ALKBH1

ALKBH1 Full Name

alkB, alkylation repair homolog 1 (E. coli)

ALKBH1 Introduction

AlkB homolog 1 (ALKBH1) is a highly versatile, Fe(II)- and 2-oxoglutarate-dependent dioxygenase that belongs to the mammalian AlkB family of DNA and RNA repair enzymes. Originally identified as a homolog of the Escherichia coli alkylation repair enzyme AlkB, ALKBH1 distinguishes itself from its family members through its unique dual localization within both the nucleus and the mitochondria. Furthermore, rather than being strictly limited to a single substrate, ALKBH1 exhibits remarkable substrate diversity, possessing the catalytic ability to oxidatively demethylate specific modifications on DNA, various RNA species, and even histone proteins.

Figure 1. Structural comparison of ALKBH1 and AlkB. (Source: Zhang M, et al. 2020)

Functionally, ALKBH1 operates as a master epigenetic and epitranscriptomic regulator. In terms of DNA maintenance, it functions as a repair enzyme that directly reverses specific alkylation lesions, such as 3-methylcytosine (3meC) and 1-methyladenine (1meA), thereby safeguarding genomic stability. However, its most profound biological impact lies in its role as an RNA demethylase. ALKBH1 is responsible for the dynamic demethylation of crucial transfer RNA (tRNA) modifications, most notably N1-methyladenosine (m1A) and 5-methylcytosine (m5C). By actively remodeling the epitranscriptomic landscape of both cytoplasmic and mitochondrial tRNAs, ALKBH1 exerts precise control over global protein translation, ribosome decoding efficiency, and overall mitochondrial respiration and cellular metabolism.

Clinically, because it fundamentally bridges metabolic sensing (via 2-oxoglutarate) with gene expression and translation, the dysregulation of ALKBH1 is intimately linked to severe human pathologies, particularly aggressive malignancies. In the oncological landscape, ALKBH1 frequently functions as a potent oncogene. It is significantly overexpressed in various cancers, including acute myeloid leukemia (AML), glioblastoma, and colorectal cancer. In these contexts, elevated ALKBH1 activity reprograms cellular translation to favor the synthesis of oncogenic proteins, directly driving tumor cell proliferation, survival under hypoxic stress, and widespread metastasis. Consequently, inhibiting ALKBH1's enzymatic activity has emerged as a highly promising therapeutic strategy to disrupt the translational machinery of cancer cells.

Alternate Names for ALKBH1

ALKBH1; alkB, alkylation repair homolog 1 (E. coli); ABH; ABH1; alkB; hABH; ALKBH; alkylated DNA repair protein alkB homolog 1; DNA lyase ABH1; alkylation repair, alkB homolog; DNA oxidative demethylase ALKBH1; alpha-ketoglutarate-dependent dioxygenase ABH1;

• 1. Zhang M, et al. Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell Res. 2020 Mar;30(3):197-210.
  2. Liu F, et al. ALKBH1-Mediated tRNA Demethylation Regulates Translation. Cell. 2016 Oct 20;167(3):816-828.e16.