ALKBH3 (AlkB Homolog 3, Alpha-Ketoglutarate Dependent Dioxygenase) is a member of ALKBH protein family. It mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A). It can repair alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation. ALKBH3 has a strong preference for single-stranded DNA. It is able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promoting DNA unwinding to generate single-stranded substrate needed for ALKBH3. ALKBH3 also acts on RNA via demethylating N(1)-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5-untranslated regions (UTRs) and in the vicinity of start codons. The oxidative demethylation requires molecular oxygen, alpha-ketoglutarate and iron.
