Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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UDG Uracil DNA glycosylase superfamily

SMART accession number:	SM00986
Description:	-
Interpro abstract (IPR005122):	This entry represents various uracil-DNA glycosylases and related DNA glycosylases ( EC 3.2.2 ), such as uracil-DNA glycosylase [ (PUBMED:7697717) ], thermophilic uracil-DNA glycosylase [ (PUBMED:10339434) ], G:T/U mismatch-specific DNA glycosylase (Mug) [ (PUBMED:9489705) ], and single-strand selective monofunctional uracil-DNA glycosylase (SMUG1) [ (PUBMED:2820976) ]. These proteins have a 3-layer alpha/beta/alpha structure. Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosylic bond, initiating the base excision repair pathway. Uracil in DNA can arise either through the deamination of cytosine to form mutagenic U:G mispairs, or through the incorporation of dUMP by DNA polymerase to form U:A pairs [ (PUBMED:17116429) ]. These aberrant uracil residues are genotoxic [ (PUBMED:16860315) ]. The sequence of uracil-DNA glycosylase is extremely well conserved [ (PUBMED:2555154) ] in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses [ (PUBMED:8389453) ].
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 48770 UDG domains in 48764 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing UDG domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with UDG domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing UDG domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Cellular role: chromatin
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Aravind L, Koonin EV
  • The alpha/beta fold uracil DNA glycosylases: a common origin with diversefates.
  • Genome Biol. 2000; 1: 7-7
  • Display abstract

  • BACKGROUND: Uracil DNA glycosylases (UDGs) are major repair enzymes thatprotect DNA from mutational damage caused by uracil incorporated as aresult of a polymerase error or deamination of cytosine. Four distinctfamilies of UDGs have been identified, which show very limited sequencesimilarity to each other, although two of them have been shown to possessthe same structural fold. The structural and evolutionary relationshipsbetween the rest of the UDGs remain uncertain. RESULTS: Using sequenceprofile searches, multiple alignment analysis and protein structurecomparisons, we show here that all known UDGs possess the same fold andmust have evolved from a common ancestor. Although all UDGs catalyzeessentially the same reaction, significant changes in the configuration ofthe catalytic residues were detected within their common fold, whichprobably results in differences in the biochemistry of these enzymes. Theextreme sequence divergence of the UDGs, which is unusual for enzymes withthe same principal activity, is probably due to the major role of theuracil-flipping caused by the conformational strain enacted by the enzymeon uracil-containing DNA, as compared with the catalytic action ofindividual polar residues. We predict two previously undetected familiesof UDGs and delineate a hypothetical scenario for their evolution.CONCLUSIONS: UDGs form a single protein superfamily with a distinctstructural fold and a common evolutionary origin. Differences in thecatalytic mechanism of the different families combined with theconstruction of the catalytic pocket have, however, resulted in extremesequence divergence of these enzymes.

  • Barrett TE et al.
  • Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatchrecognition by complementary-strand interactions.
  • Cell. 1998; 92: 117-29
  • Display abstract

  • G:U mismatches resulting from deamination of cytosine are the most commonpromutagenic lesions occurring in DNA. Uracil is removed in abase-excision repair pathway by uracil DNA-glycosylase (UDG), whichexcises uracil from both single- and double-stranded DNA. Recently, abiochemically distinct family of DNA repair enzymes has been identified,which excises both uracil and thymine, but only from mispairs withguanine. Crystal structures of the mismatch-specific uracilDNA-glycosylase (MUG) from E. coli, and of a DNA complex, reveal aremarkable structural and functional homology to UDGs despite low sequenceidentity. Details of the MUG structure explain its thymine DNA-glycosylaseactivity and the specificity for G:U/T mispairs, which derives from directrecognition of guanine on the complementary strand.

