Lysine-specific demethylase 5A - P29375 (KDM5A_HUMAN)


Protein Feature View of PDB entries mapped to a UniProtKB sequence  

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-ARNTL/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). UniProt
Catalytic Activity
3 2-oxoglutarate + N6,N6,N6-trimethyl-L-lysyl4-[histone H3] + 3 O2 = 3 CO2 + 3 formaldehyde + L-lysyl4-[histone H3] + 3 succinate UniProt
Pathway Maps
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Subunit Structure
Interacts with SUZ12; the interaction is direct (By similarity). Interacts with the viral protein-binding domain of RB1. Interacts with ESR1, MYC, MYCN and LMO2. Interacts with HDAC1 (By similarity). Interacts with ARNTL/BMAL1 and CLOCK. Interacts (via PHD-type 1 zinc finger) with histone H3 unmodified at 'Lys-4' and (via PHD-type 3 zinc finger) with histone H3 di- and trimethylated at 'Lys-4' (PubMed:19430464). UniProt
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). UniProt
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