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Information on EC 2.1.1.1 - nicotinamide N-methyltransferase and Organism(s) Homo sapiens and UniProt Accession P40261
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2.1.1.1 nicotinamide N-methyltransferaseSpecify your search results
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
nicotinamide n-methyltransferase, nicotinamide n-methyl transferase, anmt-1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
methyltransferase, nicotinamide
-
-
-
-
NNMT
NNMT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:nicotinamide N-methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9029-74-7
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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
nicotinamide + S-adenosyl-L-methionine
1-methylnicotinamide + S-adenosyl-L-homocysteine
-
-
-
?
S-adenosyl-L-methionine + 2-methoxypyridine
S-adenosyl-L-homocysteine + 1-methyl-2-methoxypyridinium
-
-
-
?
S-adenosyl-L-methionine + 2-methylpyridine
S-adenosyl-L-homocysteine + 1,2-dimethylpyridinium
-
-
-
?
S-adenosyl-L-methionine + 3-acetylpyridine
S-adenosyl-L-homocysteine + N-methyl-3-acetylpyridinium
-
-
-
?
S-adenosyl-L-methionine + 4-methylnicotinamide
S-adenosyl-L-homocysteine + 1,4-dimethylnicotinamide
-
-
-
?
S-adenosyl-L-methionine + 4-phenylpyridine
S-adenosyl-L-homocysteine + 1-methyl-4-phenylpyridine
poor substrate
-
-
?
S-adenosyl-L-methionine + isoquinoline
S-adenosyl-L-homocysteine + N-methylisoquinoline
-
-
-
?
S-adenosyl-L-methionine + nicotinimidamide
S-adenosyl-L-homocysteine + N-methylnicotinimidamide
-
-
-
?
S-adenosyl-L-methionine + norharman + H+
S-adenosyl-L-homocysteine + 2-N-methylnorharman
-
-
-
?
S-adenosyl-L-methionine + quinoline 3-carboxamide
S-adenosyl-L-homocysteine + N-methylquinoline 3-carboxamide
-
-
-
?
S-adenosyl-L-methionine + tetrahydroisoquinoline
S-adenosyl-L-homocysteine + N-methyltetrahydroisoquinoline
-
-
-
?
S-adenosyl-L-methionine + thionicotinamide
S-adenosyl-L-homocysteine + 1-methylthionicotinamide
-
-
-
?
nicotinamide + S-adenosyl-L-methionine
1-methylnicotinamide + S-adenosyl-L-homocysteine
-
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
-
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
-
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
-
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
NNMT as potential candidate for a tumor marker
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
NNMT gene polymorphism as potential marker for cardiovascular risk factors
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
NNMT potential as tumor marker
-
-
?
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
polymorphism in the nicotinamide N-methyltransferase (NNMT) gene as risk factor for complex congenital heart defects (CHDs)
-
-
?
S-adenosyl-L-methionine + quinoline
S-adenosyl-L-homocysteine + N-methylquinoline
-
-
-
?
S-adenosyl-L-methionine + quinoline
S-adenosyl-L-homocysteine + N-methylquinoline
-
-
-
-
?
additional information
?
-
NNMT uses a rapid equilibrium ordered mechanism, where NNMT first binds S-adenosyl-L-methionine, which is followed by nicotinamide. Methyl transfer occurs, and methylated nicotinamide and S-adenosylhomocysteine are released consecutively
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-
-
additional information
?
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-
NNMT uses a rapid equilibrium ordered mechanism, where NNMT first binds S-adenosyl-L-methionine, which is followed by nicotinamide. Methyl transfer occurs, and methylated nicotinamide and S-adenosylhomocysteine are released consecutively
-
-
-
additional information
?
-
-
NNMT catalyzes the N-methylation of nicotinamide and other structural analogs, and is involved in the biotransformation of many drugs and xenobiotic compounds
-
-
?
additional information
?
-
-
development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview
-
-
?
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
S-adenosyl-L-methionine + nicotinamide
S-adenosyl-L-homocysteine + 1-methylnicotinamide
-
-
-
-
?
additional information
?
-
-
NNMT catalyzes the N-methylation of nicotinamide and other structural analogs, and is involved in the biotransformation of many drugs and xenobiotic compounds
-
-
?
additional information
?
