TET3 Recombinant Protein

Function: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin

By similarity. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Ref.6

Catalytic activity: DNA 5-methylcytosine + 2-oxoglutarate + O2 = DNA 5-hydroxymethylcytosine + succinate + CO2.

Cofactor: Binds 1 Fe2+ ion per subunit

By similarity.

Subunit structure: Interacts with HCFC1 and OGT. Ref.6 Ref.7

Subcellular location: Nucleus

By similarity. Cytoplasm

By similarity. Note: At the zygotic stage, localizes in the male pronucleus, while it localizes to the cytoplasm at other preimplantation stages

By similarity.

Tissue specificity: Expressed in colon, muscle, adrenal gland and peripheral blood lymphocytes. Ref.5

Developmental stage: Expressed in fetal brain but not adult brain. Ref.5

Sequence similarities: Belongs to the TET family.

Caution: Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG.

Sequence caution: The sequence AAH22243.1 differs from that shown. Reason: Erroneous initiation. The sequence AAX93057.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAA23697.1 differs from that shown. Reason: Erroneous initiation.