Information on EC 2.1.1.1 - nicotinamide N-methyltransferase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)

The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.1.1.1
-
RECOMMENDED NAME
GeneOntology No.
nicotinamide N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + nicotinamide = S-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Nicotinate and nicotinamide metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:nicotinamide N-methyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9029-74-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
C57BL/6 mice
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-methionine + nicotinamide
L-homocysteine + 1-methylnicotinamide
show the reaction diagram
-
-
-
-
?
nicotinamide + S-adenosyl-L-methionine
1-methylnicotinamide + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 1,2,3,4-tetrahydroisoquinoline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 3-acetylpyridine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-methylnicotinamide
S-adenosyl-L-homocysteine + 1,4-dimethylnicotinamide
show the reaction diagram
S-adenosyl-L-methionine + isoquinoline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram
S-adenosyl-L-methionine + quinoline
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thionicotinamide
S-adenosyl-L-homocysteine + 3-carbamothioyl-1-methylpyridinium
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-methionine + nicotinamide
L-homocysteine + 1-methylnicotinamide
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
S-adenosyl-L-methionine
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
no effect on enzyme activity by Fe2+ and Mn2+, but Mn2+ reduces mouse CD1 brain striatum neuronal cell survival with less than 10% cells surviving at 0.1 mM Mn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-methylnicotinamide
-
product inhibition
Cd2+
-
-
Clofibrate
Cu2+
-
-
N1-methylnicotinamide
nicotinamide
S-adenosyl-L-homocysteine
-
-
additional information
-
not inhibitory: Ca2+, SKF 525A, 3,4-dimethoxy-5-hydroxybenzoic acid
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
imipramine
-
slightly but significantly activates the mouse liver NNMT enzyme and also changes the kinetic parameters Vmax, Km and Ki
Phenobarbital
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2
1,2,3,4-tetrahydroisoquinoline
-
-
1.5
Isoquinoline
-
-
0.105 - 11.8
nicotinamide
1.3
Quinoline
-
-
0.00176 - 3.5
S-adenosyl-L-methionine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.031 - 1.02
nicotinamide
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003 - 0.8
nicotinamide
267
0.009 - 39
S-adenosyl-L-methionine
24
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.57 - 50.64
nicotinamide
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.06
N1-methylnicotinamide
Homo sapiens
-
IC50 0.06 mM for human protein, 0.03 mM for recombinant protein
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0011
-
Y20A mutant protein, pH 8.6, 37°C
0.0042
-
D197A mutant protein, pH 8.6, 37°C
0.077
-
Y20F mutant protein, pH 8.6, 37°C
0.14
-
S201A mutant protein, pH 8.6, 37°C
0.15
-
wild type protein, pH 8.6, 37°C
0.18
-
K100A/E101A/E103A mutant protein, pH 8.6, 37°C
0.21
-
S213A mutant protein, pH 8.6, 37°C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.7 - 9.8
-
about 50% of maximum activity at pH 5.7 and 9.8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
elevated enzyme activity during cell differentiation in adipose tissue
Manually annotated by BRENDA team
-
no expression of NNMT in
Manually annotated by BRENDA team
-
NNMT expression increased on stimulation of the cells with interleukin 6, NNMT promoter activity dependent on the activation of Stat3
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
no expression of NNMT in
Manually annotated by BRENDA team
-
CD1 brain striatum neuronal cells
Manually annotated by BRENDA team
-
the cells show enzyme overexpression compared to both tumor-adjacent and surrounding tissue
Manually annotated by BRENDA team
-
high enzyme expression levels
Manually annotated by BRENDA team
-
sera from 24 healthy individuals, from 113 non-small cell lung cancer patients undergoing surgery, and from 50 nonneoplastic lung disease patients with chronic obstructive pulmonary disease. Serum levels of NNMT are signficantly higher in lung cancer patients, overview
Manually annotated by BRENDA team
-
colon cancer cells, NNMT expression increased on stimulation of the cells with interleukin 6
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
27000 - 30000
-
gel filtration, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 27000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-tagged K100A/E101A/E103A mutant, sitting drop vapor diffusion method, PEG3350
