KDM5D (Lysine Demethylase 5D), also known as JARID1D, is a JmjC domain-containing histone demethylase that specifically catalyzes the removal of methyl groups from histone H3 lysine 4 (H3K4me2/me3).[1] This protein is a member of the KDM5 (JARID1) family of histone demethylases, which play important roles in epigenetic regulation of gene expression.
| Property | Value |
|---|---|
| Protein Name | Lysine Demethylase 5D |
| Gene | KDM5D |
| UniProt ID | Q9Y2T7 |
| Molecular Weight | ~175 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | KDM5/JARID1 family |
KDM5D contains several functional domains:[2]
KDM5D catalyzes the oxidative demethylation of H3K4me2 and H3K4me3, histone marks associated with active transcription.[1:1] By removing these marks, KDM5D functions as a transcriptional repressor.
While KDM5D is primarily studied in the context of reproduction and cancer, the broader KDM5 family has implications for neurodegenerative diseases:[4]
KDM5D is not a direct cause of neurodegenerative diseases, but the KDM5 family is relevant to neurodegeneration research:
KDM5D has more established roles in cancer:[3:1]
Several KDM5 inhibitors are in development:[5]
Christensen J, et al. Transduction of dimensionality and transcriptional regulation by histone demethylation. Cell. 2007. ↩︎ ↩︎
Klose RJ, et al. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell. 2007. ↩︎
Kim J, et al. KDM5D-mediated demethylation of H3K4 marks male germ cell genes. Nature. 2014. ↩︎ ↩︎
Maze I, et al. Histone methylation in neuronal function. Nature Reviews Neuroscience. 2010. ↩︎
Rusche KM, et al. KDM5 histone demethylases as potential therapeutic targets. Frontiers in Cell and Developmental Biology. 2022. ↩︎