Histone lysine-specific demethylase (IPR017366)

Short name: Hist_Lys-spec_deMease

Overlapping homologous superfamilies

Family relationships



This entry represents a histone demethylase (LSD1) that specifically demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a co-repressor [PMID: 16987819]. This enzyme acts by oxidising the substrate by FAD to generate the corresponding imine, which is subsequently hydrolysed. This enzyme demethylates both mono- and di-methylated 'Lys-4' of histone H3 and may play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3 'Lys-4' on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. It may also demethylate 'Lys-9' of histone H3, a specific tag for epigenetic transcriptional repression, thereby leading to derepression of androgen receptor target genes.

This histone demethylase is a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, AOF2/LSD1, RCOR1/CoREST and PHF21A/BHC80 [PMID: 16079794]. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. In the complex, RCOR1/CoREST strongly enhances the demethylase activity and protects it from the proteasome while PHF21A/BHC80 inhibits the demethylase activity. Interacts with the androgen receptor (AR).

GO terms

Biological Process

GO:0034720 histone H3-K4 demethylation
GO:0006355 regulation of transcription, DNA-templated

Molecular Function

GO:0050660 flavin adenine dinucleotide binding

Cellular Component

GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.