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Information on EC 1.14.11.53 - mRNA N6-methyladenine demethylase and Organism(s) Mus musculus and UniProt Accession Q3TSG4
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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
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epitranscriptomic
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m6a-related
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fto-mediated
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m6a-dependent
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hnrnpa2b1
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methyltransferase-like
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hnrnpc
-
lasso
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m6a-modified
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igf2bp1
-
merip
-
merip-seq
-
m6a-binding
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected 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
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].
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
N6-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + 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-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
-
-
?
additional information
?
-
very low activity toward repairing N1-methyladenine in 49 mer single-stranded DNA
-
-
?
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
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
highly expressed during the embryonic development of the brain and decreases in the late brain development
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ALKB5_MOUSE
395
0
44411
Swiss-Prot
Mitochondrion (Reliability: 5)
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the purified recombinant mRNA N6-methyladenine demethylase appears to be more stable than the purified recombinant murine mRNA N6-methyladenine demethylase in vitro
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
FTO nhances melanoma tumorigenesis in mice. 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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jia, G.; Yang, C.G.; Yang, S.; Jian, X.; Yi, C.; Zhou, Z.; He, C.
Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO
FEBS Lett.
582
3313-3319
2008
Mus musculus (Q8BGW1), Homo sapiens (Q9C0B1)
Zheng, G.
Dahl, J.A.; Niu, Y.; Fedorcsak, P.; Huang, C.M.; Li, C.J.; Vagbo, C.B.; Shi, Y.; Wang, W.L.; Song, S.H.; Lu, Z.; Bosmans, R.P.; Dai, Q.; Hao, Y.J.; Yang, X.; Zhao, W.M.; Tong, W.M.; Wang, X.J.; Bogdan, F.; Furu, K.; Fu, Y.; Jia, G.; Zhao, X.; Liu, J.; Krokan, H.E.; Klungland, A.; Yang, Y.G.; He, C.: ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility
Mol. Cell
49
18-29
2013
Homo sapiens (Q6P6C2), Mus musculus (Q3TSG4), Mus musculus
Du, T.; Li, G.; Yang, J.; Ma, K.
RNA demethylase Alkbh5 is widely expressed in neurons and decreased during brain development
Brain Res. Bull.
163
150-159
2020
Mus musculus (Q3TSG4), Mus musculus
Yang, S.; Wei, J.; Cui, Y.H.; Park, G.; Shah, P.; Deng, Y.; Aplin, A.E.; Lu, Z.; Hwang, S.; He, C.; He, Y.Y.
m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade
Nat. Commun.
10
2782
2019
Homo sapiens (Q9C0B1), Homo sapiens, Mus musculus (Q8BGW1)
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