Information on EC 2.1.1.1 - nicotinamide N-methyltransferase:
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The expected taxonomic range for this enzyme is: Euarchontoglires

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EC NUMBERCOMMENTARY
2.1.1.1-

RECOMMENDED NAMEGeneOntology No.
nicotinamide N-methyltransferaseGO:0008112

REACTIONREACTION DIAGRAMCOMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
S-adenosyl-L-methionine + nicotinamide = S-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		----

REACTION TYPEORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
methyl group transfer----

PATHWAYKEGG LinkMetaCyc Link
Metabolic pathways01100 -
Nicotinate and nicotinamide metabolism00760 -

SYSTEMATIC NAMEIUBMB Comments
S-adenosyl-L-methionine:nicotinamide N-methyltransferase-

SYNONYMSORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
methyltransferase, nicotinamide----
nicotinamide N-methyl transferaseHomo sapiens--718554
nicotinamide N-methyltransferaseHomo sapiens--718784, 718914, 719027
NNMT----
NNMTRattus norvegicus--704426
NNMTHomo sapiens--686485, 687897, 689036, 690123, 701990, 702851, 703943, 704775, 706009
NNMTMus musculus--701990, 704426, 706094

CAS REGISTRY NUMBERCOMMENTARY
9029-74-7-

ORGANISMCOMMENTARYLITERATURESEQUENCE CODESEQUENCE DB SOURCE
Homo sapiens-441253, 441254, 441255, 441259, 441262, 662513, 701990, 703943, 704775, 718554, 718784, 719027, 719232--Manually annotated by BRENDA team
Homo sapiens-686485, 687897, 689036, 690123, 718914P40261SwissProtManually annotated by BRENDA team
Homo sapiensgene NNMT702851, 706009--Manually annotated by BRENDA team
Homo sapienspatients with idiopathic Parkinson's disease662956--Manually annotated by BRENDA team
Homo sapiensradioresistant bladder carcinoma cell line MGH-UI441260--Manually annotated by BRENDA team
Mus musculus-441256--Manually annotated by BRENDA team
Mus musculusbearing colon 26 adenocarcinoma441261--Manually annotated by BRENDA team
Mus musculusbearing Ehrlich ascites tumor441257--Manually annotated by BRENDA team
Mus musculusC57BL/6 mice704426--Manually annotated by BRENDA team
Mus musculusC57BL/6J441258--Manually annotated by BRENDA team
Mus musculusC57BL/6J mice706094--Manually annotated by BRENDA team
Mus musculusfemale and male C57BL/6J mice701990--Manually annotated by BRENDA team
Mus musculus C57BL/6JC57BL/6J441258--Manually annotated by BRENDA team
Mus musculus C57BL/6JC57BL/6J mice706094--Manually annotated by BRENDA team
Rattus norvegicus-441251, 704426--Manually annotated by BRENDA team
Rattus norvegicusbearing Walker 256 carcinosarcoma441257--Manually annotated by BRENDA team
Sus scrofa-441252--Manually annotated by BRENDA team

GENERAL INFORMATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
malfunctionHomo sapiens-depletion of NNMT affects chemotaxis and chemokinesis706009
physiological functionHomo sapiens-the enzyme is involved in tumour differentiation in oral squamous cell carcinoma, overview703943
physiological functionHomo sapiens-enzyme expression is associated with cell migration706009
physiological functionMus musculus-progression of vascular inflammation and atherosclerosis is associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous 1-methylnicotinamide plasma levels706094

