Any feedback?
Information on EC 2.7.7.1 - nicotinamide-nucleotide adenylyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9BZQ4
for references in articles please use BRENDA:EC2.7.7.1Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.7.7.1 nicotinamide-nucleotide adenylyltransferaseIUBMB Comments
Nicotinate nucleotide can also act as acceptor. See also EC 2.7.7.18 nicotinate-nucleotide adenylyltransferase.
Specify your search results
Word Map
- 2.7.7.1
- degeneration
-
wallerian
- neurodegenerative
-
neuroprotective
- amaurosis
-
leber
- nampt
-
self-destruct
-
axotomy
- riboside
- nadase
- tiazofurin
-
axonopathies
-
pro-degenerative
- analysis
- drug development
- pharmacology
- 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
Synonyms
nmnat2, nmnat, nmnat1, nmnat3, nicotinamide mononucleotide adenylyltransferase, nmn adenylyltransferase, nicotinamide mononucleotide adenylyltransferase 1, nicotinamide mononucleotide adenylyltransferase 2, namnat, hnmnat-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
NMNAT2
adenosine triphosphate-nicotinamide mononucleotide transadenylase
-
-
-
-
adenylyltransferase, nicotinamide mononucleotide
-
-
-
-
ATP:NMN adenylyltransferase
-
-
-
-
diphosphopyridine nucleotide pyrophosphorylase
-
-
-
-
NAD+ pyrophosphorylase
-
-
-
-
nicotinamide adenine dinucleotide pyrophosphorylase
-
-
-
-
nicotinamide mononucleotide adenylyltransferase
nicotinamide/nicotinic acid mononucleotide adenylyltransferase
-
nicotinate nucleotide can also act as acceptor, see also EC 2.7.7.18 nicotinate-nucleotide adenylyltransferase
NMN adenylyltransferase
-
-
-
-
NMNAT
NMNAT1
NMNAT3
PNAT
-
-
-
-
pyridine nucleotide adenylyltransferase
-
-
-
-
nicotinamide mononucleotide adenylyltransferase
-
-
-
-
NMNAT
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:nicotinamide-nucleotide adenylyltransferase
Nicotinate nucleotide can also act as acceptor. See also EC 2.7.7.18 nicotinate-nucleotide adenylyltransferase.
CAS REGISTRY NUMBER
COMMENTARY
9032-70-6
-
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
ATP + nicotinate D-ribonucleotide
diphosphate + nicotinate adenine dinucleotide
-
i.e. nicotinic acid adenine dinucleotide
-
?
ATP + tiazofurin
diphosphate + thiazole-4-carboxamide adenine dinucleotide
tiazofurin is a pro-drug that is metabolized by cytosolic nicotinamide mononucleotide adenylyltransferase2
-
-
?
ATP + tiazofurin 5'-monophosphate
?
i.e. TrMP, substrate od isozymes NMNAT1 and NMNAT3, but not of isozyme NMNAT2
-
-
?
GTP + nicotinamide ribonucleotide
diphosphate + NGD+
3% of the activity with GTP, reverse reaction with 5% of the activity with NAD+, NMNAT2
-
-
r
GTP + NMN
diphosphate + NGD+
substrates of isozyme NMNAT3
i.e. nicotinamide guanosine dinucleotide
-
?
ITP + nicotinamide ribonucleotide
diphosphate + nicotinamide hypoxanthine dinucleotide
5% of the activity with ATP, NMNAT2
-
-
?
ITP + NMN
diphosphate + inosine nicotinamide dinucleotide
substrates of isozyme NMNAT3
i.e. nicotinamide hypoxanthine dinucleotide
-
?
NADH + diphosphate
?
98% of the activity with NAD+, NMNAT2
-
-
?
nicotinamide hypoxanthine dinucleotide + diphosphate
ITP + nicotinamide ribonucleotide
37% of the activity with NAD+, NMNAT2
-
-
?
nicotinic acid adenine dinucleotide phosphate + diphosphate
?
98% of the activity with NAD+, NMNAT2
-
-
?
tiazofurin monophosphate + ATP
tiazofurin adenine dinucleotide + diphosphate
-
-
-
?
ATP + nicotinate D-ribonucleotide
diphosphate + nicotinate adenine dinucleotide
-
i.e. nicotinic acid adenine dinucleotide
-
?
ATP + nicotinic acid mononucleotide
diphosphate + nicotinic acid adenine dinucleotide
-
-
-
-
r
ATP + tiazofurin monophosphate
?
i.e. TrMP, substrate od isozymes NMNAT1 and NMNAT3, but not of isozyme NMNAT2
-
-
?
GTP + nicotinamide ribonucleotide
nicotineamide guanine dinucleotide + diphosphate
only isoenzyme NMNAT3
-
-
?
GTP + NMN
diphosphate + NGD+
substrates of isozyme NMNAT3
i.e. nicotinamide guanosine dinucleotide
-
?
ITP + nicotinamide ribonucleotide
nicotinamide hypoxanthine dinucleotide + diphosphate
only isoenzyme NMNAT3
-
-
?
ITP + NMN
diphosphate + inosine nicotinamide dinucleotide
substrates of isozyme NMNAT3
i.e. nicotinamide hypoxanthine dinucleotide
-
?
nicotinamide hypoxanthine dinucleotide + diphosphate
?
