Information on EC 3.2.2.27 - uracil-DNA glycosylase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.2.2.27
-
RECOMMENDED NAME
GeneOntology No.
uracil-DNA glycosylase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Hydrolyses single-stranded DNA or mismatched double-stranded DNA and polynucleotides, releasing free uracil
show the reaction diagram
SYSTEMATIC NAME
IUBMB Comments
uracil-DNA deoxyribohydrolase (uracil-releasing)
Uracil-DNA glycosylases are widespread enzymes that are found in all living organisms. EC 3.2.2.27 and double-stranded uracil-DNA glycosylase (EC 3.2.2.28) form a central part of the DNA-repair machinery since they initiate the DNA base-excision repair pathway by hydrolysing the N-glycosidic bond between uracil and the deoxyribose sugar thereby catalysing the removal of mis-incorporated uracil from DNA.
CAS REGISTRY NUMBER
COMMENTARY hide
59088-21-0
cf. EC 3.2.2.28
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain HJ171
UniProt
Manually annotated by BRENDA team
strain HJ171
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
strain Bristol N2
-
-
Manually annotated by BRENDA team
strain AR39
UniProt
Manually annotated by BRENDA team
strain AR39
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
SMUG1; strain GS-15, SMUG1
UniProt
Manually annotated by BRENDA team
SMUG1; strain GS-15, SMUG1
UniProt
Manually annotated by BRENDA team
HCMV
-
-
Manually annotated by BRENDA team
strain Zaire 1996, gene E4R
UniProt
Manually annotated by BRENDA team
strain Zaire 1996, gene E4R
UniProt
Manually annotated by BRENDA team
strain SN2
UniProt
Manually annotated by BRENDA team
genes Rv2464c and Rv3297, encoding MtuNei1 and MtuNei2
-
-
Manually annotated by BRENDA team
genes Rv2464c and Rv3297, encoding MtuNei1 and MtuNei2
-
-
Manually annotated by BRENDA team
strain GMD509
Uniprot
Manually annotated by BRENDA team
strain GMD509
Uniprot
Manually annotated by BRENDA team
strain HJ147
UniProt
Manually annotated by BRENDA team
strain HJ147
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
show the reaction diagram
3,N4-ethenocytosine-mismatched single-stranded DNA + H2O
3,N4-ethenocytosine + single-stranded DNA with abasic site
show the reaction diagram
-
-
-
-
?
5-fluorouracil-mismatched double-stranded DNA + H2O
5-fluorouracil + double-stranded DNA with abasic site
show the reaction diagram
5-formyluracil-mismatched double-stranded DNA + H2O
5-formyluracil + double-stranded DNA with abasic site
show the reaction diagram
5-formyluracil-mismatched single-stranded DNA + H2O
5-formyluracil + single-stranded DNA with abasic site
show the reaction diagram
-
-
-
?
5-hydroxymethyl-uracil-mismatched double-stranded DNA + H2O
5-hydroxymethyl-uracil + double-stranded DNA with abasic site
show the reaction diagram
the preferred substrate of UDGb is hydroxymethyl-uracil mispaired with guanine, followed by G-U and A-U, UDGb is active on ethenocytosine-G and 5-fluorouracil-G pairs, and UDGb also performs processing of uracil and hydroxymethyluracil from single-stranded DNA, but highly prefers double-stranded DNA substrates
-
-
?
5-hydroxymethyl-uracil-mismatched single-stranded DNA + H2O
5-hydroxymethyl-uracil + single-stranded DNA with abasic site
show the reaction diagram
the preferred substrate of UDGb is hydroxymethyl-uracil mispaired with guanine, followed by G-U and A-U, UDGb is active on ethenocytosine-G and 5-fluorouracil-G pairs, and UDGb also performs processing of uracil and hydroxymethyluracil from single-stranded DNA, but highly prefers double-stranded DNA substrates
-
-
?
