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5'-CUCGAUACG(m6A)UCCGGUCAAA-3' + 2-oxoglutarate + O2
5'-CUCGAUACGAUCCGGUCAAA-3' + formaldehyde + succinate + CO2
-
-
-
-
?
5'-UACACUCGAUCUGG(m6A)CUAAAGCUGCUC-3'-biotin + 2-oxoglutarate + O2
5'-UACACUCGAUCUGGCUAAAGCUGCUC-3'-biotin + 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-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 single-stranded DNA + 2-oxoglutarate + O2
adenine in single-stranded DNA + formaldehyde + succinate + CO2
-
the ALKBH5 catalytic domain (residues 74ā294) 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
-
-
-
?
additional information
?
-
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
-
-
737368, 737446, 738271, 738709, 738753, 739688, 742218, 742336, 743216, 743373, 743572, 743808 -
-
?
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 74ā294) 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
?
-
-
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
-
-
-
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Atherosclerosis
Fat mass and obesity-associated protein attenuates lipid accumulation in macrophage foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice.
Brain Neoplasms
ALKBH5 Drives FOXM1 Expression to Promote Brain Tumor Stem Cell Growth.
Breast Neoplasms
Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA.
Breast Neoplasms
Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.
Carcinogenesis
ALKBH5 Drives FOXM1 Expression to Promote Brain Tumor Stem Cell Growth.
Diabetes Mellitus
FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.
Diabetes Mellitus, Type 2
Association of Metabolites with Obesity and Type 2 Diabetes Based on FTO Genotype.
Diabetes Mellitus, Type 2
FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.
Endometrial Neoplasms
Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway.
Glioblastoma
ALKBH5 Drives FOXM1 Expression to Promote Brain Tumor Stem Cell Growth.
Glioblastoma
Messenger RNA Methylation Regulates Glioblastoma Tumorigenesis.
Infertility
Sequencing of FTO and ALKBH5 in men undergoing infertility work-up identifies infertility-associated variant and two missense mutations.
Insulin Resistance
FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.
Metabolic Syndrome
FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.
Neoplasm Metastasis
Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.
Neoplasms
Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA.
Neoplasms
Messenger RNA Methylation Regulates Glioblastoma Tumorigenesis.
Neoplasms
RNA epigenetic modification: N6-methyladenosine.
Obesity
Association of Metabolites with Obesity and Type 2 Diabetes Based on FTO Genotype.
Obesity
Fat mass and obesity-associated protein attenuates lipid accumulation in macrophage foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice.
Obesity
FTO mRNA Expression in Extremely Obese and Type 2 Diabetic Human Omental and Subcutaneous Adipose Tissues.
Obesity
FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.
Obesity
Lose weight with traditional chinese medicine? Potential suppression of fat mass and obesity-associated protein.
Obesity
mRNA m(6)A methylation downregulates adipogenesis in porcine adipocytes.
Obesity
Obesity and the brain: a possible genetic link.
Obesity
RNA epigenetic modification: N6-methyladenosine.
Obesity
The biology of FTO: from nucleic acid demethylase to amino acid sensor.
Obesity
The fat mass and obesity-associated (FTO) gene: Obesity and beyond?
Obesity
The role of common and rare MC4R variants and FTO polymorphisms in extreme form of obesity.
Virus Diseases
The RNA helicase DDX46 inhibits innate immunity by entrapping m(6)A-demethylated antiviral transcripts in the nucleus.
Zika Virus Infection
Dynamics of Human and Viral RNA Methylation during Zika Virus Infection.
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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
Homo sapiens (Q9C0B1), Mus musculus (Q8BGW1)
brenda
Aik, W.; Scotti, J.S.; Choi, H.; Gong, L.; Demetriades, M.; Schofield, C.J.; McDonough, M.A.
Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation
Nucleic Acids Res.
42
4741-4754
2014
Homo sapiens, Homo sapiens (Q6P6C2)
brenda
Zhou, B.; Han, Z.
Crystallization and preliminary X-ray diffraction of the RNA demethylase ALKBH5
Acta Crystallogr. Sect. F
69
1231-1234
2013
Homo sapiens
brenda
Zhu, C.; Yi, C.
Switching demethylation activities between AlkB family RNA/DNA demethylases through exchange of active-site residues
Angew. Chem. Int. Ed. Engl.
53
3659-3662
2014
Homo sapiens
brenda
Liu, K.; Ding, Y.; Ye, W.; Liu, Y.; Yang, J.; Liu, J.; Qi, C.
Structural and functional characterization of the proteins responsible for N6-methyladenosine modification and recognition
Curr. Protein Pept. Sci.
17
306-318
2016
Homo sapiens
brenda
Chen, W.; Zhang, L.; Zheng, G.; Fu, Y.; Ji, Q.; Liu, F.; Chen, H.; He, C.
Crystal structure of the RNA demethylase ALKBH5 from zebrafish
FEBS Lett.
588
892-898
2014
Danio rerio, Danio rerio (Q08BA6)
brenda
Landfors, M.; Nakken, S.; Fusser, M.; Dahl, J.A.; Klungland, A.; Fedorcsak, P.
