Affinage

ALKBH1

Nucleic acid dioxygenase ALKBH1 · UniProt Q13686

Length
389 aa
Mass
43.8 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALKBH1 is a multifunctional, predominantly mitochondrial Fe(II)/2-oxoglutarate-dependent dioxygenase that modifies tRNA, mRNA, DNA, and histones to control translation, gene expression, and stem-cell fate (PMID:18603530, PMID:28472312, PMID:32051560). As a tRNA-modifying enzyme it catalyzes stepwise oxidation of m5C34 to hm5C and then f5C at the anticodon wobble position of cytoplasmic and mitochondrial tRNAs, a modification required for efficient mitochondrial translation and respiratory complex activity (PMID:28472312); consistent with this, ALKBH1 localizes to mitochondrial RNA granules and its loss compromises respiration and triggers the mitochondrial unfolded protein response (PMID:31434717). It also acts as a demethylase, removing m1A from tRNAs to attenuate translation initiation in response to glucose availability (PMID:27745969) and erasing m3C from mRNA (PMID:31188562). In the nucleus, ALKBH1 functions as a DNA N6-methyladenine (6mA) demethylase that preferentially acts on unpaired bubble/bulge DNA—a substrate preference explained by a 'stretch-out' Flip1 conformation seen in its co-crystal structure with bulged DNA—and thereby controls transcription factor access at target promoters to direct mesenchymal stem-cell differentiation and disease processes (PMID:32051560, PMID:27785372, PMID:35018683). Beyond its dioxygenase chemistry, ALKBH1 possesses a metal-independent AP lyase activity that cleaves abasic DNA by β-elimination through an active-site lysine (Lys133), forming a stable covalent adduct with the 5'-product (PMID:19959401, PMID:23577621). ALKBH1 additionally functions as a histone H2A dioxygenase whose loss delays neural differentiation and prolongs pluripotency (PMID:22961808).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1996 Medium

    Established that the human gene is a functional homolog of a bacterial alkylation-damage response protein, framing ALKBH1 as a candidate DNA repair/dealkylation enzyme.

    Evidence cDNA cloning and complementation of an E. coli alkB mutant against MMS toxicity

    PMID:8600462

    Open questions at the time
    • Only partial rescue
    • No direct biochemical substrate identified in human cells
    • Single complementation assay
  2. 2008 High

    Defined ALKBH1 as a predominantly mitochondrial Fe(II)/2-OG dioxygenase with demethylase activity, anchoring its catalytic chemistry and subcellular home.

    Evidence Fluorescent fusion localization, fractionation, in vitro 3meC demethylation on ssDNA/RNA, and active-site mutagenesis

    PMID:18603530

    Open questions at the time
    • Physiological in vivo substrate not established
    • Nuclear vs mitochondrial functional partitioning unresolved
  3. 2008 Medium

    Linked ALKBH1 to transcriptional repression and placental/trophoblast development through a chromatin-associated interaction, expanding it beyond a damage enzyme.

    Evidence Co-IP and competition binding with Mrj/HDAC4, euchromatin immunolocalization, and Alkbh1 knockout mouse analysis

    PMID:18163532

    Open questions at the time
    • Whether catalytic activity is required for Mrj-dependent repression is unclear
    • Single-lab interaction data without reciprocal validation
  4. 2009 High

    Revealed a second, mechanistically distinct catalytic activity—AP lyase cleavage of abasic DNA—operating independently of the dioxygenase active site.

    Evidence In vitro DNA cleavage assays establishing β-elimination, EDTA-insensitivity, and metal-residue mutagenesis

    PMID:19959401

    Open questions at the time
    • Cellular relevance of AP lyase activity not demonstrated
    • Catalytic residue not yet identified
  5. 2012 High

    Identified histone H2A as a dioxygenase substrate and tied ALKBH1 to control of the pluripotency-to-differentiation transition.

