Information on EC 2.1.1.37 - DNA (cytosine-5-)-methyltransferase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.1.1.37
-
RECOMMENDED NAME
GeneOntology No.
DNA (cytosine-5-)-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + DNA containing cytosine = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
methionine metabolism
-
-
Cysteine and methionine metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:DNA (cytosine-5-)-methyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9037-42-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
both DNMT3A and DNMT3B are involved in de novo DNA methylation
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
DNA + S-adenosyl-L-methionine
DNA containing 5-methylcytosine + S-adenosyl-L-homocysteine
show the reaction diagram
S-adenosyl-L-methionine + DNA
S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine
show the reaction diagram
S-adenosyl-L-methionine + poly(dI-dC)/poly(dI-dC)
S-adenosyl-L-homocysteine + poly(dI-dC)/poly(dI-dC) containing 5-methylcytosine
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
DNA + S-adenosyl-L-methionine
DNA containing 5-methylcytosine + S-adenosyl-L-homocysteine
show the reaction diagram
S-adenosyl-L-methionine + DNA
S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epigallocatechin-3-gallate
-
competitive, the inhibitor can form hydrogen bonds with Pro1223, Glu1265, Cys1225, Ser1229 and Arg1309. Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. (-)-Epigallocatechin-3-gallate can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells
(N4-fluoroacetyl-5-azacytidine)
-
efficient inhibitor of DNA methylation in human tumor cell lines
2'-dC
-
binding modelling, overview
2'-deoxy-5-aza-cytidine
-
binding modelling, overview
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
-
;
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
-
;
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
-
;
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-methoxy-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
-
-
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-methyl-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
-
;
2-amino-4-[([(2S,3S,4R,5R)-5-[6-amino-2-(methylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-yl]methyl)sulfanyl]butanoic acid
-
;
2-pyrimidinone
-
forms a part of inhibitor 1,2-dihydropyrimidin-2-one-5-methylene-(methylsulfonium)-adenosyl, bindng structure and mechanism, overview
5-aza-2'-deoxycytidine
-
-
5-aza-cytosine
-
-
5-azacytidine
-
binding modelling, overview
5-fluorocytosine
-
-
6-Thioguanine
-
incorporation of 6-thioguanine perturbs cytosine methylation at the CpG dinucleotide site by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo. Presence of 6-thioguanine at the unmethylated CpG site abolished almost completely the methylation of its 5' adjacent cytosine by DNMT1
curcumin
-
-
decitabine
-
binding modelling, overview
EDTA
-
above 10 mM
hydralazine
iodoacetamide
-
-
NSC 106084
-
inhibition of Dnmt1
NSC 137546
-
inhibition of Dnmt1
NSC 138419
-
inhibition of Dnmt1
NSC 14778
-
inhibition of Dnmt1; inhibition of Dnmt3b
NSC 158324
-
inhibition of Dnmt1
NSC 319745
-
inhibition of Dnmt1
NSC 348926
-
slight inhibition of Dnmt1
NSC 408488
-
inhibition of Dnmt1
NSC 54162
-
inhibition of Dnmt1
NSC 56071
-
inhibition of Dnmt1
NSC 57893
-
inhibition of Dnmt1
NSC 622444
-
inhibition of Dnmt1
poly[d(G-5-azacytidine)]
-
-
-
procainamide
-
binding modelling, overview
procaine
-
binding modelling, overview
retinoblastoma gene product
-
a negative regulator of DNA methylation, binds to the allosteric site of hDNMT1 and inhibits methylation, it may regulate methylation spreading
-
RG108
-
slight inhibition of Dnmt1
S-(1-deazaadenosyl)-L-homocysteine
-
;
S-(3-deazaadenosyl)-L-homocysteine
-
;
S-(8-azaadenosyl)-L-homocysteine
-
;
S-(N-(2-biphenyl-4-ylethyl)-2-chloroadenosyl)-L-homocysteine
-
;
S-(N-(2-biphenyl-4-ylethyl)adenosyl)-L-homocysteine
-
;
S-(N-(3,5-dimethoxybenzyl)adenosyl)-L-homocysteine
-
;
S-(N-(pyridin-4-ylmethyl)adenosyl)-L-homocysteine
-
;
S-(N-benzyladenosyl)-L-homocysteine
-
;
S-(N-phenyladenosyl)-L-homocysteine
-
;
S-(N-phenylethyladenosyl)-L-homocysteine
-
;
S-(N-phenylpropyladenosyl)-L-homocysteine
-
;
S-adenosyl-L-homocysteine
S-inosinylhomocysteine
-
;
S-nebularinehomocysteine
-
;
S-Tubercidinylhomocysteine
-
;
[1,2-dihydropyrimidin-2-one]-5-methylene-(methylsulfonium)-adenosyl
-
with 2-pyrimidinone ring
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dimethyl sulfoxide
-
stimulates
methylated DNA
-
stimulated methylation spreading on unmethylated CpG sequences for full-length and the mutant lacking 121 N-terminal amino acids equally well. No stimulation of N-terminal deletion mutants lacking 501, 540, or 580 amino acids from the N-terminus