-
-
development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-(6-amino-6-oxohexyl)benzamide
inhibitor mimics the transition state of the methylation reaction
5'-([(3S)-3-amino-3-carboxypropyl][[3-(methoxycarbonyl)phenyl]methyl]amino)-5'-deoxyadenosine
-
5'-deoxy-5'-[[(3S)-3,4-diamino-4-oxobutyl][(naphthalen-2-yl)methyl]amino]adenosine
inhibitor demonstrates a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line
5'-[(3-amino-3-carboxypropyl)[3-(3-carbamoyl-4-methylphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine
-
5'-[(3-amino-3-carboxypropyl)[3-(3-carbamoylphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine
compound exhibits around 1000fold selectivity for NNMT over other methyltransferases and almost 100fold selectivity for S-5'-adenosyl-L-homocysteine hydrolase
5'-[(3-amino-3-carboxypropyl)[3-(5-carbamoyl-2-methoxyphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine
-
5'-[(4-amino-4-oxobutyl)[(naphthalen-2-yl)methyl]amino]-5'-deoxyadenosine
-
5'-[(5-amino-5-oxopentyl)[(naphthalen-2-yl)methyl]amino]-5'-deoxyadenosine
-
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carboxyphenyl)methyl]amino]-5'-deoxyadenosine
-
5'-[[(3S)-3-amino-3-carboxypropyl][4-(3-carbamoylphenyl)butyl]amino]-5'-deoxyadenosine
-
5-[[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoylphenyl)hept-6-ynoic acid
log Ki value 4.65
6-(methylamino)pyridine-3-carboxamide
compound inhibits NNMT enzymatic activity and reduces the formation of 1-methyl-nicotinamide by about 80% at 2 h when dosed in mice orally at 50 mg/kg
7-(3-carbamoylphenyl)hept-6-ynoic acid
inhibitor mimics the transition state of the methylation reaction
9-(9-amino-5,6,7,8,9-pentadeoxy-6-ethynyl-beta-D-ribo-decofuranuronosyl)-9H-purin-6-amine
log Ki value 4.32
9-[9-amino-6-[(2-carbamoylphenyl)ethynyl]-5,6,7,8,9-pentadeoxy-beta-D-ribo-decofuranuronosyl]-9H-purin-6-amine
log Ki value 4.71
9-[9-amino-6-[(3-carbamoylphenyl)ethynyl]-5,6,7,8,9-pentadeoxy-beta-D-ribo-decofuranuronosyl]-9H-purin-6-amine
high-affinity, subnanomolar NNMT inhibitor
Nickel
exposure of BEAS-2B cells to induces NNMT repression at both the protein and mRNA levels
additional information
-
not inhibitory: Ca2+, SKF 525A, 3,4-dimethoxy-5-hydroxybenzoic acid
-
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine
bisubstrate inhibitor, competitive with respect to S-adenosyl-L-methionine, noncompetitive with respect to nicotinamide
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine
inhibitor mimics the transition state of the methylation reaction
N1-methylnicotinamide
-
IC50 0.06 mM for human protein, 0.03 mM for recombinant protein
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.125
4-phenylpyridine
pH not specified in the publication, temperature not specified in the publication
0.002
S-adenosyl-L-methionine
0.0018-0.0022 mM, wild type protein, pH 8.6, 37°C
0.005
S-adenosyl-L-methionine
K100A/E101A/E103A mutant protein, pH 8.6, 37°C
0.024
S-adenosyl-L-methionine
pH 7.5, temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000093
4-phenylpyridine
pH not specified in the publication, temperature not specified in the publication
0.068
S-adenosyl-L-methionine
pH 7.5, temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0008
4-phenylpyridine
pH not specified in the publication, temperature not specified in the publication
17
S-adenosyl-L-methionine
K100A/E101A/E103A mutant protein, pH 8.6, 37°C
39
S-adenosyl-L-methionine
35-43 1/sec*mM, wild type protein, pH 8.6, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000005
9-[9-amino-6-[(3-carbamoylphenyl)ethynyl]-5,6,7,8,9-pentadeoxy-beta-D-ribo-decofuranuronosyl]-9H-purin-6-amine
pH not specified in the publication, temperature not specified in the publication
4
Dimethylsulfoxide
substrate concentration above 2.5 mM, pH not specified in the publication, temperature not specified in the publication
34
Dimethylsulfoxide
substrate concentration below 2.5 mM, pH not specified in the publication, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0175
5'-([(3S)-3-amino-3-carboxypropyl][[3-(methoxycarbonyl)phenyl]methyl]amino)-5'-deoxyadenosine
Homo sapiens
pH 8.4, 37°C
0.0014
5'-deoxy-5'-[[(3S)-3,4-diamino-4-oxobutyl][(naphthalen-2-yl)methyl]amino]adenosine
Homo sapiens
pH 8.4, 37°C
0.0139
5'-deoxy-5'-[[(naphthalen-2-yl)methyl](propan-2-yl)amino]adenosine
Homo sapiens
pH 8.4, 37°C
0.000016
5'-[(3-amino-3-carboxypropyl)[3-(3-carbamoyl-4-methylphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine
Homo sapiens
pH 7.5, 37°C
0.0000068
5'-[(3-amino-3-carboxypropyl)[3-(3-carbamoylphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine
Homo sapiens
pH 7.5, 37°C
0.000052
5'-[(3-amino-3-carboxypropyl)[3-(5-carbamoyl-2-methoxyphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine
Homo sapiens
pH 7.5, 37°C
0.1115
5'-[(4-amino-4-oxobutyl)[(naphthalen-2-yl)methyl]amino]-5'-deoxyadenosine
Homo sapiens
pH 8.4, 37°C
0.0526
5'-[(5-amino-5-oxopentyl)[(naphthalen-2-yl)methyl]amino]-5'-deoxyadenosine
Homo sapiens
pH 8.4, 37°C
0.014 - 0.029
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine
0.0234
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carboxyphenyl)methyl]amino]-5'-deoxyadenosine
Homo sapiens
pH 8.4, 37°C
0.000043
5'-[[(3S)-3-amino-3-carboxypropyl][4-(3-carbamoylphenyl)butyl]amino]-5'-deoxyadenosine
Homo sapiens
pH 7.5, 37°C
0.06
N1-methylnicotinamide
Homo sapiens
-
IC50 0.06 mM for human protein, 0.03 mM for recombinant protein
0.014
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine
Homo sapiens
pH 7.5, temperature not specified in the publication
0.029
5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine
Homo sapiens
pH 8.6, 37°C
0.0012
S-adenosyl-L-homocysteine
Homo sapiens
substrate S-adenosyl-L-methionine, pH 8.6, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000028
substrate 1-methyl-4-phenylpyridine, pH not specified in the publication, temperature not specified in the publication
additional information
additional information
association between A/G single nucleotide polymorphism of NNMT gene and total homocysteine concentration in plasma of Japanese man analyzed, genotyping by PCR followed by melting curve analysis, NNMT genotype not determined as a strong determinant of total homocysteine concentration in plasma, modifying effect on plasma homocysteine concentration not excluded
additional information
-
association between A/G single nucleotide polymorphism of NNMT gene and total homocysteine concentration in plasma of Japanese man analyzed, genotyping by PCR followed by melting curve analysis, NNMT genotype not determined as a strong determinant of total homocysteine concentration in plasma, modifying effect on plasma homocysteine concentration not excluded
