Uracil-DNA glycosylase

PDB rendering based on 1akz.

Available structures
PDB	1AKZ, 1DPU, 1EMH, 1EMJ, 1Q3F, 1SSP, 1UGH, 1YUO, 2HXM, 2OXM, 2OYT, 2SSP, 3FCF, 3FCI, 3FCK, 3FCL, 4SKN

Identifiers

Symbols

UNG; DGU; DKFZp781L1143; HIGM4; UDG; UNG1; UNG15; UNG2

External IDs

OMIM: 191525 MGI: 109352 HomoloGene: 6585 GeneCards: UNG Gene

EC number

3.2.2.27

Gene Ontology
Molecular function	• uracil DNA N-glycosylase activity • protein binding • hydrolase activity, hydrolyzing N-glycosyl compounds
Cellular component	• nucleus • mitochondrion
Biological process	• DNA repair • base-excision repair • metabolic process • somatic hypermutation of immunoglobulin genes • somatic recombination of immunoglobulin gene segments • interspecies interaction between organisms
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
109.54 – 109.55 Mb

Chr 5:
114.58 – 114.59 Mb

PubMed search

[1]

[2]

Uracil-DNA glycosylase, also known as UNG or UDG, is a human gene^[1] though orthologs exist ubiquitously among prokaryotes and eukaryotes and even in some DNA viruses. The first uracil DNA-glycosylase was isolated from Escherichia coli^[2]. The human gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2.^[1]

Interactions

Uracil-DNA glycosylase has been shown to interact with RPA2.^[3]

References

^ ^a ^b "Entrez Gene: UNG uracil-DNA glycosylase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7374.
^ Lindahl T, Ljungquist S, Siegert W, Nyberg B, Sperens B (1977). "DNA N-glycosidases: properties of uracil-DNA glycosidase from Escherichia coli". J. Biol. Chem. 252 (10): 3286–94. PMID 324994.
^ Nagelhus, T A; Haug T, Singh K K, Keshav K F, Skorpen F, Otterlei M, Bharati S, Lindmo T, Benichou S, Benarous R, Krokan H E (Mar. 1997). "A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34-kDa subunit of replication protein A". J. Biol. Chem. (UNITED STATES) 272 (10): 6561–6. doi:10.1074/jbc.272.10.6561. ISSN 0021-9258. PMID 9045683.