-
NSC 319745
-
activation of Dnmt3b
NSC 345763
-
slight activation of Dnmt1
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0008
(CGG*CCG)12
-
-
-
0.0001
(CGG*CCG)73
-
-
-
0.041 - 0.092
DNA
0.086
Micrococcus luteus DNA
-
-
-
0.52 - 1.4
mononucleosomal DNA
-
0.0077
native Micrococcus lysodeikticus DNA
-
-
-
0.015
P815 DNA
-
-
-
0.0005 - 0.0007
poly(dI-dC)*poly(dI-dC)
-
0.0005 - 0.00082
poly-(dI-dC)/poly(dI-dC)
-
0.02
pRW3602, linear
-
-
-
0.003
pRW3602, relaxed circular
-
-
-
0.023
pRW3602, supercoiled
-
-
-
0.00325 - 0.014
S-adenosyl-L-methionine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00055
(CGG*CCG)73
-
-
-
0.00305
(CGG*CGG)12
-
-
-
0.145
poly(dI-dC)*poly(dI-dC)
-
-
-
0.0511
poly(dI-dC)poly(dI-dC)
-
-
-
0.013 - 0.058
poly-(dI-dC)/poly(dI-dC)
-
0.00167
pRW3602, linear
-
-
-
0.00055
pRW3602, relaxed circular
-
-
-
0.00278
pRW3602, supercoiled
-
-
-
0.013 - 0.058
S-adenosyl-L-methionine
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00689
(-)-epigallocatechin-3-gallate
-
substrate: poly(dI-dC)/poly(dI-dC)
additional information
additional information
-
inhibition by mechanism-based inhibitors and kinetics, detailed overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.045
1-deaza-S-adenosyl-L-homocysteine
Homo sapiens;
-
isoform DNMT1, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.0029 - 0.0572
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
0.0025 - 0.0068
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
0.021 - 0.256
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
0.075
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-methoxy-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
Homo sapiens;
-
isoform DNMT1, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.001 - 0.006
2-amino-4-([[(2S,3S,4R,5R)-5-(6-amino-2-methyl-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl]sulfanyl)butanoic acid
0.216 - 0.5
2-amino-4-[([(2S,3S,4R,5R)-5-[6-amino-2-(methylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-yl]methyl)sulfanyl]butanoic acid
0.045
3-deaza-S-adenosyl-L-homocysteine
Homo sapiens;
-
isoform DNMT1, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.008
8-aza-S-adenosyl-L-homocysteine
Homo sapiens;
-
isoform DNMT1, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.017 - 0.092
NSC 14778
0.045
S-(1-deazaadenosyl)-L-homocysteine
Homo sapiens;
-
isoform DNMT3b2, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.0068
S-(3-deazaadenosyl)-L-homocysteine
Homo sapiens;
-
isoform DNMT3b2, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.003
S-(8-azaadenosyl)-L-homocysteine
Homo sapiens;
-
isoform DNMT3b2, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.0067 - 0.029
S-(N-(2-biphenyl-4-ylethyl)-2-chloroadenosyl)-L-homocysteine
0.0006 - 0.0054
S-(N-(2-biphenyl-4-ylethyl)adenosyl)-L-homocysteine
0.0009 - 0.018
S-(N-(3,5-dimethoxybenzyl)adenosyl)-L-homocysteine
0.0036 - 0.022
S-(N-(pyridin-4-ylmethyl)adenosyl)-L-homocysteine
0.001 - 0.061
S-(N-benzyladenosyl)-L-homocysteine
0.002 - 0.154
S-(N-phenyladenosyl)-L-homocysteine
0.002 - 0.027
S-(N-phenylethyladenosyl)-L-homocysteine
0.0006 - 0.0074
S-(N-phenylpropyladenosyl)-L-homocysteine
0.0003 - 0.002
S-adenosyl-L-homocysteine
1
S-inosinylhomocysteine
Homo sapiens;
-
IC50 above 1 mM, isoform DNMT1, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C; IC50 above 1 mM, isoform DNMT3b2, in 50 mM Tris-HCl pH 7.6, 5% (v/v) glycerol, 1 mM EDTA, 0.1 mg/ml bovine serum albumin, 1 mM dithiothreitol, at 37C
0.028 - 0.3
S-nebularinehomocysteine
0.0003 - 0.0015
S-Tubercidinylhomocysteine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000013
-
-
0.0000166
-
-
0.00115
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
-
-
7.8
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
additional information
-
assay carried out at room temperature
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
cell line SKGT4
Manually annotated by BRENDA team
-
colon cancer
Manually annotated by BRENDA team
-
esophageal cancer
Manually annotated by BRENDA team
-
neoplastically-transformed; neoplastically-transformed; neoplastically-transformed
Manually annotated by BRENDA team
-
prostate cancer
Manually annotated by BRENDA team
-
a human colorectal carcinoma cell line
Manually annotated by BRENDA team
-
immunohistochemical analysis
Manually annotated by BRENDA team
-
pleomorphic adenoma, adenoid cystic carcinoma, mucoepidermoid carcinoma and polymorphous low-grade adenocarcinoma of lower lip, buccal mucosa, mandible, tongue, floor, or palate. Positive nuclear and cytoplasmic labeling for DNMT1 occurs in all samples, positive nuclear labeling for DNMT3a occurs only in few neoplasms: 1 pleomorphic adenoma, 2 adenoid cystic carcinoma and 1 mucoepidermoid cases, immunohistochemical
