Full name:
Synonym: ABH5, OFOXD1
GI: 148539642
UniProt: Q6P6C2
Structures: | 4NJ4 | 4NRM | 4NRO | 4NRP | 4NRQ | 4O7X | 4OCT | 4O61 |
Enzyme type: demethylase
Position of modification - modification: m:many - A


Belongs to AlkB family of nonheme Fe(II)/a-ketoglutarate (a-KG)-dependent dioxygenases (same protein family as FTO demethylase). In vitro demethylates m6A in RNA and DNA however m6A in mRNA is a physiologically relevant substrate of ALKBH5 inside cells. Strongly prefers single-stranded substrates, exhibits an almost unnoticeable demethylation activity toward m6A in a 26-mer double-stranded RNA. ALKBH5 and its demethylation activity play important roles in mRNA export as well as roles in the association of the nuclear speckle proteins and RNA metabolism. The Alkbh5 deficiency leads to aberrant spermatogenesis and apoptosis in mouse testes. Transcriptome analysis revealed differentially expressed genes associated with spermatogenesis and the p53 functional interaction network, in line with the impaired fertility observed for the Alkbh5-/- mouse.

Protein sequence:


Enzymatic activities:

Reaction Substrate Type Position
m6A:A mRNA (m) many


Title Authors Journal Details PubMed Id DOI
ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vagbo CB, Shi Y, Wang WL, Song SH, Lu Z, Bosmans RP, Dai Q, Hao YJ, Yang X, Zhao WM, Tong WM, Wang XJ, Bogdan F, Furu K, Fu Y, Jia G, Zhao X, Liu J, Krokan HE, Klungland A, Yang YG, He C... Mol Cell [details] 23177736 -
Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1alpha (HIF-1alpha). Thalhammer A, Bencokova Z, Poole R, Loenarz C, Adam J, O'Flaherty L, Schodel J, Mole D, Giaslakiotis K, Schofield CJ, Hammond EM, Ratcliffe PJ, Pollard PJ... PLoS One [details] 21264265 -
Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation. Aik W, Scotti JS, Choi H, Gong L, Demetriades M, Schofield CJ, McDonough MA... Nucleic Acids Res [details] 24489119 -
Crystal Structures of Human RNA Demethylase Alkbh5 Reveal Basis for Substrate Recognition. Feng C, Liu Y, Wang G, Deng Z, Zhang Q, Wu W, Tong Y, Cheng C, Chen Z... J Biol Chem [details] 24616105 -
Molecular biology. Internal mRNA methylation finally finds functions. Nilsen TW... Science [details] 24626918 -
Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single stranded m6A RNA demethylation. Xu C, Liu K, Tempel W, Demetriades M, Aik W, Schofield CJ, Min J... J Biol Chem [details] 24778178 -


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