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Information on EC 3.2.2.27 - uracil-DNA glycosylase and Organism(s) Mus musculus and UniProt Accession Q6P5C5
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3.2.2.27 uracil-DNA glycosylaseIUBMB Comments
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.
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Word Map
- 3.2.2.27
-
deamination
- cytosine
- glycosylases
- endonuclease
- thymine
-
abasic
-
misincorporation
- ung2
-
uracil-containing
- duplex
-
hypermutation
- dump
- deoxyuridine
-
activation-induced
-
excises
- mispairs
-
base-excision
- dutpase
- 8-oxoguanine
-
apyrimidinic
- 5-methylcytosine
- 5-hydroxymethyluracil
-
g-quadruplexes
-
transversions
- ape1
-
thymine-dna
- formamidopyrimidine
- 5-hydroxyuracil
-
short-patch
- xrcc1
-
apurinic
-
class-switching
- 3,n4-ethenocytosine
-
translesion
-
post-replicative
- ap-endonuclease
-
aid-induced
- apobec3g
- drug development
- molecular biology
- analysis
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Hydrolyses single-stranded DNA or mismatched double-stranded DNA and polynucleotides, releasing free uracil
Synonyms
uracil-dna glycosylase, smug1, dna n-glycosylase, ung-1, ul114, uracil dna-glycosylase, uracil-dna n-glycosylase, uracil dna glycosylase 2, thd1p, mjudg, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
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
59088-21-0
cf. EC 3.2.2.28
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
uracil-mismatched single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
-
-
-
?
M6-FAM-labeled single stranded oligonucleotide + H2O
uracil + ?
-
T12-AGUA-T12
-
-
?
uracil-containing single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
-
isoform UNG1, which in contrast to isoform UNG2 lacks a PCNA-binding motif, may be specialized to act on single stranded DNA (ssDNA) through its ability to bind ssDNA-binding protein RPA
-
-
?
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
-
-
-
-
?
uracil-mismatched single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
-
-
-
-
?
additional information
?
-
SMUG1 is specialized for antimutational uracil excision in mammalian cells. Ung knockout mice display no increase in mutation frequency due to the second UDG activity, SMUG1
-
-
?
additional information
?
-
SMUG1 also excises the oxidation-damage product 5-hydroxymethyluracil, but like UNG is inactive against thymine, i.e. 5-methyluracil, displacement/replacement mechanism allowing SMUG1 to exclude thymine from its active site while accepting 5-hydroxymethyluracil, overview
-
-
?
additional information
?
-
-
deamination of cytosine in DNA leads to formation of uracil, which is removed by uracil DNA glycosylase, UNG. The N-terminus of UNG is required for class switch recombination activity, overview
-
-
?
additional information
?
-
-
uracil in single-stranded DNA, resulting from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, causing U:A pairs or U:G mismatches, respectively, has to be removed by the enzyme. Nuclear UNG2 is apparently the sole contributor to the post-replicative repair of U:A lesions and to the removal of uracil from U:G contexts in immunoglobulin genes as part of somatic hypermutation and class-switch recombination processes in adaptive immunity. UNG2 and SMUG1 contribute to U:G repair. UNG2 is highly specific for uracil, SMUG1 also efficiently removes 5-hydroxymethyluracil
-
-
?
additional information
?
-
-
uracil DNA glycosylase uses single-stranded DNA substrate, a 5'-FITC-labeled oligonucleotide of 30mer with an internal single U residue
-
-
?
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
uracil-mismatched single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
-
-
-
?
uracil-containing single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
-
isoform UNG1, which in contrast to isoform UNG2 lacks a PCNA-binding motif, may be specialized to act on single stranded DNA (ssDNA) through its ability to bind ssDNA-binding protein RPA
-
-
?
uracil-mismatched double-stranded DNA + H2O
uracil + double-stranded DNA with abasic site
-
-
-
-
?
uracil-mismatched single-stranded DNA + H2O
uracil + single-stranded DNA with abasic site
-
-
-
-
?
additional information
?
-
SMUG1 is specialized for antimutational uracil excision in mammalian cells. Ung knockout mice display no increase in mutation frequency due to the second UDG activity, SMUG1
-
-
?
additional information
?
-
-
deamination of cytosine in DNA leads to formation of uracil, which is removed by uracil DNA glycosylase, UNG. The N-terminus of UNG is required for class switch recombination activity, overview
-
-
?
additional information
?
