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Information on EC 1.14.11.53 - mRNA N6-methyladenine demethylase
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1.14.11.53 mRNA N6-methyladenine demethylaseIUBMB Comments
Contains iron(II). Catalyses oxidative demethylation of mRNA N6-methyladenine. The FTO enzyme from human can also demethylate N3-methylthymine from single stranded DNA and N3-methyluridine from single stranded RNA [1,2] with low activity .
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Word Map
- 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
The enzyme appears in viruses and cellular organisms
Reaction Schemes
N6-methyladenine in mRNA
+
+
=
adenine in mRNA
+
+
+
Synonyms
alkbh5, fat mass and obesity-associated protein, alkb homolog 5, alkbh10b, n6-methyladenosine demethylase, m6a rna demethylase, alkbh9b, alkylation repair homolog protein 5, alkbh5 demethylase, rna n6-methyladenine demethylase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ALKBH5
FTO
m6A RNA demethylase
ALKBH5
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N6-methyladenine in mRNA + 2-oxoglutarate + O2 = adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
mRNA-N6-methyladenosine,2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)
Contains iron(II). Catalyses oxidative demethylation of mRNA N6-methyladenine. The FTO enzyme from human can also demethylate N3-methylthymine from single stranded DNA and N3-methyluridine from single stranded RNA [1,2] with low activity [3].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5'-AUUCUCAm6AC-3' + 2-oxoglutarate + O2
5'-AUUCUCAAC-3' + formaldehyde + succinate + CO2
-
ssRNA substrate
-
-
?
5'-CUCGAUACG(m6A)UCCGGUCAAA-3' + 2-oxoglutarate + O2
5'-CUCGAUACGAUCCGGUCAAA-3' + formaldehyde + succinate + CO2
-
-
-
?
5'-CUGGm6ACUGG-3' + 2-oxoglutarate + O2
5'-CUGGACUGG-3' + formaldehyde + succinate + CO2
-
ssRNA substrate
-
-
?
5'-m6ACUGACUAG-3' + 2-oxoglutarate + O2
5'-m6ACUGACUAG-3' + formaldehyde + succinate + CO2
-
ssRNA substrate
-
-
?
5'-UACACUCGAUCUGG(m6A)CUAAAGCUGCUC-3'-biotin + 2-oxoglutarate + O2
5'-UACACUCGAUCUGGCUAAAGCUGCUC-3'-biotin + formaldehyde + succinate + CO2
-
-
-
-
?
biotin-AAGCTCCCATGTTAGGm6ATCAGTGTCTCGAG-biotin + 2-oxoglutarate + O2
biotin-AAGCTCCCATGTTAGGATCAGTGTCTCGAG-biotin + formaldehyde + succinate + CO2
-
-
-
?
CATGTTAGGATCAGTG + 2-oxoglutarate + O2
CATGTTAGGm6ATCAGTG + formaldehyde + succinate + CO2
-
-
-
?
CCCC(m6A)CCCCCCCCC + 2-oxoglutarate + O2
? + formaldehyde + succinate + CO2
-
30% demethylation
-
-
?
GA(m6A)CA + 2-oxoglutarate + O2
GAACA + formaldehyde + succinate + CO2
-
39% demethylation
-
-
?
GCGG(m6A)CUCCAGAUG + 2-oxoglutarate + O2
GCGGACUCCAGAUG + formaldehyde + succinate + CO2
-
31% demethylation
-
-
?
GG(m6A)CU + 2-oxoglutarate + O2
GGACU + formaldehyde + succinate + CO2
-
37% demethylation
-
-
?
