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5'-dAAAA-1-methyl-AYYAAA + 2-oxoglutarate + O2
5'-dAAAAAYYAAA + formaldehyde + succinate + CO2
Substrates: -
Products: -
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N1-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
N1-methyladenine in ssDNA + 2-oxoglutarate + O2
adenine in ssDNA + formaldehyde + succinate + CO2
Substrates: -
Products: -
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N1-methyladenine in tRNA + 2-oxoglutarate + O2
adenine in tRNA + formaldehyde + succinate + CO2
Substrates: -
Products: -
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N3-ethylthymidine in mRNA + 2-oxoglutarate + O2
thymidine in mRNA + ?
Substrates: -
Products: -
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N3-methylcytidine in mRNA + 2-oxoglutarate + O2
cytidine in mRNA + formaldehyde + succinate + CO2
-
Substrates: -
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N3-methylcytidine in tRNA + 2-oxoglutarate + O2
cytidine in tRNA + formaldehyde + succinate + CO2
Substrates: -
Products: -
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N6-methyladenine in tRNA + 2-oxoglutarate + O2
adenine in tRNA + formaldehyde + succinate + CO2
-
Substrates: -
Products: -
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RNA-N1-methyladenine + 2-oxoglutarate + O2
RNA-adenine + formaldehyde + succinate + CO2
Substrates: -
Products: -
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RNA-N6-methyladenine + 2-oxoglutarate + O2
RNA-adenine + formaldehyde + succinate + CO2
Substrates: -
Products: -
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additional information
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Substrates: ALKBH3 demethylates 3-meC, 1-meA, and N6-meA in the presence of 2-oxoglutarate and Fe(II). ALKBH3 preferentially demethylates N6-meA in tRNA
Products: -
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N1-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
-
Substrates: -
Products: -
?
N1-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
Substrates: -
Products: -
?
N1-methyladenine in mRNA + 2-oxoglutarate + O2
adenine in mRNA + formaldehyde + succinate + CO2
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Substrates: N1-methyladenine is prevalent in Homo sapiens mRNA, which shows an N1-methyladenine/adenine ratio of about 0.02%. Methylation of adenine in mRNA is reversible by ALKBH3. Recombinant ALKBH3 protein has robust demethylation activity against a synthetic RNA substrate containing a sitespecifically incorporated m1A modification
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Burkitt Lymphoma
Tp44 molecules involved in antigen-independent T cell activation are expressed on human plasma cells.
Carcinoma
High expression of a new marker PCA-1 in human prostate carcinoma.
Carcinoma
Prostate cancer antigen-1 as a potential novel marker for prostate cancer.
Carcinoma
Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer.
Carcinoma
[Expression of prostate cancer antigen-1 in prostate cancer and its clinical significance]
Carcinoma, Hepatocellular
Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma.
Cerebellar Ataxia
Cerebrospinal fluid ?? T cell frequency is age-related: a case-control study of 435 children with inflammatory and non-inflammatory neurological disorders.
Digestive System Neoplasms
Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers.
Down Syndrome
Purkinje cell cytoplasmic antibody type 1 (anti-yo) autoimmunity in a child with down syndrome.
Encephalitis
Cerebrospinal fluid ?? T cell frequency is age-related: a case-control study of 435 children with inflammatory and non-inflammatory neurological disorders.
Encephalomyelitis
Cerebrospinal fluid ?? T cell frequency is age-related: a case-control study of 435 children with inflammatory and non-inflammatory neurological disorders.
Encephalomyelitis, Acute Disseminated
Cerebrospinal fluid ?? T cell frequency is age-related: a case-control study of 435 children with inflammatory and non-inflammatory neurological disorders.
Leukemia
Antigens on human plasma cells identified by monoclonal antibodies.
Leukemia, Plasma Cell
Antigens on human plasma cells identified by monoclonal antibodies.
Lung Neoplasms
TP53 gene status is a critical determinant of phenotypes induced by ALKBH3 knockdown in non-small cell lung cancers.
Monoclonal Gammopathy of Undetermined Significance
Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients.