5-hydroxymethyluracil-mismatched double-stranded DNA + H2O
5-hydroxymethyluracil + double-stranded DNA with abasic site
show the reaction diagram
5-hydroxymethyluracil-mismatched single-stranded DNA + H2O
5-hydroxymethyluracil + single-stranded DNA with abasic site
show the reaction diagram
5-hydroxyuracil-mismatched double-stranded DNA + H2O
5-hydroxyuracil + double-stranded DNA with abasic site
show the reaction diagram
5-hydroxyuracil-mismatched single-stranded DNA + H2O
5-hydroxyuracil + single-stranded DNA with abasic site
show the reaction diagram
5-methylcytosine-mismatched double-stranded DNA + H2O
5-methylcytosine + double-stranded DNA with abasic site
show the reaction diagram
-
-
-
?
8-oxoguanine-mismatched double-stranded DNA + H2O
8-oxoguanine + double-stranded DNA with abasic site
show the reaction diagram
8-oxoguanine-mismatched single-stranded DNA + H2O
8-oxoguanine + single-stranded DNA with abasic site
show the reaction diagram
dUMP DNA + H2O
dUMP + DNA
show the reaction diagram
ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
show the reaction diagram
UDGb is active on ethenocytosine-G
-
-
?
fU-containing 10 nucleotide DNA sequence 5'-GGAGAfUCTCC-3' with opposing C, T, A, or G + H2O
?
show the reaction diagram
-
-
-
-
?
hypoxanthine-mismatched double-stranded DNA + H2O
hypoxanthine + double-stranded DNA with abasic site
show the reaction diagram
the UDGb from Pyrobaculum aerophilum, belonging to a fifth UDG family, catalyzes the removal of uracil as well as of hypoxanthine from DNA by cleavage of e.g. hypoxanthine-thymine pairs, possessing an active site, that lacks the polar amino acid residue, see also EC 3.2.2.15, substrate specificity and active site structure, overview
-
-
?
thymine-mismatched double-stranded DNA + H2O
thymine + double-stranded DNA with abasic site
show the reaction diagram
uracil-containing double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
show the reaction diagram
-
the rate of catalytic turnover (kcat), is higher with double-stranded substrate compared to single-stranded substrate (20/min versus 11/min), respectively. Catalytic efficiency is 3.5fold higher for single-stranded DNA due to the smaller Km-value
-
-
?
uracil-containing single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
show the reaction diagram
-
the rate of catalytic turnover (kcat), is higher with double-stranded substrate compared to single-stranded substrate (20/min versus 11/min), respectively. Catalytic efficiency is 3.5fold higher for single-stranded DNA due to the smaller Km-value
-
-
?
uracil-mismatched DNA + H2O
uracil + DNA with abasic site
show the reaction diagram
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
show the reaction diagram
uracil-mismatched double-stranded oligonucleotide + H2O
uracil + double-stranded oligonucleotide with abasic site
show the reaction diagram
uracil-mismatched single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
show the reaction diagram
uracil-mismatched single-stranded oligonucleotide + H2O
uracil + single-stranded oligonucleotide with abasic site
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
3,N4-ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
show the reaction diagram
3,N4-ethenocytosine-mismatched single-stranded DNA + H2O
3,N4-ethenocytosine + single-stranded DNA with abasic site
show the reaction diagram
-
-
-
-
?
5-fluorouracil-mismatched double-stranded DNA + H2O
5-fluorouracil + double-stranded DNA with abasic site
show the reaction diagram
5-formyluracil-mismatched double-stranded DNA + H2O
5-formyluracil + double-stranded DNA with abasic site
show the reaction diagram
5-formyluracil-mismatched single-stranded DNA + H2O
5-formyluracil + single-stranded DNA with abasic site
show the reaction diagram
Q53HV7
-
-
-
?
