nicotinamide riboside kinases in the regulation of NAD+ metabolism (2018), J. Mol. Endocrinol., 61, R107-R121 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene NMRK1 Homo sapiens
gene NMRK1 Mus musculus
gene NMRK2 Homo sapiens
gene NMRK2 Mus musculus
gene NMRK2 Danio rerio

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.068
-
1-(beta-D-ribofuranosyl)-nicotinamide pH and temperature not specified in the publication, with GTP Homo sapiens
0.088
-
1-(beta-D-ribofuranosyl)-nicotinamide pH and temperature not specified in the publication, with ATP Homo sapiens
0.19
-
1-(beta-D-ribofuranosyl)-nicotinamide with ATP, pH and temperature not specified in the publication Homo sapiens
30
-
1-(beta-D-ribofuranosyl)-nicotinamide with GTP, pH and temperature not specified in the publication Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Mus musculus
Mg2+ required Danio rerio

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide Homo sapiens
-
ADP + beta-nicotinamide D-ribonucleotide
-
?
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide Mus musculus
-
ADP + beta-nicotinamide D-ribonucleotide
-
?
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide Danio rerio
-
ADP + beta-nicotinamide D-ribonucleotide
-
?
GTP + 1-(beta-D-ribofuranosyl)-nicotinamide Homo sapiens
-
GDP + beta-nicotinamide D-ribonucleotide
-
?
GTP + 1-(beta-D-ribofuranosyl)-nicotinamide Mus musculus
-
GDP + beta-nicotinamide D-ribonucleotide
-
?

Organism

Organism UniProt Comment Textmining
Danio rerio F1QSN9
-
-
Homo sapiens Q9NPI5
-
-
Homo sapiens Q9NWW6
-
-
Mus musculus Q91W63
-
-
Mus musculus Q9D7C9
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brown adipose tissue
-
Mus musculus
-
kidney
-
Mus musculus
-
liver
-
Mus musculus
-
skeletal muscle
-
Mus musculus
-
skeletal muscle high expression of NRK2 Mus musculus
-
spinal ganglion
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Homo sapiens ADP + beta-nicotinamide D-ribonucleotide
-
?
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Mus musculus ADP + beta-nicotinamide D-ribonucleotide
-
?
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Danio rerio ADP + beta-nicotinamide D-ribonucleotide
-
?
GTP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Homo sapiens GDP + beta-nicotinamide D-ribonucleotide
-
?
GTP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Mus musculus GDP + beta-nicotinamide D-ribonucleotide
-
?
additional information enzyme NRK2 highly prefers ATP, while isozyme NRK1 also uses GTP with similar activity Homo sapiens ?
-
-
additional information enzyme NRK2 is restricted to ATP, while isozyme NRK1 also uses GTP Mus musculus ?
-
-

Synonyms

Synonyms Comment Organism
More see also EC 2.7.1.173 Homo sapiens
nicotinamide riboside kinase 1
-
Homo sapiens
nicotinamide riboside kinase 1
-
Mus musculus
nicotinamide riboside kinase 2
-
Homo sapiens
nicotinamide riboside kinase 2
-
Mus musculus
nicotinamide riboside kinase 2
-
Danio rerio
NMRK1
-
Homo sapiens
NMRK2
-
Homo sapiens
NMRK2
-
Danio rerio
NRK1
-
Homo sapiens
NRK1
-
Mus musculus
Nrk2
-
Homo sapiens
Nrk2
-
Mus musculus
Nrk2b
-
Danio rerio

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.34
-
1-(beta-D-ribofuranosyl)-nicotinamide pH and temperature not specified in the publication, with GTP Homo sapiens
0.6
-
1-(beta-D-ribofuranosyl)-nicotinamide pH and temperature not specified in the publication, with ATP Homo sapiens
0.75
-
1-(beta-D-ribofuranosyl)-nicotinamide with ATP, pH and temperature not specified in the publication Homo sapiens
1.7
-
1-(beta-D-ribofuranosyl)-nicotinamide with GTP, pH and temperature not specified in the publication Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens
ATP
-
Mus musculus
ATP
-
Danio rerio
GTP
-
Homo sapiens
GTP
-
Mus musculus

Expression

Organism Comment Expression
Mus musculus following injury to dorsal root ganglion neurons, Nmrk2 is the most upregulated NAD+ biosynthetic gene (by over 20fold). Mice with a loss of hexose-6-phosphate dehydrogenase (H6PDH) function, an ER-based enzyme required for local NADPH generation, manifest with severe muscle myopathy and on transcriptional analysis Nmrk2 expression is the most dysregulated gene (upregulated by over 60fold mRNA level). Nmrk2 mRNA expression is substantially induced (over 80fold) in models of lethal cardiomyopathy up
Homo sapiens Nmrk2 mRNA expression is substantially induced (over 80fold) in models of lethal cardiomyopathy up