• Structure (3D structures containing this domain)

• 3D Structures of UDG domains in PDB

  PDB code	Main view	Title
  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
  1eug		CRYSTAL STRUCTURE OF ESCHERICHIA COLI URACIL DNA GLYCOSYLASE AND ITS COMPLEXES WITH URACIL AND GLYCEROL: STRUCTURE AND GLYCOSYLASE MECHANISM REVISITED
  1eui		ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE COMPLEX WITH URACIL-DNA GLYCOSYLASE INHIBITOR PROTEIN
  1flz		URACIL DNA GLYCOSYLASE WITH UAAP
  1l9g		CRYSTAL STRUCTURE OF URACIL-DNA GLYCOSYLASE FROM T. MARITIMA
  1lau		URACIL-DNA GLYCOSYLASE
  1lqg		ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE COMPLEX WITH URACIL-DNA GLYCOSYLASE INHIBITOR PROTEIN
  1lqj		ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE
  1lqm		ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE COMPLEX WITH URACIL-DNA GLYCOSYLASE INHIBITOR PROTEIN
  1mtl		Non-productive MUG-DNA complex
  1mug		G:T/U MISMATCH-SPECIFIC DNA GLYCOSYLASE FROM E.COLI
  1mwi		Crystal structure of a MUG-DNA product complex
  1mwj		Crystal Structure of a MUG-DNA pseudo substrate complex
  1okb		crystal structure of Uracil-DNA glycosylase from Atlantic cod (Gadus morhua)
  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
  1udg		THE STRUCTURAL BASIS OF SPECIFIC BASE EXCISION REPAIR BY URACIL-DNA GLYCOSYLASE
  1udh		THE STRUCTURAL BASIS OF SPECIFIC BASE EXCISION REPAIR BY URACIL-DNA GLYCOSYLASE
  1udi		NUCLEOTIDE MIMICRY IN THE CRYSTAL STRUCTURE OF THE URACIL-DNA GLYCOSYLASE-URACIL GLYCOSYLASE INHIBITOR PROTEIN COMPLEX
  1ugh		CRYSTAL STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE IN COMPLEX WITH A PROTEIN INHIBITOR: PROTEIN MIMICRY OF DNA
  1ui0		Crystal Structure Of Uracil-DNA Glycosylase From Thermus Thermophilus HB8
  1ui1		Crystal Structure Of Uracil-DNA Glycosylase From Thermus Thermophilus HB8
  1uug		ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE:INHIBITOR COMPLEX WITH WILD-TYPE UDG AND WILD-TYPE UGI
  1vk2		Crystal structure of Uracil-DNA glycosylase (TM0511) from Thermotoga maritima at 1.90 A resolution
  1wyw		Crystal Structure of SUMO1-conjugated thymine DNA glycosylase
  1yuo		Optimisation of the surface electrostatics as a strategy for cold adaptation of uracil-DNA N-glycosylase (UNG)from atlantic cod (Gadus morhua)
  2boo		The crystal structure of Uracil-DNA N-Glycosylase (UNG) from Deinococcus radiodurans.
  2c53		A comparative study of uracil DNA glycosylases from human and herpes simplex virus type 1
  2c56		A comparative study of uracil DNA glycosylases from human and herpes simplex virus type 1
  2d07		Crystal Structure of SUMO-3-modified Thymine-DNA Glycosylase
  2d3y		Crystal structure of uracil-DNA glycosylase from Thermus Thermophilus HB8
  2ddg		Crystal structure of uracil-DNA glycosylase in complex with AP:G containing DNA
  2dem		Crystal structure of Uracil-DNA glycosylase in complex with AP:A containing DNA
  2dp6		Crystal structure of uracil-DNA glycosylase in complex with AP:C containing DNA
  2eug		CRYSTAL STRUCTURE OF ESCHERICHIA COLI URACIL DNA GLYCOSYLASE AND ITS COMPLEXES WITH URACIL AND GLYCEROL: STRUCTURE AND GLYCOSYLASE MECHANISM REVISITED
  2hxm		Complex of UNG2 and a small Molecule synthetic Inhibitor
  2j8x		Epstein-Barr virus uracil-DNA glycosylase in complex with Ugi from PBS-2
  2jhq		Crystal structure of Uracil DNA-glycosylase from Vibrio cholerae
  2l3f		Solution NMR Structure of a putative Uracil DNA glycosylase from Methanosarcina acetivorans, Northeast Structural Genomics Consortium Target MvR76
