Affinage

ALKBH1

Nucleic acid dioxygenase ALKBH1 · UniProt Q13686

Length
389 aa
Mass
43.8 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALKBH1 is a multifunctional Fe(II)/2-oxoglutarate-dependent dioxygenase that operates on both RNA and DNA substrates to regulate translation, mitochondrial function, and epigenetic gene expression. On tRNA, ALKBH1 demethylates N1-methyladenosine (m1A) to attenuate translation initiation in a glucose-responsive manner and oxidizes m5C to f5C at the wobble position of mitochondrial tRNAMet, a modification essential for mitochondrial translation and respiratory complex activity (PMID:27745969, PMID:28472312). On DNA, ALKBH1 demethylates N6-methyladenine (6mA) with a structural preference for unpairing/bubbled substrates mediated by its unique Flip1 motif, thereby controlling transcription of targets including ATF4, BMP2, HIF-1α, and AMPK pathway genes during osteogenesis, adipogenesis, and tumorigenesis (PMID:32051560, PMID:27785372, PMID:36989111). ALKBH1 additionally possesses an Fe(II)-independent AP lyase activity that cleaves abasic DNA sites through a mechanistically distinct active site involving covalent attachment at C129 (PMID:19959401, PMID:28290676).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 Low

    Early cross-linking studies failed to detect ALKBH1–DNA interaction, leaving its substrate identity and enzymatic function unresolved among AlkB family members.

    Evidence Chemical cross-linking of bacterially expressed ALKBH1 with thiol-tethered DNA probes showed no detectable binding, unlike ABH2/ABH3

    PMID:15004242

    Open questions at the time
    • Negative result obtained only with E. coli–expressed protein; post-translational modifications or cofactors absent
    • Did not test RNA substrates or non-canonical DNA structures
  2. 2008 Medium

    The finding that ALKBH1 interacts with the co-repressor Mrj and competes with HDAC4 binding established an unexpected role in transcriptional regulation and placental development, independent of any known catalytic activity.

    Evidence Co-immunoprecipitation, competition binding assays, HDAC activity assays, and Alkbh1-knockout mouse phenotyping showing impaired trophoblast differentiation

    PMID:18163532

    Open questions at the time
    • Mutual exclusivity of ALKBH1/HDAC4 for Mrj not confirmed by structural data
    • Whether ALKBH1 enzymatic activity contributes to the trophoblast phenotype was not tested
  3. 2009 High

    Discovery of AP lyase activity revealed that ALKBH1 possesses a catalytic function mechanistically distinct from canonical AlkB-family oxidative demethylation, using a separate active site that does not require Fe(II) or 2-oxoglutarate.

    Evidence In vitro AP-site cleavage assays with EDTA inhibition tests and active-site mutagenesis showing a lyase mechanism with covalent protein–DNA intermediate

    PMID:19959401

    Open questions at the time
    • Biological role of AP lyase activity in vivo not established
    • Identity of the catalytic residue(s) for the lyase reaction not fully resolved
  4. 2010 Medium

    Alkbh1-knockout mice showed spermatogenesis defects and non-Mendelian sex-ratio skewing, establishing a role in germ cell biology beyond the previously known placental phenotype.

    Evidence Alkbh1-KO mouse phenotyping with histology, apoptosis detection in spermatids, and quantitative gene expression analysis

    PMID:21072209

    Open questions at the time
    • Molecular substrate (DNA or RNA) responsible for the spermatogenesis phenotype not identified
    • Mechanism linking ALKBH1 loss to sex-ratio distortion remains unknown
  5. 2016 High

    Identification of tRNA m1A as a bona fide substrate resolved a long-standing question about ALKBH1's primary catalytic activity, showing it dynamically regulates translation initiation in response to glucose availability.

    Evidence Biochemical demethylation assays, translation initiation measurements, and glucose-deprivation experiments with genetic knockdown/overexpression

    PMID:27745969

    Open questions at the time
    • Full spectrum of tRNA targets not mapped
    • Structural basis for m1A recognition in tRNA not determined
  6. 2016 Medium

    Parallel work established ALKBH1 as a DNA N6-methyladenine (6mA) demethylase that regulates osteogenic differentiation by controlling ATF4 promoter methylation, revealing a second substrate class and a direct link to lineage commitment.