SUBSTRATEPRODUCT                      REACTION DIAGRAMORGANISM UNIPROT ACCESSION NO. COMMENTARY/
Substrate		 LITERATURE/
Substrate		 COMMENTARY/
Product		 LITERATURE/
Product		 Reversibility
r=reversible
ir=irreversible
?=not specified
nicotinamide + S-adenosyl-L-methionine1-methylnicotinamide + S-adenosyl-L-homocysteine
show the reaction diagram		Homo sapiens--719027, 718914--?
S-adenosyl-L-methionine + 1,2,3,4-tetrahydroisoquinolineS-adenosyl-L-homocysteine + ?
show the reaction diagram		Sus scrofa--441252--?
S-adenosyl-L-methionine + 3-acetylpyridineS-adenosyl-L-homocysteine + ?
show the reaction diagram		Sus scrofa--441252--?
S-adenosyl-L-methionine + 4-methylnicotinamideS-adenosyl-L-homocysteine + 1,4-dimethylnicotinamide
show the reaction diagram		Mus musculus-assay for fluorometric determination of enzyme activity706094--?
S-adenosyl-L-methionine + isoquinolineS-adenosyl-L-homocysteine + ?
show the reaction diagram		Sus scrofa--441252--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Mus musculus--441258---
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Mus musculus--701990, 706094--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiens--441255---
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiens--441253, 701990--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Sus scrofa--441252--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Rattus norvegicus-L-methionine + nicotinamide441251--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiens-NNMT as potential candidate for a tumor marker687897--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiens-NNMT gene polymorphism as potential marker for cardiovascular risk factors690123--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiens-NNMT potential as tumor marker689036--?
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiensP40261polymorphism in the nicotinamide N-methyltransferase (NNMT) gene as risk factor for complex congenital heart defects (CHDs)686485--?
S-adenosyl-L-methionine + quinolineS-adenosyl-L-homocysteine + ?
show the reaction diagram		Sus scrofa--441252--?
S-adenosyl-L-methionine + thionicotinamideS-adenosyl-L-homocysteine + 3-carbamothioyl-1-methylpyridinium
show the reaction diagram		Sus scrofa--441252--?
L-methionine + nicotinamideL-homocysteine + 1-methylnicotinamide
show the reaction diagram		Rattus norvegicus--441251--?
additional information?-Sus scrofa-enzyme may function in detoxificating of numerous alkaloids441252---
additional information?-Homo sapiens-NNMT catalyzes the N-methylation of nicotinamide and other structural analogs, and is involved in the biotransformation of many drugs and xenobiotic compounds704775---

NATURAL SUBSTRATESNATURAL PRODUCTSREACTION DIAGRAMORGANISM UNIPROT ACCESSION NO.COMMENTARY SUBSTRATELITERATURE
(Substrate)		COMMENTARY PRODUCTLITERATURE
(Product)
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Mus musculus--701990, 706094--
S-adenosyl-L-methionine + nicotinamideS-adenosyl-L-homocysteine + 1-methylnicotinamide
show the reaction diagram		Homo sapiens--701990--
L-methionine + nicotinamideL-homocysteine + 1-methylnicotinamide
show the reaction diagram		Rattus norvegicus--441251--
additional information?-Sus scrofa-enzyme may function in detoxificating of numerous alkaloids441252--
additional information?-Homo sapiens-NNMT catalyzes the N-methylation of nicotinamide and other structural analogs, and is involved in the biotransformation of many drugs and xenobiotic compounds704775--

COFACTORORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATUREIMAGE
S-adenosyl-L-methionineHomo sapiens--701990 2D-image
S-adenosyl-L-methionineMus musculus--701990, 706094 2D-image

METALS and IONS ORGANISM UNIPROT ACCESSION NO.COMMENTARY LITERATURE
No entries in this field

INHIBITORSORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
1-methylnicotinamideMus musculus-product inhibition701990 2D-image
ClofibrateMus musculus-inhibits the enzyme in liver micorosomes704426 2D-image
N1-methylnicotinamideHomo sapiens--441253 2D-image
N1-methylnicotinamideHomo sapiens-IC50 0.06 mM for human protein, 0.03 mM for recombinant protein441255 2D-image
S-adenosyl-L-homocysteineHomo sapiens--441253 2D-image
ClofibrateRattus norvegicus-inhibits the enzyme in liver microsomes704426 2D-image
additional informationHomo sapiens-not inhibitory: Ca2+, SKF 525A, 3,4-dimethoxy-5-hydroxybenzoic acid441253-

ACTIVATING COMPOUNDORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
PhenobarbitalMus musculus-activates 3-4fold in liver micorosomes704426 2D-image
PhenobarbitalRattus norvegicus-activates the enzyme in liver microsomes704426 2D-image
additional informationMus musculus-elevated enzyme activity during cell differentiation in adipose tissue701990-
additional informationMus musculus-no activation by beta-naphthoflavone and ciprofibrate704426-