98% of the activity with NAD+, NMNAT3
-
-
?
nicotinamide hypoxanthine dinucleotide + diphosphate
ITP + nicotinamide ribonucleotide
55% of the activity with NAD+, NMNAT1
-
-
?
tiazofurin monophosphate + ATP
tiazofurin adenine dinucleotide + diphosphate
-
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
central enzyme of NAD biosynthetic pathway
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
NMNAT2
-
-
r
ATP + NMN
diphosphate + NAD+
ATP binds before NMN with nuclear isozyme NMNAT1 and Golgi apparatus NMNAT2, but the opposite order is observed with the mitochondrial isozyme NMNAT3
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
-
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
strongly stereospecific: beta-, not alpha-anomer of nicotinamide ribonucleotide
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
i.e. NMN or nicotinamide mononucleotide
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
i.e. NMN or nicotinamide mononucleotide
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
i.e. NMN or nicotinamide mononucleotide
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
i.e. NMN or nicotinamide mononucleotide
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
i.e. NMN or nicotinamide mononucleotide
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
key reaction of pyridine nucleotide metabolism
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
central enzyme of NAD biosynthetic pathway
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
final step in biosynthesis of NAD+
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
NMNAT1
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
NMNAT3
-
-
r
ATP + nicotinate ribonucleotide
diphosphate + nicotinic acid-adenine dinucleotide
-
i.e. nicotinate mononucleotide
-
-
r
ATP + nicotinate ribonucleotide
diphosphate + nicotinic acid-adenine dinucleotide
i.e. nicotinate mononucleotide
-
-
r
ATP + nicotinate ribonucleotide
diphosphate + nicotinic acid-adenine dinucleotide
-
i.e. nicotinate mononucleotide
-
-
r
ATP + nicotinate ribonucleotide
diphosphate + nicotinic acid-adenine dinucleotide
i.e. nicotinate mononucleotide
-
-
r
ATP + nicotinate ribonucleotide
diphosphate + nicotinic acid-adenine dinucleotide
-
less efficient
-
-
r
ATP + NMN
diphosphate + NAD+
ATP binds before NMN with nuclear isozyme NMNAT1 and Golgi apparatus NMNAT2, but the opposite order is observed with the mitochondrial isozyme NMNAT3
-
-
?
GTP + nicotinamide ribonucleotide
diphosphate + NGD+
19% of the activity with GTP, reverse reaction with 57% of the activity with NAD+, NMNA3
-
-
r
GTP + nicotinamide ribonucleotide
diphosphate + NGD+
7% of the activity with GTP, reverse reaction with 26% of the activity with NAD+, NMNAT1
-
-
r
ITP + nicotinamide ribonucleotide
diphosphate + nicotinamide hypoxanthine dinucleotide
27% of the activity with ATP, NMNAT3
-
-
?
ITP + nicotinamide ribonucleotide
diphosphate + nicotinamide hypoxanthine dinucleotide
6% of the activity with ATP, NMNAT1
-
-
?
NADH + diphosphate
?
53% of the activity with NAD+, NMNAT1
-
-
?
NADH + diphosphate
?
99% of the activity with NAD+, NMNAT3
-
-
?
nicotinic acid adenine dinucleotide phosphate + diphosphate
?
93% of the activity with NAD+, NMNAT1
-
-
?
nicotinic acid adenine dinucleotide phosphate + diphosphate
?
as active as with NAD+, NMNAT3
-
-
?
nicotinic acid mononucleotide + ATP
nicotinic acid adenine dinucleotide + diphosphate
-
-
-
?
nicotinic acid mononucleotide + ATP
nicotinic acid adenine dinucleotide + diphosphate
activity observed with GTP, ITP
-
-
r
additional information
?
-
bifunctional enzyme, that also shows nicotinate-nucleotide adenylyltransferase activity, EC 2.7.7.18
-
-
?
additional information
?
-
NMNAT2 complexes with heat shock protein 90 (HSP90)
-
-
?
additional information
?
-
isozyme NMNAT1 directly interacts with nucleolar protein nucleomethylin, NML
-
-
?
additional information
?
-
-
isozyme NMNAT1 directly interacts with nucleolar protein nucleomethylin, NML
-
-
?
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
ATP + tiazofurin
diphosphate + thiazole-4-carboxamide adenine dinucleotide
tiazofurin is a pro-drug that is metabolized by cytosolic nicotinamide mononucleotide adenylyltransferase2
-
-
?
tiazofurin monophosphate + ATP
tiazofurin adenine dinucleotide + diphosphate
-
-
-
?
GTP + nicotinamide ribonucleotide
nicotineamide guanine dinucleotide + diphosphate
only isoenzyme NMNAT3
-
-
?
ITP + nicotinamide ribonucleotide
nicotinamide hypoxanthine dinucleotide + diphosphate
only isoenzyme NMNAT3
-
-
?
tiazofurin monophosphate + ATP
tiazofurin adenine dinucleotide + diphosphate
-
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
central enzyme of NAD biosynthetic pathway
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
key reaction of pyridine nucleotide metabolism
-
-
r
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
central enzyme of NAD biosynthetic pathway
-
-
?