N3-methylcytosine in single-stranded DNA + 2-oxoglutarate + O2
cytosine in single-stranded DNA + formaldehyde + succinate + CO2
N3-methylthymine in single-stranded DNA + 2-oxoglutarate + O2
thymine in single-stranded DNA + formaldehyde + succinate + CO2
N3-methyluracil in single-stranded mRNA + 2-oxoglutarate + O2
uracil in single-stranded mRNA + formaldehyde + succinate + CO2
N6,N6-dimethyladenosine + 2 2-oxoglutarate + 2 O2
adenosine + 2 formaldehyde + 2 succinate + 2 CO2
-
-
-
-
?
N6-methyladenine + 2-oxoglutarate + O2
adenine + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
N6-methyladenine in NANOG mRNA + 2-oxoglutarate + O2
adenine in NANOG mRNA + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in NEAT1 + 2-oxoglutarate + O2
adenine in NEAT1 + formaldehyde + succinate + CO2
substrate i.e. nuclear paraspeckle assembly transcript 1
-
-
?
N6-methyladenine in RNA + 2-oxoglutarate + O2
adenine in RNA + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in single-stranded DNA + 2-oxoglutarate + O2
adenine in single-stranded DNA + formaldehyde + succinate + CO2
the ALKBH5 catalytic domain (residues 74294) is active and can demethylate ssDNA and ssRNA with similar activity. m6A ssDNA may not be a physiologically relevant ALKBH5 substrate
-
-
?
N6-methyladenine in single-stranded DNA oligonucleotide + 2-oxoglutarate + O2
adenine in single-stranded DNA oligonucleotide + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in ZNF333 mRNA + 2-oxoglutarate + O2
adenine in ZNF333 mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenosine + 2-oxoglutarate + O2
adenosine + formaldehyde + succinate + CO2
-
-
-
-
?
N3-methylcytosine in single-stranded DNA + 2-oxoglutarate + O2
cytosine in single-stranded DNA + formaldehyde + succinate + CO2
strong preference toward N3-methylthymine over N3-methylcytosine in single-stranded DNA
-
-
?
N3-methylcytosine in single-stranded DNA + 2-oxoglutarate + O2
cytosine in single-stranded DNA + formaldehyde + succinate + CO2
strong preference toward N3-methylthymine over N3-methylcytosine in single-stranded DNA
-
-
?
N3-methylthymine in single-stranded DNA + 2-oxoglutarate + O2
thymine in single-stranded DNA + formaldehyde + succinate + CO2
strong preference toward N3-methylthymine over N3-methylcytosine in single-stranded DNA. Negligible activities against N3-methylthymine in double-stranded DNA
-
-
?
N3-methylthymine in single-stranded DNA + 2-oxoglutarate + O2
thymine in single-stranded DNA + formaldehyde + succinate + CO2
strong preference toward N3-methylthymine over N3-methylcytosine in single-stranded DNA. Negligible activities against N3-methylthymine in double-stranded DNA
-
-
?
N3-methyluracil in single-stranded mRNA + 2-oxoglutarate + O2
uracil in single-stranded mRNA + formaldehyde + succinate + CO2
2-fold preference for N3-methyluracil in single-stranded mRNA as the substrate over N3-methylthymine in single-stranded DNA. Slightly higher efficiency over that of N3-methylthymine in single-stranded DNA
-
-
?
N3-methyluracil in single-stranded mRNA + 2-oxoglutarate + O2
uracil in single-stranded mRNA + formaldehyde + succinate + CO2
2-fold preference for N3-methyluracil in single-stranded mRNA as the substrate over N3-methylthymine in single-stranded DNA. Slightly higher efficiency over that of N3-methylthymine in single-stranded DNA
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
m6A in nuclear RNA is the physiological substrate of the enzyme
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
m6A modification preferentially appears after G in the conserved motif RRm6ACH (R is A/G and H is A/C/U)
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
15-mer m6A-containing ssRNA or 15-mer m3U-containing ssRNA. Over 50-fold preference of the enzyme for m6A (at pH 7.0) over m3U (qat pH 6.0)
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
the ALKBH5 catalytic domain (residues 74294) is active and can demethylate ssDNA and ssRNA with similar activity
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
additional information
?