    Evidence siRNA knockdown and overexpression in human MSCs, ChIP for N6-mA at ATF4 promoter, in vivo bone formation assays, ATF4 rescue experiments

    PMID:27785372

    Open questions at the time
    • Whether 6mA demethylase activity is physiologically separable from tRNA demethylase activity not addressed
    • Genome-wide 6mA target landscape in MSCs not fully characterized
  7. 2017 High

    In vitro reconstitution demonstrated that ALKBH1 sequentially oxidizes m5C to hm5C and then f5C at the tRNA anticodon wobble position, a reaction essential for mitochondrial translation and respiratory function.

    Evidence In vitro reconstitution of f5C34 formation, ALKBH1-KO cell analysis of mitochondrial translation and respiratory complex activity

    PMID:28472312

    Open questions at the time
    • How ALKBH1 is recruited to specific mitochondrial tRNA substrates is unknown
    • Relative contributions of m1A demethylation versus f5C formation to mitochondrial phenotypes not disentangled
  8. 2017 High

    Detailed kinetic analysis confirmed that the AP lyase and m6A demethylase activities use distinct but partially overlapping active sites, with C129 as the primary residue for covalent AP-site intermediate formation and the AP lyase being kinetically dominant over DNA demethylation.

    Evidence Steady-state and single-turnover kinetics, site-directed mutagenesis, mass spectrometry identification of C129 adduct

    PMID:28290676

    Open questions at the time
    • Physiological relevance of the AP lyase activity in mitochondrial or nuclear DNA repair remains untested in vivo
  9. 2019 Medium

    Super-resolution imaging placed ALKBH1 at mitochondrial RNA granules, and cross-species experiments in C. elegans demonstrated that the mitochondrial function of ALKBH1 is evolutionarily conserved and triggers the mitochondrial unfolded protein response upon loss.

    Evidence 3D SIM microscopy, high-resolution respirometry, siRNA knockdown in HeLa cells, genetic knockdown in C. elegans

    PMID:31434717

    Open questions at the time
    • Whether ALKBH1 acts on additional mitochondrial RNA species at granules is unexplored
    • Mechanism by which ALKBH1 loss activates UPRmt not defined
  10. 2020 High

    Co-crystal structures of ALKBH1 with bulged DNA revealed the unique Flip1 'stretch-out' conformation and α1 helix that explain the enzyme's preference for unpairing DNA substrates, providing the first structural rationale for substrate selectivity in 6mA demethylation.

    Evidence X-ray co-crystal structure of ALKBH1 bound to bulged DNA, enzymatic profiling with various DNA topologies, structure-based mutagenesis, genomic DIP-seq/ssDNA-seq

    PMID:32051560

    Open questions at the time
    • How ALKBH1 is targeted to specific genomic unpairing regions in vivo is not known
    • No structure of ALKBH1 bound to tRNA substrates available
  11. 2020 Medium

    ALKBH1-mediated m1A demethylation of tRNAs was shown to destabilize tRNA structure and promote stress-induced tRNA cleavage into tiRNAs, linking its tRNA modification activity to stress-response signaling.

    Evidence ALKBH1 knockdown and overexpression in neuroblastoma cells with tRNA cleavage assays under multiple stress conditions

    PMID:32521209

    Open questions at the time
    • Whether tiRNA generation is a primary physiological function or a secondary consequence of tRNA destabilization is unclear
    • Stress-type specificity of the effect needs broader characterization
  12. 2021 Medium

    ALKBH1-mediated 6mA demethylation at the BMP2 promoter was shown to facilitate Oct4 binding, activating osteogenic reprogramming and vascular calcification in chronic kidney disease, extending the epigenetic role from MSCs to vascular pathology.

