BRENDA - Enzyme Database show
show all sequences of 2.4.2.12

Extension of human cell lifespan by nicotinamide phosphoribosyltransferase

van der Veer, E.; Ho, C.; ONeil, C.; Barbosa, N.; Scott, R.; Cregan, S.P.; Pickering, J.G.; J. Biol. Chem. 282, 10841-10845 (2007)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
longevity enzyme for human SMCs
Homo sapiens
Cloned(Commentary)
Commentary
Organism
a retroviral gene delivery system is used to generate human cells stably overexpressing Nampt. Introducing the Nampt gene into aging human SMCs delays senescence and substantially lengthened cell lifespan, together with enhanced resistance to oxidative stress; in pQCXIP-IHRES-PURO for retroviral delivery and stable overexpression in Phoenix-amphotropic retrovirus packaging cell line
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
FK866
Nampt antagonist, 10 nM, reduction of Nampt activity in SMCs to 22 +/-2% of baseline activity accompanied with shortened senescent-free survival; reducing Nampt activity with the antagonist FK866 induces premature senescence in smooth muscle cells
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
additional information
Homo sapiens
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
?
-
-
-
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Homo sapiens
-
nicotinamide mononucleotide + diphosphate
-
-
r
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
-
-
-
Homo sapiens
P43490
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
aorta thoracica smooth muscle
primary SMC culture, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody; primary SMC culture stably expressing Nampt, 2.1 +/-0.3 additional population doublings constituting 34 +/-4% lifespan prolongation
Homo sapiens
-
HITC6 cell
SMC clonal line, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody, 14 +/-3% of basal Nampt activity in presenescent SMC, direct relationship between Nampt activity and number of replication cycles preceeding senescence; SMC clonal line stably expressing Nampt, 7.1 +/-3.1 fold higher Nampt activity, 6.3 +/-0.3 additional population doublings constituting 71 +/-7% lifespan prolongation, 19 +/-2% reduction in number of senescent cells at passage 37 compared to control HITC6 cells is dependent on SIRT1 activity and associated with increased p53 degradation and protection against oxidative cell damage as response to 150 microM hydrogen peroxide
Homo sapiens
-
skin fibroblast
from individual with Hutchison-Gilford progeria syndrome associated with premature atherosclerosis, cell lifespan extension upon Nampt overexpression
Homo sapiens
-
vascular smooth muscle cell
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
additional information
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
680749
Homo sapiens
?
-
-
-
-
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
-
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
-
-
-
r
nictoinamide + alpha-D-5-phosphoribosyl 1-diphosphate
whole cell lysates incubated with 5 microM [carbonyl-14C]nicotinamide + 0.5 mM alpha-D-5-phosphoribosyl-1-diphosphate at pH 8.8
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
produced NMN quantified by scintillation counting
-
-
r
Application (protein specific)
Application
Commentary
Organism
medicine
longevity enzyme for human SMCs
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
a retroviral gene delivery system is used to generate human cells stably overexpressing Nampt. Introducing the Nampt gene into aging human SMCs delays senescence and substantially lengthened cell lifespan, together with enhanced resistance to oxidative stress
Homo sapiens
in pQCXIP-IHRES-PURO for retroviral delivery and stable overexpression in Phoenix-amphotropic retrovirus packaging cell line
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
FK866
reducing Nampt activity with the antagonist FK866 induces premature senescence in smooth muscle cells
Homo sapiens
FK866
Nampt antagonist, 10 nM, reduction of Nampt activity in SMCs to 22 +/-2% of baseline activity accompanied with shortened senescent-free survival
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
additional information
Homo sapiens
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
?
-
-
-
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Homo sapiens
-
nicotinamide mononucleotide + diphosphate
-
-
r
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
aorta thoracica smooth muscle
primary SMC culture, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody; primary SMC culture stably expressing Nampt, 2.1 +/-0.3 additional population doublings constituting 34 +/-4% lifespan prolongation
Homo sapiens
-
HITC6 cell
SMC clonal line, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody, 14 +/-3% of basal Nampt activity in presenescent SMC, direct relationship between Nampt activity and number of replication cycles preceeding senescence; SMC clonal line stably expressing Nampt, 7.1 +/-3.1 fold higher Nampt activity, 6.3 +/-0.3 additional population doublings constituting 71 +/-7% lifespan prolongation, 19 +/-2% reduction in number of senescent cells at passage 37 compared to control HITC6 cells is dependent on SIRT1 activity and associated with increased p53 degradation and protection against oxidative cell damage as response to 150 microM hydrogen peroxide
Homo sapiens
-
skin fibroblast
from individual with Hutchison-Gilford progeria syndrome associated with premature atherosclerosis, cell lifespan extension upon Nampt overexpression
Homo sapiens
-
vascular smooth muscle cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
additional information
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
680749
Homo sapiens
?
