EC Number   |
General Information |
Reference |
|---|
   1.14.11.54 | 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 |
738105 |
| 1.14.11.54 | 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 |
738335 |
| 1.14.11.54 | physiological function |
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 |
765803 |
| 1.14.11.54 | 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 |
765483 |
| 1.14.11.54 | 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 |
739063 |
| 1.14.11.54 | 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 |
737957 |
| 1.14.11.54 | physiological function |
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 |
739137 |
| 1.14.11.54 | 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 |
737316 |
