ALKBH5 (human, recombinant)

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is an oxidoreductase and member of the ALKBH family of nucleic acid dioxygenases.^1,2 It is composed of an N-terminal nucleotide recognition motif, a substrate specificity motif, a central double-stranded β-helix fold that contains cofactor binding- and active sites, and a disordered C-terminal arginine-serine-rich domain.¹ ALKBH5 is ubiquitously expressed with higher levels found in the lungs, testes, pancreas, spleen, and ovaries.¹ It functions as a monomer in nuclear paraspeckles and catalyzes 2-oxoglutarate- and ferrous iron-dependent demethylation of N⁶-methyladenosine (m⁶A) in messenger-, micro-, and long noncoding RNA, which impacts transcript splicing, nuclear export, translation, and cytoplasmic decay in a transcript-dependent manner.^1,3,2 The disordered C-terminal domain of ALKBH5 is involved in forming nuclear paraspeckles with other nuclear proteins, including splicing factor proline-glutamine-rich (SFPQ) and non-POU domain-containing octamer-binding protein (NONO), and nuclear paraspeckle assembly transcript 1 (NEAT1) long noncoding RNA.⁴ The levels of ALKBH5 are increased by hypoxia-inducible factor-1α (HIF-1α) in response to hypoxia in cancer cells.⁵ ALKBH5 is activated by acetylation at lysine 235 (K²³⁵), and the levels of acetylated ALKBH5 are increased in primary liver and gastric tumors.⁶ Cayman’s ALKBH5 (human, recombinant) protein can be used for enzyme activity and Western blot (WB) applications.

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1. Aik, W., Scotti, J.S., Choi, H., et al. Structure of human RNA N⁶-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation. Nucleic Acids Res. 42(7), 4741-4754 (2014).

2. Chen, X.-Y., Zhang, J., and Zhu, J.-S. The role of m6A RNA methylation in human cancer. Mol. Cancer 18(103), (2019).

3. Liu, J., Yue, Y., and He, C. Preparation of human nuclear RNA m6A methyltransferases and demethylases and biochemical characterization of their catalytic activity. Methods Enzymol. 560, 117-130 (2015).

4. Qin, X., Long, Y., Bai, X., et al. The disordered C terminus of ALKBH5 promotes phase separation and paraspeckles assembly. The Journal of Biological Chemisty 299(8), 105071 (2023).

5. Thalhammer, A., Bencokova, Z., Poole, R., et al. Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1α (HIF-1α). PLoS One 6(1), e16210 (2011).

6. Zhang, X.L., Chen, X.H., Xu, B., et al. K235 acetylation couples with PSPC1 to regulate the m6A demethylation activity of ALKBH5 and tumorigenesis. Nat. Commun. 14(1), 3815 (2023).