Thymine-DNA glycosylase

G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene.^[4][5][6] Several bacterial proteins have strong sequence homology with this protein.^[7]

TDG
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1WYW, 2D07, 2RBA, 3UFJ, 3UO7, 3UOB, 4FNC, 4JGC, 4XEG, 4Z3A, 4Z47, 4Z7B, 4Z7Z, 5CYS
Identifiers
Aliases	TDG, hThymine-DNA glycosylase, thymine DNA glycosylase
External IDs	OMIM: 601423; MGI: 3645587; HomoloGene: 2415; GeneCards: TDG; OMA:TDG - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q23.3 Start 103,965,822 bp[1] End 103,988,874 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell visceral pleura tibia endothelial cell epithelium of nasopharynx gingival epithelium parietal pleura amniotic fluid germinal epithelium hair follicle n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity transcription coregulator activity damaged DNA binding protein binding double-stranded DNA binding hydrolase activity protein kinase C binding transcription factor binding DNA N-glycosylase activity mismatched DNA binding protein domain specific binding DNA binding magnesium ion binding uracil DNA N-glycosylase activity ATP binding pyrimidine-specific mismatch base pair DNA N-glycosylase activity sodium ion binding chloride ion binding SUMO binding protein self-association G/U mismatch-specific uracil-DNA glycosylase activity Cellular component PML body plasma membrane nucleoplasm nucleus Biological process regulation of transcription, DNA-templated embryo development negative regulation of chromatin binding oxidative DNA demethylation negative regulation of transcription by RNA polymerase II negative regulation of protein binding transcription, DNA-templated cellular response to DNA damage stimulus depyrimidination DNA demethylation base-excision repair DNA repair DNA mismatch repair regulation of gene expression, epigenetic base-excision repair, AP site formation regulation of DNA N-glycosylase activity chromatin organization regulation of embryonic development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6996 545124 Ensembl ENSG00000139372 n/a UniProt Q13569 n/a RefSeq (mRNA) NM_001008411 NM_003211 NM_001363612 XM_006521630 RefSeq (protein) NP_003202 NP_001350541 n/a Location (UCSC) Chr 12: 103.97 – 103.99 Mb n/a PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine moieties from G/T mismatches by hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of DNA and the mispaired thymine. With lower activity, this enzyme also removes thymine from C/T and T/T mispairings. TDG can also remove uracil and 5-bromouracil from mispairings with guanine. TDG knockout mouse models showed no increase in mispairing frequency suggesting that other enzymes, like the functional homologue MBD4, may provide functional redundancy. This gene may have a pseudogene in the p arm of chromosome 12.^[6]

Additionally, in 2011, the human thymine DNA glycosylase (hTDG) was reported to efficiently excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), the key oxidation products of 5-methylcytosine in genomic DNA.^[8] Later on, the crystal structure of the hTDG catalytic domain in complex with duplex DNA containing 5caC was published, which supports the role of TDG in mammalian 5-methylcytosine demethylation.^[9]

Interactions

Thymine-DNA glycosylase has been shown to interact with:

• CREB-binding protein,^[10]
• Estrogen receptor alpha,^[11]
• Promyelocytic leukemia protein,^[12]
• SUMO3,^[13] and
• Small ubiquitin-related modifier 1.^[13][14]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

See also

• DNA-deoxyinosine glycosylase
• SMUG1
• Uracil-DNA glycosylase
• MBD4