AlkB homolog 4, lysine demethylase (ALKBH4)

AlkB homolog 4, lysine demethylase (ALKBH4) is a member of the AlkB family of Fe(II)/2-oxoglutarate-dependent dioxygenases with demethylase activity on both proteins and nucleic acids[5]. ALKBH4 specifically catalyzes the demethylation of monomethylated lysine-84 in actin, regulating actomyosin structure, cytokinesis, and cell migration through modification of actin–myosin interactions[1][2][4][7]. It also demethylates N6-methyladenine in DNA, influencing chromatin organization and Polycomb silencing, and can regulate DNA methylation indirectly by controlling DNMT1 protein levels[4]. ALKBH4 interacts with chromatin-associated and transcriptional proteins, indicating roles in epigenetic regulation and gene expression[3][6]. Loss or deficiency of ALKBH4 is associated with defects in cell division, migration, spermatogenesis, and is embryonically lethal in knockout mice, underscoring its essential function in development[2][4]. While implicated in cancer progression, especially by influencing cell cycle and migration, there are no current therapeutics directly targeting this enzyme, and its foundational role in fundamental cellular processes presents safety concerns for therapeutic modulation.

Other names

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4ABH4FLJ20013Alkylated DNA repair protein alkB homolog 4DNA N6-methyl adenine demethylase ALKBH4Lysine-specific demethylase ALKBH4alkylation repair homolog 4probable alpha-ketoglutarate-dependent dioxygenase ABH4