General Information

General Information Comment Organism
malfunction a murine NRK1 loss-of-function model does not exhibit any gross phenotypic abnormalities, with steady state NAD+ levels unaffected, at least in the tissues that are examined (liver, skeletal muscle, brown adipose and kidney) Mus musculus
malfunction a murine NRK2 loss-of-function model does not exhibit any gross phenotypic abnormalities, with steady state NAD+ levels unaffected, at least in the tissues that are examined (liver, skeletal muscle, brown adipose and kidney) Mus musculus
metabolism the enzyme is involved in the NAD+ biosynthesis pathway. In the initial step of the pathway, NRK activity catalyses the phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN). Importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD+ precursor molecules, with a particular focus on the nicotinamide riboside kinase pathway at both a tissue-specific and systemic level, overview Danio rerio
metabolism the enzyme is involved in the NAD+ biosynthesis pathway. In the initial step of the pathway, NRK activity catalyses the phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN). Importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD+ precursor molecules, with a particular focus on the nicotinamide riboside kinase pathway at both a tissue-specific and systemic level, regulation of the NRK enzymes, overview. Alternatively, NRK activity can phosphorylate nicotinic acid riboside (NaR) to nicotinic acid mononucleotide (NaMN), see for EC 2.7.1.173 Homo sapiens
metabolism the enzyme is involved in the NAD+ biosynthesis pathway. In the initial step of the pathway, NRK activity catalyses the phosphorylation of nicotinamide riboside (NR) to nicotinamide mononucleotide (NMN). Importance of different salvage pathways involved in metabolising the vitamin B3 class of NAD+ precursor molecules, with a particular focus on the nicotinamide riboside kinase pathway at both a tissue-specific and systemic level, regulation of the NRK enzymes, overview. Alternatively, NRK activity can phosphorylate nicotinic acid riboside (NaR) to nicotinic acid mononucleotide (NaMN), see for EC 2.7.1.173 Mus musculus
additional information proposed NRK expression in disease and potential therapeutic interventions Homo sapiens
additional information proposed NRK expression in disease and potential therapeutic interventions Mus musculus
physiological function although NRK1 and NRK2 do not appear critical in mice for endogenous NR salvage to NAD+, their activity has been determined essential for the utilisation of exogenous NR and, more surprisingly, NMN. Without expression of the NRK enzymes in tissues, the NAD+-boosting effects of nicotinamide riboside (NR) and NMN supplementation is blocked, whilst expression of alternative NAD+ biosynthesis enzymes remains comparable to wild-type mice. Phosphorylation of NR by NRK1 appears preferred to NRK2 even in skeletal muscle where Nmrk2 is specifically expressed and found at substantially higher mRNA levels than Nmrk1 Mus musculus
physiological function although NRK1 and NRK2 do not appear critical in mice for endogenous NR salvage to NAD+, their activity has been determined essential for the utilisation of exogenous NR and, more surprisingly, NMN. Without expression of the NRK enzymes in tissues, the NAD+-boosting effects of nicotinamide riboside (NR) and NMN supplementation is blocked, whilst expression of alternative NAD+ biosynthesis enzymes remains comparable to wild-type mice. Phosphorylation of NR by NRK1 appears preferred to NRK2 even in skeletal muscle where Nmrk2 is specifically expressed and found at substantially higher mRNA levels than Nmrk1. In NAD+ deficiency, NRK2 may be induced to aid NAD+ biosynthesis. NRK2 appears to play a redundant role in NAD+ biosynthesis along with NRK1, at least in unchallenged models, its highly regulated expression particularly in times of stress suggest it may have role beyond NAD+ metabolism Mus musculus
physiological function NRK2 appears to play a redundant role in NAD+ biosynthesis along with NRK1, at least in unchallenged models, its highly regulated expression particularly in times of stress suggest it may have role beyond NAD+ metabolism Homo sapiens
physiological function NRK2 appears to play a redundant role in NAD+ biosynthesis along with NRK1, at least in unchallenged models, its highly regulated expression particularly in times of stress suggest it may have role beyond NAD+ metabolism Danio rerio

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.057
-
1-(beta-D-ribofuranosyl)-nicotinamide with GTP, pH and temperature not specified in the publication Homo sapiens
3.95
-
1-(beta-D-ribofuranosyl)-nicotinamide with ATP, pH and temperature not specified in the publication Homo sapiens
5
-
1-(beta-D-ribofuranosyl)-nicotinamide pH and temperature not specified in the publication, with GTP Homo sapiens
6.82
-
1-(beta-D-ribofuranosyl)-nicotinamide pH and temperature not specified in the publication, with ATP Homo sapiens