1.14.11.53: mRNA N6-methyladenine demethylase
This is an abbreviated version!
For detailed information about mRNA N6-methyladenine demethylase, go to the full flat file.
Word Map on EC 1.14.11.53
-
1.14.11.53
-
demethylation
-
demethylases
-
mettl14
-
reader
-
writer
-
erasers
-
ythdf1
-
methyltransferases
-
epitranscriptomic
-
m6a-related
-
fto-mediated
-
m6a-dependent
-
hnrnpa2b1
-
methyltransferase-like
-
hnrnpc
-
lasso
-
m6a-modified
-
igf2bp1
-
merip
-
merip-seq
-
m6a-binding
- 1.14.11.53
-
demethylation
- demethylases
- mettl14
-
reader
-
writer
-
erasers
-
ythdf1
- methyltransferases
-
epitranscriptomic
-
m6a-related
-
fto-mediated
-
m6a-dependent
-
hnrnpa2b1
-
methyltransferase-like
-
hnrnpc
-
lasso
-
m6a-modified
-
igf2bp1
-
merip
-
merip-seq
-
m6a-binding
Reaction
Synonyms
AlkB homolog 5, ALKBH10B, ALKBH5, ALKBH5 demethylase, ALKBH9B, alkylation repair homolog protein 5, fat mass and obesity-associated enzyme, fat mass and obesity-associated protein, FTO, m6A mRNA demethylase, m6A RNA demethylase, m6A-RNA demethylase, N6-methyladenosine demethylase, RNA N6-methyladenine demethylase
ECTree
1.14.11.53 mRNA N6-methyladenine demethylaseAdvanced search results
results (
results (General Information
General Information on EC 1.14.11.53 - mRNA N6-methyladenine demethylase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
malfunction
metabolism
physiological function
additional information
isoforms ALKBH9A and ALKBH9C are not involved in alfalfa mosaic virus infrection
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
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
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
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
metabolism
-
the enzyme enhances NANOG mRNA stability by catalyzing m6A demethylation
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
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
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
physiological function
-
enzyme expression promotes m6A RNA demethylation in hypoxic breast cancer cells
physiological function
-
the enzyme FTO plays a role in human obesity and energy utilization. FTO is involved in various diseases including cardiovascular diseases,Alzheimer's disease, type II diabetes, breast cancer, and end-stage renal disease. The enzyme ALKHB5 is involoved in sperm development
physiological function
-
the enzyme triggers inclusion of alternatively spliced exons and regulates expression of last exons
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
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
physiological function
ALKBH5 mRNA and protein expression are upregulated during osteoblast differentiation. ALKBH5 knockdown suppresses osteoblast differentiation, mineralization, and the expression of osteogenic biomarkers. ALKBH5 overexpression promotes osteogenesis. Knockdown of ALKBH5 significantly impaires the mRNA stability of the transcription factor Runx2
physiological function
ALKBH9B interacts with the coat protein of alfalfa mosaic virus, causing a profound impact on the viral infection cycle. Residues located between 387 and 427 are critical for the interaction with the alfalfa mosaic virus coat protein, which should be critical for modulating the viral infection process. ALKBH9B deletions of either N-terminal 20 residues or the C-terminal's last 40 amino acids impede their accumulation in siRNA bodies
physiological function
ALKBH9B might be required by alfalfa mosaic virus to invade the vascular tissues. Alfalfa mosaic virus cell-to-cell movement among mesophyll cells is reduced in the absence of ALKBH9B and absence of ALKBH9B affects the viral replication cycle
physiological function
-
flavin mononucleotide functions as an artificial m6A demethylase. FMN mediates substantial photochemical demethylation of m6A residues of RNA in live cells
physiological function
FTO acts as a senescence-retarding protein via N6-methyladenosine, and transcription factor subunit FOS knockdown significantly alleviates the aging of FTO-knockdown granulosa cells. FTO-knockdown granulosa cells show faster aging-related phenotypes, and increased N6-methyladenosine levels are found in the FOS-mRNA 3'UTR
physiological function
FTO loss-of-function mutations reduce the proliferation rate of cancer cells. FTO knockdown also inhibits the colony formation ability of lung cancer cells. FTO knockdown reduces lung cancer cells growth in vivo. FTO decreases the m6A level and increases mRNA stability of ubiquitin-specific protease (USP7), which relies on the demethylase activity of FTO
physiological function
HCT-116 cells show high expression of both FTO and programmed cell death-ligand 1 (PD-L1) proteins. The knockdown of FTO decreases mRNA and protein levels of PD-L1 in HCT-116 cells. Upon depletion of FTO in HCT-116 cells in the presence of IFN-gamma to upregulate PD-L1 expression, PD-L1 expression is reduced in an IFN-gamma signaling-independent manner. PD-L1 mRNA is m6A-modified and FTO binds to the PD-L1 mRNA in HCT-116 cells
physiological function
knockdown of FTO increases m6A methylation in critical protumorigenic melanoma cell-intrinsic genes including PD-1, CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma
physiological function
knockdown of FTO increases m6A methylation in critical protumorigenic melanoma cell-intrinsic genes including PD-1, CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma and sensitizes melanoma to anti-PD-1 treatment in mice
physiological function
ROS significantly induces global mRNA N6-methyladenosine levels by modulating ALKBH5 post-translational modifications, leading to the rapid and efficient induction of thousands of genes. DNA damage repair genes are ALKBH5 downstream targets induced by ROS. ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5m6A demethylase activity by blocking substrate accessibility
physiological function
substrate NEAT1 is a potential binding long noncoding lncRNA of ALKBH5. NEAT1 is overexpressed in gastric cancer cells and tissue. Knockdown of NEAT1 significantly represses invasion and metastasis of gastric cancer cells. ALKBH5 affects the m6A level of NEAT1. The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects gastric cancer invasion and metastasis