Manually annotated by BRENDA team
-
cell lines TE-3 and TE-12
Manually annotated by BRENDA team
-
CD4+, ranscript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus, an autoimmune disease with CD4+ T cells with hypomethylated DNA. It is possible that patients are reacting indirectly to an underlying DNA hypomethylation status by increasing the mRNA levels of DNA methyltransferases when the disease is definitely active, overview
Manually annotated by BRENDA team
-
B lymphoblast cell line containing wild-type p53. The interaction between p53 and DNMT1 controls DNA methylation of the p16ink4A promoter that consequently reduces the level of the p16ink4A
Manually annotated by BRENDA team
-
B lymphoblast cell line with mutant p53. Mutant p53 loses its ability to suppress DNMT1 expression, and thus enhances methylation levels of the p16ink4A promoter and subsequently down-regulates p16ink4A protein
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120000
-
glycerol density gradient sedimentation
135000
-
glycerol gradient centrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
IL-6 enhances the nuclear translocation of DNA cytosine-5-methyltransferase 1 (DNMT1) via phosphorylation of the nuclear localization sequence by the AKT kinase
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
rather unstable
65
-
20 min, inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, stable for at least several weeks
-
-80C, 30% glycerol, activity decays at a rate of about 15% in 2 weeks
-
-80C, little loss of activity after 4 weeks, significant loss of activity after 6 weeks
-
-80C, stable for at least 3 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNMT3B copurifies with several components of the condensin complex and KIF4A
-
Hitrap SP-Sepharose column chromatography; Q-Sepharose column chromatography and Hitrap heparin column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNMT1 and DNMT3a, expression analysis of the isozymes in salivary gland neoplasmata
-
DNMT1, overexpression of HA-tagged CXXC deletion DNMT1 mutant, expression of wild-type and deletion mutant enzymes in COS-7 cells and Escherichia coli, CXXC deleted DNMT1, mutant DNMT1DELTACXXC, is localized on replication foci
-
expressed in High Five insect cells; expressed in High Five insect cells
-
expression in Sf9 cells
-
expression of the enzyme by using a protein splicing fusion partner in a baculovirus expression vector
-
transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus, phenotype, overview
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C667G
-
zinc-finger-domain point mutation in the CXXC motif abolishes unmethylated DNA binding activity
C667G/C670G
-
zinc-finger-domain point mutation in the CXXC motif abolishes unmethylated DNA binding activity
C670G
-
zinc-finger-domain point mutation in the CXXC motif abolishes unmethylated DNA binding activity
DELAT1-501
-
to accelerate the rate of DNMT1 with the hemimethylated substrate, the 501 amino acids at the N terminus are deleted. Truncated DNMT1 exhibits a 4fold increased kcat/Km as compared with the full-length enzyme and does not require allosteric activation by hemimethylated DNA
DELTA1-501
-
no stimulation by methylated DNA
DELTA1-540
-
no stimulation by methylated DNA
DELTA1-580
-
no stimulation by methylated DNA
H286A/R287A
-
allosteric activation by methylated DNA is reduced, 6.5 fold decrease in the ratio turnover number/Km-value compared to wild-type enzyme
K284A/K285A
-
allosteric activation by methylated DNA is reduced, 1.7fold decrease in the ratio turnover number/Km-value compared to wild-type enzyme
additional information
-
construction of zinc-finger-domain point mutant and deletion mutant DNMT1 clones, CXXC deleted DNMT1, i.e. mutant DNMT1DELTACXXC and DNMT1 lacking the first 580 amino acids, i.e. DNMT1DELTA580. The latter prefers binding to unmethylated DNA instead of hemimethylated or fully methylated DNA like the wild-type enzyme. Deletion of CXXC domain in DNMT1 does not affect replication foci occupancy during DNA replication. A permanent cell line with DNMT1DELTACXXC displays partial loss of genomic methylation on rDNA loci, despite the presence of endogenous wild-type enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
-
using a truncated and highly active form of human DNMT1 and a designed hemimethylated DNA substrate, a robust, efficient, and economical fluorescence assay is developped suitable for in vitro high-throughput screening of DNMT1
drug development
-
Dnmt inhibition is a promising strategy for the treatment of various developmental and proliferative diseases, particularly cancers