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| PROSITE documentation PDOC00121 |
Uracil-DNA glycosylase signature
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: Last update:December 2004 / Pattern and text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Sancar A. Sancar G.B. |
| Title | DNA repair enzymes. | |
| Source | Annu. Rev. Biochem. 57:29-67(1988). | |
| PubMed ID | 3052275 |
| 2 | Authors | Olsen L.C. Aasland R. Wittwer C.U. Krokan H.E. Helland D.E. |
| Title | Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme. | |
| Source | EMBO J. 8:3121-3125(1989). | |
| PubMed ID | 2555154 |
| 3 | Authors | Upton C. Stuart D.T. McFadden G. |
| Title | Identification of a poxvirus gene encoding a uracil DNA glycosylase. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 90:4518-4522(1993). | |
| PubMed ID | 8389453 |
| 4 | Authors | Slupphaug G. Markussen F.-H. Olsen L.C. Aasland R. Aarsaether N. Bakke O. Krokan H.E. Helland D.E. |
| Title | Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene. | |
| Source | Nucleic Acids Res. 21:2579-2584(1993). | |
| PubMed ID | 8332455 |
| 5 | Authors | Savva R. McAuley-Hecht K. Brown T. Pearl L. |
| Title | The structural basis of specific base-excision repair by uracil-DNA glycosylase. | |
| Source | Nature 373:487-493(1995). | |
| PubMed ID | 7845459 | |
| DOI | 10.1038/373487a0 |
| 6 | Authors | Mol C.D. Arvai A.S. Slupphaug G. Kavli B. Alseth I. Krokan H.E. Tainer J.A. |
| Title | Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis. | |
| Source | Cell 80:869-878(1995). | |
| PubMed ID | 7697717 |
| 7 | Authors | Mueller S.J. Caradonna S. |
| Title | Isolation and characterization of a human cDNA encoding uracil-DNA glycosylase. | |
| Source | Biochim. Biophys. Acta 1088:197-207(1991). | |
| PubMed ID | 2001396 |
| 8 | Authors | Meyer-Siegler K. Mauro D.J. Seal G. Wurzer J. Deriel J.K. Sirover M.A. |
| Source | Proc. Natl. Acad. Sci. U.S.A. 88:8460-8464(1991). |
| 9 | Authors | Mueller S.J. Caradonna S. |
| Title | Cell cycle regulation of a human cyclin-like gene encoding uracil-DNA glycosylase. | |
| Source | J. Biol. Chem. 268:1310-1319(1993). | |
| PubMed ID | 8419333 |
| 10 | Authors | Barnes D.E. Lindahl T. Sedgwick B. |
| Source | Curr. Opin. Cell Biol. 5:424-433(1993). |
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