UniProtKB - Q13569 (TDG_HUMAN)
G/T mismatch-specific thymine DNA glycosylase
TDG
Functioni
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.
7 PublicationsCatalytic activityi
- Hydrolyzes mismatched double-stranded DNA and polynucleotides, releasing free thymine. EC:3.2.2.29
GO - Molecular functioni
- ATP binding Source: CAFA
- chloride ion binding Source: CAFA
- damaged DNA binding Source: ProtInc
- DNA binding Source: UniProtKB
- DNA-binding transcription factor binding Source: Ensembl
- DNA N-glycosylase activity Source: UniProtKB
- double-stranded DNA binding Source: UniProtKB
- G/U mismatch-specific uracil-DNA glycosylase activity Source: CAFA
- magnesium ion binding Source: CAFA
- mismatched DNA binding Source: UniProtKB
- protein domain specific binding Source: Ensembl
- protein homodimerization activity Source: UniProtKB
- protein kinase C binding Source: Ensembl
- protein self-association Source: CAFA
- pyrimidine-specific mismatch base pair DNA N-glycosylase activity Source: UniProtKB
- sodium ion binding Source: CAFA
- SUMO binding Source: CAFA
- transcription coregulator activity Source: Ensembl
- uracil DNA N-glycosylase activity Source: CAFA
GO - Biological processi
- base-excision repair Source: UniProtKB
- base-excision repair, AP site formation Source: CAFA
- depyrimidination Source: Reactome
- DNA demethylation Source: UniProtKB
- mismatch repair Source: UniProtKB
- negative regulation of chromatin binding Source: Ensembl
- negative regulation of protein binding Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: Ensembl
- oxidative DNA demethylation Source: Reactome
- regulation of DNA N-glycosylase activity Source: CAFA
- regulation of embryonic development Source: UniProtKB
- regulation of gene expression, epigenetic Source: UniProtKB
Keywordsi
Molecular function | Activator, Chromatin regulator, Hydrolase |
Biological process | DNA damage, DNA repair, Transcription, Transcription regulation |
Enzyme and pathway databases
BRENDAi | 3.2.2.29, 2681 |
PathwayCommonsi | Q13569 |
Reactomei | R-HSA-110328, Recognition and association of DNA glycosylase with site containing an affected pyrimidine R-HSA-110329, Cleavage of the damaged pyrimidine R-HSA-110357, Displacement of DNA glycosylase by APEX1 R-HSA-3108214, SUMOylation of DNA damage response and repair proteins R-HSA-5221030, TET1,2,3 and TDG demethylate DNA |
SignaLinki | Q13569 |
Names & Taxonomyi
Protein namesi | Recommended name: G/T mismatch-specific thymine DNA glycosylase (EC:3.2.2.29)Alternative name(s): Thymine-DNA glycosylase Short name: hTDG |
Gene namesi | Name:TDG |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11700, TDG |
MIMi | 601423, gene |
neXtProti | NX_Q13569 |
VEuPathDBi | HostDB:ENSG00000139372 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
- PML body Source: Ensembl
Plasma Membrane
- plasma membrane Source: HPA
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 140 | N → A: Loss of DNA glycosylase activity but still able to bind DNA. 1 Publication | 1 | |
Mutagenesisi | 145 | A → G: Increased DNA glycosylase activity on G/T mispairs. 1 Publication | 1 | |
Mutagenesisi | 151 | H → A or Q: Increased DNA glycosylase activity on G/T mispairs. 1 Publication | 1 | |
Mutagenesisi | 191 | N → A: Reduced DNA glycosylase activity on G/T and G/U mispairs. 1 Publication | 1 | |
Mutagenesisi | 197 | T → A: Reduced DNA glycosylase activity on G/T mispairs. 1 Publication | 1 | |
Mutagenesisi | 281 | R → A: Restores the DNA-binding ability of the sumoylated form. 1 Publication | 1 | |
Mutagenesisi | 310 | E → Q: Restores the DNA-binding ability of the sumoylated form. 2 Publications | 1 | |
Mutagenesisi | 315 | F → A: Restores the DNA-binding ability of the sumoylated form. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 6996 |
OpenTargetsi | ENSG00000139372 |
PharmGKBi | PA36419 |
Miscellaneous databases
Pharosi | Q13569, Tbio |
Genetic variation databases
BioMutai | TDG |
DMDMi | 46397791 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000185777 | 1 – 410 | G/T mismatch-specific thymine DNA glycosylaseAdd BLAST | 410 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 103 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 248 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 330 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||
Cross-linki | 330 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Ubl conjugationProteomic databases
EPDi | Q13569 |
MassIVEi | Q13569 |
MaxQBi | Q13569 |
PaxDbi | Q13569 |
PeptideAtlasi | Q13569 |
PRIDEi | Q13569 |
ProteomicsDBi | 59573 |
PTM databases
iPTMneti | Q13569 |
PhosphoSitePlusi | Q13569 |
Expressioni
Gene expression databases
Bgeei | ENSG00000139372, Expressed in forebrain and 247 other tissues |
ExpressionAtlasi | Q13569, baseline and differential |
Genevisiblei | Q13569, HS |
Organism-specific databases
HPAi | ENSG00000139372, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
Interacts with AICDA and GADD45A.