KM VALUE [mM]KM VALUE [mM] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.2-1,2,3,4-tetrahydroisoquinolineSus scrofa--441252 2D-image
1.5-IsoquinolineSus scrofa--441252 2D-image
0.105-NicotinamideHomo sapiens-K100A/E101A/E103A mutant protein, pH 8.6, 37°C718914 2D-image
0.24-NicotinamideHomo sapiens-Y20F mutant protein, pH 8.6, 37°C718914 2D-image
0.347-NicotinamideHomo sapiens--441253 2D-image
0.37-NicotinamideMus musculus--441258 2D-image
0.38-NicotinamideHomo sapiens-recombinant protein441255 2D-image
0.4-NicotinamideHomo sapiens-0.43-0.38 mM, wild type protein, pH 8.6, 37°C718914 2D-image
0.43-NicotinamideHomo sapiens--441255 2D-image
0.63-NicotinamideHomo sapiens-Y20A mutant protein, pH 8.6, 37°C718914 2D-image
0.83-NicotinamideSus scrofa--441252 2D-image
11.8-NicotinamideHomo sapiens-D197A mutant protein, pH 8.6, 37°C718914 2D-image
1.3-QuinolineSus scrofa--441252 2D-image
0.00176-S-adenosyl-L-methionineHomo sapiens--441253 2D-image
0.0018-S-adenosyl-L-methionineHomo sapiens--441255 2D-image
0.002-S-adenosyl-L-methionineHomo sapiens-0.0018-0.0022 mM, wild type protein, pH 8.6, 37°C718914 2D-image
0.0022-S-adenosyl-L-methionineHomo sapiens-recombinant protein441255 2D-image
0.005-S-adenosyl-L-methionineHomo sapiens-K100A/E101A/E103A mutant protein, pH 8.6, 37°C718914 2D-image
0.0065-S-adenosyl-L-methionineMus musculus--441258 2D-image
0.016-S-adenosyl-L-methionineSus scrofa--441252 2D-image
0.028-S-adenosyl-L-methionineHomo sapiens-Y20F mutant protein, pH 8.6, 37°C718914 2D-image
2.73-S-adenosyl-L-methionineHomo sapiens-D197A mutant protein, pH 8.6, 37°C718914 2D-image
3.5-S-adenosyl-L-methionineHomo sapiens-Y20A mutant protein, pH 8.6, 37°C718914 2D-image

TURNOVER NUMBER [1/s] TURNOVER NUMBER MAXIMUM[1/s] SUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.031-NicotinamideHomo sapiens-Y20A mutant protein, pH 8.6, 37°C718914 2D-image
0.036-NicotinamideHomo sapiens-D197A mutant protein, pH 8.6, 37°C718914 2D-image
0.041-NicotinamideHomo sapiens-Y20F mutant protein, pH 8.6, 37°C718914 2D-image
0.077-NicotinamideHomo sapiens-0.43-0.38 mM, wild type protein, pH 8.6, 37°C718914 2D-image
0.083-NicotinamideHomo sapiens-K100A/E101A/E103A mutant protein, pH 8.6, 37°C718914 2D-image

kcat/KM VALUE [1/mMs-1]kcat/KM VALUE [1/mMs-1] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.003-NicotinamideHomo sapiens-D197A mutant protein, pH 8.6, 37°C71891414486
0.005-NicotinamideHomo sapiens-Y20A mutant protein, pH 8.6, 37°C71891414486
0.17-NicotinamideHomo sapiens-Y20F mutant protein, pH 8.6, 37°C71891414486
0.19-NicotinamideHomo sapiens-0.18-0.2 1/sec*mM, wild type protein, pH 8.6, 37°C71891414486
0.8-NicotinamideHomo sapiens-K100A/E101A/E103A mutant protein, pH 8.6, 37°C71891414486
0.009-S-adenosyl-L-methionineHomo sapiens-Y20A mutant protein, pH 8.6, 37°C71891416346
0.013-S-adenosyl-L-methionineHomo sapiens-D197A mutant protein, pH 8.6, 37°C71891416346
1.5-S-adenosyl-L-methionineHomo sapiens-Y20F mutant protein, pH 8.6, 37°C71891416346
17-S-adenosyl-L-methionineHomo sapiens-K100A/E101A/E103A mutant protein, pH 8.6, 37°C71891416346
39-S-adenosyl-L-methionineHomo sapiens-35-43 1/sec*mM, wild type protein, pH 8.6, 37°C71891416346