additional information
expression levels of NNMT in oral squamous cell carcinoma (OSCC), quantitative real-time PCR, Western-Blot and immunohistochemical analyses, upregulation in tumor cells, correlation between NNMT upregulation and favorable prognosis of oral squamous cell carcinoma patients
additional information
signal transducers and activators of transcription 3 (Stat3)-regulated genes analyzed, expression of NNMT in cancer cells, promoter activity determined after transfection experiments with NNMT promoter-luciferase reporter construct, real-time PCR, Western-Blot and immunohistochemistry, correlation between the expression of NNMT and activated Stat3 in colon cancer cells, NNMT determined as a Stat3-regulated gene and as a potential tumor marker
additional information
-
signal transducers and activators of transcription 3 (Stat3)-regulated genes analyzed, expression of NNMT in cancer cells, promoter activity determined after transfection experiments with NNMT promoter-luciferase reporter construct, real-time PCR, Western-Blot and immunohistochemistry, correlation between the expression of NNMT and activated Stat3 in colon cancer cells, NNMT determined as a Stat3-regulated gene and as a potential tumor marker
additional information
study population, DNA analysis and allelic discrimination assay of the NNMT gene, distribution of nicotinamide N-methyltransferase genotypes in families, children carrying the NNMT A allele face additional risk of congenital heart defects (CHDs) in combination with peri-conception exposure to medicines and/or a low dietary nicotinamide intake
additional information
-
study population, DNA analysis and allelic discrimination assay of the NNMT gene, distribution of nicotinamide N-methyltransferase genotypes in families, children carrying the NNMT A allele face additional risk of congenital heart defects (CHDs) in combination with peri-conception exposure to medicines and/or a low dietary nicotinamide intake
additional information
-
activity in different individuals, correlation with phenotypic differences
additional information
-
quantitative enzyme activity analysis in 25 non-smalll cell lung cancer samples
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
NNMT expression increased on stimulation of the cells with interleukin 6, NNMT promoter activity dependent on the activation of Stat3
breast cancer cells with high and constitutive expression of NNMT
-
the cells show enzyme overexpression compared to both tumor-adjacent and surrounding tissue
-
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
additional information
colon cancer cells with high and constitutive expression of NNMT
colon cancer cells, NNMT expression increased on stimulation of the cells with interleukin 6
-
the enzyme is robustly expressed in neurones in all regions of the brain
-
the enzyme is significantly overexpressed in a variety of diseases ranging from cancer to hepatic cirrhosis
-
serum levels of NNMT are signficantly higher in lung cancer patients, overview
-
sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells at elevated N-methylnicotinamide levels
additional information
-
high enzyme activity in papillary carcinoma cell lines, no or low activity in normal thyroid tissue, thyroid primary cultures, anaplastic cancer cells, and medullary cancer cells
additional information
-
enzyme expression levels in healthy oral mucosa and in oral squamous cell carcinomas, overview
additional information
-
nicotinamide N-methyltransferase is overexpressed in several malignancies, including colorectal cancer cells. No constitutive expresion of the enzyme in colorectal cancer cells line SW480
additional information
-
no activity in the SH-SY5Y human neuroblastoma cell line and in N27 cells
additional information
-
no enzyme activity in SH-SY5Y human neuroblastoma cells
additional information
-
SH-SY5Y human neuroblastoma cells have no endogenous expression of enzyme NNMT
additional information
-
the enzyme is overexpressed in many human cancers and is associated with poor prognosis
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
metabolism
physiological function
additional information
physiological function
cells expressing NMMT are less sensitive to beta-carbolines such as norharman
physiological function
down-regulation of NNMT in colorectal cancer HT-29 cells diminishes 5-fluorouracil resistance, while overexpression of NNMT in SW-480 cells enhances it. NNMT reduces reactive oxygen species production induced by 5-fluorouracil by increasing 1-methylnicotinamide in colorectal cancer cells. The reduction in ROS leads to inactivation of the ASK1-p38 mitogen-activated protein kinase pathway, which reduces 5-fluorouracil-induced apoptosis. In nude mice implanted with colorectal cancer xenografts, NNMT attenuates 5-fluorouracil-induced inhibition of colorectal cancer tumor growth
physiological function
exposure of BEAS-2B cells to nickel increases histone H3K9 dimethylation (H3K9me2), suppresses the expressions of H3K9me2-associated genes MAP2K3 and DKK1, and induces NNMT repression at both the protein and mRNA levels. Over-expression of NNMT inhibits nickel-induced H3K9me2 and alters the cellular SAM/SAH ratio
physiological function
exposure of BEAS-2B cells to nickel increases histone H3K9 dimethylation, suppresses the expressions of H3K9me2-associated genes MAP2K3 and DKK1, and induces NNMT repression at both the protein and mRNA levels. Overexpression of NNMT inhibits nickel-induced H3K9me2 and alters the cellular SAM/SAH ratio
physiological function
shRNA-mediated downregulation of NNMT expression levels inhibits the proliferation and density?-ependent growth of SCC-12 cells. The migration and invasion ofSCC cells are markedly decreased in NNMT-nockdown cells. High NNMT expression levels are accompanied by high expression levels of EMT-ssociated genes, and NNMT knockdown effectively suppresses the expression of matrix metalloproteinase 9, osteopontin, versican core protein and zinc finger protein SNAI2 in SCC-12 cells
physiological function
the expression level of NNMT is elevated in the peripheral blood and tissues of patients with prostate cancer. The overexpression of NNMT enhances PC-3 cell viability, invasion and migration capacity. The overexpression of NNMT significantly increases the mRNA level of sirtuin 1 in PC-3 cells. Nicotinamide treatment significantly suppresses the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT
physiological function
the expression of NNMT in the SH-SY5Y cell-line has no effect on cell death, viability, ATP content or mitochondrial membrane potential
malfunction
-
enzyme NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. Enzyme silencing markedly reduces cell proliferation, whereas enzyme overexpression promotes cell growth moderately. Knockdown of NNMT also significantly suppresses the migration and invasion capacities of pancreatic cancer PANC-1 cells. Enzyme NNMT upregulation enhances cell migration and invasion capacities. In addition, NNMT knockdown cells are much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-overexpressing cells show opposite effects although the effects are not so striking
malfunction
-
nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma
malfunction
-
shRNA-mediated gene silencing of NNMT leads to a significntl inhibition of cell proliferation and colony formation ability, downregulation of the enzyme significantly reduces the tumorigenicity of A-549 cells
malfunction
-
the enzyme effects on neurons are reduced in cells lacking epinephrin EFNB2 or Akt
metabolism
-
NNMTexpression is significantly positively associated with pAkt/protein kinase B expression
metabolism
-
the effects of enzyme NNMT expression in SH-SY5Y cells, e.g. protection against the toxicity of the Complex I (CxI) inhibitors 1-methyl-4-phenylpyridinium ion and rotenone, are mediated via increased CxI activity and ATP production and the sequential activation of the epinephrin EFNB2 and Akt signalling pathways
physiological function
-
the enzyme is involved in tumour differentiation in oral squamous cell carcinoma, overview
physiological function
-
effect of enzyme NNMT expression on cell survival under metabolic stress, the enzyme promotes cell survival and growth and increases cell migration and invasion capacities , NNMT-expressing cells demonstrate enhanced resistance to rapamycin, phenotype, overview
physiological function
-
expression of enzyme NNMT in enzyme-deficient SH-SY5Y human neuroblastoma cells significantly increases the expression of all three sirtuins, class III DNA deacetylase enzymes known to regulate mitochondrial energy production and cell cycle. Sirtuin 3 is a key mediator of NNMT-induced complex I activity and ATP synthesis. Central role for enzyme NNMT in the regulation of energy homeostasis
physiological function
-
nicotinamide N-methyltransferase is involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, it enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells. The enzyme significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice, and inhibits apoptosis, it promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS levels. 1-Methylnicotinamide also accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP levels. The enzyme may play a vital role in energy balance and ROS induction, 1-Methylnicotinamide is beneficial in conditions such as inflammation and antioxidation
physiological function
-
role of nicotinamide N-methyltransferase in non-small cell lung cancer
physiological function
-
the enzyme is overexpressed in many human cancers and is associated with poor prognosis. Enzyme NNMT might play a significant role in tumor progression and shorter survival time in patients with nasopharyngeal carcinoma, and it might promote the activation of MMP-2 via a pathway that sequentially involves pAkt signaling pathway
physiological function
-
the enzyme NNMT expression protects against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis, mediated via protection of the NDUFS3 subunit of CxI from degradation by increased 1-methylnicotinamide production. The enzyme expression increases neurite branching and the presynaptic marker synaptophysin, synaptophysin expression is induced by the enzyme. 1-Methylnicotinamide replicates the effects of enzyme NNMT expression upon SH-SY5Y neurite branching, effects of NNMT expression on neuron morphology and differentiation, overview. Recombinant NNMT-V5 expression in SH-SY5Y cells changes cellular morphology and increases dopamine uptake and release. The effects of enzyme NNMT expression in SH-SY5Y cells, e.g. protection against the toxicity of the Complex I (CxI) inhibitors 1-methyl-4-phenylpyridinium ion and rotenone, are mediated via increased CxI activity and ATP production and the sequential activation of the epinephrin EFNB2 and Akt signalling pathways. The enzyme NNMT reduces cholinergic phenotype but does not induce terminal differentiation
additional information
-
in vitro overexpression of the enzyme has revealed many cytoprotective effects of NNMT, in particular increased complex I activity and ATP synthesis. siRNA-mediated silencing of sirtuin 3 expression decreases complex I activity in NNMT-expressing SH-SY5Y cells to that observed in wild-type SH-SY5Y, and significantly reduces cellular ATP content also
additional information
-
recombinant ectopic expression of NNMT in enzyme-deficient SH-SY5Y human neuroblastoma cells increased adenosine triphosphate synthesis and complex I activity, effects of which are replicated by the addition of 1-methylnicotinamide. The enzyme expression protects against the toxicity of mitochondrial toxins and abolishes the toxic effects of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine, and reduced that of rotenone, while 1-methylnicotinamide significantly reduces the toxicity of rotenone, but has no effect on the toxicity of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine. The enzyme is cytoprotective against toxins that inhibit various aspects of mitochondrial function, which are not mediated solely via increased 1-methylnicotinamide production, but in combination with other unidentified mechanisms
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). NNMT_HUMAN
264
0
29574
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
docking of inhibitors to the NNMT nicotinamide-binding site produces a robust correlation between ligand-enzyme interaction docking scores and experimentally calculated IC50 values
His-tagged K100A/E101A/E103A mutant, sitting drop vapor diffusion method, PEG3350
in complex with inhibitor (2S,5S)-2-amino-5-(((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-7-(3-carbamoylphenyl)hept-6-ynoic acid. The alkynyl linker is able to span the methyl transfer tunnel of NNMT with ideal shape complementarity
in complex with inhibitor 5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine
in complex with inhibitors (S)-amino-4-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(3-(3-carbamoylphenyl)propyl)amino)butanoic acid and (S)-2-amino-4-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(3-(3-carbamoylphenyl)prop-2-yn-1-yl)amino)butanoic acid
in silico molecular docking. Substrate 4-phenylpyridine binds to the active site of NNMT in two non-redundant poses, one a substrate binding mode and the other an inhibitory mode
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K100A/E101A/E103A
His-tagged version, crystallization facilitated by reducing the entropy of three surface exposed residues
additional information
additional information
-
enzyme upregulation correlates with tumour differentiation in oral squamous cell carcinoma cells
additional information
-
identification of 11 single nucleotide polymorphisms in the 5'-UTR and 3'-UTR, as well as in exon 1 and intron 2, overview
additional information
-
siRNA knockdown of NNMT in SLT4 cells causes decreased cell proliferation in bladder cancer, the enzyme expression is associated with cell migration
additional information
-
downregulation of enzyme NNMT expression in HT-29 cells. Balb/c mice are injected with NNMT-transfected SW-480 cells, the enzyme significantly accelerates cell proliferation and enhances tumorigenicity in mice
additional information
-
enzyme expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling
additional information
-
forced NNMT overexpression strongly induces the invasive capacity in human embryonic kidney 293 cells
additional information
-
gain-of-function non-coding micro-RNA-1291 (miR-1291) transfected to PANC-1 cells lead to a significantly altered metabolome for the human pancreatic carcinoma cells, phenotype with a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, are elevated in miR-1291-expressing PANC-1. N-methylnicotinamide is elevated to the greatest extent associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. The expression of NNMT mRNA is inversely correlated with pancreatic tumor size in the xenograft mouse model
additional information
-
transfection of pancreatic cancer cell line PANC-1 with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Enzyme silencing markedly reduces cell proliferation, whereas enzyme overexpression promotes cell growth moderately. Enzyme knockdown by specific siRNA
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli, NNMT promoter region, promoter-luciferase reporter construct generated, pGL2 vector
expression in Escherichia coli
gene NNMT, expression fo the GST-tagged enzyme in Escherichia coli strain JM109
-
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
-
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
exposure of BEAS-2B cells to induces NNMT repression at both the protein and mRNA levels
exposure to nickel induces NNMT repression at both the protein and mRNA levels
expression is upregulated in the cutaneous squamous cell carcinoma SCC-12 cell line
patients with manifest type 2 diabetes have an approximately twofold higher NNMTexpression both in omental and subcutaneous white adipose tissue compared with controls
the expression level of NNMT is elevated in the peripheral blood and tissues of patients with prostate cancer
expression is significantly elevated in a number of cancers, expression is significantly increased in the brains of patients who have died of Parkinsons 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
-
The activity levels are statistically significantly higher in oral squamous cell carcinoma than in adjacent normal oral mucosa
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a NNMT activity assay using ultra-high-performance hydrophilic interaction chromatography. It allows for rapid separation of the reaction products, coupled with quadrupole time-of-flight mass spectrometric detection for enhanced sensitivity and enabling high-throughput sample analysis
medicine
pharmacology
diagnostics
drug development
-
the enzyme might be a good molecular target for lung cancer therapy
medicine
pharmacology
-
the enzyme might be a good molecular target for lung cancer therapy
medicine
epidemiologic study to analyze risk factors for complex congenital heart defects (CHDs) and multifactorial aetiology
medicine
down-regulation of NNMT in colorectal cancer HT-29 cells diminishes 5-fluorouracil resistance, while overexpression of NNMT in SW-480 cells enhances it
medicine
patients with manifest type 2 diabetes have an approximately twofold higher NNMT expression both in omental and subcutaneous white adipose tissue compared with controls. Plasma 1-methylnicotinamide concentration correlates with increased tissue NNMT expression and the degree of insulin resistance
medicine
the expression level of NNMT is elevated in the peripheral blood and tissues of patients with prostate cancer. The overexpression of NNMT enhances PC-3 cell viability, invasion and migration capacity. The overexpression of NNMT significantly increases the mRNA level of sirtuin 1 in PC-3 cells. Nicotinamide treatment significantly suppresses the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT
diagnostics
-
high enzyme expression levels in oral squamous cell carcinoma cells indicates a favourable prognosis in patients, whereas the absence of NNMT expression constitutes a hallmark of aggressive biological behaviour
diagnostics
-
NNMT is useful as a biomarker of lung cancer, stages I-III. The sensitivity of the detection in non-small cell lung cancer cells at 90% specficity increases from 25% to 32% when NNMT is used in combination with carcinoembryonic antigen, method development, overview
diagnostics
-
the enzyme may serve as a potential biomarker for tumor diagnosis and a therapeutic target
medicine
-
enzyme protein level is significantly elevated in younger patients with Parkinson's disease
medicine
-
significantly increased levels of enzyme protein and activity in brain of patients with Parkinson´s disease, study on brain tissue distribution
medicine
-
expression of enzyme is significantly higher in cerebellum of patients with idiopathic Parkinson's disease than in control groups
medicine
-
significantly higher enzyme activity in papillary thyroid carcinoma cell lines than in controls
medicine
-
inhibition of NNMT activity is a promising therapeutic target for cancer therapy
medicine
-
the enzyme may serve as a potential biomarker for tumor diagnosis and a therapeutic target
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rini, J.; Szumlanski, C.; Guerciolini, R.; Weinshilboum, R.M.