5-hydroxymethyl-uracil-mismatched double-stranded DNA + H2O
5-hydroxymethyl-uracil + double-stranded DNA with abasic site
show the reaction diagram
Q8ZXE0, Q8ZYS2
the preferred substrate of UDGb is hydroxymethyl-uracil mispaired with guanine, followed by G-U and A-U, UDGb is active on ethenocytosine-G and 5-fluorouracil-G pairs, and UDGb also performs processing of uracil and hydroxymethyluracil from single-stranded DNA, but highly prefers double-stranded DNA substrates
-
-
?
5-hydroxymethyl-uracil-mismatched single-stranded DNA + H2O
5-hydroxymethyl-uracil + single-stranded DNA with abasic site
show the reaction diagram
Q8ZXE0, Q8ZYS2
the preferred substrate of UDGb is hydroxymethyl-uracil mispaired with guanine, followed by G-U and A-U, UDGb is active on ethenocytosine-G and 5-fluorouracil-G pairs, and UDGb also performs processing of uracil and hydroxymethyluracil from single-stranded DNA, but highly prefers double-stranded DNA substrates
-
-
?
5-hydroxymethyluracil-mismatched double-stranded DNA + H2O
5-hydroxymethyluracil + double-stranded DNA with abasic site
show the reaction diagram
-
-
-
-
?
5-hydroxymethyluracil-mismatched single-stranded DNA + H2O
5-hydroxymethyluracil + single-stranded DNA with abasic site
show the reaction diagram
5-hydroxyuracil-mismatched double-stranded DNA + H2O
5-hydroxyuracil + double-stranded DNA with abasic site
show the reaction diagram
-
-
-
-
?
5-hydroxyuracil-mismatched single-stranded DNA + H2O
5-hydroxyuracil + single-stranded DNA with abasic site
show the reaction diagram
5-methylcytosine-mismatched double-stranded DNA + H2O
5-methylcytosine + double-stranded DNA with abasic site
show the reaction diagram
Q9V4D8
-
-
-
?
ethenocytosine-mismatched double-stranded DNA + H2O
3,N4-ethenocytosine + double-stranded DNA with abasic site
show the reaction diagram
Q8ZXE0, Q8ZYS2
UDGb is active on ethenocytosine-G
-
-
?
hypoxanthine-mismatched double-stranded DNA + H2O
hypoxanthine + double-stranded DNA with abasic site
show the reaction diagram
Q8ZXE0, Q8ZYS2
the UDGb from Pyrobaculum aerophilum, belonging to a fifth UDG family, catalyzes the removal of uracil as well as of hypoxanthine from DNA by cleavage of e.g. hypoxanthine-thymine pairs, possessing an active site, that lacks the polar amino acid residue, see also EC 3.2.2.15, substrate specificity and active site structure, overview
-
-
?
thymine-mismatched double-stranded DNA + H2O
thymine + double-stranded DNA with abasic site
show the reaction diagram
Q9V4D8
-
-
-
?
uracil-mismatched DNA + H2O
uracil + DNA with abasic site
show the reaction diagram
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
show the reaction diagram
uracil-mismatched single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
Q7WYV4
the UDG possesses a [4Fe-4S] cluster, distant from the active site, which interacts with loop structures and is unessential to the activity but necessary for stabilizing the loop structures
Iron-sulfur cluster
-
the [4Fe-4S]-binding cluster is important for the DNA binding and catalytic activity
KCl
activates optimal at 25 mM, recombinant UDG
Mg2+
-
strongly stimulating at physiological concentrations; strongly stimulating at physiological concentrations, 10fold for Ung2 at 10 mM. Mg2+ increases the preference of hUNG2 toward uracil in ssDNA nearly 40fold
additional information
divalent cations are not required for the activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1'-cyano-2'-deoxyuridine
4(6)-aminouracil
-
4-hydroxymercuribenzoate