ATP + nicotinamide ribonucleotide
diphosphate + NAD+
-
final step in biosynthesis of NAD+
-
-
?
additional information
?
-
bifunctional enzyme, that also shows nicotinate-nucleotide adenylyltransferase activity, EC 2.7.7.18
-
-
?
additional information
?
-
NMNAT2 complexes with heat shock protein 90 (HSP90)
-
-
?
additional information
?
-
isozyme NMNAT1 directly interacts with nucleolar protein nucleomethylin, NML
-
-
?
additional information
?
-
-
isozyme NMNAT1 directly interacts with nucleolar protein nucleomethylin, NML
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Zn2+
Co2+
Mg2+
Ni2+
Zn2+
additional information
additional information
NMNAT activity requires the presence of divalent cations.
additional information
NMNAT activity requires the presence of divalent cations.
additional information
NMNAT activity requires the presence of divalent cations.
additional information
-
NMNAT activity requires the presence of divalent cations.
additional information
NMNAT activity requires the presence of divalent cations.
additional information
NMNAT activity requires the presence of divalent cations.
additional information
NMNAT activity requires the presence of divalent cations.
additional information
-
NMNAT activity requires the presence of divalent cations.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
diphosphate
product inhibition, noncompetitive for isozyme NMNAT1, and mixed-type for isozymes NMNAT2 and NMNAT3, both versus ATP and NMN
NaAD+
i.e. nicotinic acid adenine dinucleotide, product inhibition, competitive for isozyme NMNAT3, and mixed-type for isozymes NMNAT1 and NMNAT2 NMN, and vice versa against ATP
NAD+
product inhibition, competitive for isozyme NMNAT3, and mixed-type for isozymes NMNAT1 and NMNAT2 NMN, and vice versa against ATP
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
-
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
-
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
-
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
i.e. Np3AD
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
i.e. Np4AD
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
i.e. Nap4AD
2-(4-chloroanilino)naphtho[2,3-d][1,3]thiazole-4,9-dione
i.e. NSC-631529, 3.5% residual activity at 0.02 mM
chloro(triethylphosphine) gold
i.e. NSC-313981, more than 75% inhibition at 0.02 mM
-
diphosphate
product inhibition, noncompetitive for isozyme NMNAT1, and mixed-type for isozymes NMNAT2 and NMNAT3, both versus ATP and NMN
NaAD+
i.e. nicotinic acid adenine dinucleotide, product inhibition, competitive for isozyme NMNAT3, and mixed-type for isozymes NMNAT1 and NMNAT2 NMN, and vice versa against ATP
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
-
P1-(adenosine-5')-P4-(nicotinamide ribose-5')tetraphosphate
-
no effect at 0.1 mM
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
-
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
-
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
i.e. Np3AD
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
i.e. Np4AD
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
i.e. Nap4AD
S,S'-(2Z)-but-2-ene-1,4-diyl bis(4-methylbenzene-1-sulfonothioate)
i.e NSC-624158, 2.1% residual activity at 0.02 mM
gallotannin
polyphenolic plant metabolite that inhibits all three human NMNATs
-
gallotannin
polyphenolic plant metabolite that inhibits all three human NMNATs
-
NAD+
product inhibition, competitive for isozyme NMNAT3, and mixed-type for isozymes NMNAT1 and NMNAT2 NMN, and vice versa against ATP
additional information
-
no inhibition by pyrimidine or purine bases, oxy- and deoxynucleosides, cAMP, halogenated and methylated nucleobases, oxy- and deoxyribose, oxy- and deoxyribose 5-phosphate, D-alpha-glucose, D-alpha-glucose 1-phosphate, D-alpha-glucose 6-phosphate, D-alpha-glucose 1,6-diphosphate, D-alpha-fructose, D-alpha-fructose 1,6-diphosphate, alpha-nicotinamide ribonucleotide
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
epigallocatechin gallate
0.05 mM, 2.28fold activation, NMNAT2
epigallocatechin gallate
0.05 mM, 1.4fold activation, NMNAT3
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0145
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT2
0.0677
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT1
0.111
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT3
0.37
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT1
2.1
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT3
100
tiazofurin riboside 5'-monophosphate
above, pH 7.5, 37°C, isozyme NMNAT2
0.0145
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT2
0.0677
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT1
0.111
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT3
0.37
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT1
2.1
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT3
100
tiazofurin riboside 5'-monophosphate
above, pH 7.5, 37°C, isozyme NMNAT2
additional information
additional information
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
-
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
additional information
additional information
-
initial and steady-state kinetics, kinetic mechanisms of the three NMNAT isozymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.8
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT3
6.9
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT2
42.9
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT1
0.42
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT3
0.55
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT2
14.9
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT1
3.8
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT3
6.9
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT2
42.9
nicotinic acid mononucleotide
pH 7.5, 37°C, isozyme NMNAT1
0.42
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT3
0.55
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT2
14.9
tiazofurin riboside 5'-monophosphate
pH 7.5, 37°C, isozyme NMNAT1
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.16
diphosphate
product inhibition of NMNAT2, substrate NMN
0.361
diphosphate
product inhibition of NMNAT2, substrate ATP
0.0315
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
substrate: NMN, isoenzyme: NMNAT2
0.0359
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
substrate: ATP, isoenzyme: NMNAT2
0.1745
P1-(adenosine-5')-P3-(nicotinic-acid-riboside-5')-triphosphate
substrate: ATP, isoenzyme: NMNAT2
0.3283