    Evidence VSMC-targeted AAV delivery in CKD mice, ChIP for Oct4 at BMP2 promoter, in vivo calcification assays

    PMID:34003800

    Open questions at the time
    • Whether 6mA at Oct4 binding sites is a general mechanism across tissues is unknown
    • Contribution of tRNA-level activities to the vascular phenotype not excluded
  13. 2022 Medium

    Discovery that ALKBH1 demethylates m1A on METTL3 mRNA to upregulate METTL3 expression revealed a cross-talk between m1A erasure and the m6A epitranscriptomic pathway, with downstream consequences for colorectal cancer metastasis via SMAD7 suppression.

    Evidence m1A methylation analysis of METTL3 mRNA, m6A analysis of SMAD7 mRNA, knockdown/overexpression, in vitro and in vivo metastasis assays

    PMID:36550779

    Open questions at the time
    • Whether mRNA m1A demethylation is a general ALKBH1 activity beyond tRNA is not established by independent groups
    • Direct binding of ALKBH1 to METTL3 mRNA not shown
  14. 2023 Medium

    Genome-wide 6mA profiling in gastric cancer established that ALKBH1 represses NRF1-driven transcription of AMPK pathway genes by demethylating 6mA at NRF1 binding sites near TSSs, promoting the Warburg metabolic shift and tumorigenesis.

    Evidence DIP-seq for 6mA, ChIP for NRF1, ALKBH1-KO mouse model of chemically induced gastric cancer, RNA-seq, metabolic assays

    PMID:36989111

    Open questions at the time
    • Generality of the NRF1-6mA regulatory axis across cancer types is untested
    • Whether ALKBH1 enzymatic activity or scaffolding function drives the phenotype not formally distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ALKBH1's multiple enzymatic activities (tRNA m1A demethylation, tRNA m5C oxidation, DNA 6mA demethylation, AP lyase) are coordinated across subcellular compartments, and which activity drives specific developmental and disease phenotypes, remains unresolved.
  • No structure of ALKBH1 bound to tRNA substrate exists
  • Relative in vivo contributions of each enzymatic activity to specific phenotypes have not been separated by activity-specific separation-of-function mutations
  • Regulation of ALKBH1 itself (post-translational modifications, interactors controlling substrate selectivity) is largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0140097 catalytic activity, acting on DNA 4 GO:0140098 catalytic activity, acting on RNA 4 GO:0003723 RNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-4839726 Chromatin organization 2
Partners
METTL3MRJNANOGSOX2

