Alkylated DNA repair protein alkB homolog 8

Definition:

Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain. Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA. Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly). Required for normal survival after DNA damage. May inhibit apoptosis and promote cell survival and angiogenesis.

References:

[1]. Keiji Shimada, et al. A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression. Cancer Res. 2009 Apr 1;69(7):3157-64. [Content Brief]

[2]. Erwin van den Born, et al. ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA. Nat Commun. 2011 Feb 1;2:172. [Content Brief]

[3]. Dragony Fu, et al. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol Cell Biol. 2010 May;30(10):2449-59. [Content Brief]

[4]. Dorota Monies, et al. Recessive Truncating Mutations in ALKBH8 Cause Intellectual Disability and Severe Impairment of Wobble Uridine Modification. Am J Hum Genet. 2019 Jun 6;104(6):1202-1209. [Content Brief]

[5]. Lene Songe-Møller, et al. Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol Cell Biol. 2010 Apr;30(7):1814-27. [Content Brief]

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