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol stabilizes
-
thiols required for stability during isolation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20% glycerol w/v, stable for 1 month, partially purified enzyme
-
4°C, 20% glycerol w/v, pH 7.6, 30% loss of activity, purified enzyme
-
4°C, 20% w/v glycerol, stable for 1 week, partially purified enzyme
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-tagged K100A/E101A/E103A mutant, immobilized metal ion affinity chromatography (Ni2+), gel filtration
-
recombinant GST-tagged enzyme from Escherichia coli strain JM109 by glutathione affinity chromatography and cleavage of the tag by thrombin
-
recombinant protein, gel fitration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli, NNMT promoter region, promoter-luciferase reporter construct generated, pGL2 vector
-
expressed in HEK293 cells
-
gene NNMT, expression fo the GST-tagged enzyme in Escherichia coli strain JM109
-
gene NNMT, expression profiling in bladder cancer cell lines, overview
-
gene NNMT, genotyping, no allelic or genotypic association of the genetic variations of NNMT with spina bifida in the population of white non-hispanic individuals from California
-
gene NNMT, quantitative enzyme expression anaysis in 124 nasopharyngeal carcinoma samples, analysis of associations between NNMT and pAktSer473 expression and other important clinicopathologic variables, overview
-
overexpressed in SH-SY5Y cell line
-
quantitative real-time PCR enzyme expression analysis in non-smalll cell lung cancer samples
-
recombinant ectopic expression of NNMT in enzyme-deficient SH-SY5Y human neuroblastoma cells increasing adenosine triphosphate synthesis and complex I activity
-
recombinant enzyme overexpression in PANC-1 cells, quantitative real-time PCR enzyme expression analysis
-
recombinant overexpression of enzyme NNMT in colorectal cancer cells line SW480 which lacks constitutive NNMT expression, quantitative real-time PCR analysis
-
recombinant stable expression of NNMT-V5 in SH-SY5Y cells increases complex I activity via sirtuin 3
-
stable recombinant expression of enzyme NNMT in the SH-SY5Y human neuroblastoma cell line, which has no endogenous enzyme expression, at levels of activity comparable with that in Parkinson's disease brain, recombinant expression of enzyme NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increases neurite branching, synaptophysin expression and dopamine accumulation and release. Recombinant NNMT-V5 expression in SH-SY5Y cells changes cellular morphology and increases dopamine uptake and release. Transient expression of enzyme NNMT in N27 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is significantly elevated in a number of cancers, expression is significantly increased in the brains of patients who have died of Parkinson’s disease
-
expression is significantly elevated in the diaphragm and quadriceps muscles of patients with chronic obstructive pulmonary disease. The relative induction of expression is greater in the quadriceps muscle (10-fold) than it is in the diaphragm(2-fold). Expression correlates negatively with these verity of chronic obstructive pulmonary disease and limb muscle wasting. Expression in skeletal myoblasts is significantly induced by IL-6, transforming growth factor beta, and tumor necrosis factor-alpha. Overexpression in myoblasts triggers a significant increase in proliferation and migration, but has no influence on cell death
-
gain-of-function non-coding micro-RNA-1291 miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression
-
hepatic expression of Nnmt is highly variable and correlates with multiple metabolic parameters in mice
highly upregulated inclear cell renal carcinoma cell
-
progression of vascular inflammation and atherosclerosis is associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous 1-methylnicotinamide plasma levels
The activity levels are statistically significantly higher in oral squamous cell carcinoma than in adjacent normal oral mucosa
-
the enzyme is induced by nicotinic acid in adipose tissue
-
the enzyme is induced by nicotinic acid in white adipose tissue, but chronic treatment does not cause hyperhomocysteinemia, overview
-
the NNMT gene is differentially upregulated in nasopharyngeal cancer tissues
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D197A
-
active site residue
K100A/E101A/E103A
-
His-tagged version, crystallization facilitated by reducing the entropy of three surface exposed residues
S201A
-
active site residue
S213A
-
active site residue
Y20A
-
active site residue
Y20F
-
active site residue
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
drug development
-
the enzyme might be a good molecular target for lung cancer therapy
medicine
pharmacology