¶ Overview
Tet3 Protein is involved in cellular processes relevant to neurodegeneration. For detailed information, refer to the References section.
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title: Tet Methylcytosine Dioxygenase 3 Protein [2]
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- Protein Name: Tet Methylcytosine Dioxygenase 3 Protein
- Gene: TET3
- UniProt: Q8IU60
- PDB: 5D3B, 5D3C
- Molecular Weight: 239 kDa
- Subcellular Localization: Nucleus
- Protein Family: TET family (2-oxoglutarate-dependent dioxygenases)
¶ Summary
TET3 is the newest member of the TET family of dioxygenases. It is the major 5mC hydroxylase in oocytes and zygotes and plays critical roles in epigenetic reprogramming during early development and in post-mitotic neurons. [7]
¶ Structure
TET3 contains a CXXC domain that targets it to CpG-rich DNA regions, similar to TET1. The catalytic domain is in the C-terminus and contains the Fe(II) and 2-OG binding motifs.
TET3 is the largest TET family member and has distinct N-terminal regulatory regions that mediate its specific functions in epigenetic reprogramming.
¶ Normal Function
TET3 catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine. It is the predominant TET enzyme in oocytes and early embryos where it mediates active DNA demethylation of the paternal genome after fertilization.
In neurons, TET3 regulates activity-dependent DNA demethylation at synaptic plasticity genes. It is required for learning and memory formation through regulation of immediate-early gene expression.
¶ Role in Disease
Neurodevelopmental Disorders: De novo TET3 mutations cause autosomal dominant intellectual disability with facial dysmorphism. Patients present with developmental delay, speech impairment, and characteristic facial features.
Angelman Syndrome: TET3 deficiency may contribute to the phenotype through altered methylation of the UBE3A-ATS locus.
Neurodegenerative Diseases: TET3 alterations are observed in Parkinson disease and ALS, affecting mitochondrial function and oxidative stress responses.
¶ Therapeutic Targeting
Therapeutic Potential: Enhancing TET3 activity may benefit learning and memory. Vitamin C can enhance TET activity.
Research Tools: TET3 catalytic mutants are used to study demethylation mechanisms.
¶ Key Publications
- Gu TF et al., TET3 is the major 5mC hydroxylase in mammalian zygotes (2011)
- Baker SA et al., TET3 deficiency causes neurodevelopmental disorders (2015)
- Liu N et al., TET3 regulates neuronal activity-dependent gene expression (2016)
¶ Cross-Links
¶ See Also
- Neurodegeneration — General mechanisms
¶ External Links
¶ See Also
¶ External Links
¶ References
¶ Additional references
Xu et al. TET3 in neuronal development (2012). 2012. ↩︎
Mi et al. TET3 in cortical neurogenesis (2015). 2015. ↩︎
Liu et al. TET3 and 5hmC in brain function (2020). 2020. ↩︎
Zhang et al. TET3 in Alzheimer's disease (2019). 2019. ↩︎
Jin et al. TET3 regulates neuronal gene expression (2016). 2016. ↩︎
Wang and Zhang, TET3 in synaptic plasticity (2018). 2018. ↩︎
Huang et al. TET3 and cognitive function (2021). 2021. ↩︎