Monoclonal Gammopathy of Undetermined Significance
Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells.
Multiple Myeloma
Elimination of myeloma cells from bone marrow by using monoclonal antibodies and magnetic immunobeads.
Multiple Myeloma
Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients.
Multiple Myeloma
Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells.
Neoplasms
Anti-yo associated paraneoplastic cerebellar degeneration in a man with large cell cancer of the lung.
Neoplasms
Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma.
Neoplasms
Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs.
Neoplasms
Elimination of myeloma cells from bone marrow by using monoclonal antibodies and magnetic immunobeads.
Neoplasms
Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers.
Neoplasms
Hairy cell leukemia: a tumor of pre-plasma cells.
Neoplasms
High expression of a new marker PCA-1 in human prostate carcinoma.
Neoplasms
Immunologic heterogeneity of diffuse large cell lymphoma.
Neoplasms
Paraneoplastic Cerebellar Degeneration (PCD) associated with PCA-1 antibodies in established cancer patients.
Neoplasms
Paraneoplastic gastrointestinal motor dysfunction: clinical and laboratory characteristics.
Neoplasms
Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer.
Neoplasms
Proteins of human urine. II. Identification by two-dimensional electrophoresis of a new candidate marker for prostatic cancer.
Neoplasms
Response patterns of hairy cell leukemia to B-cell mitogens and growth factors.
Neoplasms
[Expression of prostate cancer antigen-1 in prostate cancer and its clinical significance]
Neoplasms, Second Primary
Paraneoplastic Cerebellar Degeneration (PCD) associated with PCA-1 antibodies in established cancer patients.
Nervous System Diseases
Purkinje cell cytoplasmic antibody type 1 (anti-yo) autoimmunity in a child with down syndrome.
Ovarian Neoplasms
Paraneoplastic Cerebellar Degeneration (PCD) associated with PCA-1 antibodies in established cancer patients.
Paraneoplastic Cerebellar Degeneration
Paraneoplastic Cerebellar Degeneration (PCD) associated with PCA-1 antibodies in established cancer patients.
Paraneoplastic Syndromes
Paraneoplastic Cerebellar Degeneration (PCD) associated with PCA-1 antibodies in established cancer patients.
Paraproteinemias
Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients.
Paraproteinemias
Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells.
Plasmacytoma
Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody.
Pleural Effusion
Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1.
Prostatic Hyperplasia
Anti-Tumor Effect of AlkB Homolog 3 Knockdown in Hormone- Independent Prostate Cancer Cells.
Prostatic Hyperplasia
High expression of a new marker PCA-1 in human prostate carcinoma.
Prostatic Hyperplasia
Proteins of human urine. II. Identification by two-dimensional electrophoresis of a new candidate marker for prostatic cancer.
Prostatic Intraepithelial Neoplasia
High expression of a new marker PCA-1 in human prostate carcinoma.
Prostatic Intraepithelial Neoplasia
Prostate cancer antigen-1 as a potential novel marker for prostate cancer.
Prostatic Intraepithelial Neoplasia
[Expression of prostate cancer antigen-1 in prostate cancer and its clinical significance]
Prostatic Neoplasms
Anti-Tumor Effect of AlkB Homolog 3 Knockdown in Hormone- Independent Prostate Cancer Cells.
Prostatic Neoplasms
Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma.
Prostatic Neoplasms
Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs.
Prostatic Neoplasms
High expression of a new marker PCA-1 in human prostate carcinoma.
Prostatic Neoplasms
Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor HUHS015 using sodium salt.
Prostatic Neoplasms
Novel Metabolically Stable PCA-1/ALKBH3 Inhibitor Has Potent Antiproliferative Effects on DU145 Cells
Prostatic Neoplasms
Prostate cancer antigen-1 as a potential novel marker for prostate cancer.
Prostatic Neoplasms
Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer.
Prostatic Neoplasms
[Effect of downregulation of prostate cancer antigen-1 expression on malignant biological behavior of prostate cancer LNCaP cells].
