PROSITE documentation PDOC00121

{PDOC00121}
{PS00130; U_DNA_GLYCOSYLASE}
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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).

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