-
1 mM, 94% inhibition
4-methylindole
-
4-methylindole is an adenine isostere incapable of hydrogen bonding, and its pair with Thy is inherently prone to spontaneous opening, structure of hUNGin a complex with DNA containing a Thy:4-methylindole pair, a DNA mimic, overview
5-Azauracil
strong inhibition
5-halogenated uracil analogues
-
-
Alba protein
-
a small basic chromatin protein, repression of UDG1 activity
-
apurinic/apyrimidinic site
-
the enzyme is product-inhibited by both uracil and apurinic/apyrimidinic sites
-
Bacillus subtilis Ung inhibitor
-
-
-
DNA containing 1'-cyano-2'-deoxyuridine
-
G-U dsDNA
Q7WYV4
product inhibition
-
MgCl2
NaCl
10fold inhibition at 10 mM, the viral enzyme is strongly inhibited by physiological concentrations of NaCl and MgCl2
Sso7d protein
-
a small basic chromatin protein, slight repression of UDG1 activity
-
UGD inhibition protein from Bacillus subtilis
phage PBS-2-encoded uracil DNA glycosylase inhibitor, UDG forms a dissociable, activity-reduced complex with the inhibitor protein Ugi in 1:1 molar stoichiometry
-
UGI inhibitor
-
Ugi peptide
-
-
-
UNG inhibitor Ugi
-
from the Bacillus subtilis bacteriophage PBS2
-
Uracil
uracil-DNA glycosylase inhibitor protein
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
APE1
-
has a strong stimulatory effect on hSMUG1 against dsU, apparently because of enhanced dissociation of hSMUG1 from AP sites in dsDNA. AP sites inhibit hSMUG1
-
Proliferating cell nuclear antigen
the enzyme is stimulated by wild-type Pyrococcus furiosus proliferating cell nuclear antigen but not by a monomeric mutant of the Pyrococcus furiosus proliferating cell nuclear antigen in vitro
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0046
5-hydroxymethyluracil-mismatched double-stranded DNA with U-A mismatch
-
pH 7.5, 30°C, recombinant hSMUG1
-
0.0027
5-hydroxymethyluracil-mismatched double-stranded DNA with U-G mismatch
-
pH 7.5, 30°C, recombinant hSMUG1
-
0.0038
5-hydroxymethyluracil-mismatched single-stranded DNA
-
pH 7.5, 30°C, recombinant hSMUG1
-
0.0005
dsDNA-uracil
-
pH 7.5, 37°C
-
0.0004 - 0.0028
dUMP DNA
-
0.0005
ssDNA-uracil
-
pH 7.5, 37°C
-
0.000054 - 0.00007
uracil-containing double-stranded DNA
-
0.000008 - 0.000011
uracil-containing single-stranded DNA
-
0.000015 - 0.256
uracil-mismatched double-stranded DNA
-
0.0007 - 0.004
uracil-mismatched double-stranded DNA with U-A mismatch
-
0.0000022 - 0.0013
uracil-mismatched double-stranded DNA with U-G mismatch
-
0.0005 - 0.0083
uracil-mismatched single-stranded DNA
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.015
5-hydroxymethyluracil-mismatched double-stranded DNA with U-A mismatch
Homo sapiens
-
pH 7.5, 30°C, recombinant hSMUG1
-
0.04
5-hydroxymethyluracil-mismatched double-stranded DNA with U-G mismatch
Homo sapiens
-
pH 7.5, 30°C, recombinant hSMUG1
-
0.098
5-hydroxymethyluracil-mismatched single-stranded DNA
Homo sapiens
-
pH 7.5, 30°C, recombinant hSMUG1
-
0.55
dsDNA-uracil
Archaeoglobus fulgidus
-
pH 7.5, 37°C
-
154 - 821
dUMP DNA
-
0.0002 - 0.0003
fU-containing 10 nucleotide DNA sequence 5'-GGAGAfUCTCC-3' with opposing C, T, A, or G
Homo sapiens
-
pH 7.5
-
0.917
ssDNA-uracil
Archaeoglobus fulgidus
-
pH 7.5, 37°C
-
0.33 - 0.85
uracil-containing double-stranded DNA
-
0.18 - 0.27
uracil-containing single-stranded DNA
-
0.0175 - 15.58
uracil-mismatched double-stranded DNA
-
5.9
uracil-mismatched double-stranded DNA with A/U mismatch
Chlamydia pneumoniae
Q9Z7D3
pH 8.0, 37°C, recombinant wild-type enzyme