Prostatic Neoplasms
[Expression of prostate cancer antigen-1 in prostate cancer and its clinical significance]
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physiological function
1-methyladenine and 3-methylcytosine lesions in DNA/RNA contribute to the cytotoxicity of methylating agents. These lesions are directly reversed by ABH3 in humans
physiological function
ALKBH3 binds to transcription associated locations, such as places of promoter-proximal paused RNA polymerase II and enhancers. ALKBH3 strongly binds to the transcription initiation sites of a small number of highly active gene promoters characterized by high levels of transcriptional regulators, including transcription factors, the Mediator complex, cohesin, histone modifiers, and active histone marks. ALKBH3 does not directly influence the transcription of its target genes, but its depletion induces an upregulation of ALKBH3 non-bound inflammatory genes
physiological function
ALKBH3 is associated with the activating signal cointegrator complex ASCC. ALKBH3 is overexpressed in various cancers, and both ALKBH3 and ASCC are important for alkylation damage resistance in these tumor cell lines. ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. In cell lines that are dependent on ALKBH3 and ASCC3 for alkylation damage resistance, loss of ALKBH3 or ASCC3 leads to increased 3-methylcytosine and reduced cell proliferation. ALKBH3 catalytic activity is important for alkylation damage resistance
physiological function
human adenocarcinomas and squamous cell carcinomas of the lung show overexpression of Alkbh3 and the percentage of cells positive for Alkbh3 also correlates statistically to recurrence-free survival in adenocarcinoma. Knockdown of Alkbh3 by siRNA transfection induces expression of p21WAF1/Cip1 and p27Kip1 in the human lung adenocarcinoma cell line A-549, resulting in cell cycle arrest, senescence and strong suppression of cell growth in vitro. In vivo, peritoneal tumour growth and dissemination is inhibited in nude mice, previously inoculated with the A-549 cell line, by intraperitoneal injection of Alkbh3 siRNA plus atelocollagen
physiological function
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N1-methyladenine in mRNA can be reversed by ALKBH3. Adenine methylation responds dynamically to stimuli, and hundreds of stress-induced N1-methyladenine sites can be identified. Knockout and overexpression of ALKBH3 in HEK-293T cells leads to an increased or decreased N1-methyladenine/adenine ratio in mRNA, respectively
physiological function
the absence of Alkbh3 does not lead to a statistically significant change in the transcriptional blockage or mutagenic properties of O2-ethyl-deoxythymidine, O4-ethyl-deoxythymidine, N3-carboxymethyl-deoxythymidine, and O4-carboxymethyl-deoxythymidine in mammalian cells. N3-ethyl-deoxythymidine induces a substantially higher degree of A to U mutation (about 31%) in Alkbh3-deficient cells than in the wildtype background. N3-ethyl-deoxythymidine, but not other lesions, can be repaired by Alkbh3 in mammalian cells
physiological function
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ALKBH3 effectively demethylates 1-meA and 3-meC within endogenously methylated RNA and also N6-methyladenine (N6-meA) in mammalian transfer RNA. ALKBH3-demethylated tRNA significantly enhances protein translation efficiency. ALKBH3 knockdown in human cancer cells impairs cellular proliferation and suppresses the nascent protein synthesis that is usually accompanied by accumulation of the methylated RNAs
physiological function
ALKBH3 is a 1-methyladenosine and 3-methylcytidine demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. The m1A demethylated tRNA is more sensitive to angiogenin cleavage, followed by generating tRNA-derived small RNAs around the anticodon regions. in ALKBH3-/- HeLa cells, m1A level of tRNA in cytoplasm, but not in nucleus, is remarkably higher than that of wild type cells. Deletion of ALKBH3 significantly increases the m1A levels of most target tRNAs such as tRNAGluCTC, tRNASeCTCA, tRNAGlyGCC, tRNAHisGTG, tRNASerGCT, tRNAGlnCTG, tRNAValCAC, tRNAArgCCT, tRNALeuCAA, tRNAGlyCCC, tRNAAlaCGC and tRNAeMetCAT. m1A levels of some targets, such as tRNALysCTT and tRNAAsnGTT, are not affected. m3C levels of target tRNA are significantly upregulated in Alkbh3-/- HeLa cells
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You, C.; Wang, P.; Nay, S.L.; Wang, J.; Dai, X.; OConnor, T.R.; Wang, Y.