Caradonna S, Muller-Weeks S (2002). "The nature of enzymes involved in uracil-DNA repair: isoform characteristics of proteins responsible for nuclear and mitochondrial genomic integrity". Curr. Protein Pept. Sci. 2 (4): 335–47. doi:10.2174/1389203013381044. PMID 12369930.
Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell Biol. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
Van Maele B, Debyser Z (2005). "HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins". AIDS reviews 7 (1): 26–43. PMID 15875659.
Slupphaug G, Olsen LC, Helland D, et al. (1991). "Cell cycle regulation and in vitro hybrid arrest analysis of the major human uracil-DNA glycosylase". Nucleic Acids Res. 19 (19): 5131–7. doi:10.1093/nar/19.19.5131. PMC 328866. PMID 1923798. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=328866.
Muller SJ, Caradonna S (1991). "Isolation and characterization of a human cDNA encoding uracil-DNA glycosylase". Biochim. Biophys. Acta 1088 (2): 197–207. PMID 2001396.
Olsen LC, Aasland R, Wittwer CU, et al. (1990). "Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme". EMBO J. 8 (10): 3121–5. PMC 401392. PMID 2555154. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=401392.
Nagelhus TA, Slupphaug G, Lindmo T, Krokan HE (1995). "Cell cycle regulation and subcellular localization of the major human uracil-DNA glycosylase". Exp. Cell Res. 220 (2): 292–7. doi:10.1006/excr.1995.1318. PMID 7556436.
Mol CD, Arvai AS, Sanderson RJ, et al. (1995). "Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA". Cell 82 (5): 701–8. doi:10.1016/0092-8674(95)90467-0. PMID 7671300.
Mol CD, Arvai AS, Slupphaug G, et al. (1995). "Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis". Cell 80 (6): 869–78. doi:10.1016/0092-8674(95)90290-2. PMID 7697717.
Haug T, Skorpen F, Lund H, Krokan HE (1994). "Structure of the gene for human uracil-DNA glycosylase and analysis of the promoter function". FEBS Lett. 353 (2): 180–4. doi:10.1016/0014-5793(94)01042-0. PMID 7926048.
Slupphaug G, Markussen FH, Olsen LC, et al. (1993). "Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene". Nucleic Acids Res. 21 (11): 2579–84. doi:10.1093/nar/21.11.2579. PMC 309584. PMID 8332455. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=309584.
Bouhamdan M, Benichou S, Rey F, et al. (1996). "Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme". J. Virol. 70 (2): 697–704. PMC 189869. PMID 8551605. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=189869.
Kavli B, Slupphaug G, Mol CD, et al. (1996). "Excision of cytosine and thymine from DNA by mutants of human uracil-DNA glycosylase". EMBO J. 15 (13): 3442–7. PMC 451908. PMID 8670846. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=451908.
Haug T, Skorpen F, Kvaløy K, et al. (1997). "Human uracil-DNA glycosylase gene: sequence organization, methylation pattern, and mapping to chromosome 12q23-q24.1". Genomics 36 (3): 408–16. doi:10.1006/geno.1996.0485. PMID 8884263.
Slupphaug G, Mol CD, Kavli B, et al. (1996). "A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA". Nature 384 (6604): 87–92. doi:10.1038/384087a0. PMID 8900285.
Nilsen H, Otterlei M, Haug T, et al. (1997). "Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene". Nucleic Acids Res. 25 (4): 750–5. doi:10.1093/nar/25.4.750. PMC 146498. PMID 9016624. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=146498.
Nagelhus TA, Haug T, Singh KK, et al. (1997). "A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34-kDa subunit of replication protein A". J. Biol. Chem. 272 (10): 6561–6. doi:10.1074/jbc.272.10.6561. PMID 9045683.
Selig L, Benichou S, Rogel ME, et al. (1997). "Uracil DNA glycosylase specifically interacts with Vpr of both human immunodeficiency virus type 1 and simian immunodeficiency virus of sooty mangabeys, but binding does not correlate with cell cycle arrest". J. Virol. 71 (6): 4842–6. PMC 191711. PMID 9151883. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=191711.
Withers-Ward ES, Jowett JB, Stewart SA, et al. (1997). "Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair". J. Virol. 71 (12): 9732–42. PMC 230283. PMID 9371639. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=230283.
Haug T, Skorpen F, Aas PA, et al. (1998). "Regulation of expression of nuclear and mitochondrial forms of human uracil-DNA glycosylase". Nucleic Acids Res. 26 (6): 1449–57. doi:10.1093/nar/26.6.1449. PMC 147431. PMID 9490791. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147431.

PDB gallery

1akz: HUMAN URACIL-DNA GLYCOSYLASE

1emh: CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO UNCLEAVED SUBSTRATE-CONTAINING DNA

1emj: URACIL-DNA GLYCOSYLASE BOUND TO DNA CONTAINING A 4'-THIO-2'DEOXYURIDINE ANALOG PRODUCT

1q3f: Uracil DNA glycosylase bound to a cationic 1-aza-2'-deoxyribose-contianing DNA

1ssp: WILD-TYPE URACIL-DNA GLYCOSYLASE BOUND TO URACIL-CONTAINING DNA

1ugh: CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE IN COMPLEX WITH A PROTEIN INHIBITOR: PROTEIN MIMICRY OF DNA

1yuo: Optimisation of the surface electrostatics as a strategy for cold adaptation of uracil-DNA N-glycosylase (UNG)from atlantic cod (Gadus morhua)

2hxm: Complex of UNG2 and a small Molecule synthetic Inhibitor

2ssp: LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA

4skn: A NUCLEOTIDE-FLIPPING MECHANISM FROM THE STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO DNA

Uracil-DNA glycosylase

Interactions

References

Further reading