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PROSITE documentation PDOC00121

Uracil-DNA glycosylase signature





Description

Uracil-DNA glycosylase (EC 3.2.2.-) (UNG) [1] is a DNA repair enzyme that excises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in DNA can arise as a result of misincorportation of dUMP residues by DNA polymerase or deamination of cytosine.

The sequence of uracil-DNA glycosylase is extremely well conserved [2] in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses [3].

In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human UNG1 protein is transported to both the mitochondria and the nucleus [4]. The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localization [4], but the presence of a mitochondrial transit peptide has not been directly demonstrated.

As a signature for this type of enzyme, we selected the most N-terminal conserved region. This region contains an aspartic acid residue which has been proposed, based on X-ray structures [5,6] to act as a general base in the catalytic mechanism.

Note:

In humans, two additional sequences of UNG have been reported [7,8]. These isozymes are not evolutionary related to other known UNG. One of them is a glyceraldehyde 3-phosphate dehydrogenase [8] and the other related to cyclins [9]. Data available on three proteins proposed to be human uracil-DNA glycosylases is discussed in [10].

Expert(s) to contact by email:

Aasland R.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

U_DNA_GLYCOSYLASE, PS00130; Uracil-DNA glycosylase signature  (PATTERN)


References

1AuthorsSancar A. Sancar G.B.
TitleDNA repair enzymes.
SourceAnnu. Rev. Biochem. 57:29-67(1988).
PubMed ID3052275

2AuthorsOlsen L.C. Aasland R. Wittwer C.U. Krokan H.E. Helland D.E.
TitleMolecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme.
SourceEMBO J. 8:3121-3125(1989).
PubMed ID2555154

3AuthorsUpton C. Stuart D.T. McFadden G.
TitleIdentification of a poxvirus gene encoding a uracil DNA glycosylase.
SourceProc. Natl. Acad. Sci. U.S.A. 90:4518-4522(1993).
PubMed ID8389453

4AuthorsSlupphaug G. Markussen F.-H. Olsen L.C. Aasland R. Aarsaether N. Bakke O. Krokan H.E. Helland D.E.
TitleNuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene.
SourceNucleic Acids Res. 21:2579-2584(1993).
PubMed ID8332455

5AuthorsSavva R. McAuley-Hecht K. Brown T. Pearl L.
TitleThe structural basis of specific base-excision repair by uracil-DNA glycosylase.
SourceNature 373:487-493(1995).
PubMed ID7845459
DOI10.1038/373487a0

6AuthorsMol C.D. Arvai A.S. Slupphaug G. Kavli B. Alseth I. Krokan H.E. Tainer J.A.
TitleCrystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis.
SourceCell 80:869-878(1995).
PubMed ID7697717

7AuthorsMueller S.J. Caradonna S.
TitleIsolation and characterization of a human cDNA encoding uracil-DNA glycosylase.
SourceBiochim. Biophys. Acta 1088:197-207(1991).
PubMed ID2001396

8AuthorsMeyer-Siegler K. Mauro D.J. Seal G. Wurzer J. Deriel J.K. Sirover M.A.
SourceProc. Natl. Acad. Sci. U.S.A. 88:8460-8464(1991).

9AuthorsMueller S.J. Caradonna S.
TitleCell cycle regulation of a human cyclin-like gene encoding uracil-DNA glycosylase.
SourceJ. Biol. Chem. 268:1310-1319(1993).
PubMed ID8419333

10AuthorsBarnes D.E. Lindahl T. Sedgwick B.
SourceCurr. Opin. Cell Biol. 5:424-433(1993).



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