KDM5A
Domain
The GSGFP motif is required for the interaction with SUZ12 (By similarity). The ARID domain specifically binds to the CCGCCC motif and is required for the lysine-specific histone demethylase activity (PubMed:18270511). The PHD-type 3 zinc finger is required for the interaction with histone H3 di- and trimethylated at 'Lys-4' (PubMed:19430464).
Function
Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (PubMed:19430464). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (PubMed:27427228).
Involvement in disease
A chromosomal aberration involving KDM5A has been found in M5 type acute myeloid leukemia. Translocation t(11;12)(p15;p13) with NUP98.
Chromosomal aberrations involving KDM5A have been found in M7 type childhood acute myeloid leukemia. Translocation t(11;12)(p15;p13) with NUP98.
El Hayek-Chahrour neurodevelopmental syndrome
NEDEHC
An autosomal recessive neurodevelopmental disorder characterized by lack of speech, intellectual disability, autism, and developmental delay.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the JARID1 histone demethylase family.
Cellular localization
- Nucleus
- Nucleolus
- Nucleus
- Occupies promoters of genes involved in RNA metabolism and mitochondrial function.
Alternative names
JARID1A, RBBP2, RBP2, KDM5A, Lysine-specific demethylase 5A, Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, Retinoblastoma-binding protein 2, [histone H3]-trimethyl-L-lysine(4) demethylase 5A, RBBP-2