Human liver nicotinamide N-methyltransferase: ion-pairing radiochemical assay, biochemical properties and individual variation
Clin. Chim. Acta
186
359-374
1990
Homo sapiens
Smith, M.L.; Burnett, D.; Bennett, P.; Waring, R.H.; Brown, H.M.; Williams, A.C.; Ramsden, D.B.
A direct correlation between nicotinamide N-methyltransferase activity and protein levels in human liver cytosol
Biochim. Biophys. Acta
1442
238-244
1998
Homo sapiens
Aksoy, S.; Szumlanski, C.L.; Weinshilboum, R.M.
Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization
J. Biol. Chem.
269
14835-14840
1994
Homo sapiens
Aoyama, K.; Matsubara, K.; Kondo, M.; Murakawa, Y.; Suno, M.; Yamashita, K.; Yamaguchi, S.; Kobayashi, S.
Nicotinamide-N-methyltransferase is higher in the lumbar cerebrospinal fluid of patients with Parkinson's disease
Neurosci. Lett.
298
78-80
2001
Homo sapiens
Kassem, H.S.; Sangar, V.; Cowan, R.; Clarke, N.; Margison, G.P.
A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer
Int. J. Cancer
101
454-460
2002
Homo sapiens
Parsons, R.B.; Smith, M.L.; Williams, A.C.; Waring, R.H.; Ramsden, D.B.
Expression of nicotinamide N-methyltransferase (E.C. 2.1.1.1) in the Parkinsonian brain
J. Neuropathol. Exp. Neurol.
61
111-124
2002
Homo sapiens
Xu, J.; Moatamed, F.; Caldwell, J.S.; Walker, J.R.; Kraiem, Z.; Taki, K.; Brent, G.A.; Hershman, J.M.
Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells
J. Clin. Endocrinol. Metab.
88
4990-4996
2003
Homo sapiens
Parsons, R.B.; Smith, S.W.; Waring, R.H.; Williams, A.C.; Ramsden, D.B.
High expression of nicotinamide N-methyltransferase in patients with idiopathic Parkinson's disease
Neurosci. Lett.
342
13-16
2003
Homo sapiens
van Driel, L.M.; Smedts, H.P.; Helbing, W.A.; Isaacs, A.; Lindemans, J.; Uitterlinden, A.G.; van Duijn, C.M.; de Vries, J.H.; Steegers, E.A.; Steegers-Theunissen, R.P.
Eight-fold increased risk for congenital heart defects in children carrying the nicotinamide N-methyltransferase polymorphism and exposed to medicines and low nicotinamide
Eur. Heart J.
29
1424-1431
2008
Homo sapiens (P40261), Homo sapiens
Tomida, M.; Ohtake, H.; Yokota, T.; Kobayashi, Y.; Kurosumi, M.
Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells
J. Cancer Res. Clin. Oncol.
134
551-559
2008
Homo sapiens (P40261), Homo sapiens
Sartini, D.; Santarelli, A.; Rossi, V.; Goteri, G.; Rubini, C.; Ciavarella, D.; Lo Muzio, L.; Emanuelli, M.
Nicotinamide N-methyltransferase upregulation inversely correlates with lymph node metastasis in oral squamous cell carcinoma
Mol. Med.
13
415-421
2007
Homo sapiens (P40261)
Zhang, L.; Miyaki, K.; Araki, J.; Nakayama, T.; Muramatsu, M.
The relation between nicotinamide N-methyltransferase gene polymorphism and plasma homocysteine concentration in healthy Japanese men
Thromb. Res.
121
55-58
2007
Homo sapiens (P40261), Homo sapiens
Riederer, M.; Erwa, W.; Zimmermann, R.; Frank, S.; Zechner, R.
Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteine
Atherosclerosis
204
412-417
2009
Homo sapiens, Mus musculus
Lu, W.; Zhu, H.; Wen, S.; Yang, W.; Shaw, G.M.; Lammer, E.J.; Finnell, R.H.
Nicotinamide N-methyl transferase (NNMT) gene polymorphisms and risk for spina bifida
Birth Defects Res. Part A Clin. Mol. Teratol.
82
670-675
2008
Homo sapiens
Emanuelli, M.; Santarelli, A.; Sartini, D.; Ciavarella, D.; Rossi, V.; Pozzi, V.; Rubini, C.; Lo Muzio, L.
Nicotinamide N-methyltransferase upregulation correlates with tumour differentiation in oral squamous cell carcinoma
Histol. Histopathol.