P1-(adenosine-5')-P3-(nicotinic-acid-riboside-5')-triphosphate
substrate: NMN, isoenzyme: NMNAT2
0.0242
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
substrate: ATP, isoenzyme: NMNAT2
0.0258
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
substrate: NMN, isoenzyme: NMNAT2
0.1257
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
substrate: NMN, isoenzyme: NMNAT2
0.6576
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
substrate: ATP, isoenzyme: NMNAT2
0.0315
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NMN
0.0359
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.0406
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0563
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0668
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NMN
0.089
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NMN
0.0242
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.0258
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NMN
0.0298
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0311
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NMN
0.0492
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0736
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NMN
0.0217
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NaMN
0.0328
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0369
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NaMN
0.0431
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0591
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0679
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NMN
0.0845
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0883
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NMN
0.1257
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NaMN
0.1745
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.3283
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NMN
0.6576
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.175
diphosphate
product inhibition of NMNAT1, substrate ATP
0.334
diphosphate
product inhibition of NMNAT3, substrate ATP
0.39
diphosphate
product inhibition of NMNAT1, substrate NMN
0.0406
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
substrate: ATP, isoenzyme: NMNAT3
0.0563
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
substrate: ATP, isoenzyme: NMNAT1
0.0668
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
substrate: NMN, isoenzyme: NMNAT3
0.089
P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate
substrate: NMN, isoenzyme: NMNAT1
0.0328
P1-(adenosine-5')-P3-(nicotinic-acid-riboside-5')-triphosphate
substrate: ATP, isoenzyme: NMNAT3
0.0591
P1-(adenosine-5')-P3-(nicotinic-acid-riboside-5')-triphosphate
substrate: ATP, isoenzyme: NMNAT1
0.0679
P1-(adenosine-5')-P3-(nicotinic-acid-riboside-5')-triphosphate
substrate: NMN, isoenzyme: NMNAT1
0.0883
P1-(adenosine-5')-P3-(nicotinic-acid-riboside-5')-triphosphate
substrate: NMN, isoenzyme: NMNAT3
0.0298
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
substrate: ATP, isoenzyme: NMNAT3
0.0311
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
substrate: NMN, isoenzyme: NMNAT1
0.0492
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
substrate: ATP, isoenzyme: NMNAT1
0.0736
P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate
substrate: NMN, isoenzyme: NMNAT3
0.0217
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
substrate: NMN, isoenzyme: NMNAT3
0.0369
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
substrate: NMN, isoenzyme: NMNAT1
0.0431
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
substrate: ATP, isoenzyme: NMNAT3
0.0845
P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate
substrate: ATP, isoenzyme: NMNAT1
0.0315
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NMN
0.0359
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.0406
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0563
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0668
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NMN
0.089
P1-(nicotinamide-riboside-5')-P3-(adenosine-5')-triphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NMN
0.0242
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.0258
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NMN
0.0298
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0311
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NMN
0.0492
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0736
P1-(nicotinamide-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NMN
0.0217
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NaMN
0.0328
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0369
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NaMN
0.0431
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate ATP
0.0591
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0679
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate NMN
0.0845
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT1, versus substrate ATP
0.0883
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT3, versus substrate NMN
0.1257
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NaMN
0.1745
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
0.3283
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate NMN
0.6576
P1-(nicotinate-riboside-5')-P4-(adenosine-5')-tetraphosphate
pH 7.5, 37°C, isozyme NMNAT2, versus substrate ATP
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00026
2,3-dibromo-1,4-naphthoquinone
Homo sapiens
substrate diphosphate, pH 7.4, 23°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15.4
recombinant enzyme, purification step: Superose 12, with dATP as substrate
51
recombinant enzyme, purification step: Superose 12, with NMN and ATP as substrate
76.5
recombinant enzyme, purification step: Superose 12, with nicotinic acid mononucleotide as substrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.7 - 4.8
-
isoelectric focusing, LKB 8100 ampholine column filled with a linear gradient of glycerol containing 1% ampholine carrier ampholytes
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
hepatocellular carcinoma cell line, predominance of isozyme NMNAT1, isozyme NMNAT3 is only present in liver and HepG2 cells
hNMNAT-2 is markedly expressed in the islets of Langerhans. However, the pancreatic exocrine cells exhibit weak expression of hNMNAT-2 protein. Sections of pancreas from insulinoma patients show strong expression of hNMNAT-2 protein in the insulin-producing tumour cells, acinar cells exhibit low expression of hNMNAT-2 protein
