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ALKBH8 (alkylated DNA repair protein AlkB homolog 8) is a 664 amino acid protein that is encoded by a gene located on chromosome 11. ALKBH8 contains one RRM (RNA recognition motif) domain and belongs to the AlkB family of proteins. ALKBH8 is one of many homologs of the Escherichia coli protein AlkB. AlkB functions to protect DNA and RNA against damage from environmental methylating compounds by directly reversing 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) cytotoxic alkylation lesions in DNA and RNA. The enzyme acts by oxidative demethylation, utilizing ferrous iron and alpha-ketoglutarate as cofactors, 2-oxoglutarate as a co-substrate and molecular oxygen as the oxidizing agent. Three isoforms exist for ALKBH8 due alternative splicing of the gene. Protein function: 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 (PubMed:20123966, PubMed:20308323). Catalyzes the last step in the formation of 5- methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). 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) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182). [The UniProt Consortium]
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