    Evidence In vitro activity assay, mass spectrometry of histones from Alkbh1-/- cells, and ESC differentiation phenotyping

    PMID:22961808

    Open questions at the time
    • Specific modified residue/position on H2A not fully defined
    • Mechanistic link between H2A modification and differentiation genes incomplete
  6. 2013 High

    Resolved the AP lyase mechanism to an imine-forming active-site lysine, defining the chemistry of covalent product trapping.

    Evidence Site-directed mutagenesis (Lys133 primary, Lys154 opportunistic), NaBH4 substrate trapping, and adduct domain mapping

    PMID:23577621

    Open questions at the time
    • In vivo role of covalent adduct formation unknown
    • Relationship to genomic abasic-site processing not established
  7. 2016 High

    Established ALKBH1 as a dynamic m1A tRNA demethylase coupling nutrient status to translation initiation, a major shift toward an RNA-regulatory role.

    Evidence Biochemical demethylation, ribosome profiling, polysome analysis, and glucose-deprivation experiments with knockdown/overexpression

    PMID:27745969

    Open questions at the time
    • Full set of tRNA m1A targets not enumerated
    • Signaling linking glucose to ALKBH1 activity unresolved
  8. 2016 Medium

    Connected ALKBH1 to nuclear DNA 6mA demethylation and promoter-level gene control, defining an epigenetic-regulatory function.

    Evidence Knockdown/overexpression with dot blot, ChIP at the ATF4 promoter, and rescue in osteogenic differentiation/bone formation

    PMID:27785372

    Open questions at the time
    • Direct demethylase action on genomic 6mA versus indirect effects not fully separated
    • Single-lab finding
  9. 2016 Medium

    Placed ALKBH1 within the core pluripotency network through reciprocal regulation with SOX2/NANOG.

    Evidence Filter binding, ELISA, Co-IP, ChIP, and miRNA analysis

    PMID:26765775

    Open questions at the time
    • Direct vs bridged interactions not distinguished
    • Catalytic requirement unclear
  10. 2017 High

    Defined the stepwise tRNA wobble-modification chemistry (m5C34→hm5C→f5C) and established its requirement for mitochondrial translation and respiration.

    Evidence In vitro reconstitution, LC-MS/MS of tRNA modifications, and mitochondrial translation/respiratory complex assays in knockout cells

    PMID:28472312

    Open questions at the time
    • Full tRNA substrate repertoire across compartments incomplete
    • Regulation of the two-step oxidation in vivo unknown
  11. 2017 Medium

    Showed ALKBH1 mRNA m1A demethylation can rewire an m6A/SMAD7 axis driving cancer cell migration and invasion.

    Evidence Knockdown, m1A-RIP, m6A-seq, SMAD7 rescue, and xenografts

    PMID:36550779

    Open questions at the time
    • Direct vs indirect m1A targets on METTL3 mRNA not fully resolved
    • Single-lab pathway model
  12. 2017 High

    Quantitatively compared activities, showing AP lyase greatly exceeds 6mA/m6A demethylase activity and identifying the primary covalent adduct site.

    Evidence Steady-state and single-turnover kinetics, methylation-sensitive restriction assays, and mutagenesis (C129 adduct site)

    PMID:28290676 PMID:29097205

    Open questions at the time
    • Reconciliation of low in vitro 6mA activity with strong in vivo 6mA phenotypes unresolved
    • Physiological dominance among activities unclear
  13. 2019 Medium

    Added m3C in mRNA to the ALKBH1 eraser repertoire.

    Evidence In vitro demethylation and bidirectional cellular manipulation with mass-spectrometric m3C quantification

    PMID:31188562

    Open questions at the time
    • Specific mRNA targets and functional consequences not mapped
    • Single-lab finding
  14. 2019 High

    Localized ALKBH1 to mitochondrial RNA granules and demonstrated a conserved requirement for respiration and proteostasis.

    Evidence Super-resolution 3D-SIM, respirometry, EM, and C. elegans UPRmt reporter assays with knockdown

    PMID:31434717

    Open questions at the time
    • Molecular composition of ALKBH1-containing granules undefined
    • Link from granule localization to specific tRNA targets not directly shown
  15. 2020 High

    Provided the structural basis for ALKBH1's nuclear 6mA demethylase substrate preference, explaining selectivity for unpaired DNA.