hepatocellular carcinoma cell line, isozyme NMNAT2 is found exclusively in SK-HEP1 cells
hepatocellular carcinoma cell line, predominance of isozyme NMNAT1, isozyme NMNAT3 is only present in liver and HepG2 cells
NMNAT1 expression level is significantly reduced in a subset of lung tumor cell lines
hepatocellular carcinoma cell line, isozyme NMNAT2 is found exclusively in SK-HEP1 cells
additional information
hNMNAT-2, whole cerebrum, cerebellum, occipital, frontal and temporal lobe cortices, and the putamen. The medulla shows minimal expression, none is detectable in the spinal cord
in vertebrates, the isoform NMNAT2 is highly expressed in the brain
predominance of isozyme NMNAT1, isozyme NMNAT3 is only present in liver and HepG2 cells
predominance of isozyme NMNAT1, isozyme NMNAT3 is only present in liver and HepG2 cells
additional information
isoform Nmat2 is not detected in HEK-293T cells, NIH-3T3 cells, U-343 cells, U-87 cells, and primary glia cells
additional information
isozyme NMNAT1 expression is down-regulated in a subset of human tumors, quantitative PCR expression analysis in 28 cell lines, overview
additional information
-
isozyme NMNAT1 expression is down-regulated in a subset of human tumors, quantitative PCR expression analysis in 28 cell lines, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
in HeLa cells, in addition to Golgi, isoform Nmnat2 localizes to Rab7-containing late endosomes
additional information
in vertebrates, the isoform NMNAT2 functions as a cytosolic protein bound to Golgi-derived vesicles through the palmitoylation of several cysteine residues
-
isoform Nmnat2 is enriched in numerous membrane compartments including synaptic terminals
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
gene expression of NAD+ synthesizing enzymes in the NAD+ salvage pathways can be modulated by p53
physiological function
malfunction
the chromosomal region encoding the nuclear NAD+ synthesis enzyme NMNAT1 is frequently deleted in human cancer, which may contribute to tumor development. Knockdown of NMNAT1 enhances rRNA transcription and promotes cell death after nutrient deprivation. Heterozygous deletion of NMNAT1 in lung tumor cell lines correlates with low expression level and increased sensitivity to DNA damage. NMNAT1 knockdown stimulates p53 acetylation level before and after DNA damage with doxorubicin
metabolism
NMNAT1 catalyzes NAD+ synthesis in the last step of a salvage synthesis pathway that recycles nicotinamide (NAM) back to NAD+. NMNAT1 deletion in tumors may contribute to transformation by increasing rRNA synthesis, but may also increase sensitivity to nutrient stress and DNA damage
physiological function
malfunction
colorectal cancer cells, that exhibit low levels of NMNAT2 and are refractory to tiazofurin, can be rendered sensitive to Tiazofurin by overexpressing NMNAT2
malfunction
knockdown of NMNAT-2 significantly reduces cellular NAD+ levels and protects cells from p53-dependent cell death upon DNA damage. p53 knockdown abolishes NMNAT-2 expression upon actinomycin D treatment. In NMNAT-2-knockdown cells, actinomycin D treatment does not result in enhanced immunoreactivity
physiological function
overexpression of isoform Nmnat2 is toxic to primary neurons resulting in pervasive cell death
physiological function
the enzyme is a target for the tumor suppressor p53, a major player in cancer signaling pathways, that is an important regulator of cellular metabolism. Determination of an important functional role of NMNAT-2 in p53-mediated signaling. Enzyme NMNAT-2 plays an important role in p53-mediated cell death upon DNA damage
physiological function
tiazofurin is a pro-drug that is metabolized by cytosolic nicotinamide mononucleotide adenylyltransferase2 (NMNAT2) to thiazole-4-carboxamide adenine dinucleotide, a potent inhibitor of inosine 5'-monophosphate dehydrogenase required for cellular guanylate synthesis. Resistance of colorectal cancer cell-kill to Tiazofurin can be overcome by sequentially overexpressing hNMNAT2 and then facilitating the uptake of Tiazofurin by folate-tethered nanoparticles, which enter cells via folate receptors
physiological function
the enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) acts not only as a NAD synthase involved in axonal maintenance but as a molecular chaperone helping neurons to overcome protein unfolding and protein aggregation, molecular mechanism, overview. NMNAT2 acts as a molecular chaperone that cooperates with HSP90 to refold denatured proteins (foldase activity) and independently prevents protein unfolding (holdase activity). In vertebrates, the isoform NMNAT2, highly expressed in the brain, functions as a cytosolic protein bound to Golgi-derived vesicles through the palmitoylation of several cysteine residues. NMNAT2 seems to be essential for axonal growth or maintenance during embryogenesis. Enzyme NMNAT2 complexes with heat shock protein 90 (HSP90), an abundant and ubiquitous molecular chaperone that plays an essential role in maintaining protein homeostasis
physiological function
-
NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at the crossroads of multiple cellular processes
physiological function
nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription and plays a role in preventing cell death after damage. It interacts with the nucleolar repressor protein nucleomethylin. Isozyme NMNAT1 participates in the regulation of rRNA biosynthesis, possibly by producing a local supply of NAD+. And NMNAT1 may be regulated by recruitment into complexes that consume NAD+. The enzyme is recruited into a ternary complex containing the NAD+-dependent deacetylase SirT1. NMNAT1 expression stimulates the deacetylase function of SirT1 to deacetylate p53. Nucleolar protein nucleomethylin, NML, promotes interaction between SirT1 and NMNAT1, and NMNAT1 is recruited to the nucleolar transcriptional repressor complex eNoSC by NML
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). NMNA2_HUMAN
307
0
34439
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32700
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
34000
36000
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
31900
32700
33000
36000
37000
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
32700
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
36000
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
hexamer
tetramer
?