Ki VALUE [mM]Ki VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

IC50 VALUE [mM]IC50 VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.06-N1-methylnicotinamideHomo sapiens-IC50 0.06 mM for human protein, 0.03 mM for recombinant protein441255 2D-image

SPECIFIC ACTIVITY [µmol/min/mg] SPECIFIC ACTIVITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
0.0011-Homo sapiens-Y20A mutant protein, pH 8.6, 37°C718914
0.0042-Homo sapiens-D197A mutant protein, pH 8.6, 37°C718914
0.077-Homo sapiens-Y20F mutant protein, pH 8.6, 37°C718914
0.14-Homo sapiens-S201A mutant protein, pH 8.6, 37°C718914
0.15-Homo sapiens-wild type protein, pH 8.6, 37°C718914
0.18-Homo sapiens-K100A/E101A/E103A mutant protein, pH 8.6, 37°C718914
0.21-Homo sapiens-S213A mutant protein, pH 8.6, 37°C718914
additional information-Sus scrofa-assay441252
additional information-Homo sapiens-activity in different individuals, correlation with phenotypic differences441254
additional information-Mus musculus-activity in male animals of different inbred strains441258
additional information-Homo sapiens-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 intake686485
additional information-Homo sapiens-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 marker687897
additional information-Homo sapiens-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 patients689036
additional information-Homo sapiens-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 excluded690123

pH OPTIMUMpH MAXIMUMORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
7.2-Sus scrofa--441252
7.2-Mus musculus-assay at701990
7.4-Mus musculus--441258
8.6-Mus musculus-assay at, substrate 4-methoxybenzaldehyde706094

pH RANGEpH RANGE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
5.79.8Sus scrofa-about 50% of maximum activity at pH 5.7 and 9.8441252

TEMPERATURE OPTIMUMTEMPERATURE OPTIMUM MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
25-Sus scrofa-assay at441252
37-Mus musculus-assay at701990, 706094

TEMPERATURE RANGE TEMPERATURE MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