    Evidence Co-crystal structure with bulged DNA revealing a 'stretch-out' Flip1, in vitro substrate profiling, mutagenesis, and ssDNA-seq/DIP-seq genomic mapping

    PMID:32051560

    Open questions at the time
    • How base-unpairing regions are generated/recognized in vivo unknown
    • Genome-wide functional consequences of 6mA removal incomplete
  16. 2020 Medium

    Showed m1A demethylation by ALKBH1 governs stress-dependent tRNA cleavage and tiRNA generation, defining a context-specific stress role.

    Evidence Knockdown/overexpression, small RNA-seq, and viability assays across stress conditions

    PMID:32521209

    Open questions at the time
    • Stress-specific regulatory inputs to ALKBH1 unknown
    • Direct vs indirect effects on cleavage not separated
  17. 2020 High

    A second crystal structure defined the N-terminal domain's role in substrate recognition and validated catalytic residues for demethylation.

    Evidence 3.1-Å X-ray structure of mouse ALKBH1 with mutagenesis of catalytic residues

    PMID:33068553

    Open questions at the time
    • Substrate-bound conformation for tRNA not captured
    • N-terminal recognition mechanism not directly visualized with substrate
  18. 2021 Medium

    Established a recurring mechanistic theme in which ALKBH1-driven 6mA demethylation alters transcription-factor binding to control stem-cell lineage choice and disease (vascular calcification, bone/fat balance, adipogenesis).

    Evidence In vivo overexpression/knockout, 6mA-DIP/DIP-seq, TF ChIP (Oct4, OPTN/HIF-1 axis), and epistatic rescue (BMP2/Oct4; HIF-1α/GYS1)

    PMID:34003800 PMID:34922943 PMID:35018683

    Open questions at the time
    • Whether 6mA changes are direct catalytic products vs downstream effects not fully resolved
    • Mechanism of locus-specific targeting unknown
  19. 2023 Medium

    Extended the 6mA/transcription-factor model to gastric carcinogenesis via NRF1-dependent AMPK suppression and metabolic reprogramming.

    Evidence ALKBH1 knockout mouse GC model, 6mA-DIP-seq, NRF1 ChIP-seq, and metabolic assays

    PMID:36989111

    Open questions at the time
    • Direct demethylation at NRF1 sites vs indirect chromatin effects not fully separated
    • Single-lab tumor model