x * 36000, isozyme NMNAT1, SDS-PAGE, x * 37000, isozyme NMNAT2, SDS-PAGE, x * 32700, isozyme NMNAT3, SDS-PAGE
hexamer
alpha/beta-topology subunits, X-ray crystallography, barrel-like hexamer
hexamer
-
alpha/beta-topology subunits, X-ray crystallography, barrel-like hexamer
hexamer
alpha/beta-topology subunits, X-ray crystallography, barrel-like hexamer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
in vertebrates, the isoform NMNAT2 functions as a cytosolic protein bound to Golgi-derived vesicles through the palmitoylation of several cysteine residues
palmitoylation
palmitoylation
isoform Nmnat2 is palmitoylated in vitro (at Cys164 and Cys165) and this modification is required for membrane association
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
homology modeling of structure, based on structures of isoform NMNAT1 and NMNAT3 and molecular docking of potential inhibitors
hanging drop vapor diffusion method, 20 mg/ml protein mixed with an equal volume of reservoir solution containing 1.8 M ammonium sulfate, 0.1 M Tris, pH 8 and 4% v/v isopropyl alcohol, 4-5 days at 20°C, monoclinic space group P21 if 20% glycerol is used, hexagonal space group P6322 if light paraffin oil is used
hanging drop vapor diffusion method, 20 mg/ml protein mixed with an equal volume of reservoir solution containing 100 mM sodium cacodylate, pH 6-7, 200 mM Li2SO4 and 20-25% polyethylene glycol 400
-
hanging drop vapor diffusion method, 25 mg/ml protein in 100 mM HEPES, pH 7.2, 0.5 M NaCl, 2 mM dithiothreitol, 1 mM EDTA and 0.03% Brij-35 was incubated with 10 mM NAD+ and then mixed with an equal volume of reservoir solution containing 0.1 mM sodium acetate, pH 4.2-6.4 and 1.6-1.8 mM sodium formate at 20°C for 1-2 weeks, monoclinic space group P21
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C164A/C165A
the isoform NMAT2 mutant is consistently more strongly expressed than the wild type protein
C164S/C165S
the mutant protein is not palmitoylated (soluble), appears diffuse in the cytoplasm and does not colocalize with GM130. However, the mutant is fully active and shows even higher kcat values compared to the wild type enzyme
H24A
protein expressed from the mutant construct is greatly reduced in activity compared with the wild-type protein
W92G
protein expressed from the mutant construct is greatly reduced in activity compared with the wild-type protein
additional information
additional information
H1299 human non-small lung cancer cell line, which lacks expression of endogenous p53 due to homozygous partial deletion of the p53 gene, is used to construct a stable cell line expressing wild-type p53 under the control of doxycycline. mRNA levels of NAD+ synthetic enzymes, including NAMPT, NMNAT1, NMNAT2, and NMNAT3, are compared in the presence or absence of p53 by semi-quantitative PCR: only the NMNAT2 mRNA level is significantly elevated by ectopic p53 expression. Although genes NMNAT1 and NMNAT3 are also induced, their expression levels are significantly lower than those of NMNAT?2
additional information
-
H1299 human non-small lung cancer cell line, which lacks expression of endogenous p53 due to homozygous partial deletion of the p53 gene, is used to construct a stable cell line expressing wild-type p53 under the control of doxycycline. mRNA levels of NAD+ synthetic enzymes, including NAMPT, NMNAT1, NMNAT2, and NMNAT3, are compared in the presence or absence of p53 by semi-quantitative PCR: only the NMNAT2 mRNA level is significantly elevated by ectopic p53 expression. Although genes NMNAT1 and NMNAT3 are also induced, their expression levels are significantly lower than those of NMNAT?2
additional information
mutation R232Q in one allele plus a single duplication of a cytosine at position 403 in exon 5 resulting in a frameshift and premature stop after 44 amino acids lead to a loss of NMNAT2 function, identified in fetus with akinesia deformation sequence, severely reduced skeletal muscle mass and hydrops fetalis
additional information
-
mutation R232Q in one allele plus a single duplication of a cytosine at position 403 in exon 5 resulting in a frameshift and premature stop after 44 amino acids lead to a loss of NMNAT2 function, identified in fetus with akinesia deformation sequence, severely reduced skeletal muscle mass and hydrops fetalis
additional information
isozyme NMNAT1 knockdown by expression of NMNAT1 specific siRNA. NMNAT1 knockdown promotes glucose starvation-induced cell death
additional information
-
isozyme NMNAT1 knockdown by expression of NMNAT1 specific siRNA. NMNAT1 knockdown promotes glucose starvation-induced cell death
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
extremely labile in crude extracts, even in the presence of PMSF and sodium metabisulfite, EDTA or DTT does not stabilize
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, in stroma-free lysate: 30% loss of activity within 2-3 days, in washed erythrocytes: up to 1 month
-