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Mammalian ALKBH1 functions as a tRNA demethylase, mediating demethylation of N1-methyladenosine (m1A) in tRNAs. The ALKBH1-catalyzed demethylation of target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis; this process is dynamic and responds to glucose availability. Biochemical demethylation assays, translation initiation assays, glucose availability experiments, genetic knockdown/overexpression Cell High 27745969
2017 ALKBH1 is an RNA dioxygenase responsible for formation of 5-hydroxymethyl-2′-O-methylcytidine (hm5Cm) and 5-formyl-2′-O-methylcytidine (f5Cm) at position 34 of the anticodon in cytoplasmic tRNALeu, and for f5C at position 34 in mitochondrial tRNAMet. In vitro reconstitution showed ALKBH1 first hydroxylates m5C34 to hm5C34, then oxidizes it to f5C34. ALKBH1-knockout cells show strong reduction in mitochondrial translation and respiratory complex activities. ALKBH1 also has demethylation activity toward m1A in mitochondrial tRNAs. In vitro reconstitution of f5C34 formation, ALKBH1-knockout cell analysis, mitochondrial translation assays, respiratory complex activity assays Nucleic acids research High 28472312
2020 ALKBH1 functions as a nuclear eraser of N6-methyladenine (N6-mA) in unpairing regions (e.g., stress-induced DNA double-helix destabilization regions) of mammalian genomes. Enzymatic profiling showed ALKBH1 prefers bubbled or bulged DNAs over ssDNA or dsDNA. Co-crystal structural studies revealed an ALKBH1-specific 'stretch-out' conformation of its 'Flip1' motif and an α1 helix that facilitate recognition of unpairing substrates with a flipped N6-mA base. Enzymatic profiling with various DNA substrates, X-ray co-crystal structure of ALKBH1 bound to bulged DNA, structure-based mutagenesis, ssDNA-seq and DIP-seq genomic analyses Cell research High 32051560
2008 ALKBH1 (Alkbh1) localizes to nuclear euchromatin and interacts with Mrj, an essential placental gene that mediates gene repression by recruiting class II histone deacetylases (HDACs). Competition experiments showed Alkbh1 and HDAC4 binding to Mrj are mutually exclusive, causing decreased HDAC activity and increased target gene expression. Alkbh1-null mice have impaired placental trophoblast lineage differentiation. Immunolocalization, co-immunoprecipitation, competition binding assays, HDAC activity assays, Alkbh1 knockout mouse phenotyping Developmental dynamics Medium 18163532
2010 Mice lacking Alkbh1 display non-Mendelian inheritance, skewed sex ratio (against females) of paternal origin, apoptotic spermatids in testes, and misexpression of Bmp2, 4 and 7 at E11.5. Alkbh1 is upregulated >10-fold in pachythene spermatocytes, suggesting a role in spermatogenesis and sex-ratio distribution. Alkbh1 knockout mouse generation, quantitative gene expression, histological analysis, apoptosis detection PloS one Medium 21072209
2009 Human AlkB homolog 1 (ABH1/ALKBH1) exhibits an unexpected DNA lyase activity at abasic (AP) sites. This AP lyase activity does not require Fe2+ or 2-oxoglutarate and is unaffected by mutation of metal-binding residues, indicating a distinct active site from the demethylation active site. The enzyme cleaves AP sites by a lyase mechanism and remains covalently associated with the 5'-DNA product. In vitro AP-site cleavage assays, EDTA inhibition tests, active-site mutagenesis, mechanistic analysis of lyase vs hydrolysis DNA repair High 19959401
2017 Biochemical characterization confirmed that human ALKBH1 has both AP lyase activity (cleaving AP sites with predominant covalent attachment to C129) and m6A DNA demethylase activity. The m6A demethylase activity is very low compared to AP lyase activity. Site-directed mutagenesis revealed distinct but partially overlapping active sites for the two reactions. Steady-state and single-turnover kinetics, site-directed mutagenesis, methylation-sensitive restriction endonuclease assay, mass spectrometry Biochemistry High 28290676
2017 ALKBH1 produced in mammalian cells is similar to bacterially produced ALKBH1 in m6A demethylase and AP lyase activities, and forms a covalent adduct with the 5' product of the AP lyase reaction. Subcellular fractionation studies confirmed ALKBH1 is primarily localized to mitochondria in human cells. ALKBH1-deficient HEK293 cells (CRISPR/Cas9 KO) show increased mtDNA copy number and mitochondrial dysfunction. Enzymatic activity assays, subcellular fractionation, CRISPR/Cas9 knockout, citrate synthase activity assays, growth measurements Biochemical and biophysical research communications Medium 29097205
2019 Alkbh1 localizes to mitochondrial RNA granules as visualized by super-resolution 3D SIM microscopy. Alkbh1 knockdown impairs mitochondrial respiration and cell growth in HeLa cells, and triggers the mitochondrial unfolded protein response (UPRmt) in C. elegans, where the mitochondrial role of Alkbh1 is conserved. Super-resolution 3D SIM microscopy, electron microscopy, high-resolution respirometry, siRNA knockdown, C. elegans genetic knockdown Journal of cell science Medium 31434717