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which of ALKBH1's many biochemical activities (tRNA f5C/hm5C synthesis, m1A/m3C/6mA demethylation, AP lyase, histone modification) dominate in a given cell type and how its activities are partitioned and regulated across mitochondrial, nuclear, and cytoplasmic compartments.
  • No unified model reconciling low in vitro 6mA demethylase activity with robust in vivo 6mA phenotypes
  • Compartment-specific substrate targeting mechanisms unknown
  • Functional hierarchy among activities undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0003723 RNA binding 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-392499 Metabolism of proteins 2
Partners
HDAC4MRJ/DNAJB6NANOGSOX2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human ALKBH1 (hABH) was cloned and shown to partially rescue E. coli alkB mutant cells from MMS-induced cell death when expressed in bacteria, demonstrating functional conservation of the DNA alkylation damage response protein from bacteria to humans. Complementation assay in E. coli alkB mutant; cDNA cloning and expression Nucleic acids research Medium 8600462
2008 Human ALKBH1 (hABH1) localizes primarily to mitochondria, as demonstrated by fluorescent fusion protein expression, immunocytochemistry, and Western blot fractionation. Placing a fluorescent tag at the N-terminus interferes with mitochondrial targeting and increases nuclear fraction. ALKBH1 demethylates 3-methylcytosine (3meC) in single-stranded DNA and RNA in vitro, and site-specific mutagenesis confirmed that the putative Fe(II) and 2-oxoglutarate binding residues are essential for this activity. Fluorescent fusion protein localization; immunocytochemistry; Western blot fractionation; in vitro demethylation assay with methylated oligonucleotides; site-directed mutagenesis of active-site residues The Journal of biological chemistry High 18603530
2008 ALKBH1 (ABH1) interacts with Mrj, an essential placental gene that mediates gene repression by recruiting class II histone deacetylases (HDACs). ALKBH1 binding to Mrj is mutually exclusive with HDAC4 binding, causing decreased HDAC activity and increased target gene expression. ALKBH1 localizes to nuclear euchromatin and is required for trophoblast lineage differentiation. Co-immunoprecipitation; competition binding experiments; immunolocalization; Alkbh1 knockout mouse analysis Developmental dynamics Medium 18163532
2009 ALKBH1 (ABH1) possesses a DNA lyase activity at abasic (AP) sites in DNA, cleaving DNA via a lyase (β-elimination) mechanism rather than hydrolysis, with the enzyme remaining covalently associated with the 5'-DNA product. This AP lyase activity does not require Fe(2+) or 2-oxoglutarate and is not inhibited by EDTA, and mutagenesis of the metal-binding residues does not abolish lyase activity, indicating a distinct active site from the demethylation activity. In vitro DNA cleavage assay; mechanism determination (lyase vs. hydrolysis); EDTA inhibition; site-directed mutagenesis of metal-binding residues DNA repair High 19959401
2012 ALKBH1 is a histone dioxygenase that acts specifically on histone H2A. In vitro enzyme activity assays demonstrated this activity, and mass spectrometric analysis showed that histone H2A from Alkbh1−/− mice is improperly methylated. Loss of Alkbh1 delays neural differentiation and prolongs pluripotency marker expression in embryonic stem cells. In vitro enzyme activity assay; mass spectrometry of histones from knockout cells; genome-wide expression analysis; chromatin immunoprecipitation; Alkbh1 knockout mouse ESC differentiation Stem cells (Dayton, Ohio) High 22961808
2013 ALKBH1 AP lyase activity proceeds via imine formation with an active-site lysine residue; primary catalytic residue is Lys133, with Lys154 and other lysines serving opportunistic roles. The enzyme forms a stable covalent adduct with the 5'-DNA product (containing an α,β-unsaturated aldehyde) even without reducing agent, with the N-terminal domain as the main linkage site. Site-directed mutagenesis; substrate trapping with NaBH4; identification of covalent 5'-product adduct by domain mapping The Biochemical journal High 23577621
2016 Mammalian ALKBH1 is a tRNA demethylase that mediates demethylation of N1-methyladenosine (m1A) in tRNAs. 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 to affect translation. Biochemical demethylation assay; ribosome profiling; polysome analysis; glucose deprivation experiments; ALKBH1 knockdown/overexpression Cell High 27745969