0-3°C, E. coli enzyme: 31 days stable, yeast enzyme: 22% loss of activity within 31 days
-
4°C, in 50 mM potassium phosphate buffer, pH 7.4, 1 mM DTT, 1 mM KCl, 1 mM MgCl2, 0.5 mM EDTA, 1 mM PMSF, several months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged isozymes NMNAT1, NMNAT2, and NMNAT3 from Escherichia coli strain BL21(DE3) by nickel or TALON affinity chromatography
co-purification of recombinant His6-tagged NMNAT1 and GST-tagged NML from Escherichia coli, His6-NMNAT1 is pulled down by beads loaded with GST-NML, but not by GST suggesting that the two proteins interact directly
recombinant His-tagged isozymes NMNAT1, NMNAT2, and NMNAT3 from Escherichia coli strain BL21(DE3) by nickel or TALON affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NMNAT2, semi-quantitative and real-time PCR enzyme expression analysis
gene NMNAT2, transfection of hNMNAT2 results in a six- and threefold cytoplasmic overexpression in Caco-2 and HT-29 cell lines, respectively, correlating with Tiazofurin-induced enhanced cell killing
His-tagged isozymes NMNAT1, NMNAT2, and NMNAT3, expression in Escherichia coli strain BL21(DE3)
gene NMNAT1, recombinant expression in H-1299 and U2-O2 cells, recombinant co-expression of His6-tagged NMNAT1 and GST-tagged NML in Escherichia coli, co-expression of FLAG-tagged nucleomethylin and Myc-tagged NMNAT1 in H-1299 cells
His-tagged isozymes NMNAT1, NMNAT2, and NMNAT3, expression in Escherichia coli strain BL21(DE3)
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
NMNAT-2 expression is induced upon DNA damage in a p53-dependent manner. Two putative p53 binding sites are identified within the human NMNAT-2 gene, and both are functional in a p53-dependent manner, overview. DNA damage agents, actinomycin D and doxorubicin, and Nutlin-3a, a p53 stabilizer that disrupts interaction of p53 with its negative regulator MDM2, in a time-dependent manner in control but not in p53-knockdown U2-OS cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
loss of function mutations in two stillborn siblings lead to fetal akinesia deformation sequence, severely reduced skeletal muscle mass and hydrops fetalis. Both protein variants are incapable of supporting axon survival in mouse primary neuron cultures when overexpressed. Variants display altered protein stability and/or defects in NAD+ synthesis and chaperone functions
analysis
development of a bioluminescent assay using Photinus pyralis ATP-dependent luciferase and luciferin for NMNAT1 in a 384-well plate format, for screening of forward and reverse reactions
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Emanuelli, M.; Natalini, P.; Raffaelli, N.; Ruggieri, S.; Vita, A.; Magni, G.
NAD biosynthesis in human placenta: purification and characterization of homogeneous NMN adenylyltransferase
Arch. Biochem. Biophys.
298
29-34
1992
Homo sapiens
Sestini, S.; Ricci, C.; Micheli, V.; Pompucci, G.
Nicotinamide mononucleotide adenylyltransferase activity in human erythrocytes
Arch. Biochem. Biophys.
302
206-211
1993
Homo sapiens
Uhr, M.L.; Smulson, M.
NMN adenylyltransferase: its association with chromatin and with poly(ADP-ribose) polymerase
Eur. J. Biochem.
128
435-443
1982
Homo sapiens, Sus scrofa
Raffaelli, N.; Sorci, L.; Amici, A.; Emanuelli, M.; Mazzola, F.; Magni, G.
Identification of a novel human nicotinamide mononucleotide adenylyltransferase
Biochem. Biophys. Res. Commun.
297
835-840
2002
Homo sapiens
Zhang, X.; Kurnasov, O.V.; Karthikeyan, S.; Grishin, N.V.; Osterman, A.L.; Zhang, H.
Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis
J. Biol. Chem.
278
13503-13511
2003
Homo sapiens
Garavaglia, S.; D'Angelo, I.; Emanuelli, M.; Carnevali, F.; Pierella, F.; Magni, G.; Rizzi, M.
Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis
J. Biol. Chem.
277
8524-8530
2002
Homo sapiens (Q9HAN9), Homo sapiens
Zhou, T.; Kurnasov, O.; Tomchick, D.R.; Binns, D.D.; Grishin, N.V.; Marquez, V.E.; Osterman, A.L.; Zhang, H.
Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin
J. Biol. Chem.
277
13148-13154
2002
Homo sapiens (Q9HAN9), Homo sapiens
Emanuelli, M.; Carnevali, F.; Saccucci, F.; Pierella, F.; Amici, A.; Raffaelli, N.; Magni, G.
Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase
J. Biol. Chem.
276
406-412
2001
Homo sapiens (Q9HAN9), Homo sapiens
Werner, E.; Ziegler, M.; Lerner, F.; Schweiger, M.; Heinemann, U.
Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN
FEBS Lett.
516
239-244
2002
Homo sapiens (Q9HAN9), Homo sapiens
Franchetti, P.; Cappellacci, L.; Pasqualini, M.; Grifantini, M.; Lorenzi, T.; Raffaelli, N.; Magni, G.
Dinucleoside polyphosphate NAD analogs as potential NMN adenylyltransferase inhibitors. Synthesis and biological evaluation
Nucleosides Nucleotides Nucleic Acids
22
865-868
2003
Saccharomyces cerevisiae, Homo sapiens, Methanocaldococcus jannaschii
Yalowitz, J.A.; Jayaram, H.N.
Modulation of cytotoxicity of benzamide riboside by expression of NMN adenylyltransferase
Curr. Med. Chem.
