KDM2B
Description
The KDM2B (lysine demethylase 2B) is a protein-coding gene located on chromosome 12.
The human KDM2B gene encodes the protein lysine (K)-specific demethylase 2B. KDM2B is widely expressed in embryonic tissues, particularly in the developing central nervous system of vertebrates, and its expression persists in most adult organs. The protein resides in the nucleoplasm, concentrated in the nucleolus where it binds the transcribed region of ribosomal RNA, repressing the transcription of ribosomal RNA genes, which inhibits cell growth and proliferation. KDM2B possesses several domains, including a JmjC domain with histone demethylase activity, specifically demethylating trimethylated Lys-4 and dimethylated Lys-36 of histone H3. Its ZF-CxxC DNA binding domain enables KDM2B to recognize and bind unmethylated DNA in CpG islands. Consequently, KDM2B recruits the non-canonical polycomb repressive complex 1.1 (ncPRC1) to unmethylated CpG islands through direct interaction with BCOR and PCGF1, resulting in mono-ubiquitylation of histone H2A on K119 and gene repression. KDM2B belongs to the F-box protein family, characterized by an approximately 40 amino acid F-box motif. F-box proteins are subunits of the SCF (SKP1-cullin-F-box) ubiquitin protein ligase complex, involved in phosphorylation-dependent ubiquitination. They are classified into three groups: Fbws with WD-40 domains, Fbls with leucine-rich repeats, and Fbxs with diverse protein-protein interaction modules or no recognizable motifs. KDM2B falls under the Fbls class.
KDM2B is a histone demethylase that removes methyl groups from lysine 4 and lysine 36 of histone H3, playing a crucial role in the histone code. It preferentially demethylates trimethylated H3 Lys-4 and dimethylated H3 Lys-36, with weaker or no activity on mono- and tri-methylated H3 Lys-36. KDM2B binds to the transcribed region of ribosomal RNA and represses its transcription, leading to inhibition of cell growth and proliferation. It may also act as a substrate-recognition component in the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex.
KDM2B is also known as CXXC2, FBXL10, Fbl10, JHDM1B, PCCX2.