2016 ALKBH1 functions as a demethylase for DNA N6-methyladenine (N6-mA), and its depletion in human mesenchymal stem cells increases genomic DNA N6-mA levels. Mechanistically, ALKBH1 depletion leads to accumulation of N6-mA on the ATF4 promoter, silencing ATF4 transcription and reducing osteogenic differentiation. ALKBH1 knockdown and overexpression; dot blot for N6-mA; ChIP at ATF4 promoter; in vivo bone formation assay; adenovirus-mediated ATF4 rescue Bone research Medium 27785372
2016 ALKBH1 interacts with core pluripotency transcription factors SOX2 and NANOG (which bind the ALKBH1 promoter), and protein-protein interactions between ALKBH1 and these factors were identified. Loss of ALKBH1 affects the expression of developmentally important miRNAs involved in regulation of NANOG, SOX2, and neural differentiation. Nitrocellulose filter binding; ELISA; Co-IP; miRNA analysis; ChIP Cellular physiology and biochemistry Medium 26765775
2017 ALKBH1 is responsible for biogenesis of 5-hydroxymethyl-2'-O-methylcytidine (hm5Cm) and 5-formyl-2'-O-methylcytidine (f5Cm) at position 34 (anticodon first position) of cytoplasmic tRNALeu, and f5C at position 34 of mitochondrial tRNAMet. In vitro reconstitution showed ALKBH1 first hydroxylates m5C34 to form hm5C34, then oxidizes it to f5C34. ALKBH1-knockout cells exhibited strong reduction in mitochondrial translation and reduced respiratory complex activities, demonstrating that f5C34 formation by ALKBH1 is required for efficient mitochondrial function. Additionally, m1A levels in two mitochondrial tRNAs increased in ALKBH1-knockout cells, indicating ALKBH1 also has demethylation activity toward m1A in mt-tRNAs. ALKBH1 knockout cell analysis; in vitro tRNA modification reconstitution; LC-MS/MS analysis of tRNA modifications; mitochondrial translation assay; respiratory complex activity measurement Nucleic acids research High 28472312
2017 ALKBH1 is capable of demethylating m1A in METTL3 mRNA in colorectal cancer cells. Knockdown of ALKBH1 decreases METTL3 expression (likely due to m1A stabilization), which in turn reduces m6A modification of SMAD7 mRNA, leading to increased SMAD7 expression. Cell migration and invasion defects from ALKBH1 depletion are rescued by SMAD7 silencing. ALKBH1 knockdown; m1A-RIP; m6A-seq; Western blot; rescue experiment with SMAD7 siRNA; in vivo xenograft Molecular oncology Medium 36550779
2017 ALKBH1 produced in mammalian cells displays m6A demethylase and AP lyase activities comparable to bacterially produced protein; it forms a covalent adduct with the 5'-product of the lyase reaction. Subcellular fractionation studies confirmed ALKBH1 is primarily mitochondrial in two human cell strains. ALKBH1-deficient HEK293 cells (CRISPR/Cas9) showed increased mtDNA copy number and mitochondrial dysfunction. ALKBH1 mammalian expression; biochemical activity assays; subcellular fractionation; CRISPR/Cas9 knockout; citrate synthase activity assay; growth measurements Biochemical and biophysical research communications High 29097205
2017 Steady-state and single-turnover kinetics for ALKBH1 AP lyase cleavage were determined; the α,β-unsaturated aldehyde of the 5'-product reacts predominantly with C129 of ALKBH1, but secondary sites also generate covalent adducts. The 6-methyladenine demethylase activity of ALKBH1 was found to be very low (less than half that of the AP lyase activity under identical conditions), suggesting it is unlikely to represent the major cellular function. Steady-state and single-turnover kinetics; methylation-sensitive restriction endonuclease assay; site-directed mutagenesis; identification of primary covalent adduct site (C129) Biochemistry High 28290676
2019 ALKBH1 demethylates N3-methylcytidine (m3C) in mRNA of mammalian cells in vitro. Overexpression of ALKBH1 in cultured human cells decreases the level of m3C in mRNA, and knockdown increases m3C levels, establishing ALKBH1 as an eraser enzyme for m3C in mRNA. In vitro demethylation assay; ALKBH1 overexpression and knockdown; quantitative measurement of m3C in mRNA by mass spectrometry/chemical methods ACS chemical biology Medium 31188562