25
15-20
2010
Homo sapiens
Tomida, M.; Mikami, I.; Takeuchi, S.; Nishimura, H.; Akiyama, H.
Serum levels of nicotinamide N-methyltransferase in patients with lung cancer
J. Cancer Res. Clin. Oncol.
135
1223-1229
2009
Homo sapiens
Wu, Y.; Siadaty, M.S.; Berens, M.E.; Hampton, G.M.; Theodorescu, D.
Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration
Oncogene
27
6679-6689
2008
Homo sapiens
Kim, H.C.; Mofarrahi, M.; Vassilakopoulos, T.; Maltais, F.; Sigala, I.; Debigare, R.; Bellenis, I.; Hussain, S.N.
Expression and functional significance of nicotinamide N-methyl transferase in skeletal muscles of patients with chronic obstructive pulmonary disease
Am. J. Respir. Crit. Care Med.
181
797-805
2010
Homo sapiens
Parsons, R.B.; Aravindan, S.; Kadampeswaran, A.; Evans, E.A.; Sandhu, K.K.; Levy, E.R.; Thomas, M.G.; Austen, B.M.; Ramsden, D.B.
The expression of nicotinamide N-methyltransferase increases ATP synthesis and protects SH-SY5Y neuroblastoma cells against the toxicity of Complex I inhibitors
Biochem. J.
436
145-155
2011
Homo sapiens
Peng, Y.; Sartini, D.; Pozzi, V.; Wilk, D.; Emanuelli, M.; Yee, V.C.
Structural basis of substrate recognition in human nicotinamide N-methyltransferase
Biochemistry
50
7800-7808
2011
Homo sapiens (P40261), Homo sapiens
Sartini, D.; Pozzi, V.; Renzi, E.; Morganti, S.; Rocchetti, R.; Rubini, C.; Santarelli, A.; Lo Muzio, L.; Emanuelli, M.
Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous cell carcinoma: basis for the development of a noninvasive diagnostic test for early-stage disease
Biol. Chem.
393
505-511
2012
Homo sapiens
Tang, S.W.; Yang, T.C.; Lin, W.C.; Chang, W.H.; Wang, C.C.; Lai, M.K.; Lin, J.Y.
Nicotinamide N-methyltransferase induces cellular invasion through activating matrix metalloproteinase-2 expression in clear cell renal cell carcinoma cells
Carcinogenesis
32
138-145
2011
Homo sapiens
Xie, X.; Yu, H.; Wang, Y.; Zhou, Y.; Li, G.; Ruan, Z.; Li, F.; Wang, X.; Liu, H.; Zhang, J.
Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells
Arch. Biochem. Biophys.
564
52-66
2014
Homo sapiens
Liu, K.Y.; Mistry, R.J.; Aguirre, C.A.; Fasouli, E.S.; Thomas, M.G.; Klamt, F.; Ramsden, D.B.; Parsons, R.B.
Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3
Biochem. Biophys. Res. Commun.
467
491-496
2015
Homo sapiens
Sartini, D.; Seta, R.; Pozzi, V.; Morganti, S.; Rubini, C.; Zizzi, A.; Tomasetti, M.; Santarelli, L.; Emanuelli, M.
Role of nicotinamide N-methyltransferase in non-small cell lung cancer: in vitro effect of shRNA-mediated gene silencing on tumourigenicity
Biol. Chem.
396
225-234
2015
Homo sapiens
Bi, H.C.; Pan, Y.Z.; Qiu, J.X.; Krausz, K.W.; Li, F.; Johnson, C.H.; Jiang, C.T.; Gonzalez, F.J.; Yu, A.M.
N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis
Carcinogenesis
35
2264-2272
2014
Homo sapiens
Sartini, D.; Morganti, S.; Guidi, E.; Rubini, C.; Zizzi, A.; Giuliante, R.; Pozzi, V.; Emanuelli, M.
Nicotinamide N-methyltransferase in non-small cell lung cancer: promising results for targeted anti-cancer therapy
Cell Biochem. Biophys.
67
865-873
2013
Homo sapiens
Thomas, M.G.; Saldanha, M.; Mistry, R.J.; Dexter, D.T.; Ramsden, D.B.; Parsons, R.B.
Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling
Cell Death Dis.
4
e669
2013
Homo sapiens
Yu, T.; Wang, Y.T.; Chen, P.; Li, Y.H.; Chen, Y.X.; Zeng, H.; Yu, A.M.; Huang, M.; Bi, H.C.
Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress
Cell. Physiol. Biochem.
35
710-721
2015
Homo sapiens
Milani, Z.H.; Ramsden, D.B.; Parsons, R.B.
Neuroprotective effects of nicotinamide N-methyltransferase and its metabolite 1-methylnicotinamide
J. Biochem. Mol. Toxicol.
27
451-456
2013
Homo sapiens
Patel, M.; Vasaya, M.M.; Asker, D.; Parsons, R.B.
HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples: evidence for substrate inhibition kinetics
J. Chromatogr. B
921-922
87-95
2013
Oryctolagus cuniculus, Homo sapiens, Mus musculus
Win, K.T.; Lee, S.W.; Huang, H.Y.; Lin, L.C.; Lin, C.Y.; Hsing, C.H.; Chen, L.T.; Li, C.F.
Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma
Tumour Biol.
