AlkB homolog 3, alpha-ketoglutarate-dependent dioxygenase (ALKBH3)

AlkB homolog 3, alpha-ketoglutarate-dependent dioxygenase (ALKBH3) is an enzyme encoded by the human ALKBH3 gene. It belongs to the AlkB family of Fe(II)/2-oxoglutarate-dependent dioxygenases, characterized by a jelly-roll beta-fold and structural domains suited for substrate binding and catalysis[4][1][2]. ALKBH3 directly repairs alkylation-damaged nucleic acids by removing methyl groups from 1-methyladenine and 3-methylcytosine in single-stranded DNA and RNA, contributing to genome and transcriptome integrity, particularly under stress from environmental or therapeutic methylating agents[1][3][4]. ALKBH3 also acts as an RNA demethylase, with activity against N6-methyladenine in tRNA, thereby promoting efficient protein translation and regulating gene expression on the epigenetic level[3]. Overexpression of ALKBH3 is observed in multiple human cancers, where it influences tumor progression, making it a proposed therapeutic and diagnostic target[1][3][5]. Its activity depends on iron and 2-oxoglutarate as cofactors, and it works in conjunction with DNA repair complexes such as the ASCC, further highlighting its central role in alkylation damage response[1]. Although as of now there is limited information on direct pharmacological inhibition, its molecular mechanism suggests that ALKBH3 modulation could have significant therapeutic implications, especially in oncology.

Other names

ALKBH3ABH3DEPC-1DEPC1PCA1hABH3alkB homolog 3

Oxidative demethylation of 1-methyladenine (m1A) and 3-methylcytosine (m3C) lesions in single-stranded DNA and RNA; Repair of methylation-induced DNA/RNA damage; Epigenetic regulation via RNA demethylation