2019 ALKBH1 localizes to mitochondrial RNA granules (visualized by super-resolution 3D SIM microscopy). ALKBH1 knockdown impacts mitochondrial respiration (high-resolution respirometry) but not mitochondrial structure. Downregulation of ALKBH1 (but not ALKBH7) triggers the mitochondrial unfolded protein response (UPRmt) in C. elegans, indicating a conserved mitochondrial role. Super-resolution 3D SIM microscopy; electron microscopy; high-resolution respirometry; C. elegans UPRmt reporter assay; ALKBH1 knockdown Journal of cell science High 31434717
2020 Mammalian ALKBH1 functions as a nuclear N6-mA demethylase that preferentially acts on unpairing (bubbled or bulged) DNA rather than single-stranded or double-stranded DNA. Crystal structure of ALKBH1 bound to a 21-mer bulged DNA revealed an unexpected 'stretch-out' conformation of the 'Flip1' motif (which in other demethylases bends to facilitate base flipping), explaining the preference for unpairing substrates. Structure-based mutagenesis validated key elements including an ALKBH1-specific α1 helix. Genomic analyses showed significant co-occurrence of base unpairing regions with N6-mA in mouse genome. In vitro enzymatic profiling with bubble/bulge substrates; co-crystal structure of ALKBH1-bulged DNA complex; structure-based mutagenesis; ssDNA-seq; DIP-seq (N6-mA genomic mapping) Cell research High 32051560
2020 ALKBH1 demethylation of m1A in tRNA is stress-specific: its impact on cell fate and tRNA cleavage depends on the demethylating capacity of the particular stress. ALKBH1 knockdown or overexpression differentially affects tRNA cleavage and tiRNA generation in a stress-context-dependent manner, and ALKBH1 KD fails to rescue tRNAs from cleavage following demethylating stresses. ALKBH1 gene knockdown and overexpression; small RNA sequencing; cell viability assays under different stress conditions RNA biology Medium 32521209
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 and may be responsible for recognition of nucleic acid substrates. Mutagenesis of essential residues Y184, H231, D233, H287, R338, and R344 demonstrated their contribution to m6A demethylation activity. X-ray crystallography (3.1 Å); site-directed mutagenesis of catalytic residues; m6A demethylation activity assay Biochemical pharmacology High 33068553
2021 ALKBH1-demethylated DNA 6mA modification facilitates binding of transcription factor Oct4 to the BMP2 promoter, activating BMP2 transcription. This leads to osteogenic reprogramming of vascular smooth muscle cells (VSMCs) and progression of vascular calcification in chronic kidney disease. Either BMP2 or Oct4 depletion alleviated ALKBH1 procalcifying effects. ALKBH1 overexpression/shRNA with AAV in vivo; ChIP for Oct4 at BMP2 promoter; 6mA DIP; BMP2/Oct4 knockdown epistasis; calcification assays The Journal of clinical investigation Medium 34003800
2021 ALKBH1 mediates DNA 6mA demethylation at the promoter region of optineurin (OPTN) in bone marrow mesenchymal stem cells, regulating BMSC fate between osteogenic and adipogenic differentiation. BMSC-specific Alkbh1 knockout mice exhibited reduced bone mass and increased marrow adiposity; Alkbh1 overexpression in aged mice attenuated bone loss. BMSC-specific Alkbh1 conditional knockout mouse; ChIP for N6-mA at OPTN promoter; micro-CT; histomorphometry; adeno-associated virus overexpression Cell proliferation Medium 35018683
2021 ALKBH1-mediated DNA 6mA demethylation regulates adipogenic differentiation of mesenchymal stem cells and 3T3-L1 preadipocytes through HIF-1 signaling; ALKBH1 depletion causes hypermethylation of HIF-1α and its downstream target GYS1, and simultaneous overexpression of HIF-1α and GYS1 rescues adipogenic commitment of ALKBH1-deficient cells. ALKBH1 knockdown/overexpression; RNA-seq; N6-mA-DIP-seq; rescue by HIF-1α and GYS1 overexpression; adipogenic differentiation assays The Journal of biological chemistry Medium 34922943
2023 ALKBH1 promotes gastric carcinogenesis by mediating DNA 6mA demethylation at NRF1-binding sequences near transcription start sites. ALKBH1-induced 6mA demethylation inhibits NRF1-driven transcription of downstream targets including AMPK pathway genes, suppressing AMPK signaling and causing a metabolic shift toward the Warburg effect. ALKBH1 knockout in mice impairs chemically induced gastric carcinogenesis. ALKBH1 knockout mouse (chemically induced GC model); 6mA-DIP-seq; NRF1 ChIP-seq; ALKBH1 KO and overexpression; metabolic assays Cell reports Medium 36989111