34
3923-3931
2013
Homo sapiens
Thomas, M.G.; Sartini, D.; Emanuelli, M.; van Haren, M.J.; Martin, N.I.; Mountford, D.M.; Barlow, D.J.; Klamt, F.; Ramsden, D.B.; Reza, M.; Parsons, R.B.
Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous beta-carboline norharman evidence for a novel detoxification pathway
Biochem. J.
473
3253-3267
2016
Homo sapiens (P40261)
Loring, H.S.; Thompson, P.R.
Kinetic mechanism of nicotinamide N-methyltransferase
Biochemistry
57
5524-5532
2018
Homo sapiens (P40261), Homo sapiens
Ruf, S.; Hallur, M.S.; Anchan, N.K.; Swamy, I.N.; Murugesan, K.R.; Sarkar, S.; Narasimhulu, L.K.; Putta, V.P.R.K.; Shaik, S.; Chandrasekar, D.V.; Mane, V.S.; Kadnur, S.V.; Suresh, J.; Bhamidipati, R.K.; Singh, M.; Burri, R.R.; Kristam, R.; Schreuder, H.; Czech, J.; Rudolph, C.; Marker, A.; Langer, T.; Mullangi,
Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase
Bioorg. Med. Chem. Lett.
28
922-925
2018
Homo sapiens (P40261)
Li, Q.; He, M.D.; Mao, L.; Wang, X.; Jiang, Y.L.; Li, M.; Lu, Y.H.; Yu, Z.P.; Zhou, Z.
Nicotinamide N-methyltransferase suppression participates in nickel-induced histone H3 lysine9 dimethylation in BEAS-2B cells
Cell. Physiol. Biochem.
41
2016-2026
2017
Homo sapiens (P40261), Homo sapiens
Kannt, A.; Pfenninger, A.; Teichert, L.; Toenjes, A.; Dietrich, A.; Schoen, M.R.; Kloeting, N.; Blueher, M.
Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance
Diabetologia
58
799-808
2015
Homo sapiens (P40261)
van Haren, M.J.; Thomas, M.G.; Sartini, D.; Barlow, D.J.; Ramsden, D.B.; Emanuelli, M.; Klamt, F.; Martin, N.I.; Parsons, R.B.
The kinetic analysis of the N-methylation of 4-phenylpyridine by nicotinamide N-methyltransferase Evidence for a novel mechanism of substrate inhibition
Int. J. Biochem. Cell Biol.
98
127-136
2018
Homo sapiens (P40261), Homo sapiens
Neelakantan, H.; Wang, H.Y.; Vance, V.; Hommel, J.D.; McHardy, S.F.; Watowich, S.J.
Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase
J. Med. Chem.
60
5015-5028
2017
Homo sapiens (P40261)
Babault, N.; Allali-Hassani, A.; Li, F.; Fan, J.; Yue, A.; Ju, K.; Liu, F.; Vedadi, M.; Liu, J.; Jin, J.
Discovery of bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT)
J. Med. Chem.
61
1541-1551
2018
Homo sapiens (P40261), Homo sapiens
Chen, D.; Li, L.; Diaz, K.; Iyamu, I.D.; Yadav, R.; Noinaj, N.; Huang, R.
Novel propargyl-linked bisubstrate analogues as tight-binding inhibitors for nicotinamide N-methyltransferase
J. Med. Chem.
62
10783-10797
2019
Homo sapiens (P40261)
Gao, Y.; van Haren, M.J.; Moret, E.E.; Rood, J.J.M.; Sartini, D.; Salvucci, A.; Emanuelli, M.; Craveur, P.; Babault, N.; Jin, J.; Martin, N.I.
Bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT) with enhanced activity
J. Med. Chem.
62
6597-6614
2019
Homo sapiens (P40261), Homo sapiens
Policarpo, R.L.; Decultot, L.; May, E.; Kuzmic, P.; Carlson, S.; Huang, D.; Chu, V.; Wright, B.A.; Dhakshinamoorthy, S.; Kannt, A.; Rani, S.; Dittakavi, S.; Panarese, J.D.; Gaudet, R.; Shair, M.D.
High-affinity alkynyl bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT)
J. Med. Chem.
62
9837-9873
2019
Homo sapiens (P40261)
You, Z.; Liu, Y.; Liu, X.
Nicotinamide N-methyltransferase enhances the progression of prostate cancer by stabilizing sirtuin 1
Oncol. Lett.
15
9195-9201
2018
Homo sapiens (P40261), Homo sapiens
Hah, Y.; Cho, H.; Jo, S.; Park, Y.; Yoon, T.; Heo, E.
Nicotinamide N-methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells
Oncol. Rep.
42
1805-1814
2019
Homo sapiens (P40261)
Xie, X.; Liu, H.; Wang, Y.; Zhou, Y.; Yu, H.; Li, G.; Ruan, Z.; Li, F.; Wang, X.; Zhang, J.
Nicotinamide N-methyltransferase enhances resistance to 5-fluorouracil in colorectal cancer cells through inhibition of the ASK1-p38 MAPK pathway
Oncotarget
7
45837-45848
2016
Homo sapiens (P40261), Homo sapiens
van Haren, M.J.; Taig, R.; Kuppens, J.; Sastre Torano, J.; Moret, E.E.; Parsons, R.B.; Sartini, D.; Emanuelli, M.; Martin, N.I.
Inhibitors of nicotinamide N-methyltransferase designed to mimic the methylation reaction transition state
Org. Biomol. Chem.
15
6656-6667
2017
Homo sapiens (P40261)
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