-
very low activity toward repairing N1-methyladenine in 49 mer single-stranded DNA
-
-
?
additional information
?
-
negligible activity with m6A-containing dsDNA and dsRNA. Treatment with one molar equivalent of enzyme at 16°C overnight results in a demethylation yield of 40% for dsDNA and 24% for dsRNA, respectively
-
-
?
additional information
?
-
-
negligible activity with m6A-containing dsDNA and dsRNA. Treatment with one molar equivalent of enzyme at 16°C overnight results in a demethylation yield of 40% for dsDNA and 24% for dsRNA, respectively
-
-
?
additional information
?
-
-
the enzyme binds preferentially to pre-mRNAs in intronic regions, in the proximity of alternatively spliced exons and poly(A) sites
-
-
?
additional information
?
-
very low activity toward repairing N1-methyladenine in 49 mer single-stranded DNA
-
-
?
additional information
?
-
-
poor substrates: N1-methyladenosine, O2'-methyladenosine, 5-methylcytosine, and 5-methyluridine
-
-
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
N6-methyladenine in NANOG mRNA + 2-oxoglutarate + O2
adenine in NANOG mRNA + formaldehyde + succinate + CO2
-
-
-
-
?
additional information
?
-
-
the enzyme binds preferentially to pre-mRNAs in intronic regions, in the proximity of alternatively spliced exons and poly(A) sites
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
m6A in nuclear RNA is the physiological substrate of the enzyme
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
m6A modification preferentially appears after G in the conserved motif RRm6ACH (R is A/G and H is A/C/U)
-
-
?
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Mn2+
the enzyme requires binding of the cosubstrate 2-oxoglutarate and Fe2+ for catalysis. In the crystallization trial, Fe2+ is replaced with Mn2+ to obtain a catalytically inactive form of the enzyme
Fe2+
the enzyme requires binding of the cosubstrate 2-oxoglutarate and Fe2+ for catalysis
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-[(1-hydroxy-2-oxo-2-phenylethyl)sulfanyl]acetic acid
cell proliferation of cell lines HL-60, CCRF-CEM, and K562 is suppressed at low micromolar concentrations. The effect is low or negligible in Jurkat cells and glioblastoma cell line A-172
-
4-[[(furan-2-yl)methyl]amino]-1,2-diazinane-3,6-dione
cell proliferation of cell lines HL-60, CCRF-CEM, and K562 is suppressed at low micromolar concentrations. The effect is low or negligible in Jurkat cells and glioblastoma cell line A-172
-
additional information
-
the presence of S-adenosyl-L-homocysteine, NaCl, MgCl2, dimethylsulfoxide, and Triton X-100 does not influence enzyme activity
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00166
N6-methyladenine in mRNA
-
pH and temperature not specified in the publication
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0029
N6-methyladenine in mRNA
-
pH and temperature not specified in the publication
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.75
N6-methyladenine in mRNA
-
pH and temperature not specified in the publication
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00084
2-[(1-hydroxy-2-oxo-2-phenylethyl)sulfanyl]acetic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00179
4-[[(furan-2-yl)methyl]amino]-1,2-diazinane-3,6-dione
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6
demethylation of N3-methylthymine in single-stranded DNA and N3-methyluracil in single-stranded RNA
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
21
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
highly expressed during the embryonic development of the brain and decreases in the late brain development
brenda
of ovaries, N6-methyladenosine increases in granulosa cells of human aged ovaries , while FTO-knockdown granulosa cells show faster aging-related phenotypes
brenda
m6A demethylase FTO is downregulated and N6-methyladenosine increases in granulosa cells of human aged ovaries
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
localised in nuclear speckles, which are subnuclear structures that are enriched in pre-messenger RNA splicing factors
brenda
localised in nuclear speckles, which are subnuclear structures that are enriched in pre-messenger RNA splicing factors
brenda