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 586 12226667
2002 AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 506 12226668
1989 ABH and related histo-blood group antigens; immunochemical differences in carrier isotypes and their distribution. Vox sanguinis 459 2464874
2016 ALKBH1-Mediated tRNA Demethylation Regulates Translation. Cell 407 27745969
2001 The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome biology 361 11276424
2015 The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond. The Journal of biological chemistry 338 26152727
2017 AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. Scientific reports 267 28205560
2017 ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications. Nucleic acids research 224 28472312
2008 Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature 207 18432238
2006 Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB. Nature 190 16482161
2003 Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB. BMC genomics 177 14667252
2001 ABH and Lewis histo-blood group antigens in cancer. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 170 11297197
2004 AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Molecular cell 169 15469826
2015 Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. Cell reports 168 26686626
2005 AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo. Nature structural & molecular biology 163 16200073
2008 Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA. The Journal of biological chemistry 153 18603530
2010 Gene diversity of CYP153A and AlkB alkane hydroxylases in oil-degrading bacteria isolated from the Atlantic Ocean. Environmental microbiology 137 20148932
2005 Repair of methylation damage in DNA and RNA by mammalian AlkB homologues. The Journal of biological chemistry 119 16174769
2004 Substrate specificities of bacterial and human AlkB proteins. Nucleic acids research 111 15229293
2011 ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer. British journal of cancer 104 21285982
2012 ALKBH1 is a histone H2A dioxygenase involved in neural differentiation. Stem cells (Dayton, Ohio) 98 22961808
2008 Viral AlkB proteins repair RNA damage by oxidative demethylation. Nucleic acids research 96 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 93 17979886
2020 Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA. Cell research 88 32051560
2017 A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair. Nature 87 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 81 32642789
2016 Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage. The Journal of biological chemistry 78 27015802
2010 Diversity and abundance of oil-degrading bacteria and alkane hydroxylase (alkB) genes in the subtropical seawater of Xiamen Island. Microbial ecology 78 20683589
2003 Minimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase. The Journal of biological chemistry 74 12944387
2021 ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease. The Journal of clinical investigation 73 34003800
2017 Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions. Chemical research in toxicology 72 28269980
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
2020 The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. RNA biology 70 32521209
1996 Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair. Nucleic acids research 67 8600462
1987 ABH and Lewis blood group expression in colorectal carcinoma. Cancer research 67 3815366
2019 DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro. Nucleic acids research 66 31114894
2015 Non-homologous functions of the AlkB homologs. Journal of molecular cell biology 66 26003568
1985 Molecular cloning and characterization of the alkB gene of Escherichia coli. Molecular & general genetics : MGG 65 3884973
2011 Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification. The Journal of biological chemistry 64 22065580
2010 Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects. PloS one 63 21072209
2020 ALKBH1 promotes lung cancer by regulating m6A RNA demethylation. Biochemical pharmacology 61 33068553
2019 AlkB Homologue 1 Demethylates N3-Methylcytidine in mRNA of Mammals. ACS chemical biology 61 31188562
2004 Determinants of ABH expression on human blood platelets. Blood 61 15613545
2023 Structure and mechanism of the alkane-oxidizing enzyme AlkB. Nature communications 58 37069165
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 56 31070258
2017 Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes. PLoS biology 54 29107960
2016 DNA N6-methyladenine demethylase ALKBH1 enhances osteogenic differentiation of human MSCs. Bone research 53 27785372
2009 Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites. DNA repair 51 19959401
2019 Biologic roles of the ABH and Lewis histo-blood group antigens part II: thrombosis, cardiovascular disease and metabolism. Vox sanguinis 50 31090093