2016 ALKBH1 acts as a demethylase for DNA N6-methyladenine (N6-mA) and regulates osteogenic differentiation of human MSCs. Knockdown of ALKBH1 increased genomic DNA N6-mA levels and reduced osteogenic gene expression; mechanistically, ALKBH1 depletion caused accumulation of N6-mA on the ATF4 promoter, silencing ATF4 transcription. siRNA knockdown, overexpression, alkaline phosphatase activity assays, in vivo bone formation, ChIP assay for N6-mA at ATF4 promoter, adenovirus-mediated ATF4 rescue Bone research Medium 27785372
2016 SOX2 and NANOG bind the ALKBH1 promoter, and ALKBH1 physically interacts with these core transcription factors of the pluripotency network (SOX2, NANOG) in embryonic stem cells. Loss of ALKBH1 affects expression of developmentally important miRNAs regulating NANOG, SOX2, and neural differentiation. Co-immunoprecipitation, ELISA, double-filter nitrocellulose binding assay for promoter binding, miRNA analysis, immunocytochemistry Cellular physiology and biochemistry Medium 26765775
2020 ALKBH1-mediated demethylation of m1A in tRNAs destabilizes tRNA structure and enhances tRNA cleavage and tiRNA generation in a stress-specific manner. ALKBH1 knockdown or overexpression modulates tRNA cleavage and cell fate following specific stresses, but this effect is impacted by the demethylating capacity of the stress itself. ALKBH1 gene knockdown and overexpression in rat neuroblastoma cells, tRNA cleavage assays under multiple stress conditions RNA biology Medium 32521209
2021 ALKBH1-mediated DNA 6mA demethylation in vascular smooth muscle cells facilitates binding of Oct4 to the BMP2 promoter, activating BMP2 transcription and triggering osteogenic reprogramming and vascular calcification in chronic kidney disease. ALKBH1 overexpression aggravated while ALKBH1 depletion blunted vascular calcification in vivo. VSMC-targeted AAV delivery of Alkbh1 or shRNA in CKD mice, ChIP assay for Oct4 binding at BMP2 promoter, in vitro and in vivo calcification assays Journal of clinical investigation Medium 34003800
2020 Crystal structure of mouse ALKBH1 at 3.1 Å resolution revealed that the N-terminal domain forms close contacts with the core catalytic domain. Key residues (Y184, H231, D233, H287, R338, R344) are essential for m6A demethylation activity, as shown by mutagenesis. X-ray crystallography, active-site mutagenesis, biochemical m6A demethylase assays Biochemical pharmacology High 33068553
2022 ALKBH1-mediated DNA m6A (N6-mA) demethylation regulates bone marrow mesenchymal stem cell fate during aging. Alkbh1 knockout promoted adipogenic and inhibited osteogenic differentiation of BMSCs, causing reduced bone mass. Mechanistically, ChIP assays identified optineurin (OPTN) as a downstream target regulated by ALKBH1-mediated N6-mA modification. BMSC-specific Alkbh1 knockout mice, micro-CT, ChIP assay for N6-mA at OPTN promoter, cell differentiation assays Cell proliferation Medium 35018683
2021 ALKBH1-mediated DNA 6mA demethylation promotes adipogenic differentiation by regulating HIF-1 signaling. Depletion of ALKBH1 causes hypermethylation of HIF-1α and GYS1 promoters. Simultaneous overexpression of HIF-1α and GYS1 rescues adipogenic commitment in ALKBH1-deficient cells. RNA-seq, N6-mA-DNA-IP-seq, siRNA knockdown, overexpression, adipogenic differentiation assays Journal of biological chemistry Medium 34922943
2022 ALKBH1 mediates m1A demethylation of METTL3 mRNA, which upregulates METTL3 expression. Increased METTL3 then promotes m6A modification of SMAD7 mRNA, leading to reduced SMAD7 expression and enhanced colorectal cancer metastasis. siRNA knockdown, overexpression, m1A methylation analysis of METTL3 mRNA, m6A analysis of SMAD7 mRNA, in vitro and in vivo metastasis assays Molecular oncology Medium 36550779
2023 ALKBH1 mediates DNA 6mA demethylation to repress gene expression at NRF1 binding sequences near transcription start sites in gastric cancer. ALKBH1-induced 6mA demethylation inhibits NRF1-driven transcription of AMPK signaling pathway genes, causing a metabolic shift toward the Warburg effect. ALKBH1 knockout in mice impairs chemically induced gastric carcinogenesis. ChIP for NRF1 binding, DIP-seq for 6mA, ALKBH1 KO mouse model, RNA-seq, metabolic assays Cell reports Medium 36989111
2004 Chemical cross-linking studies showed that ABH1 (ALKBH1) failed to cross-link to single-stranded or modified DNA probes, unlike ABH2 and ABH3 which showed structural and functional similarities to E. coli AlkB. This suggested that ALKBH1 does not interact with DNA substrates in its E. coli-expressed form. Chemical cross-linking with thiol-tethered DNA probes, SDS-PAGE analysis of disulfide-linked protein-DNA complexes, active-site mutagenesis Nucleic acids research Low 15004242
2007 Subcellular localization studies showed that EmGFP-hABH1 (ALKBH1) localizes to both the cytoplasm and nucleus in HeLa cells. EmGFP fusion protein live-cell imaging and fluorescence microscopy Journal of cellular and molecular medicine Low 17979886