5 PublicationsBinary interactionsi
Q13569
GO - Molecular functioni
- DNA-binding transcription factor binding Source: Ensembl
- protein domain specific binding Source: Ensembl
- protein homodimerization activity Source: UniProtKB
- protein kinase C binding Source: Ensembl
- protein self-association Source: CAFA
- SUMO binding Source: CAFA
Protein-protein interaction databases
BioGRIDi | 112855, 49 interactors |
DIPi | DIP-32709N |
ELMi | Q13569 |
IntActi | Q13569, 29 interactors |
MINTi | Q13569 |
STRINGi | 9606.ENSP00000376611 |
Miscellaneous databases
RNActi | Q13569, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q13569 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13569 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 37 – 97 | DisorderedSequence analysisAdd BLAST | 61 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 56 – 97 | Basic and acidic residuesSequence analysisAdd BLAST | 42 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG4120, Eukaryota |
GeneTreei | ENSGT00390000000987 |
HOGENOMi | CLU_045775_1_0_1 |
InParanoidi | Q13569 |
OMAi | LPVKYKM |
OrthoDBi | 1209629at2759 |
PhylomeDBi | Q13569 |
TreeFami | TF328764 |
Family and domain databases
CDDi | cd10028, UDG-F2_TDG_MUG, 1 hit |
DisProti | DP00719 |
Gene3Di | 3.40.470.10, 1 hit |
InterProi | View protein in InterPro IPR015637, MUG/TDG IPR003310, TDG-like_euk IPR005122, Uracil-DNA_glycosylase-like IPR036895, Uracil-DNA_glycosylase-like_sf |
PANTHERi | PTHR12159, PTHR12159, 1 hit |
Pfami | View protein in Pfam PF03167, UDG, 1 hit |
SUPFAMi | SSF52141, SSF52141, 1 hit |
TIGRFAMsi | TIGR00584, mug, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MEAENAGSYS LQQAQAFYTF PFQQLMAEAP NMAVVNEQQM PEEVPAPAPA
60 70 80 90 100
QEPVQEAPKG RKRKPRTTEP KQPVEPKKPV ESKKSGKSAK SKEKQEKITD
110 120 130 140 150
TFKVKRKVDR FNGVSEAELL TKTLPDILTF NLDIVIIGIN PGLMAAYKGH
160 170 180 190 200
HYPGPGNHFW KCLFMSGLSE VQLNHMDDHT LPGKYGIGFT NMVERTTPGS
210 220 230 240 250
KDLSSKEFRE GGRILVQKLQ KYQPRIAVFN GKCIYEIFSK EVFGVKVKNL
260 270 280 290 300
EFGLQPHKIP DTETLCYVMP SSSARCAQFP RAQDKVHYYI KLKDLRDQLK
310 320 330 340 350
GIERNMDVQE VQYTFDLQLA QEDAKKMAVK EEKYDPGYEA AYGGAYGENP
360 370 380 390 400
CSSEPCGFSS NGLIESVELR GESAFSGIPN GQWMTQSFTD QIPSFSNHCG
410
TQEQEEESHA
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG8JL98 | G8JL98_HUMAN | G/T mismatch-specific thymine DNA g... | TDG | 406 | Annotation score: | ||
F5H0I7 | F5H0I7_HUMAN | G/T mismatch-specific thymine DNA g... | TDG | 257 | Annotation score: | ||
B4E127 | B4E127_HUMAN | G/T mismatch-specific thymine DNA g... | TDG | 267 | Annotation score: | ||
F5H539 | F5H539_HUMAN | G/T mismatch-specific thymine DNA g... | TDG | 138 | Annotation score: | ||