-
-
-
-
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
-
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
-
-
-
r
nictoinamide + alpha-D-5-phosphoribosyl 1-diphosphate
whole cell lysates incubated with 5 microM [carbonyl-14C]nicotinamide + 0.5 mM alpha-D-5-phosphoribosyl-1-diphosphate at pH 8.8
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
produced NMN quantified by scintillation counting
-
-
r
Other publictions for EC 2.4.2.12
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
735765
Clark
Application of virtual screeni ...
Homo sapiens
Bioorg. Med. Chem. Lett.
26
2920-2926
2016
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-
17
-
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1
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2
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1
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13
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13
17
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1
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1
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735766
Chen
Identification of benzothiophe ...
Homo sapiens
Bioorg. Med. Chem. Lett.
26
765-768
2016
-
-
-
-
-
-
17
-
-
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1
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2
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3
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1
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14
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14
17
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1
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3
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1
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735872
Grolla
Extracellular nicotinamide pho ...
Homo sapiens
Br. J. Pharmacol.
173
2182-2194
2016
-
-
-
-
14
-
1
-
1
-
-
1
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1
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49
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1
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1
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1
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14
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1
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1
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1
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49
-
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1
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2
1
1
2
-
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736091
Fang
Analysis of the nicotinamide p ...
Danio rerio
FEBS J.
282
2858-2878
2015
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1
1
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3
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1
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1
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1
1
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736115
Marletta
Crystal structure of human nic ...
Homo sapiens
FEBS Open Bio
5
419-428
2015
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1
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1
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4
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1
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737247
Xu
Discovery and characterization ...
Homo sapiens
Sci. Rep.
5
10043
2015
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49
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1
1
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2
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4
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1
1
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48
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48
49
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1
1
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4
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1
1
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737279
Zabka
Retinal toxicity, in vivo and ...
Homo sapiens, Rattus norvegicus
Toxicol. Sci.
144
163-172
2015
-
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-
-
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-
14
-
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2
-
7
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6
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2
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14
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6
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2
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735760
Zheng
Discovery of potent and effica ...
Homo sapiens
Bioorg. Med. Chem. Lett.
24
337-343
2014
-
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-
18
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1
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1
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14
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18
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736003
Hsu
The function of nicotinamide p ...
Homo sapiens
DNA Repair
23
64-68
2014
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1
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1
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1
1
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1
1
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736227
Pittelli
Nicotinamide phosphoribosyltra ...
Homo sapiens, Mus musculus
Immunol. Cell Biol.
92
191-199
2014
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2
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2
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4
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2
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2
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2
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3
3
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735758
Zheng
Identification of amides deriv ...
Homo sapiens
Bioorg. Med. Chem. Lett.
23
5488-5497
2013
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32
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6
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28
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32
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6
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736436
Tan
Pharmacological inhibition of ...
Homo sapiens
J. Biol. Chem.
288
3500-3511
2013
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1
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12
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12
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2
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736612
Zheng
Structure-based discovery of n ...
Homo sapiens
J. Med. Chem.
56
6413-6433
2013
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40
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5
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1
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35
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40
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5
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723576
Bowlby
Nicotinamide phosphoribosyl tr ...
Homo sapiens
PLoS ONE
7
e40195
2012
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5
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1
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723588
Liu
Nicotinamide phosphoribosyltra ...
Mus musculus
PLoS ONE
7
e44933
2012
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721273
Zhang
A fluorometric assay for high- ...
Mus musculus
Anal. Biochem.
412
18-25
2011
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1
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4
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4
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722099
Friebe
Leucocytes are a major source ...
Homo sapiens
Diabetologia
54
1200-1211
2011
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722182
Dahl
Nicotinamide phosphoribosyltra ...
Homo sapiens
Eur. J. Clin. Invest.
41
1098-1104
2011
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722560
Zhang
Nicotinamide phosphoribosyltra ...
Homo sapiens
J. Bioanal. Biomed.
3
13-25
2011
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1
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2
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1
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1
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2
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1
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9
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1
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1
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1
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1
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9
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1
1
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1
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2
2
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