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 583 12226667
2002 AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 505 12226668
1989 ABH and related histo-blood group antigens; immunochemical differences in carrier isotypes and their distribution. Vox sanguinis 458 2464874
2016 ALKBH1-Mediated tRNA Demethylation Regulates Translation. Cell 402 27745969
2015 ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nature methods 383 26237225
2015 The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond. The Journal of biological chemistry 333 26152727
2017 AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. Scientific reports 263 28205560
2017 ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic acids research 218 28472312
2004 Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 205 15381779
2010 Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Molecular and cellular biology 177 20308323
2003 Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB. BMC genomics 177 14667252
2004 AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Molecular cell 168 15469826
2015 Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. Cell reports 165 26686626
2005 AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo. Nature structural & molecular biology 163 16200073
2010 Gene diversity of CYP153A and AlkB alkane hydroxylases in oil-degrading bacteria isolated from the Atlantic Ocean. Environmental microbiology 137 20148932
2009 A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression. Cancer research 130 19293182
2004 Substrate specificities of bacterial and human AlkB proteins. Nucleic acids research 110 15229293
2011 ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer. British journal of cancer 103 21285982
1992 Genetic regulation of the expression of ABH and Lewis antigens in tissues. APMIS. Supplementum 103 1520528
2008 Viral AlkB proteins repair RNA damage by oxidative demethylation. Nucleic acids research 95 18718927
2004 Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins. Nucleic acids research 95 15576352
2007 Expression and sub-cellular localization of human ABH family molecules. Journal of cellular and molecular medicine 92 17979886
1994 Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton blood group antigens. The Journal of clinical investigation 92 7521882
2020 Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell research 85 32051560
2017 A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair. Nature 85 29144457
2003 The selectivity and inhibition of AlkB. The Journal of biological chemistry 83 12517755
2020 Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family. Cellular and molecular life sciences : CMLS 78 32642789
2010 Diversity and abundance of oil-degrading bacteria and alkane hydroxylase (alkB) genes in the subtropical seawater of Xiamen Island. Microbial ecology 78 20683589
2016 Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage. The Journal of biological chemistry 77 27015802
2021 ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease. The Journal of clinical investigation 73 34003800
2012 Novel AlkB dioxygenases--alternative models for in silico and in vivo studies. PloS one 72 22291995
2008 Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Developmental dynamics : an official publication of the American Association of Anatomists 72 18163532
1993 Identification of a major encephalitogenic epitope of proteolipid protein (residues 56-70) for the induction of experimental allergic encephalomyelitis in Biozzi AB/H and nonobese diabetic mice. Journal of immunology (Baltimore, Md. : 1950) 71 7685799
2017 Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions. Chemical research in toxicology 70 28269980
2020 The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. RNA biology 69 32521209
1987 ABH and Lewis blood group expression in colorectal carcinoma. Cancer research 67 3815366
1985 Molecular cloning and characterization of the alkB gene of Escherichia coli. Molecular & general genetics : MGG 65 3884973
2015 Non-homologous functions of the AlkB homologs. Journal of molecular cell biology 64 26003568
2010 Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects. PloS one 62 21072209
