Q13569 · TDG_HUMAN
- ProteinG/T mismatch-specific thymine DNA glycosylase
- GeneTDG
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids410 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
Catalytic activity
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameG/T mismatch-specific thymine DNA glycosylase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13569
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 140 | Loss of DNA glycosylase activity but still able to bind DNA. | ||||
Sequence: N → A | ||||||
Mutagenesis | 145 | Increased DNA glycosylase activity on G/T mispairs. | ||||
Sequence: A → G | ||||||
Mutagenesis | 151 | Increased DNA glycosylase activity on G/T mispairs. | ||||
Sequence: H → A or Q | ||||||
Mutagenesis | 191 | Reduced DNA glycosylase activity on G/T and G/U mispairs. | ||||
Sequence: N → A | ||||||
Mutagenesis | 197 | Reduced DNA glycosylase activity on G/T mispairs. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_018892 | 199 | in dbSNP:rs4135113 | |||
Sequence: G → S | ||||||
Mutagenesis | 281 | Restores the DNA-binding ability of the sumoylated form. | ||||
Sequence: R → A | ||||||
Mutagenesis | 310 | Restores the DNA-binding ability of the sumoylated form. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 315 | Restores the DNA-binding ability of the sumoylated form. | ||||
Sequence: F → A | ||||||
Natural variant | VAR_059450 | 367 | in dbSNP:rs2888805 | |||
Sequence: V → L | ||||||
Natural variant | VAR_018893 | 367 | in dbSNP:rs2888805 | |||
Sequence: V → M | ||||||
Natural variant | VAR_050140 | 381 | in dbSNP:rs3953597 | |||
Sequence: G → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 475 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000185777 | 1-410 | G/T mismatch-specific thymine DNA glycosylase | |||
Sequence: MEAENAGSYSLQQAQAFYTFPFQQLMAEAPNMAVVNEQQMPEEVPAPAPAQEPVQEAPKGRKRKPRTTEPKQPVEPKKPVESKKSGKSAKSKEKQEKITDTFKVKRKVDRFNGVSEAELLTKTLPDILTFNLDIVIIGINPGLMAAYKGHHYPGPGNHFWKCLFMSGLSEVQLNHMDDHTLPGKYGIGFTNMVERTTPGSKDLSSKEFREGGRILVQKLQKYQPRIAVFNGKCIYEIFSKEVFGVKVKNLEFGLQPHKIPDTETLCYVMPSSSARCAQFPRAQDKVHYYIKLKDLRDQLKGIERNMDVQEVQYTFDLQLAQEDAKKMAVKEEKYDPGYEAAYGGAYGENPCSSEPCGFSSNGLIESVELRGESAFSGIPNGQWMTQSFTDQIPSFSNHCGTQEQEEESHA | ||||||
Cross-link | 103 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 248 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 330 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 330 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K |
Post-translational modification
Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces dissociation of the product DNA.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer. Interacts with AICDA and GADD45A.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q13569 | AICDA Q9GZX7 | 5 | EBI-348333, EBI-3834328 | |
BINARY | Q13569 | APBB2 Q92870-2 | 3 | EBI-348333, EBI-21535880 | |
BINARY | Q13569 | GADD45A P24522 | 3 | EBI-348333, EBI-448167 | |
BINARY | Q13569 | GRN P28799 | 3 | EBI-348333, EBI-747754 | |
BINARY | Q13569 | HSPB1 P04792 | 3 | EBI-348333, EBI-352682 | |
BINARY | Q13569 | KIF1B O60333-2 | 3 | EBI-348333, EBI-10975473 | |
BINARY | Q13569 | NCOA1 Q15788 | 8 | EBI-348333, EBI-455189 | |
BINARY | Q13569 | NCOA1 Q15788-2 | 2 | EBI-348333, EBI-5327712 | |
BINARY | Q13569 | NEFL P07196 | 3 | EBI-348333, EBI-475646 | |
BINARY | Q13569 | PMP22 A0A6Q8PF08 | 3 | EBI-348333, EBI-50433196 | |
BINARY | Q13569 | PRPS1 P60891 | 3 | EBI-348333, EBI-749195 | |
BINARY | Q13569 | RNF11 Q9Y3C5 | 3 | EBI-348333, EBI-396669 | |
XENO | Q13569 | Rnf4 O88846 | 2 | EBI-348333, EBI-7258907 | |
BINARY | Q13569 | SNCA P37840 | 3 | EBI-348333, EBI-985879 | |
BINARY | Q13569 | SUMO1 P63165 | 3 | EBI-348333, EBI-80140 | |
BINARY | Q13569 | SUMO2 P61956 | 2 | EBI-348333, EBI-473220 | |
BINARY | Q13569 | TTR P02766 | 3 | EBI-348333, EBI-711909 | |
BINARY | Q13569 | WFS1 O76024 | 3 | EBI-348333, EBI-720609 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 37-97 | Disordered | ||||
Sequence: EQQMPEEVPAPAPAQEPVQEAPKGRKRKPRTTEPKQPVEPKKPVESKKSGKSAKSKEKQEK | ||||||
Compositional bias | 56-97 | Basic and acidic residues | ||||
Sequence: EAPKGRKRKPRTTEPKQPVEPKKPVESKKSGKSAKSKEKQEK |
Sequence similarities
Belongs to the uracil-DNA glycosylase (UDG) superfamily. TDG/mug family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length410
- Mass (Da)46,053
- Last updated2004-04-13 v2
- Checksum33752B26EBC789AE
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 56-97 | Basic and acidic residues | ||||
Sequence: EAPKGRKRKPRTTEPKQPVEPKKPVESKKSGKSAKSKEKQEK | ||||||
Sequence conflict | 91 | in Ref. 1; AAC50540 | ||||
Sequence: S → P | ||||||
Sequence conflict | 268 | in Ref. 4; AAH37557 | ||||
Sequence: V → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U51166 EMBL· GenBank· DDBJ | AAC50540.1 EMBL· GenBank· DDBJ | mRNA | ||
AF545435 EMBL· GenBank· DDBJ | AAN16399.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC078819 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC037557 EMBL· GenBank· DDBJ | AAH37557.1 EMBL· GenBank· DDBJ | mRNA |