1992 Basic biochemistry of cell surface carbohydrates and aspects of the tissue distribution of histo-blood group ABH and related glycosphingolipids. APMIS. Supplementum 50 1520526
1986 Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA. The Journal of biological chemistry 50 3536913
2007 Kinetic studies of Escherichia coli AlkB using a new fluorescence-based assay for DNA demethylation. Nucleic acids research 49 18003660
2022 Alkbh1-mediated DNA N6-methyladenine modification regulates bone marrow mesenchymal stem cell fate during skeletal aging. Cell proliferation 47 35018683
2008 AlkB demethylases flip out in different ways. DNA repair 43 18723127
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
1988 Expression of ABH and X (Lex) antigens on platelets and lymphocytes. Blood 39 3281720
2010 Analyses of both the alkB gene transcriptional start site and alkB promoter-inducing properties of Rhodococcus sp. strain BCP1 grown on n-alkanes. Applied and environmental microbiology 38 21193665
1981 Insights into the expression of ABH and Lewis antigens through human bone marrow transplantation. American journal of human genetics 38 6167165
2016 Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA. Chemical research in toxicology 36 26919079
2010 Divergent ß-hairpins determine double-strand versus single-strand substrate recognition of human AlkB-homologues 2 and 3. Nucleic acids research 36 20525795
2003 AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. Trends in biochemical sciences 34 12517444
2022 ALKBH1-mediated m1 A demethylation of METTL3 mRNA promotes the metastasis of colorectal cancer by downregulating SMAD7 expression. Molecular oncology 33 36550779
2021 Expression and molecular profiles of the AlkB family in ovarian serous carcinoma. Aging 33 33744868
2012 Changes in protein dynamics of the DNA repair dioxygenase AlkB upon binding of Fe(2+) and 2-oxoglutarate. Biochemistry 33 22443471
2004 Preparation and characterization of the native iron(II)-containing DNA repair AlkB protein directly from Escherichia coli. Journal of the American Chemical Society 33 15612731
1989 ABH blood group antigen expression, synthesis, and degradation in human colonic adenocarcinoma cell lines. Cancer research 32 2545345
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
2009 Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair. Mutagenesis 29 19892776
2023 The role of demethylase AlkB homologs in cancer. Frontiers in oncology 28 37007161
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
2007 Bacterial DNA repair genes and their eukaryotic homologues: 3. AlkB dioxygenase and Ada methyltransferase in the direct repair of alkylated DNA. Acta biochimica Polonica 28 17823664
2021 Inhibition of AlkB Nucleic Acid Demethylases: Promising New Epigenetic Targets. Journal of medicinal chemistry 26 34792334
2019 Mitochondrial Alkbh1 localizes to mtRNA granules and its knockdown induces the mitochondrial UPR in humans and C. elegans. Journal of cell science 26 31434717
2017 Biochemical Characterization of AP Lyase and m6A Demethylase Activities of Human AlkB Homologue 1 (ALKBH1). Biochemistry 26 28290676
2009 Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria. Nucleic acids research 26 19786499
1998 ABH antigens on human platelets: expression on the glycosyl phosphatidylinositol-anchored protein CD109. The Journal of laboratory and clinical medicine 26 9708575
2023 Medium-chain alkane biodegradation and its link to some unifying attributes of alkB genes diversity. The Science of the total environment 25 36948313
2023 Structure and Function of Alkane Monooxygenase (AlkB). Accounts of chemical research 25 38032826
2018 The AlkB Family of Fe (II)/Alpha-Ketoglutarate-Dependent Dioxygenases Modulates Embryogenesis through Epigenetic Regulation. Current stem cell research & therapy 24 29076432
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
2006 Direct removal of alkylation damage from DNA by AlkB and related DNA dioxygenases. Methods in enzymology 24 16793366
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
2022 An Overview of the Electron-Transfer Proteins That Activate Alkane Monooxygenase (AlkB). Frontiers in microbiology 22 35295299
2021 DNA demethylase ALKBH1 promotes adipogenic differentiation via regulation of HIF-1 signaling. The Journal of biological chemistry 22 34922943
2020 Therapeutic potential of ALKB homologs for cardiovascular disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 32942149
2013 A covalent protein-DNA 5'-product adduct is generated following AP lyase activity of human ALKBH1 (AlkB homologue 1). The Biochemical journal 22 23577621
1997 An alkB gene homolog is differentially transcribed during the Caulobacter crescentus cell cycle. Journal of bacteriology 22 9150207
2021 Demethyltransferase AlkBH1 substrate diversity and relationship to human diseases. Molecular biology reports 21 34046849

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