Roles of Aag, Alkbh2, and Alkbh3 in the repair of carboxymethylated and ethylated thymidine lesions
ACS Chem. Biol.
11
1332-1338
2016
Mus musculus (Q8K1E6)
brenda
Tasaki, M.; Shimada, K.; Kimura, H.; Tsujikawa, K.; Konishi, N.
ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer
Br. J. Cancer
104
700-706
2011
Homo sapiens (Q96Q83)
brenda
Sundheim, O.; Vagbo, C.; Bjoras, M.; Sousa, M.; Talstad, V.; Aas, P.; Drablos, F.; Krokan, H.; Tainer, J.; Slupphaug, G.
Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage
EMBO J.
25
3389-3397
2006
Homo sapiens (Q96Q83)
brenda
Liefke, R.; Windhof-Jaidhauser, I.M.; Gaedcke, J.; Salinas-Riester, G.; Wu, F.; Ghadimi, M.; Dango, S.
The oxidative demethylase ALKBH3 marks hyperactive gene promoters in human cancer cells
Genome Med.
7
66
2015
Homo sapiens (Q96Q83)
brenda
Dango, S.; Mosammaparast, N.; Sowa, M.E.; Xiong, L.J.; Wu, F.; Park, K.; Rubin, M.; Gygi, S.; Harper, J.W.; Shi, Y.
DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation
Mol. Cell
44
373-384
2011
Homo sapiens (Q96Q83)
brenda
Li, X.; Xiong, X.; Wang, K.; Wang, L.; Shu, X.; Ma, S.; Yi, C.
Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome
Nat. Chem. Biol.
12
311-316
2016
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
Escherichia coli (P05050)
brenda
Ueda, Y.; Kitae, K.; Ooshio, I.; Fusamae, Y.; Kawaguchi, M.; Jingushi, K.; Harada, K.; Hirata, K.; Tsujikawa, K.
A real-time PCR-based quantitative assay for 3-methylcytosine demethylase activity of ALKBH3
Biochem. Biophys. Rep.
5
476-481
2016
Homo sapiens (Q96Q83), Homo sapiens
brenda
Beharry, A.A.; Lacoste, S.; OConnor, T.R.; Kool, E.T.
Fluorescence monitoring of the oxidative repair of DNA alkylation damage by ALKBH3, a prostate cancer marker
J. Am. Chem. Soc.
138
3647-3650
2016
Homo sapiens (Q96Q83)
brenda
Woo, H.H.; Chambers, S.K.
Human ALKBH3-induced m1A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells
Biochim. Biophys. Acta Gene Regul. Mech.
1862
35-46
2019
Homo sapiens (Q96Q83)
brenda
Esteve-Puig, R.; Climent, F.; Pineyro, D.; Domingo-Domenech, E.; Davalos, V.; Encuentra, M.; Rea, A.; Espejo-Herrera, N.; Soler, M.; Lopez, M.; Ortiz-Barahona, V.; Tapia, G.; Navarro, J.; Cid, J.; Farre, L.; Villanueva, A.; Casanova, I.; Mangues, R.
Epigenetic loss of m1A RNA demethylase ALKBH3 in Hodgkin lymphoma targets collagen, conferring poor clinical outcome
Blood
137
994-999
2021
Homo sapiens (Q96Q83)
brenda
Chen, Z.; Qi, M.; Shen, B.; Luo, G.; Wu, Y.; Li, J.; Lu, Z.; Zheng, Z.; Dai, Q.; Wang, H.
Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs
Nucleic Acids Res.
47
2533-2545
2019
Homo sapiens (Q96Q83)
brenda
Ueda, Y.; Ooshio, I.; Fusamae, Y.; Kitae, K.; Kawaguchi, M.; Jingushi, K.; Hase, H.; Harada, K.; Hirata, K.; Tsujikawa, K.
AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells
Sci. Rep.
7
42271
2017
Bombyx mori
brenda