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This study characterized ALKBH1 to be a mitochondrial-localized protein with N6-methyldeoxyadenosine demethylation activity. Loss of ALKBH1 also disrupted mitochondrial OXPHOS function.
Localization and subcellular fractionation studies with the endogenous protein in two cell strains confirm that ALKBH1 is primarily in the mitochondria.
Nuclear and mitochondrial ALKBH1 play distinct roles in tRNA modification.
The authors identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m(5)C34 of mt-tRNA(M)(et) to generate an f(5)C34 modification.
The authors postulate that the very low 6-methyl adenine oxygenase activity associated with ALKBH1 is unlikely to represent the major function of the enzyme in the cell, while the cellular role of the lyase activity (including its subsequent covalent attachment to DNA) remains uncertain.
The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis.
AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. (Review)
ALKBH1's role in class switch recombination and abasic site cleavage during base excision repair
Primary and secondary lysine residues of ALKBH1 are involved in lyase reactions and form a covalent adduct with the 5'DNA product, demonstrating two plausible chemical mechanisms to account for the covalent attachment.
Homology modeling and different tertiary structure based study were performed on human AlkB homolog hABH1.
show that ABH1 unexpectedly has a second activity, cleaving DNA at abasic (AP) sites such as those arising spontaneously from alkylation-dependent depurination reactions.
AlkB homologues, hABH2 and hABH3, also are oxidative DNA demethylases; AlkB and hABH3, but not hABH2, also repair RNA
hABH1 is a functional mitochondrial AlkB homolog that repairs 3-methylcytosine in single-stranded DNA and RNA.
The lack of ALKBH1 affected the expression of developmentally important miRNAs, which are involved in the regulation of NANOG, SOX2 and neural differentiation.
Results suggest that ALKBH1 is involved in neural development by modifying the methylation status of histone H2A.
The study reports a remarkable >1000-fold upregulation of individual piRNAs in pachytene spermatocytes isolated from Alkbh1-deficient murine testes.
Data suggest that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development.
Alkbh1 performs important functions in placental trophoblast lineage differentiation and participates in mechanisms of transcriptional regulation.
This gene encodes a homolog to the E. coli alkB gene product. The E. coli alkB protein is part of the adaptive response mechanism of DNA alkylation damage repair. It is involved in damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine.
alkylated DNA repair protein alkB homolog 1
, DNA lyase ABH1
, DNA oxidative demethylase ALKBH1
, alkylation repair, alkB homolog
, alpha-ketoglutarate-dependent dioxygenase ABH1