Uracil-DNA glycosylase

NameUracil-DNA glycosylase
Synonyms
  • 3.2.2.27
  • DGU
  • UDG
  • UNG1
  • UNG15
Gene NameUNG
OrganismHuman
Amino acid sequence
>lcl|BSEQ0007234|Uracil-DNA glycosylase
MIGQKTLYSFFSPSPARKRHAPSPEPAVQGTGVAGVPEESGDAAAIPAKKAPAGQEEPGT
PPSSPLSAEQLDRIQRNKAAALLRLAARNVPVGFGESWKKHLSGEFGKPYFIKLMGFVAE
ERKHYTVYPPPHQVFTWTQMCDIKDVKVVILGQDPYHGPNQAHGLCFSVQRPVPPPPSLE
NIYKELSTDIEDFVHPGHGDLSGWAKQGVLLLNAVLTVRAHQANSHKERGWEQFTDAVVS
WLNQNSNGLVFLLWGSYAQKKGSAIDRKRHHVLQTAHPSPLSVYRGFFGCRHFSKTNELL
QKSGKKPIDWKEL
Number of residues313
Molecular Weight34645.27
Theoretical pI9.85
GO Classification
Functions
  • damaged DNA binding
  • uracil DNA N-glycosylase activity
Processes
  • base-excision repair
  • viral process
  • base-excision repair, AP site formation
  • depyrimidination
  • positive regulation of isotype switching
  • somatic hypermutation of immunoglobulin genes
  • somatic recombination of immunoglobulin gene segments
  • DNA repair
Components
  • nucleoplasm
  • mitochondrion
  • nucleus
General FunctionUracil dna n-glycosylase activity
Specific FunctionExcises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID37599
UniProtKB IDP13051
UniProtKB Entry NameUNG_HUMAN
Cellular LocationMitochondrion
Gene sequence
>lcl|BSEQ0012634|Uracil-DNA glycosylase (UNG)
ATGGGCGTCTTCTGCCTTGGGCCGTGGGGGTTGGGCCGGAAGCTGCGGACGCCTGGGAAG
GGGCCGCTGCAGCTCTTGAGCCGCCTCTGCGGGGACCACTTGCAGGCCATCCCAGCCAAG
AAGGCCCCGGCTGGGCAGGAGGAGCCTGGGACGCCGCCCTCCTCGCCGCTGAGTGCCGAG
CAGTTGGACCGGATCCAGAGGAACAAGGCCGCGGCCCTGCTCAGACTCGCGGCCCGCAAC
GTGCCCGTGGGCTTTGGAGAGAGCTGGAAGAAGCACCTCAGCGGGGAGTTCGGGAAACCG
TATTTTATCAAGCTAATGGGATTTGTTGCAGAAGAAAGAAAGCATTACACTGTTTATCCA
CCCCCACACCAAGTCTTCACCTGGACCCAGATGTGTGACATAAAAGATGTGAAGGTTGTC
ATCCTGGGACAGGATCCATATCATGGACCTAATCAAGCTCACGGGCTCTGCTTTAGTGTT
CAAAGGCCTGTTCCGCCTCCGCCCAGTTTGGAGAACATTTATAAAGAGTTGTCTACAGAC
ATAGAGGATTTTGTTCATCCTGGCCATGGAGATTTATCTGGGTGGGCCAAGCAAGGTGTT
CTCCTTCTCAACGCTGTCCTCACGGTTCGTGCCCATCAAGCCAACTCTCATAAGGAGCGA
GGCTGGGAGCAGTTCACTGATGCAGTTGTGTCCTGGCTAAATCAGAACTCGAATGGCCTT
GTTTTCTTGCTCTGGGGCTCTTATGCTCAGAAGAAGGGCAGTGCCATTGATAGGAAGCGG
CACCATGTACTACAGACGGCTCATCCCTCCCCTTTGTCAGTGTATAGAGGGTTCTTTGGA
TGTAGACACTTTTCAAAGACCAATGAGCTGCTGCAGAAGTCTGGCAAGAAGCCCATTGAC
TGGAAGGAGCTGTGA
GenBank Gene IDX15653
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:12572
Chromosome Location12
Locus12q23-q24.1
References
  1. Olsen LC, Aasland R, Wittwer CU, Krokan HE, Helland DE: Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme. EMBO J. 1989 Oct;8(10):3121-5. 2555154
  2. Haug T, Skorpen F, Lund H, Krokan HE: Structure of the gene for human uracil-DNA glycosylase and analysis of the promoter function. FEBS Lett. 1994 Oct 17;353(2):180-4. 7926048
  3. Nilsen H, Otterlei M, Haug T, Solum K, Nagelhus TA, Skorpen F, Krokan HE: Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene. Nucleic Acids Res. 1997 Feb 15;25(4):750-5. 9016624
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  6. Slupphaug G, Markussen FH, Olsen LC, Aasland R, Aarsaether N, Bakke O, Krokan HE, Helland DE: Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene. Nucleic Acids Res. 1993 Jun 11;21(11):2579-84. 8332455
  7. Kavli B, Slupphaug G, Mol CD, Arvai AS, Peterson SB, Tainer JA, Krokan HE: Excision of cytosine and thymine from DNA by mutants of human uracil-DNA glycosylase. EMBO J. 1996 Jul 1;15(13):3442-7. 8670846
  8. Bouhamdan M, Benichou S, Rey F, Navarro JM, Agostini I, Spire B, Camonis J, Slupphaug G, Vigne R, Benarous R, Sire J: Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme. J Virol. 1996 Feb;70(2):697-704. 8551605
  9. Otterlei M, Haug T, Nagelhus TA, Slupphaug G, Lindmo T, Krokan HE: Nuclear and mitochondrial splice forms of human uracil-DNA glycosylase contain a complex nuclear localisation signal and a strong classical mitochondrial localisation signal, respectively. Nucleic Acids Res. 1998 Oct 15;26(20):4611-7. 9753728
  10. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  11. Guo C, Zhang X, Fink SP, Platzer P, Wilson K, Willson JK, Wang Z, Markowitz SD: Ugene, a newly identified protein that is commonly overexpressed in cancer and binds uracil DNA glycosylase. Cancer Res. 2008 Aug 1;68(15):6118-26. doi: 10.1158/0008-5472.CAN-08-1259. 18676834
  12. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. 18220336
  13. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  14. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  15. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  16. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  17. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  18. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  19. Mol CD, Arvai AS, Slupphaug G, Kavli B, Alseth I, Krokan HE, Tainer JA: Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis. Cell. 1995 Mar 24;80(6):869-78. 7697717
  20. Mol CD, Arvai AS, Sanderson RJ, Slupphaug G, Kavli B, Krokan HE, Mosbaugh DW, Tainer JA: Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA. Cell. 1995 Sep 8;82(5):701-8. 7671300
  21. Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA: A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature. 1996 Nov 7;384(6604):87-92. 8900285
  22. Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA: Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J. 1998 Sep 1;17(17):5214-26. 9724657
  23. Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S, Catalan N, Yel L, Forveille M, Kavli B, Krokan HE, Ochs HD, Fischer A, Durandy A: Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol. 2003 Oct;4(10):1023-8. Epub 2003 Sep 7. 12958596
  24. Kavli B, Andersen S, Otterlei M, Liabakk NB, Imai K, Fischer A, Durandy A, Krokan HE, Slupphaug G: B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. J Exp Med. 2005 Jun 20;201(12):2011-21. 15967827