{PDOC00121}
{PS00130; U_DNA_GLYCOSYLASE}
{BEGIN}
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* Uracil-DNA glycosylase signature *
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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.
-Consensus pattern: [KR]-[LIVA]-[LIVC]-[LIVM]-x-G-[QI]-D-P-Y
[D is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-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.; aasland@bio.uib.no
-Last update: December 2004 / Pattern and text revised.
[ 1] Sancar A., Sancar G.B.
"DNA repair enzymes."
Annu. Rev. Biochem. 57:29-67(1988).
PubMed=3052275
[ 2] Olsen L.C., Aasland R., Wittwer C.U., Krokan H.E., Helland D.E.
"Molecular cloning of human uracil-DNA glycosylase, a highly conserved
DNA repair enzyme."
EMBO J. 8:3121-3125(1989).
PubMed=2555154
[ 3] Upton C., Stuart D.T., McFadden G.
"Identification of a poxvirus gene encoding a uracil DNA
glycosylase."
Proc. Natl. Acad. Sci. U.S.A. 90:4518-4522(1993).
PubMed=8389453
[ 4] Slupphaug G., Markussen F.-H., Olsen L.C., Aasland R., Aarsaether N.,
Bakke O., Krokan H.E., Helland D.E.
"Nuclear and mitochondrial forms of human uracil-DNA glycosylase are
encoded by the same gene."
Nucleic Acids Res. 21:2579-2584(1993).
PubMed=8332455
[ 5] Savva R., McAuley-Hecht K., Brown T., Pearl L.
"The structural basis of specific base-excision repair by uracil-DNA
glycosylase."
Nature 373:487-493(1995).
PubMed=7845459; DOI=10.1038/373487a0
[ 6] Mol C.D., Arvai A.S., Slupphaug G., Kavli B., Alseth I., Krokan H.E.,
Tainer J.A.
"Crystal structure and mutational analysis of human uracil-DNA
glycosylase: structural basis for specificity and catalysis."
Cell 80:869-878(1995).
PubMed=7697717
[ 7] Mueller S.J., Caradonna S.
"Isolation and characterization of a human cDNA encoding uracil-DNA
glycosylase."
Biochim. Biophys. Acta 1088:197-207(1991).
PubMed=2001396
[ 8] Meyer-Siegler K., Mauro D.J., Seal G., Wurzer J., Deriel J.K.,
Sirover M.A.
Proc. Natl. Acad. Sci. U.S.A. 88:8460-8464(1991).
[ 9] Mueller S.J., Caradonna S.
"Cell cycle regulation of a human cyclin-like gene encoding uracil-DNA
glycosylase."
J. Biol. Chem. 268:1310-1319(1993).
PubMed=8419333
[10] Barnes D.E., Lindahl T., Sedgwick B.
Curr. Opin. Cell Biol. 5:424-433(1993).
{END}