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Information on EC 1.14.11.51 - DNA N6-methyladenine demethylase and Organism(s) Homo sapiens and UniProt Accession Q13686
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1.14.11.51 DNA N6-methyladenine demethylaseIUBMB Comments
Contains iron(II). Catalyses oxidative demethylation of DNA N6-methyladenine, a prevalent modification in LINE-1 transposons, which are specifically enriched on the human X chromosome.
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Word Map
- 1.14.11.51
- dioxygenase
-
demethylation
- histone
-
2-oxoglutarate-dependent
-
abasic
-
alkbh7
-
eraser
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
N6-methyladenine in DNA
+
+
=
adenine in DNA
+
+
+
Synonyms
nmad-1, dna 6ma demethylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
DNA-N6-methyladenosine,2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)
Contains iron(II). Catalyses oxidative demethylation of DNA N6-methyladenine, a prevalent modification in LINE-1 transposons, which are specifically enriched on the human X chromosome.
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 DNA + 2-oxoglutarate + O2
adenine in DNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in DNA + 2-oxoglutarate + O2
adenine in DNA + formaldehyde + succinate + CO2
-
-
-
-
?
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 DNA + 2-oxoglutarate + O2
adenine in DNA + formaldehyde + succinate + CO2
-
-
-
?
N6-methyladenine in DNA + 2-oxoglutarate + O2
adenine in DNA + formaldehyde + succinate + CO2
-
-
-
-
?
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
-
enzyme-depleted mesenchymal stem cells exhibit a restricted capacity for bone formation in vivo
physiological function
-
enzyme overexpression enhances osteoblastic differentiation of mesenchymal stem cells
physiological function
ALKBH1 overexpression decreases hepatocellular carcinoma cell viability, induces apoptosis, and decreases migration and invasion
physiological function
knockdown of ALKBH1 inhibits adipogenic differentiation in both mesenchymal stem cells and 3T3-L1 preadipocytes, while overexpression of ALKBH1 leads to increased adipogenesis. Hypoxia-inducible factor HIF-1 signaling is a crucial downstream target of ALKBH1 activity. Depletion of ALKBH1 leads to hypermethylation of both HIF-1alpha and its downstream target GYS1
physiological function
the 6-methyl adenine demethylase activity is very low. The demethylase activity is less than half that of the apurinic/apyrimidinic lyase activity when ALKBH1 samples are assayed using identical buffer conditions. The two enzymatic activities are located in distinct but partially overlapping active sites for the two reactions
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). ALKB1_HUMAN
389
0
43832
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C118A
m6A demethylase activity similar to wild-type, about 25% decrease in apurinic/apyrimidinic lyase activity
C118A/C129A
about 50% decrease in m6A demethylase activity, about 20% decrease in apurinic/apyrimidinic lyase activity
C129A
about 90% decrease in m6A demethylase activity, about 30% decrease in apurinic/apyrimidinic lyase activity
D233A
H113A/C118A/C129A/H134A
no residual m6A demethylase activity, about 55% decrease in apurinic/apyrimidinic lyase activity
H231A
H287A
K133A
about 50% decrease in m6A demethylase activity, about 45% decrease in apurinic/apyrimidinic lyase activity
R338A
residue plays an important role in substrate recognition and catalysis
R344A
mutation in highly conserved residue, strong decrease in demethylation ability
Y184A
mutation in highly conserved residue, strong decrease in demethylation ability
D233A
no residual m6A demethylase activity, about 30% decrease in apurinic/apyrimidinic lyase activity
D233A
residue plays an important role in substrate recognition and catalysis
H231A
no residual m6A demethylase activity, about 20% decrease in apurinic/apyrimidinic lyase activity
H231A
residue plays an important role in substrate recognition and catalysis
H287A
no residual m6A demethylase activity, about 25% decrease in apurinic/apyrimidinic lyase activity
H287A
residue plays an important role in substrate recognition and catalysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression in human mesenchymal stem cells is upregulated during osteogenic induction
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of assay method using a methylation-sensitive restriction endonuclease
medicine
medicine
ALKBH1 overexpression decreases hepatocellular carcinoma cell viability, induces apoptosis, and decreases migration and invasion. 23779 gain-of-6 mA regions and 11240 loss-of-6 mA regions are differentially identified in hepatocellular carcinoma tissues. The differential gain and loss of 6 mA regions are considerably enriched in intergenic regions. 7% of the differential 6 mA modifications are associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes, and 17 are common to oncogenes and TSGs
medicine
expression levels of ALKBH1 in lung cancer tissues and cells are up regulated. The invasion and migration abilities of lung cancer cells are significantly suppressed in vitro upon the silencing of ALKBH1 while they are significantly promoted upon its overexpression
medicine
in patients with chronic kidney disease, leukocyte 6mA levels are significantly reduced as the severity of vascular calcification increases. Decreased 6mA demethylation results from the upregulation of ALKBH1. ALKBH1 overexpression aggravates whereas its depletion blunts vascular calcification progression and osteogenic reprogramming in vivo and in vitro
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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 (Q13686)
-
Zhou, C.; Liu, Y.; Li, X.; Zou, J.; Zou, S.
DNA N6-methyladenine demethylase ALKBH1 enhances osteogenic differentiation of human MSCs
Bone Res.
4
16033
2016
Homo sapiens
Li, H.; Zhang, Y.; Guo, Y.; Liu, R.; Yu, Q.; Gong, L.; Liu, Z.; Xie, W.; Wang, C.
ALKBH1 promotes lung cancer by regulating m6A RNA demethylation
Biochem. Pharmacol.
189
114284
2021
Homo sapiens (Q13686), Mus musculus (P0CB42)
Mueller, T.A.; Tobar, M.A.; Perian, M.N.; Hausinger, R.P.
Biochemical characterization of AP lyase and m(6)A demethylase activities of human AlkB homologue 1 (ALKBH1)
Biochemistry
56
1899-1910
2017
Homo sapiens (Q13686)
Lin, Q.; Chen, J.W.; Yin, H.; Li, M.A.; Zhou, C.R.; Hao, T.F.; Pan, T.; Wu, C.; Li, Z.R.; Zhu, D.; Wang, H.F.; Huang, M.S.
DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development
Genomics
114
110265
2022
Homo sapiens (Q13686)
Liu, Y.; Chen, Y.; Wang, Y.; Jiang, S.; Lin, W.; Wu, Y.; Li, Q.; Guo, Y.; Liu, W.; Yuan, Q.
DNA demethylase ALKBH1 promotes adipogenic differentiation via regulation of HIF-1 signaling
J. Biol. Chem.
298
101499
2022
Homo sapiens (Q13686)
Ouyang, L.; Su, X.; Li, W.; Tang, L.; Zhang, M.; Zhu, Y.; Xie, C.; Zhang, P.; Chen, J.; Huang, H.
ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease
J. Clin. Invest.
131
e146985
2021
Homo sapiens (Q13686), Mus musculus (P0CB42)
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