Sequencing of FTO and ALKBH5 in men undergoing infertility work-up identifies an infertility-associated variant and two missense mutations
Fertil. Steril.
105
1170-1179
2016
Homo sapiens
brenda
Feng, C.; Liu, Y.; Wang, G.; Deng, Z.; Zhang, Q.; Wu, W.; Tong, Y.; Cheng, C.; Chen, Z.
Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition
J. Biol. Chem.
289
11571-11583
2014
Homo sapiens, Homo sapiens (Q6P6C2)
brenda
Xu, C.; Liu, K.; Tempel, W.; Demetriades, M.; Aik, W.; Schofield, C.J.; Min, J.
Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation
J. Biol. Chem.
289
17299-17311
2014
Homo sapiens, Homo sapiens (Q6P6C2)
brenda
Li, F.; Kennedy, S.; Hajian, T.; Gibson, E.; Seitova, A.; Xu, C.; Arrowsmith, C.H.; Vedadi, M.
A Radioactivity-based assay for screening human m6A-RNA methyltransferase, METTL3-METTL14 complex, and demethylase ALKBH5
J. Biomol. Screen.
21
290-297
2016
Homo sapiens
brenda
Shen, F.; Huang, W.; Huang, J.T.; Xiong, J.; Yang, Y.; Wu, K.; Jia, G.F.; Chen, J.; Feng, Y.Q.; Yuan, B.F.; Liu, S.M.
Decreased N6-methyladenosine in peripheral blood RNA from diabetic patients is associated with FTO expression rather than ALKBH5
J. Clin. Endocrinol. Metab.
100
E148-E154
2015
Homo sapiens
brenda
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, Mus musculus (Q3TSG4)
brenda
Jia, G.; Fu, Y.; Zhao, X.; Dai, Q.; Zheng, G.; Yang, Y.; Yi, C.; Lindahl, T.; Pan, T.; Yang, Y.G.; He, C.
N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
Nat. Chem. Biol.
7
885-887
2011
Homo sapiens, Homo sapiens (Q9C0B1)
brenda
Han, Z.; Niu, T.; Chang, J.; Lei, X.; Zhao, M.; Wang, Q.; Cheng, W.; Wang, J.; Feng, Y.; Chai, J.
Crystal structure of the FTO protein reveals basis for its substrate specificity
Nature
464
1205-1209
2010
Homo sapiens (Q9C0B1)
brenda
Huang, Y.; Yan, J.; Li, Q.; Li, J.; Gong, S.; Zhou, H.; Gan, J.; Jiang, H.; Jia, G.F.; Luo, C.; Yang, C.G.
Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5
Nucleic Acids Res.
43
373-384
2015
Homo sapiens, Homo sapiens (Q6P6C2)
brenda
Zhang, C.; Samanta, D.; Lu, H.; Bullen, J.W.; Zhang, H.; Chen, I.; He, X.; Semenza, G.L.
Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA
Proc. Natl. Acad. Sci. USA
113
E2047-E2056
2016
Homo sapiens
brenda
Zou, S.; Toh, J.D.; Wong, K.H.; Gao, Y.G.; Hong, W.; Woon, E.C.
N6-methyladenosine: a conformational marker that regulates the substrate specificity of human demethylases FTO and ALKBH5
Sci. Rep.
6
25677
2016
Homo sapiens
brenda
Chandola, U.; Das, R.; Panda, B.
Role of the N6-methyladenosine RNA mark in gene regulation and its implications on development and disease
Brief. Funct. Genomics
14
169-179
2015
Homo sapiens
brenda
Liu, K.; Ding, Y.; Ye, W.; Liu, Y.; Yang, J.; Liu, J.; Qi, C.
Structural and functional characterization of the proteins responsible for N6-methyladenosine modification and recognition
Curr. Protein Pept. Sci.
17
306-318
2015
Homo sapiens
brenda
Ye, F.; Zhang, L.; Jin, L.; Zheng, M.; Jiang, H.; Luo, C.
Repair of methyl lesions in RNA by oxidative demethylation
MedChemComm
5
1797-1803
2014
Homo sapiens
-
brenda
Bartosovic, M.; Molares, H.C.; Gregorova, P.; Hrossova, D.; Kudla, G.; Vanacova, S.
N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3-end processing
Nucleic Acids Res.
45
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2017
Homo sapiens
brenda
Berulava, T.; Rahmann, S.; Rademacher, K.; Klein-Hitpass, L.; Horsthemke, B.
N6-adenosine methylation in miRNAs
PLoS ONE
10
e0118438
2015
Homo sapiens
brenda
Yang, Y.; Huang, W.; Huang, J.T.; Shen, F.; Xiong, J.; Yuan, E.F.; Qin, S.S.; Zhang, M.; Feng, Y.Q.; Yuan, B.F.; Liu, S.M.
Increased N6-methyladenosine in human sperm RNA as a risk factor for asthenozoospermia
Sci. Rep.
6
24345
2016
Homo sapiens
brenda