InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TDG

Summary

InnateDB Protein

IDBP-244771.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TDG

Protein Name

thymine-DNA glycosylase

Synonyms

hTDG;

Species

Homo sapiens

Ensembl Protein

ENSP00000376611

InnateDB Gene

IDBG-54193 (TDG)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:21862836, ECO:0000269PubMed:22327402, ECO:0000269PubMed:22573813, ECO:0000269PubMed:22962365, ECO:0000269PubMed:8127859, ECO:0000269PubMed:8407958, ECO:0000269PubMed:8662714}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:8662714}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 45 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	45 [view]
Protein-Protein	44 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001104	RNA polymerase II transcription cofactor activity
GO:0003684	damaged DNA binding
GO:0003690	double-stranded DNA binding
GO:0005080	protein kinase C binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008263	pyrimidine-specific mismatch base pair DNA N-glycosylase activity
GO:0016798	hydrolase activity, acting on glycosyl bonds
GO:0019104	DNA N-glycosylase activity
GO:0019904	protein domain specific binding
GO:0030983	mismatched DNA binding
GO:0032183	SUMO binding
GO:0042803	protein homodimerization activity
GO:0043566	structure-specific DNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006281	DNA repair
GO:0006284	base-excision repair
GO:0006285	base-excision repair, AP site formation
GO:0006298	mismatch repair
GO:0006366	transcription from RNA polymerase II promoter
GO:0009790	embryo development
GO:0016568	chromatin modification
GO:0032091	negative regulation of protein binding
GO:0035562	negative regulation of chromatin binding
GO:0040029	regulation of gene expression, epigenetic
GO:0045008	depyrimidination
GO:0080111	DNA demethylation