pI VALUEpI VALUE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

SOURCE TISSUE ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE SOURCE
253J laval cellHomo sapiens--706009Manually annotated by BRENDA team
3T3-L1 cellMus musculus-elevated enzyme activity during cell differentiation in adipose tissue701990Manually annotated by BRENDA team
adipocyteHomo sapiens--701990Manually annotated by BRENDA team
adipocyteMus musculus-NNMT expression profile, overview701990Manually annotated by BRENDA team
adipose tissueHomo sapiens--701990Manually annotated by BRENDA team
adipose tissueMus musculus-expression analysis, overview701990Manually annotated by BRENDA team
adipose tissueMus musculus--706094Manually annotated by BRENDA team
adrenal glandMus musculus--706094Manually annotated by BRENDA team
bladderHomo sapiens--441260, 706009Manually annotated by BRENDA team
bloodHomo sapiens--686485Manually annotated by BRENDA team
blood plasmaHomo sapiens--690123Manually annotated by BRENDA team
brainHomo sapiens-lumbar cerebrospinal fluid441259Manually annotated by BRENDA team
brainHomo sapiens--441262Manually annotated by BRENDA team
brainMus musculus--706094Manually annotated by BRENDA team
carcinoma cellHomo sapiens-papillary thyroid carcinoma cell662513Manually annotated by BRENDA team
carcinoma cellMus musculus--706094Manually annotated by BRENDA team
clear cell adenocarcinoma cellHomo sapiens--719232Manually annotated by BRENDA team
diaphragmHomo sapiens--718554Manually annotated by BRENDA team
embryonic fibroblastMus musculus--701990Manually annotated by BRENDA team
epitheliumHomo sapiens--703943Manually annotated by BRENDA team
heartMus musculus--706094Manually annotated by BRENDA team
HEK-293 cellHomo sapiens-no expression of NNMT in687897Manually annotated by BRENDA team
Hep-G2 cellHomo sapiens-NNMT expression increased on stimulation of the cells with interleukin 6, NNMT promoter activity dependent on the activation of Stat3687897Manually annotated by BRENDA team
HT-29 cellHomo sapiens-colon cancer cells with high and constitutive expression of NNMT687897Manually annotated by BRENDA team
HT-29 cellHomo sapiens--704775Manually annotated by BRENDA team
kidneyMus musculus--706094Manually annotated by BRENDA team
liverSus scrofa--441252Manually annotated by BRENDA team
liverHomo sapiens--441253, 441254, 441255, 701990Manually annotated by BRENDA team
liverMus musculus-expression analysis, overview701990Manually annotated by BRENDA team
liverMus musculus--441257, 441258, 441261, 704426Manually annotated by BRENDA team
liverRattus norvegicus--441251, 441257, 704426Manually annotated by BRENDA team
liverMus musculus-high enzyme activity. Enzyme upregulation in vascular inflammation and atherosclerosis, overview706094Manually annotated by BRENDA team
lungMus musculus--706094Manually annotated by BRENDA team
lung cancer cellHomo sapiens-serum levels of NNMT are signficantly higher in lung cancer patients, overview704775Manually annotated by BRENDA team
lymph nodeHomo sapiens--703943Manually annotated by BRENDA team
MCF-7 cellHomo sapiens-no expression of NNMT in687897Manually annotated by BRENDA team
MDA-MB-468 cellHomo sapiens-breast cancer cells with high and constitutive expression of NNMT687897Manually annotated by BRENDA team
oral mucosaHomo sapiens--689036, 703943Manually annotated by BRENDA team
oral squamous cell carcinoma cellHomo sapiens-high enzyme expression levels703943Manually annotated by BRENDA team
oral squamous cell carcinoma cell lineHomo sapiens--689036Manually annotated by BRENDA team
placentaMus musculus--706094Manually annotated by BRENDA team
quadricepsHomo sapiens--718554Manually annotated by BRENDA team
serumHomo sapiens-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, overview704775Manually annotated by BRENDA team
skeletal muscleMus musculus--706094Manually annotated by BRENDA team
SLT4 cellHomo sapiens--706009Manually annotated by BRENDA team
squamous cell carcinoma cellHomo sapiens--719027Manually annotated by BRENDA team
SW-480 cellHomo sapiens-colon cancer cells, NNMT expression increased on stimulation of the cells with interleukin 6687897Manually annotated by BRENDA team
urinary bladder cancer cellHomo sapiens--706009Manually annotated by BRENDA team
MDA-MB-468 cellHomo sapiens--704775Manually annotated by BRENDA team
additional informationHomo sapiens-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 cells662513Manually annotated by BRENDA team
additional informationHomo sapiens-enzyme expression levels in healthy oral mucosa and in oral squamous cell carcinomas, overview703943Manually annotated by BRENDA team

LOCALIZATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY GeneOntology No. LITERATURE SOURCE
cytoplasmHomo sapiens--5737703943Manually annotated by BRENDA team
cytosolHomo sapiens--5829441254Manually annotated by BRENDA team
cytosolMus musculus--5829441258, 706094Manually annotated by BRENDA team
microsomeMus musculus, Rattus norvegicus---704426Manually annotated by BRENDA team
solubleRattus norvegicus---441251Manually annotated by BRENDA team

PDBSCOPCATHORGANISM
2iip, downloadSCOP (2iip)CATH (2iip)Homo sapiens
3rod, downloadSCOP (3rod)CATH (3rod)Homo sapiens
2i62, downloadSCOP (2i62)CATH (2i62)Mus musculus

MOLECULAR WEIGHT MOLECULAR WEIGHT MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
2700030000Sus scrofa-gel filtration, SDS-PAGE441252

SUBUNITS ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
?Homo sapiens-x * 29000, SDS-PAGE, recombinant protein441255
?Homo sapiens-x * 30000, Western blot analysis719027
monomerSus scrofa-1 * 27000, SDS-PAGE441252

POSTTRANSLATIONAL MODIFICATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

Crystallization/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
His-tagged K100A/E101A/E103A mutant, sitting drop vapor diffusion method, PEG3350Homo sapiens-718914

pH STABILITYpH STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

TEMPERATURE STABILITYTEMPERATURE STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
No entries in this field

GENERAL STABILITYORGANISM UNIPROT ACCESSION NO.LITERATURE
glycerol stabilizesSus scrofa-441252
thiols required for stability during isolationSus scrofa-441252

