UniProt functional annotation for Q13569



	UniProt functional annotation for Q13569

UniProt code: Q13569.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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

Catalytic activity: Reaction=Hydrolyzes mismatched double-stranded DNA and polynucleotides, releasing free thymine.; EC=3.2.2.29;

Subunit: Homodimer. Interacts with AICDA and GADD45A. {ECO:0000269|PubMed:18587051, ECO:0000269|PubMed:21722948, ECO:0000269|PubMed:22327402, ECO:0000269|PubMed:22573813, ECO:0000269|PubMed:22962365}.

Subcellular location: Nucleus {ECO:0000269|PubMed:8662714}.

Ptm: Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces dissociation of the product DNA. {ECO:0000269|PubMed:11889051}.

Similarity: Belongs to the uracil-DNA glycosylase (UDG) superfamily. TDG/mug family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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


Catalytic activity:		Reaction=Hydrolyzes mismatched double-stranded DNA and polynucleotides, releasing free thymine.; EC=3.2.2.29;
Subunit:		Homodimer. Interacts with AICDA and GADD45A. {ECO:0000269\|PubMed:18587051, ECO:0000269\|PubMed:21722948, ECO:0000269\|PubMed:22327402, ECO:0000269\|PubMed:22573813, ECO:0000269\|PubMed:22962365}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:8662714}.
Ptm:		Sumoylation on Lys-330 by either SUMO1 or SUMO2 induces dissociation of the product DNA. {ECO:0000269\|PubMed:11889051}.
Similarity:		Belongs to the uracil-DNA glycosylase (UDG) superfamily. TDG/mug family. {ECO:0000305}.