EC Number   |
General Information |
Reference |
|---|
   1.14.11.53 | malfunction |
Alkbh5-deficient male mice have increased m6A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase stage spermatocytes |
739064 |
| 1.14.11.53 | malfunction |
enzyme knockdown in MDAMB-231 human breast cancer cells significantly reduces their capacity for tumor initiation as a result of reduced numbers of breast cancer stem cells |
739559 |
| 1.14.11.53 | 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 |
765684 |
| 1.14.11.53 | 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 |
765684 |
| 1.14.11.53 | metabolism |
during the reaction, the hv-excited FMN abstracts one electron and one proton from N6-methyl in m6A, probably via a proton-coupled electron transfer pathway, to give the deprotonated amine radical cation and the semiquinone radical of FMNH. A second proton-coupled electron transfer then leads to the formation of the corresponding imine with the concomitant reduction of the FMNH radical to FMNH2. The N,O-hemiacetal hm6A is formed from the hydration of II[4a,b] and it quickly oxidizes to N6-formyladenosine, followed by water-assisted decomposition to yield the adenosine and formic acid. Alternatively, a direct loss of formaldehyde from N6-formyladenosine would also afford adenosine |
763890 |
| 1.14.11.53 | metabolism |
N6-methylation of adenosine is the most ubiquitous and abundant modification of nucleoside in eukaryotic mRNA and long non-coding RNA. This modification plays an essential role in the regulation of mRNA translation and RNA metabolism |
738609 |
| 1.14.11.53 | metabolism |
the enzyme enhances NANOG mRNA stability by catalyzing m6A demethylation |
739559 |
| 1.14.11.53 | more |
isoforms ALKBH9A and ALKBH9C are not involved in alfalfa mosaic virus infrection |
764745 |
| 1.14.11.53 | physiological function |
ALKBH10B mutants are hypersensitive to abscisic acid, osmotic and salt stress during seed germination. The expression of several abscisic acid response genes is upregulated in the mutants. abscisic acid signaling genes, including PYR1, PYL7, PYL9, ABI1, and SnRK2.2 are N6-methyladenine-hypermethylated in the mutants after abscisic acid treatment |
764790 |
| 1.14.11.53 | physiological function |
ALKBH5 demethylates zinc finger protein ZNF333 mRNA, leading to enhanced ZNF333 expression by abolishing m6A-YTHDF2-dependent mRNA degradation. ALKBH5 activates CDX2 and downstream intestinal markers by targeting the ZNF333/CYLD axis and activating NF-kappaB signaling. p65, the key transcription factor of the canonical NF-kappaB pathway, enhances the transcription activity of ALKBH5 in the nucleus. ALKBH5 levels are positively correlated with ZNF333 and CDX2 levels in gastric intestinal metaplasia tissues |
765411 |