ORGANIC SOLVENT ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
No entries in this field

OXIDATION STABILITY ORGANISM UNIPROT ACCESSION NO. LITERATURE
No entries in this field

STORAGE STABILITY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-20°C, 20% glycerol w/v, stable for 1 month, partially purified enzymeSus scrofa-441252
4°C, 20% glycerol w/v, pH 7.6, 30% loss of activity, purified enzymeSus scrofa-441252
4°C, 20% w/v glycerol, stable for 1 week, partially purified enzymeSus scrofa-441252

Purification/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
His-tagged K100A/E101A/E103A mutant, immobilized metal ion affinity chromatography (Ni2+), gel filtrationHomo sapiens-718914
recombinant GST-tagged enzyme from Escherichia coli strain JM109 by glutathione affinity chromatography and cleavage of the tag by thrombinHomo sapiens-704775
recombinant protein, gel fitrationHomo sapiens-687897
-Sus scrofa-441252

Cloned/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-Homo sapiens-441255
expressed in Escherichia coli BL21(DE3)Homo sapiens-718914
expressed in Escherichia coli, NNMT promoter region, promoter-luciferase reporter construct generated, pGL2 vectorHomo sapiens-687897
expressed in HEK293 cellsHomo sapiens-719232
gene NNMT, expression fo the GST-tagged enzyme in Escherichia coli strain JM109Homo sapiens-704775
gene NNMT, expression profiling in bladder cancer cell lines, overviewHomo sapiens-706009
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 CaliforniaHomo sapiens-702851
overexpressed in SH-SY5Y cell lineHomo sapiens-718784
-Mus musculus-441256

EXPRESSION ORGANISM UNIPROT ACCESSION NO. LITERATURE
the enzyme is induced by nicotinic acid in adipose tissueHomo sapiens-701990
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 deathHomo sapiens-718554
expression is significantly elevated in a number of cancers, expression is significantly increased in the brains of patients who have died of Parkinson’s diseaseHomo sapiens-718784
The activity levels are statistically significantly higher in oral squamous cell carcinoma than in adjacent normal oral mucosaHomo sapiens-719027
highly upregulated inclear cell renal carcinoma cellHomo sapiens-719232
the enzyme is induced by nicotinic acid in white adipose tissue, but chronic treatment does not cause hyperhomocysteinemia, overviewMus musculus-701990
progression of vascular inflammation and atherosclerosis is associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous 1-methylnicotinamide plasma levelsMus musculus-706094

ENGINEERINGORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
D197AHomo sapiens-active site residue718914
S201AHomo sapiens-active site residue718914
S213AHomo sapiens-active site residue718914
Y20AHomo sapiens-active site residue718914
Y20FHomo sapiens-active site residue718914
K100A/E101A/E103AHomo sapiens-His-tagged version, crystallization facilitated by reducing the entropy of three surface exposed residues718914
additional informationHomo sapiens-identification of 11 single nucleotide polymorphisms in the 5'-UTR and 3'-UTR, as well as in exon 1 and intron 2, overview702851
additional informationHomo sapiens-enzyme upregulation correlates with tumour differentiation in oral squamous cell carcinoma cells703943
additional informationHomo sapiens-siRNA knockdown of NNMT in SLT4 cells causes decreased cell proliferation in bladder cancer, the enzyme expression is associated with cell migration706009

Renatured/COMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
No entries in this field

APPLICATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
diagnosticsHomo sapiens-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 behaviour703943
diagnosticsHomo sapiens-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, overview704775
medicineHomo sapiens-enzyme protein level is significantly elevated in younger patients with Parkinson's disease441259
medicineHomo sapiens-possibly involved in response to radiation441260
medicineHomo sapiens-significantly increased levels of enzyme protein and activity in brain of patients with Parkinson´s disease, study on brain tissue distribution441262
medicineHomo sapiens-significantly higher enzyme activity in papillary thyroid carcinoma cell lines than in controls662513
medicineHomo sapiens-expression of enzyme is significantly higher in cerebellum of patients with idiopathic Parkinson's disease than in control groups662956
medicineHomo sapiens-epidemiologic study to analyze risk factors for complex congenital heart defects (CHDs) and multifactorial aetiology686485
pharmacologyHomo sapiens-molecular targets for cancer therapy and diagnosis687897
pharmacologyHomo sapiens-NNMT as potential biomarker and therapeutic target689036
pharmacologyHomo sapiens-biomarkers for cardiovascular risk factors690123
medicineMus musculus-enzyme activity correlates with tumor growth and morphological changes resembling apoptosis441257
medicineMus musculus-levels of hepatic enzyme activity are closely associated with the degree of weight loss, use as marker of cancer cachexia441261
medicineRattus norvegicus-enzyme activity correlates with tumor growth and morphological changes resembling apoptosis441257