  2oxm		Crystal structure of a UNG2/modified DNA complex that represent a stabilized short-lived extrahelical state in ezymatic DNA base flipping
  2oyt		Crystal Structure of UNG2/DNA(TM)
  2rba		Structure of Human Thymine DNA Glycosylase Bound to Abasic and Undamaged DNA
  2ssp		LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA
  2uug		ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE:INHIBITOR COMPLEX WITH H187D MUTANT UDG AND WILD-TYPE UGI
  2zhx		Crystal structure of Uracil-DNA Glycosylase from Mycobacterium tuberculosis in complex with a proteinaceous inhibitor
  3a7n		Crystal structure of uracil-DNA glycosylase from Mycobacterium tuberculosis
  3cxm		Leishmania naiffi uracil-DNA glycosylase in complex with 5-bromouracil
  3eug		CRYSTAL STRUCTURE OF ESCHERICHIA COLI URACIL DNA GLYCOSYLASE AND ITS COMPLEXES WITH URACIL AND GLYCEROL: STRUCTURE AND GLYCOSYLASE MECHANISM REVISITED
  3fcf		Complex of UNG2 and a fragment-based designed inhibitor
  3fci		Complex of UNG2 and a fragment-based designed inhibitor
  3fck		Complex of UNG2 and a fragment-based design inhibitor
  3fcl		Complex of UNG2 and a fragment-based designed inhibitor
  3ikb		The structure of a conserved protein from Streptococcus mutans UA159.
  3tkb		crystal structure of human uracil-DNA glycosylase D183G/K302R mutant
  3tr7		Structure of a uracil-DNA glycosylase (ung) from Coxiella burnetii
  3uf7		Co-crystal structure of Escherichia coli uracil-DNA glycosylase and a C-terminal fragement of the single-stranded DNA-binding protein
  3ufj		Human Thymine DNA Glycosylase Bound to Substrate Analog 2'-fluoro-2'-deoxyuridine
  3ufm		Co-crystal structure of Deinococcus radiodurans uracil-DNA glycosylase and the C-terminus of the single-stranded DNA-binding protein
  3uo7		Crystal structure of Human Thymine DNA Glycosylase Bound to Substrate 5-carboxylcytosine
  3uob		Crystal structure of Human Thymine DNA Glycosylase Bound to Substrate Analog 2'-deoxy-2'-beta-fluoro-cytidine
  3wdf		Staphylococcus aureus UDG
  3wdg		Staphylococcus aureus UDG / UGI complex
  3zoq		Structure of BsUDG-p56 complex
  3zor		Structure of BsUDG
  4eug		Crystallographic and Enzymatic Studies of an Active Site Variant H187Q of Escherichia Coli Uracil DNA Glycosylase: Crystal Structures of Mutant H187Q and its Uracil Complex
  4fnc		Human TDG in a post-reactive complex with 5-hydroxymethyluracil (5hmU)
  4jgc		Human TDG N140A mutant IN A COMPLEX WITH 5-carboxylcytosine (5caC)
  4l5n		Crystallographic Structure of HHV-1 Uracil-DNA Glycosylase complexed with the Bacillus phage PZA inhibitor protein p56
  4lyl		4LYL
  4skn		A NUCLEOTIDE-FLIPPING MECHANISM FROM THE STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO DNA
  4uqm		4UQM
  4wpk		4WPK
  4wpl		4WPL
  4wru		4WRU
  4wrv		4WRV
  4wrw		4WRW
  4wrx		4WRX
  4wry		4WRY
  4wrz		4WRZ
  4ws0		4WS0
  4ws1		4WS1
  4ws2		4WS2
  4ws3		4WS3
  4ws4		4WS4
  4ws5		4WS5
  4ws6		4WS6
  4ws7		4WS7
  4ws8		4WS8
  4xeg		4XEG
  4z3a		4Z3A
  4z47		4Z47
  4z7b		4Z7B
  4z7z		4Z7Z
  4zbx		4ZBX
  4zby		4ZBY
  4zbz		4ZBZ
  5ayr		5AYR
  5ays		5AYS
  5cys		5CYS
  5eug		CRYSTALLOGRAPHIC AND ENZYMATIC STUDIES OF AN ACTIVE SITE VARIANT H187Q OF ESCHERICHIA COLI URACIL DNA GLYCOSYLASE: CRYSTAL STRUCTURES OF MUTANT H187Q AND ITS URACIL COMPLEX
  5ff8		5FF8
  5h93		5H93
  5h98		5H98
  5h99		5H99
  5h9i		5H9I
  5hf7		5HF7
  5jk7		5JK7
  5jxy		5JXY
  5t2w		5T2W

• Links (links to other resources describing this domain)

• PFAM	UDG
  INTERPRO	IPR005122

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