Protein Variants | Comment | Organism |
---|---|---|
K132Q | mutant furnishes the ALKBH5 enzyme with an m6A demethylation profile that resembles that of isoform FTO | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q6P6C2 | isoform ALKBH5 | - |
Homo sapiens | Q9C0B1 | - |
- |
Synonyms | Comment | Organism |
---|---|---|
FTO | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
metabolism | comparison of isoforms FTO and ALKBH5. FTO behaves like a classical nonheme Fe(II)-2OG-dependent dioxygenase by performing stepwise oxidation, whereas ALKBH5 catalyzes a unique direct 6-methyladenosine-to-adenosine conversion with rapid release of formaldehyde. A catalytic R130/K132/Y139 triad within ALKBH5 facilitates release of formaldehyde via an covalent-based demethylation mechanism with direct detection of a covalent intermediate. In a mechanistic model for ALKBH5, K132 promotes Schiff base formation on hm6A, which may then undergo subsequent nucleophilic attack by K132 or Y139. Y139 may alternatively play a role in nucleobase recognition via hydrogen bonding to the N6 nitrogen. Formation of a methylene bridge between K132 and Y139 is a probable intermediate prior to hydrolysis and may facilitate release of adeosine | Homo sapiens |
metabolism | comparison of isoforms FTO and ALKBH5. FTO follows a traditional oxidative N-demethylation pathway to catalyze conversion of m6A to hm6A with subsequent slow release of adenosine and formaldehyde. FTO behaves like a classical nonheme Fe(II)-2OG-dependent dioxygenase by performing stepwise oxidation, whereas ALKBH5 catalyzes a unique direct 6-methyladenosine-to-adeosine conversion. FTO gives 6-hydroxymethyladenosine as a major product and 6-formyladenosine as a minorproduct | Homo sapiens |