-
-
uracil in single-stranded DNA, resulting from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, causing U:A pairs or U:G mismatches, respectively, has to be removed by the enzyme. Nuclear UNG2 is apparently the sole contributor to the post-replicative repair of U:A lesions and to the removal of uracil from U:G contexts in immunoglobulin genes as part of somatic hypermutation and class-switch recombination processes in adaptive immunity. UNG2 and SMUG1 contribute to U:G repair. UNG2 is highly specific for uracil, SMUG1 also efficiently removes 5-hydroxymethyluracil
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ugi
-
a specific peptide inhibitor of UNG, inhibits class switch recombination without reducing DNA cleavage of the switch region, confirming dispensability of UNG in DNA cleavage in class switch recombination
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
low catalytic turnover of SMUG1 compared with UNG-type enzymes
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
UNG2 is cell-cycle regulated with the highest protein level in early to mid-S-phase, in agreement with its role in the repair of incorporated uracils
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
enzyme deficiency enhances translesion polymerase recruitment and inhibits S-S synapse formation during class switch recombination
physiological function
physiological function
-
involvement but dispensability of UNG in DNA cleavage in class switch recombination
physiological function
-
the DNA base excision repair enzyme is essential for class switch recombination
physiological function
-
the noncanonical function of the enzyme regulates the steps after activation-induced cytidine deaminase-induced DNA cleavage: errorprone repair suppression in S region somatic hypermutation and end-joining promotion in class switch recombination
physiological function
-
isoform UNG1 supports antibody class switching and repairs genomic uracil in the cell nucleus
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). SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
UNG2 also undergoes sequential phosphorylations at Ser23, Thr60 and Ser64 during the cell cycle. Monophosphorylation at Ser23 in the G1/early S-phase apparently increases association with RPA and replicating chromatin and markedly increases the catalytic turnover number
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D145N
-
the mutant shows increased class switch recombination efficiency and reduced uracil removal activity compared to the wild type enzyme
DELTA90/W231A
H239L
-
a SMUG1 mutant, the mutation affects the stabilization of transition state
H268L
-
the mutant shows increased class switch recombination efficiency and reduced deoxyuracil removal activity compared to the wild type enzyme
additional information
DELTA90/W231A
-
the mutant shows reduced class switch recombination efficiency and reduced deoxyuracil removal activity compared to the wild type enzyme
additional information
Ung knockout mice display no increase in mutation frequency due to the second UDG activity, SMUG1
additional information
-
UNG deficiency reduces CSR efficiency to one tenth, but catalytically inactive mutants of UNG are fully proficient in CSR and several mutants at noncatalytic sites loose CSR activity. CSR activity by many UNG mutants critically depends on its N-terminal domain, irrespective of their enzymatic activities
additional information
-
Ung knockout, Smug1 siRNA knockdown and Ung knockout/Smug1 knockdown mouse cells show that Smug1 and Ung2 are both required for the prevention of mutations and that their functions are not redundant
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wibley J.E.; Waters T.R.; Haushalter K.; Verdine G.L.; Pearl L.H.
Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1
Mol. Cell
11
1647-59
2003
Mus musculus (Q6P5C5)
Visnes, T.; Doseth, B.; Pettersen, H.; Hagen, L.; Sousa, M.; Akbari, M.; Otterlei, M.; Kavli, B.; Slupphaug, G.; Krokan, H.
Uracil in DNA and its processing by different DNA glycosylases
Philos. Trans. R. Soc. Lond. B Biol. Sci.
364
563-568
2009
Homo sapiens, Mus musculus
Begum, N.A.; Stanlie, A.; Doi, T.; Sasaki, Y.; Jin, H.W.; Kim, Y.S.; Nagaoka, H.; Honjo, T.
Further evidence for involvement of a noncanonical function of uracil DNA glycosylase in class switch recombination
Proc. Natl. Acad. Sci. USA
106
2752-2757
2009
Mus musculus
Yousif, A.S.; Stanlie, A.; Begum, N.A.; Honjo, T.
Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination
Int. Immunol.
26
575-578
2014
Mus musculus
Yousif, A.S.; Stanlie, A.; Mondal, S.; Honjo, T.; Begum, N.A.
Differential regulation of S-region hypermutation and class-switch recombination by noncanonical functions of uracil DNA glycosylase
Proc. Natl. Acad. Sci. USA
111
E1016-E1024
2014
Mus musculus
Sarno, A.; Lundbaek, M.; Liabakk, N.B.; Aas, P.A.; Mjelle, R.; Hagen, L.; Sousa, M.M.L.; Krokan, H.E.; Kavli, B.
Uracil-DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil
Nucleic Acids Res.
47
4569-4585
2019
Mus musculus, Homo sapiens (P13051), Homo sapiens
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