AlkB homolog 5, RNA demethylase (ALKBH5)

AlkB homolog 5, RNA demethylase (ALKBH5) is an iron(II)- and alpha-ketoglutarate-dependent dioxygenase that catalyzes the removal of N6-methyladenosine (m6A) marks from single-stranded RNA, thereby regulating RNA stability, translation, and decay[1][3][5]. As one of the two major m6A RNA demethylases in mammals (the other being FTO), ALKBH5 plays essential roles in post-transcriptional regulation of gene expression, particularly in processes such as germ cell development, spermatogenesis, and apoptosis[1][3][5]. It also modulates mRNA export, influences immune cell migration and response, and can rewire cellular metabolism in macrophages[4][5]. Dysregulation or mutation of ALKBH5 is implicated in cancer (both as an oncogene and tumor suppressor in various contexts), infertility, immune dysregulation, and other diseases[2][5]. Structurally, ALKBH5 is part of the AlkB family, showing specificity for single-stranded RNA substrates due to unique features of its \"lid region\" and a key disulfide bond that controls access to the active site[1][3]. Targeting ALKBH5 therapeutically is a topic of emerging interest in oncology and immunology, though drug candidates are still in preclinical development.

Other names

RNA demethylase ALKBH5ABH5OFOXD1OFOXDFLJ20308alkBalkB homolog 5Alkylated DNA repair protein alkB homolog 5Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5AlkB family member 5Alkylation repair homolog 5Probable alpha-ketoglutarate-dependent dioxygenase ABH5Oxoglutarate and iron-dependent oxygenase domain containing

Competitive inhibition of active site (for inhibitors: mainly small molecules designed on the basis of the alkB/ALKBH5 family core catalytic structure, often α-ketoglutarate analogs)[1]. Inhibition of m6A demethylation (increased m6A levels, altered gene expression, cellular apoptosis, or differentiation, depending on context)[2].