DISEASETITLE OF PUBLICATIONLINK TO PUBMED
Adenocarcinoma- PubMed
Adenoma, Oxyphilic- PubMed
Carcinoma- PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed
Carcinoma, Hepatocellular- PubMed,  PubMed
Carcinoma, Non-Small-Cell Lung- PubMed
Carcinoma, Renal Cell- PubMed,  PubMed,  PubMed
Carcinoma, Squamous Cell- PubMed,  PubMed,  PubMed
Cell Transformation, Neoplastic- PubMed
Colorectal Neoplasms- PubMed,  PubMed
Glioma- PubMed
Heart Defects, Congenital- PubMed
Hepatitis- PubMed
Hyperhomocysteinemia- PubMed
Leukemia- PubMed
Lung Neoplasms- PubMed,  PubMed
Neoplasm Metastasis- PubMed
Neoplasms- PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed,  PubMed
Parkinson Disease- PubMed,  PubMed,  PubMed
Pulmonary Disease, Chronic Obstructive- PubMed
Spinal Dysraphism- PubMed
Stomach Neoplasms- PubMed,  PubMed
Stroke- PubMed
Thyroid Neoplasms- PubMed,  PubMed,  PubMed
Urinary Bladder Neoplasms- PubMed,  PubMed,  PubMed

