Protein: G/T mismatch-specific thymine DNA glycosylase (EC 3.2.2.29) (Thymine-DNA glycosylase) (hTDG) (Q13569)
Organism: Homo sapiens (Human)
Function: DNA glycosylase that plays a key role in active DNA demethylation: specifically recognizes and binds 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates their excision through base-excision repair (BER) to install an unmethylated cytosine. Cannot remove 5-hydroxymethylcytosine (5hmC). According to an alternative model, involved in DNA demethylation by mediating DNA glycolase activity toward 5-hydroxymethyluracil (5hmU) produced by deamination of 5hmC. Also involved in DNA repair by acting as a thymine-DNA glycosylase that mediates correction of G/T mispairs to G/C pairs: in the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. Its role in the repair of canonical base damage is however minor compared to its role in DNA demethylation. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine.
Subcellular location: Nucleus {ECO:0000269|PubMed:8662714}.
Sequence: MEAENAGSYSLQQAQAFYTFPFQQLMAEAPNMAVVNEQQMPEEVPAPAPAQEPVQEAPKGRKRKPRTTEPKQPVEPKKPVESKKSGKSAKSKEKQEKITDTFKVKRKVDRFNGVSEAELLTKTLPDILTFNLDIVIIGINPGLMAAYKGHHYPGPGNHFWKCLFMSGLSEVQLNHMDDHTLPGKYGIGFTNMVERTTPGSKDLSSKEFREGGRILVQKLQKYQPRIAVFNGKCIYEIFSKEVFGVKVKNLEFGLQPHKIPDTETLCYVMPSSSARCAQFPRAQDKVHYYIKLKDLRDQLKGIERNMDVQEVQYTFDLQLAQEDAKKMAVKEEKYDPGYEAAYGGAYGENPCSSEPCGFSSNGLIESVELRGESAFSGIPNGQWMTQSFTDQIPSFSNHCGTQEQEEESHA
InterPro domains: - IPR005122: Uracil-DNA glycosylase-like (domain) [129-289]
- IPR015637: Uracil DNA glycosylase family 2 (family) [29-347]
- IPR003310: G/T mismatch-specific thymine DNA glycosylasee TDG-like, eukaryotes (family) [2-329]
- IPR036895: Uracil-DNA glycosylase-like domain superfamily (homologous_superfamily) [105-308]
Interaction partners: - Small ubiquitin-related modifier 1
- Small ubiquitin-related modifier 2
- Growth arrest and DNA damage-inducible protein GADD45 alpha
- DNA
- Single-strand selective monofunctional uracil DNA glycosylase
- SUMO-conjugating enzyme UBC9
- Uracil-DNA glycosylase
- DNA repair nuclease/redox regulator APEX1
- DNA
- Methyl-CpG-binding domain protein 4
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:1901363 (heterocyclic compound binding), GO:0003700 (DNA-binding transcription factor activity), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0001217 (DNA-binding transcription repressor activity), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0001227 (DNA-binding transcription repressor activity, RNA polymerase II-specific), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0016043 (cellular component organization), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0006325 (chromatin organization), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:0006338 (chromatin remodeling), GO:0098732 (macromolecule deacylation), GO:2001141 (regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0016570 (histone modification), GO:0035601 (protein deacylation), GO:0006357 (regulation of transcription by RNA polymerase II), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0016575 (histone deacetylation), GO:0006476 (protein deacetylation), GO:0045892 (negative regulation of DNA-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)