9
749-758
2002
Saccharomyces cerevisiae, Homo sapiens, Mammalia, Mus musculus
Yalowitz, J.A.; Xiao, S.; Biju, M.P.; Antony, A.C.; Cummings, O.W.; Deeg, M.A.; Jayaram, H.N.
Characterization of human brain nicotinamide 5'-mononucleotide adenylyltransferase-2 and expression in human pancreas
Biochem. J.
377
317-326
2004
Homo sapiens (Q9BZQ4), Homo sapiens
Magni, G.; Amici, A.; Emanuelli, M.; Orsomando, G.; Raffaelli, N.; Ruggieri, S.
Structure and function of nicotinamide mononucleotide adenylyltransferase
Curr. Med. Chem.
11
873-885
2004
Bacillus subtilis, Bos taurus, Haemophilus influenzae, Homo sapiens, Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, Saccharolobus solfataricus, Saccharomyces cerevisiae
Berger, F.; Lau, C.; Dahlmann, M.; Ziegler, M.
Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms
J. Biol. Chem.
280
36334-36341
2005
Homo sapiens (Q96T66), Homo sapiens (Q9BZQ4), Homo sapiens (Q9HAN9), Homo sapiens
Sorci, L.; Cimadamore, F.; Scotti, S.; Petrelli, R.; Cappellacci, L.; Franchetti, P.; Orsomando, G.; Magni, G.
Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis
Biochemistry
46
4912-4922
2007
Homo sapiens (Q96T66), Homo sapiens (Q9BZQ4), Homo sapiens (Q9HAN9), Homo sapiens
Berger, F.; Lau, C.; Ziegler, M.
Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1
Proc. Natl. Acad. Sci. USA
104
3765-3770
2007
Escherichia coli, Homo sapiens
Zhai, R.G.; Rizzi, M.; Garavaglia, S.
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme
Cell. Mol. Life Sci.
66
2805-2818
2009
Synechocystis sp., Bacillus anthracis, Escherichia coli, Haemophilus influenzae, Homo sapiens, Staphylococcus aureus, Pseudomonas aeruginosa, Methanothermobacter thermautotrophicus (O26253), Methanocaldococcus jannaschii (Q57961)
Lau, C.; Niere, M.; Ziegler, M.
The NMN/NaMN adenylyltransferase (NMNAT) protein family
Front. Biosci.
14
410-431
2009
Arabidopsis thaliana, Escherichia coli (P0A752), Saccharomyces cerevisiae (P53204), Homo sapiens (Q96T66), Homo sapiens
Lau, C.; Dolle, C.; Gossmann, T.; Agledal, L.; Niere, M.; Ziegler, M.
Isoform-specific targeting and interaction domains in human nicotinamide mononucleotide adenylyltransferases
J. Biol. Chem.
285
18868-18876
2010
Homo sapiens (Q96T66), Homo sapiens (Q9BZQ4), Homo sapiens (Q9HAN9), Homo sapiens
Mayer, P.R.; Huang, N.; Dewey, C.M.; Dries, D.R.; Zhang, H.; Yu, G.
Expression, localization, and biochemical characterization of nicotinamide mononucleotide adenylyltransferase 2
J. Biol. Chem.
285
40387-40396
2010
Mus musculus, Homo sapiens (Q9BZQ4)
Kusumanchi, P.; Zhang, Y.; Jani, M.B.; Jayaram, N.H.; Khan, R.A.; Tang, Y.; Antony, A.C.; Jayaram, H.N.
Nicotinamide mononucleotide adenylyltransferase2 overexpression enhances colorectal cancer cell-kill by Tiazofurin
Cancer Gene Ther.
20
403-412
2013
Homo sapiens (Q9BZQ4)
Pan, L.Z.; Ahn, D.G.; Sharif, T.; Clements, D.; Gujar, S.A.; Lee, P.W.
The NAD+ synthesizing enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT-2) is a p53 downstream target
Cell Cycle
13
1041-1048
2014
Homo sapiens (Q9BZQ4), Homo sapiens
Song, T.; Yang, L.; Kabra, N.; Chen, L.; Koomen, J.; Haura, E.B.; Chen, J.
The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription
J. Biol. Chem.
288
20908-20917
2013
Homo sapiens (Q9HAN9), Homo sapiens
Lavado-Roldan, A.; Fernandez-Chacon, R.
Two for the price of one a neuroprotective chaperone kit within NAD synthase protein NMNAT2
PLoS Biol.
14
e1002522
2016
Homo sapiens (Q9BZQ4)
Lukacs, M.; Gilley, J.; Zhu, Y.; Orsomando, G.; Angeletti, C.; Liu, J.; Yang, X.; Park, J.; Hopkin, R.J.; Coleman, M.P.; Zhai, R.G.; Stottmann, R.W.
Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence
Exp. Neurol.
320
112961
2019
Homo sapiens (Q9BZQ4), Homo sapiens
Eren, G.
Homology modeling of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 Insights into isoenzyme-specific differences using molecular docking simulatons
Lett. Drug Des. Discov.
14
727-736
2017
Homo sapiens (Q9BZQ4)
-
EXTERNAL LINKS (specific for EC-Number 2.7.7.1)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