REF. AUTHORS TITLE JOURNAL VOL. PAGES YEAR ORGANISM (UNIPROT ACCESSION NO.)LINK TO PUBMEDSOURCE
441251Cantoni, G.L.Methylation of nicotinamide with a soluble enzyme system from rat liverJ. Biol. Chem.189203-2171951Rattus norvegicus PubMed
441252Alston, T.A.; Abeles, R.H.Substrate specificity of nicotinamide methyltransferase isolated from porcine liverArch. Biochem. Biophys.260601-6081988Sus scrofa PubMed
441253Rini, J.; Szumlanski, C.; Guerciolini, R.; Weinshilboum, R.M.Human liver nicotinamide N-methyltransferase: ion-pairing radiochemical assay, biochemical properties and individual variationClin. Chim. Acta186359-3741990Homo sapiens PubMed
441254Smith, 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 cytosolBiochim. Biophys. Acta1442238-2441998Homo sapiens PubMed
441255Aksoy, S.; Szumlanski, C.L.; Weinshilboum, R.M.Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterizationJ. Biol. Chem.26914835-148401994Homo sapiens PubMed
441256Yan, L.; Otterness, D.M.; Kozak, C.A.; Weinshilboum, R.M.Mouse nicotinamide N-methyltransferase gene: molecular cloning, structural characterization, and chromosomal localizationDNA Cell Biol.17659-6671998Mus musculus PubMed
441257Fujimura, S.; Okamura, A.; Ohmura, Y.; Moriyama, Y.; Ohwada, H.; Horitsu, K.; Ohkubo, M.Nicotinamide methyltransferase activity and cell-death in the liver of the mouse bearing Ehrlich ascites tumorAdv. Exp. Med. Biol.398507-5111996Mus musculus, Rattus norvegicus PubMed
441258Scheller, T.; Orgacka, H.; Szumlanski, C.L.; Weinshilboum, R.M.Mouse liver nicotinamide N-methyltransferase pharmacogenetics: biochemical properties and variation in activity among inbred strainsPharmacogenetics643-531996Mus musculus, Mus musculus C57BL/6J PubMed
441259Aoyama, 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 diseaseNeurosci. Lett.29878-802001Homo sapiens PubMed
441260Kassem, 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 cancerInt. J. Cancer101454-4602002Homo sapiens PubMed
441261Okamura, A.; Ohmura, Y.; Islam, M.M.; Tagawa, M.; Horitsu, K.; Moriyama, Y.; Fujimura, S.Increased hepatic nicotinamide N-methyltransferase activity as a marker of cancer cachexia in mice bearing colon 26 adenocarcinomaJpn. J. Cancer Res.89649-6561998Mus musculus PubMed
441262Parsons, 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 brainJ. Neuropathol. Exp. Neurol.61111-1242002Homo sapiens PubMed
662513Xu, 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 cellsJ. Clin. Endocrinol. Metab.884990-49962003Homo sapiens PubMed
662956Parsons, 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 diseaseNeurosci. Lett.34213-162003Homo sapiens PubMed
686485van 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 nicotinamideEur. Heart J.291424-14312008Homo sapiens, Homo sapiens (P40261) PubMed
687897Tomida, M.; Ohtake, H.; Yokota, T.; Kobayashi, Y.; Kurosumi, M.Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cellsJ. Cancer Res. Clin. Oncol.134551-5592008Homo sapiens, Homo sapiens (P40261) PubMed
689036Sartini, 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 carcinomaMol. Med.13415-4212007Homo sapiens (P40261), Homo sapiens PubMed
690123Zhang, L.; Miyaki, K.; Araki, J.; Nakayama, T.; Muramatsu, M.The relation between nicotinamide N-methyltransferase gene polymorphism and plasma homocysteine concentration in healthy Japanese menThromb. Res.12155-582007Homo sapiens, Homo sapiens (P40261) PubMed
701990Riederer, M.; Erwa, W.; Zimmermann, R.; Frank, S.; Zechner, R.Adipose tissue as a source of nicotinamide N-methyltransferase and homocysteineAtherosclerosis204412-4172009Homo sapiens, Mus musculus PubMed
702851Lu, 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 bifidaBirth Defects Res. Part A Clin. Mol. Teratol.82670-6752008Homo sapiens PubMed
703943Emanuelli, 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 carcinomaHistol. Histopathol.2515-202010Homo sapiens PubMed
704426Dostalek, M.; Hardy, K.D.; Milne, G.L.; Morrow, J.D.; Chen, C.; Gonzalez, F.J.; Gu, J.; Ding, X.; Johnson, D.A.; Johnson, J.A.; Martin, M.V.; Guengerich, F.P.Development of oxidative stress by cytochrome P450 induction in rodents is selective for barbiturates and related to loss of pyridine nucleotide-dependent protective systemsJ. Biol. Chem.28317147-171572008Mus musculus, Rattus norvegicus PubMed
704775Tomida, M.; Mikami, I.; Takeuchi, S.; Nishimura, H.; Akiyama, H.Serum levels of nicotinamide N-methyltransferase in patients with lung cancerJ. Cancer Res. Clin. Oncol.1351223-12292009Homo sapiens PubMed
706009Wu, 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 migrationOncogene276679-66892008Homo sapiens PubMed
706094Mateuszuk, L.; Khomich, T.I.; Slominska, E.; Gajda, M.; Wojcik, L.; Lomnicka, M.; Gwozdz, P.; Chlopicki, S.Activation of nicotinamide N-methyltrasferase and increased formation of 1-methylnicotinamide (MNA) in atherosclerosisPharmacol. Rep.6176-852009Mus musculus, Mus musculus C57BL/6J PubMed
718554Kim, 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 diseaseAm. J. Respir. Crit. Care Med.181797-8052010Homo sapiens PubMed
718784Parsons, 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 inhibitorsBiochem. J.436145-1552011Homo sapiens PubMed
718914Peng, Y.; Sartini, D.; Pozzi, V.; Wilk, D.; Emanuelli, M.; Yee, V.C.Structural basis of substrate recognition in human nicotinamide N-methyltransferaseBiochemistry507800-78082011Homo sapiens, Homo sapiens (P40261) PubMed
719027Sartini, 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 diseaseBiol. Chem.393505-5112012Homo sapiens PubMed
719232Tang, 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 cellsCarcinogenesis32138-1452011Homo sapiens PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 2.1.1.1)
ExplorEnz
ExPASy
KEGG
MetaCyc
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
SYSTERS
Protein Mutant Database
InterPro (database of protein families, domains and functional sites)