2009 Expression of alkane monooxygenase (alkB) genes by plant-associated bacteria in the rhizosphere and endosphere of Italian ryegrass (Lolium multiflorum L.) grown in diesel contaminated soil. Environmental pollution (Barking, Essex : 1987) 61 19773105
2004 Determinants of ABH expression on human blood platelets. Blood 61 15613545
2020 ALKBH1 promotes lung cancer by regulating m6A RNA demethylation. Biochemical pharmacology 58 33068553
2019 ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy. Scientific reports 58 31519943
2006 Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins. Journal of inorganic biochemistry 58 16469386
2014 Switching demethylation activities between AlkB family RNA/DNA demethylases through exchange of active-site residues. Angewandte Chemie (International ed. in English) 57 24596302
2019 Biologic roles of the ABH and Lewis histo-blood group antigens Part I: infection and immunity. Vox sanguinis 55 31070258
2023 Structure and mechanism of the alkane-oxidizing enzyme AlkB. Nature communications 54 37069165
2016 DNA N6-methyladenine demethylase ALKBH1 enhances osteogenic differentiation of human MSCs. Bone research 53 27785372
2004 Cloning and functional analysis of alkB genes in Alcanivorax borkumensis SK2. Environmental microbiology 53 14871203
2008 Dynamic states of the DNA repair enzyme AlkB regulate product release. EMBO reports 52 18617893
1994 The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity. Journal of bacteriology 52 7928996
1991 Mononuclear cell trafficking and plasma protein extravasation into the CNS during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice. Journal of the neurological sciences 52 1919601
2009 Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites. DNA repair 51 19959401
2017 Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes. PLoS biology 50 29107960
2019 Biologic roles of the ABH and Lewis histo-blood group antigens part II: thrombosis, cardiovascular disease and metabolism. Vox sanguinis 49 31090093
2004 Aberrant activity of the DNA repair enzyme AlkB. Journal of inorganic biochemistry 48 15134932
2022 Alkbh1-mediated DNA N6-methyladenine modification regulates bone marrow mesenchymal stem cell fate during skeletal aging. Cell proliferation 47 35018683
2015 Differential repair of etheno-DNA adducts by bacterial and human AlkB proteins. DNA repair 41 25797601
2020 MiRNA-339-5p suppresses the malignant development of gastric cancer via targeting ALKBH1. Experimental and molecular pathology 39 32380054
2003 DNA repair by bacterial AlkB proteins. Research in microbiology 39 14527653
1981 Insights into the expression of ABH and Lewis antigens through human bone marrow transplantation. American journal of human genetics 38 6167165
2002 Alkane biodegradation in Pseudomonas aeruginosa strains isolated from a polluted zone: identification of alkB and alkB-related genes. Research in microbiology 36 12234007
2021 Expression and molecular profiles of the AlkB family in ovarian serous carcinoma. Aging 33 33744868
2003 AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. Trends in biochemical sciences 33 12517444
2000 Encephalitogenic and immunogenic potential of the stress protein alphaB-crystallin in Biozzi ABH (H-2A(g7)) mice. Journal of neuroimmunology 32 10683514
2022 ALKBH1-mediated m1 A demethylation of METTL3 mRNA promotes the metastasis of colorectal cancer by downregulating SMAD7 expression. Molecular oncology 31 36550779
2009 Chloroacetaldehyde-induced mutagenesis in Escherichia coli: the role of AlkB protein in repair of 3,N(4)-ethenocytosine and 3,N(4)-alpha-hydroxyethanocytosine. Mutation research 31 19941873
2014 Alternative Pathway for the Reaction Catalyzed by DNA Dealkylase AlkB from Ab Initio QM/MM Calculations. Journal of chemical theory and computation 30 25400523
2004 Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies. Nucleic acids research 30 15004242
1994 Expression of mucin peptide and blood group ABH- and Lewis-related carbohydrate antigens in normal human conjunctiva. Investigative ophthalmology & visual science 30 7510273
2013 Alkane hydroxylase gene (alkB) phylotype composition and diversity in northern Gulf of Mexico bacterioplankton. Frontiers in microbiology 29 24376439
