ALKBH1


Description

The ALKBH1 (alkB homolog 1, histone H2A dioxygenase) is a protein-coding gene located on chromosome 14.

ALKBH1 is a human gene that encodes a protein involved in the repair and modification of nucleic acids, such as DNA and tRNA. It is a dioxygenase that requires molecular oxygen, alpha-ketoglutarate, and iron for its activity. ALKBH1 mainly acts as a tRNA demethylase, removing N(1)-methyladenine from various tRNAs. It also plays a role in regulating translation initiation and elongation in response to glucose deprivation. In addition, ALKBH1 demethylates DNA and mRNA, and exhibits DNA lyase activity.

ALKBH1 is a dioxygenase that acts on nucleic acids, including DNA and tRNA. It requires molecular oxygen, alpha-ketoglutarate, and iron. While ALKBH1 has been shown to have several activities, recent research indicates that it primarily functions on tRNAs, mediating their demethylation or oxidation depending on the cellular context and location. ALKBH1 acts as a tRNA demethylase, removing N(1)-methyladenine from various tRNAs, particularly at position 58 (m1A58) within a stem-loop structure. It also plays a role in regulating translation initiation and elongation in response to glucose deprivation. ALKBH1 demethylates tRNA(Met), impacting translation initiation, and promotes translation elongation by preferentially recruiting N(1)-methyladenine-containing tRNAs to polysomes. Within mitochondria, ALKBH1 specifically interacts with mt-tRNA(Met) and oxidizes methylated cytosine(34) to form 5-formylcytosine (f(5)c). The f(5)c modification at the wobble position of mt-tRNA(Met) allows for recognition of the AUA codon in addition to AUG, expanding codon recognition during mitochondrial translation. ALKBH1 specifically demethylates DNA methylated at the 6th position of adenine (N(6)-methyladenosine) DNA, which is present at certain L1 elements in embryonic stem cells, likely contributing to their silencing. ALKBH1 also demethylates mRNAs containing N(3)-methylcytidine modifications. Additionally, ALKBH1 can repair alkylated single-stranded DNA through oxidative demethylation, although with limited activity. It exhibits DNA lyase activity, introducing double-stranded breaks at abasic sites by cleaving both single-stranded and double-stranded DNA, with a preference for double-stranded DNA containing two abasic sites. This lyase activity does not require alpha-ketoglutarate or iron and results in an irreversible covalent protein-DNA adduct with the 5' DNA product. Importantly, this lyase activity is not essential for base excision repair or class switch recombination during B lymphocyte activation. ALKBH1 may contribute to placental trophoblast lineage differentiation. It exists as a monomer.

ALKBH1 is also known as ABH, ABH1, ALKBH, alkB, hABH.

Associated Diseases



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