This entry represents the RNA recognition motif (RRM) of ALKBH8 (Alkylated DNA repair protein alkB homologue 8), which plays a crucial role in the DNA damage survival pathway through a distinct mechanism involving the regulation of tRNA modification. It catalyzes the methylation of tRNA to yield 5-methylcarboxymethyl uridine (mcm5U) at the wobble position of the anticodon loop via its methyltransferase domain []. It binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyluridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyl uridine and has a preference for tRNA(Gly) []. It is essential in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals []. ALKBH8 contains the characteristic AlkB domain that is composed of a tRNA methyltransferase motif, a motif homologous to the bacterial AlkB DNA/RNA repair enzyme, and a dioxygenase catalytic core domain encompassing cofactor-binding sites for iron and 2-oxoglutarate. In addition, unlike other AlkB homologues, ALKBH8 contains an N-terminal RNA recognition motif (RRM) and a C-terminal S-adenosylmethionine (SAM)-dependent methyltransferase (MT) domain [].