-
0.052 - 2.28
uracil-mismatched double-stranded DNA with U-A mismatch
-
0.0014 - 5.57
uracil-mismatched double-stranded DNA with U-G mismatch
-
0.083 - 46.1
uracil-mismatched single-stranded DNA
-
additional information
additional information
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4714 - 15740
uracil-containing double-stranded DNA
19750
16360 - 33750
uracil-containing single-stranded DNA
19751
5.5 - 1840
uracil-mismatched double-stranded DNA
1958
154.9 - 36000
uracil-mismatched single-stranded DNA
5425
additional information
additional information
Archaeoglobus fulgidus
-
higher catalytic efficiency (kcat/Km) towards single-stranded DNA due to the smaller Km value
2
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0046 - 0.0138
1'-cyano-2'-deoxyuridine
0.1315 - 0.2457
DNA containing 1'-cyano-2'-deoxyuridine
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000088
G-U dsDNA
Thermus thermophilus
Q7WYV4
pH 7.5, 37°C, family 4 UDG
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.009
-
pH 7.5, 80°C
0.01
purified recombinant MUG
0.82
-
pH 7.0, 80°C
1.15
-
pH 6.5, 80°C
1.2
-
pH 6.5, 90°C
1.23
-
pH 6.5, 100°C
1.33
-
pH 7.0, 100°C
1.67
-
pH 7.0, 90°C
1.78
-
pH 5.8, 100°C
2.67
-
pH 5.8, 80°C
2.9
-
pH 5.8, 90°C
9.05
-
pH 6.0, 100°C
11.1
-
pH 6.0, 80°C
11.9
-
pH 6.0, 90°C
13.1
-
pH 5.8, 90°C
13.7
-
pH 5.8, 100°C
14.7
-
pH 5.8, 80°C
379
-
purified enzyme
6697
purified recombinant UDG
14000
purified native enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2
-
native enzyme. Adaption to the neutral conditions in the Archaeoglobus fulgidus cytoplasm might be due to covalent modifications or accessory factors, or due to a different folding when expressed in the native host
7 - 8
-
assay at
7 - 9
-
-
7 - 7.5
-
hSMUG1; hUNG2
7 - 7.5
recombinant UDG
7.8
-
assay at
8.5 - 9
second optimum
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 7
-
pH 4.0: about 25% of maximal activity, pH 7.0: about 25% of maximal activity
5.3 - 10.4
-
-
6 - 9
recombinant UDG, inactive at pH 5.5, pH profile
7 - 10
-
inactive at pH 10.0
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 25
recombinant UDG
30
-
assay at; assay at
30 - 37
-
assay at
65
-
recombinant enzyme
75
-
the enzyme has an optimal activity temperature below the growth temperature of the organism of 80-90°C
additional information
cold-active UDG
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10 - 50
recombinant UDG, inactive above 50°C, temperature profile
20 - 50
-
fluorescence and activity measurements following incubation at different temperatures suggest the following model describing structure-activity relationships: at temperatures from 20 to 50°C the protein exists as a compact protein exhibiting low enzyme activity, whereas at temperatures above 50°C, the Afung conformation opens up, which is associated with the acquisition of high enzyme activity
37 - 65
-
the enzyme is more active at 65°C than at 37°C
65 - 100
-
65°C: about 55% of maximal activity, 100°C: about 50% of maximal activity
additional information
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.7
-
isoelectric focusing
6.97
sequence calculation
9
-
above, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cells from liver and colon
Manually annotated by BRENDA team
-
colorectal carcinoma cell line
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
colon adenocarcinoma cell line
Manually annotated by BRENDA team
-
low expression level of UNG2
Manually annotated by BRENDA team