H0YH18 | H0YH18_HUMAN | G/T mismatch-specific thymine DNA g... | TDG | 111 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 91 | S → P in AAC50540 (PubMed:8662714).Curated | 1 | |
Sequence conflicti | 268 | V → G in AAH37557 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018892 | 199 | G → S1 PublicationCorresponds to variant dbSNP:rs4135113Ensembl. | 1 | |
Natural variantiVAR_059450 | 367 | V → L. Corresponds to variant dbSNP:rs2888805Ensembl. | 1 | |
Natural variantiVAR_018893 | 367 | V → M1 PublicationCorresponds to variant dbSNP:rs2888805Ensembl. | 1 | |
Natural variantiVAR_050140 | 381 | G → E. Corresponds to variant dbSNP:rs3953597Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U51166 mRNA Translation: AAC50540.1 AF545435 Genomic DNA Translation: AAN16399.1 AC078819 Genomic DNA No translation available. BC037557 mRNA Translation: AAH37557.1 |
CCDSi | CCDS9095.1 |
RefSeqi | NP_003202.3, NM_003211.4 |
Genome annotation databases
Ensembli | ENST00000392872; ENSP00000376611; ENSG00000139372 |
GeneIDi | 6996 |
KEGGi | hsa:6996 |
MANE-Selecti | ENST00000392872.8; ENSP00000376611.3; NM_003211.6; NP_003202.3 |
UCSCi | uc001tkg.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U51166 mRNA Translation: AAC50540.1 AF545435 Genomic DNA Translation: AAN16399.1 AC078819 Genomic DNA No translation available. BC037557 mRNA Translation: AAH37557.1 |
CCDSi | CCDS9095.1 |
RefSeqi | NP_003202.3, NM_003211.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1WYW | X-ray | 2.10 | A | 112-339 | [»] | |
2D07 | X-ray | 2.10 | A | 112-339 | [»] | |
2RBA | X-ray | 2.79 | A/B | 111-308 | [»] | |
3UFJ | X-ray | 2.97 | A/B | 111-308 | [»] | |
3UO7 | X-ray | 3.00 | A/B | 111-308 | [»] | |
3UOB | X-ray | 3.01 | A/B | 111-308 | [»] | |
4FNC | X-ray | 2.49 | A | 111-308 | [»] | |
4JGC | X-ray | 2.58 | A | 111-308 | [»] | |
4XEG | X-ray | 1.72 | A | 111-308 | [»] | |
4Z3A | X-ray | 1.72 | A | 111-308 | [»] | |
4Z47 | X-ray | 1.45 | A | 111-308 | [»] | |
4Z7B | X-ray | 2.02 | A | 111-308 | [»] | |
4Z7Z | X-ray | 1.83 | A | 111-308 | [»] | |
5CYS | X-ray | 2.45 | A | 111-308 | [»] | |
5FF8 | X-ray | 1.70 | A | 82-308 | [»] | |
5HF7 | X-ray | 1.54 | A | 82-308 | [»] | |
5JXY | X-ray | 1.71 | A | 111-308 | [»] | |
5T2W | X-ray | 2.20 | A | 82-308 | [»] | |
6U15 | X-ray | 2.40 | A | 82-308 | [»] | |
6U16 | X-ray | 1.60 | A | 82-308 | [»] | |
6U17 | X-ray | 1.55 | A | 82-308 | [»] | |
SMRi | Q13569 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112855, 49 interactors |
DIPi | DIP-32709N |
ELMi | Q13569 |
IntActi | Q13569, 29 interactors |
MINTi | Q13569 |
STRINGi | 9606.ENSP00000376611 |
PTM databases
iPTMneti | Q13569 |
PhosphoSitePlusi | Q13569 |
Genetic variation databases
BioMutai | TDG |
DMDMi | 46397791 |