2022 AlkB RNA demethylase homologues and N6 -methyladenosine are involved in Potyvirus infection. Molecular plant pathology 28 35700092
2016 Role of ALKBH1 in the Core Transcriptional Network of Embryonic Stem Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 26765775
1994 Demonstration of HLA and ABH antigens in fresh and frozen human menisci by immunohistochemistry. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 28 7983550
2023 The role of demethylase AlkB homologs in cancer. Frontiers in oncology 27 37007161
1998 Immunohistochemical expression of ABH/Lewis-related antigens in primary breast carcinomas and metastatic lymph node lesions. Cancer detection and prevention 27 9824372
2017 Biochemical Characterization of AP Lyase and m6A Demethylase Activities of Human AlkB Homologue 1 (ALKBH1). Biochemistry 26 28290676
1998 ABH antigens on human platelets: expression on the glycosyl phosphatidylinositol-anchored protein CD109. The Journal of laboratory and clinical medicine 26 9708575
1979 ABH and Lewis antigens on lymphocytes: screening of pregnant women's sera with the B-cell cytotoxicity test. Transplantation proceedings 26 394439
2019 Mitochondrial Alkbh1 localizes to mtRNA granules and its knockdown induces the mitochondrial UPR in humans and C. elegans. Journal of cell science 25 31434717
2009 Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria. Nucleic acids research 25 19786499
2023 Medium-chain alkane biodegradation and its link to some unifying attributes of alkB genes diversity. The Science of the total environment 24 36948313
2021 Inhibition of AlkB Nucleic Acid Demethylases: Promising New Epigenetic Targets. Journal of medicinal chemistry 24 34792334
2017 Characterization of human AlkB homolog 1 produced in mammalian cells and demonstration of mitochondrial dysfunction in ALKBH1-deficient cells. Biochemical and biophysical research communications 24 29097205
2023 The N6-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis by disrupting NRF1 binding capacity. Cell reports 23 36989111
2022 Genome-wide identification of the AlkB homologs gene family, PagALKBH9B and PagALKBH10B regulated salt stress response in Populus. Frontiers in plant science 23 36204058
1980 ABH and Lewis glycosyltransferases in human red cells, lymphocytes and platelets. Revue francaise de transfusion et immuno-hematologie 23 6773534
2014 Mechanism of repair of acrolein- and malondialdehyde-derived exocyclic guanine adducts by the α-ketoglutarate/Fe(II) dioxygenase AlkB. Chemical research in toxicology 22 25157679
1997 An alkB gene homolog is differentially transcribed during the Caulobacter crescentus cell cycle. Journal of bacteriology 22 9150207
2023 Structure and Function of Alkane Monooxygenase (AlkB). Accounts of chemical research 21 38032826
2022 An Overview of the Electron-Transfer Proteins That Activate Alkane Monooxygenase (AlkB). Frontiers in microbiology 21 35295299
2021 Demethyltransferase AlkBH1 substrate diversity and relationship to human diseases. Molecular biology reports 21 34046849
2021 DNA demethylase ALKBH1 promotes adipogenic differentiation via regulation of HIF-1 signaling. The Journal of biological chemistry 21 34922943
2010 TP53 regulates human AlkB homologue 2 expression in glioma resistance to Photofrin-mediated photodynamic therapy. British journal of cancer 21 20661249
1995 Suppression of Escherichia coli alkB mutants by Saccharomyces cerevisiae genes. Journal of bacteriology 21 7665478
2020 Therapeutic potential of ALKB homologs for cardiovascular disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 32942149
2017 High-Throughput Small RNA Sequencing Enhanced by AlkB-Facilitated RNA de-Methylation (ARM-Seq). Methods in molecular biology (Clifton, N.J.) 20 28349464
2010 The role of AlkB protein in repair of 1,N⁶-ethenoadenine in Escherichia coli cells. Mutagenesis 20 21193516
2005 Independent and interchangeable multimerization domains of the AbrB, Abh, and SpoVT global regulatory proteins. Journal of bacteriology 19 16159768
2023 ALKBH1 contributes to renal cell carcinoma progression by reducing N6-methyladenine of GPR137. European journal of clinical investigation 18 36920340