Proteomic databases
EPDi | Q13569 |
MassIVEi | Q13569 |
MaxQBi | Q13569 |
PaxDbi | Q13569 |
PeptideAtlasi | Q13569 |
PRIDEi | Q13569 |
ProteomicsDBi | 59573 |
Protocols and materials databases
Antibodypediai | 30563, 409 antibodies from 31 providers |
DNASUi | 6996 |
Genome annotation databases
Ensembli | ENST00000392872; ENSP00000376611; ENSG00000139372 |
GeneIDi | 6996 |
KEGGi | hsa:6996 |
MANE-Selecti | ENST00000392872.8; ENSP00000376611.3; NM_003211.6; NP_003202.3 |
UCSCi | uc001tkg.4, human |
Organism-specific databases
CTDi | 6996 |
DisGeNETi | 6996 |
GeneCardsi | TDG |
HGNCi | HGNC:11700, TDG |
HPAi | ENSG00000139372, Low tissue specificity |
MIMi | 601423, gene |
neXtProti | NX_Q13569 |
OpenTargetsi | ENSG00000139372 |
PharmGKBi | PA36419 |
VEuPathDBi | HostDB:ENSG00000139372 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4120, Eukaryota |
GeneTreei | ENSGT00390000000987 |
HOGENOMi | CLU_045775_1_0_1 |
InParanoidi | Q13569 |
OMAi | LPVKYKM |
OrthoDBi | 1209629at2759 |
PhylomeDBi | Q13569 |
TreeFami | TF328764 |
Enzyme and pathway databases
BRENDAi | 3.2.2.29, 2681 |
PathwayCommonsi | Q13569 |
Reactomei | R-HSA-110328, Recognition and association of DNA glycosylase with site containing an affected pyrimidine R-HSA-110329, Cleavage of the damaged pyrimidine R-HSA-110357, Displacement of DNA glycosylase by APEX1 R-HSA-3108214, SUMOylation of DNA damage response and repair proteins R-HSA-5221030, TET1,2,3 and TDG demethylate DNA |
SignaLinki | Q13569 |
Miscellaneous databases
BioGRID-ORCSi | 6996, 41 hits in 1012 CRISPR screens |
ChiTaRSi | TDG, human |
EvolutionaryTracei | Q13569 |
GeneWikii | Thymine-DNA_glycosylase |
GenomeRNAii | 6996 |
Pharosi | Q13569, Tbio |
PROi | PR:Q13569 |
RNActi | Q13569, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000139372, Expressed in forebrain and 247 other tissues |
ExpressionAtlasi | Q13569, baseline and differential |
Genevisiblei | Q13569, HS |
Family and domain databases
CDDi | cd10028, UDG-F2_TDG_MUG, 1 hit |
DisProti | DP00719 |
Gene3Di | 3.40.470.10, 1 hit |
InterProi | View protein in InterPro IPR015637, MUG/TDG IPR003310, TDG-like_euk IPR005122, Uracil-DNA_glycosylase-like IPR036895, Uracil-DNA_glycosylase-like_sf |
PANTHERi | PTHR12159, PTHR12159, 1 hit |
Pfami | View protein in Pfam PF03167, UDG, 1 hit |
SUPFAMi | SSF52141, SSF52141, 1 hit |
TIGRFAMsi | TIGR00584, mug, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TDG_HUMAN | |
Accessioni | Q13569Primary (citable) accession number: Q13569 Secondary accession number(s): Q8IUZ6, Q8IZM3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | April 13, 2004 | |
Last modified: | February 23, 2022 | |
This is version 187 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families