P0CB42 · ALKB1_MOUSE

  • Protein
    Nucleic acid dioxygenase ALKBH1
  • Gene
    Alkbh1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Dioxygenase that acts as on nucleic acids, such as DNA and tRNA (PubMed:27027282, PubMed:27745969).
Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:27027282).
A number of activities have been described for this dioxygenase, but recent results suggest that it mainly acts as on tRNAs and mediates their demethylation or oxidation depending on the context and subcellular compartment (By similarity).
Mainly acts as a tRNA demethylase by removing N1-methyladenine from various tRNAs, with a preference for N1-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs (PubMed:27745969).
Acts as a regulator of translation initiation and elongation in response to glucose deprivation: regulates both translation initiation, by mediating demethylation of tRNA(Met), and translation elongation, N1-methyladenine-containing tRNAs being preferentially recruited to polysomes to promote translation elongation (By similarity).
In mitochondrion, specifically interacts with mt-tRNA(Met) and mediates oxidation of mt-tRNA(Met) methylated at cytosine34 to form 5-formylcytosine (f5c) at this position (By similarity).
mt-tRNA(Met) containing the f5c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation (By similarity).
Specifically demethylates DNA methylated on the 6th position of adenine (N6-methyladenosine) DNA (PubMed:27027282).
N6-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (PubMed:27027282).
Demethylates mRNAs containing N3-methylcytidine modification (By similarity).
Also able to repair alkylated single-stranded DNA by oxidative demethylation, but with low activity (By similarity).
Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites (By similarity).
DNA lyase activity does not require alpha-ketboglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5' DNA product (By similarity).
DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation (PubMed:23825659).
May play a role in placental trophoblast lineage differentiation (PubMed:18163532).

Caution

H2A histone demethylase activity was observed in vitro (PubMed:22961808).
The relevance of such activity is however unclear and additional experimental evidence would be needed to confirm this activity in vivo
The DNA N6-methyl adenine demethylase activity is subject to discussion. While DNA N6-methyl adenine demethylase activity was observed by a report (PubMed:27027282).
Another group was unable to detect clear DNA N6-methyl adenine demethylase activity in vivo (PubMed:27745969).

Catalytic activity

Cofactor

Fe2+ (UniProtKB | Rhea| CHEBI:29033 )

Note: Binds 1 Fe2+ ion per subunit.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site144substrate
Binding site175-177substrate
Binding site220-2222-oxoglutarate (UniProtKB | ChEBI)
Binding site231Fe cation (UniProtKB | ChEBI); catalytic
Binding site233Fe cation (UniProtKB | ChEBI); catalytic
Binding site233substrate
Binding site287Fe cation (UniProtKB | ChEBI); catalytic
Binding site338-3442-oxoglutarate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentendoplasmic reticulum
Cellular Componenteuchromatin
Cellular Componentmitochondrion
Cellular Componentnucleoplasm
Cellular Componentnucleus
Molecular Function2-oxoglutarate-dependent dioxygenase activity
Molecular Functionbroad specificity oxidative DNA demethylase activity
Molecular Functionchemoattractant activity
Molecular Functionclass I DNA-(apurinic or apyrimidinic site) endonuclease activity
Molecular FunctionDNA N6-methyladenine demethylase activity
Molecular Functionferrous iron binding
Molecular Functionoxidative RNA demethylase activity
Molecular FunctiontRNA binding
Molecular FunctiontRNA demethylase activity
Biological Processcell differentiation
Biological Processdevelopmental growth
Biological ProcessDNA alkylation repair
Biological Processin utero embryonic development
Biological Processnegative regulation of neuron apoptotic process
Biological Processneuron migration
Biological Processneuron projection development
Biological Processoxidative RNA demethylation
Biological Processplacenta development
Biological Processpositive regulation of gene expression, epigenetic
Biological Processregulation of gene expression
Biological Processregulation of mitochondrial translation
Biological Processregulation of translational elongation
Biological Processregulation of translational initiation
Biological Processregulation of translational initiation by tRNA modification
Biological ProcessRNA repair
Biological ProcesstRNA wobble cytosine modification

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Nucleic acid dioxygenase ALKBH1
  • EC number
  • Alternative names
    • Alkylated DNA repair protein alkB homolog 1
    • Alpha-ketoglutarate-dependent dioxygenase ABH1
    • DNA 6mA demethylase
    • DNA N6-methyl adenine demethylase ALKBH1
      (EC:1.14.11.51
      ) . EC:1.14.11.51 (UniProtKB | ENZYME | Rhea)
    • DNA lyase ABH1
      (EC:4.2.99.18
      ) . EC:4.2.99.18 (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      Alkbh1
    • Synonyms
      Abh
      , Alkbh

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P0CB42

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli.

Keywords

Phenotypes & Variants

Disruption phenotype

Deficiency results in 80% reduction of the litter size due to embryonic lethality (PubMed:21072209, PubMed:23825659).
Surviving pups exhibit a gender bias in favor of males (70% males and 30% females) (PubMed:21072209, PubMed:23825659).
Intrauterine growth retardation and placental defects. Altered expression of trophoblast lineage-specific genes (PubMed:18163532).
Increased N6-methyladenosine (m6A) DNA (PubMed:27027282).
No effect on H2AK118 or H2AK119 methylation, suggesting that Alkbh1 does not act as a histone demethylase in vivo (PubMed:27027282).
Cells show an strong increase of N1-methyladenine-containing tRNAs (PubMed:27745969).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis233Loss of activity.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 26 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00003864531-389Nucleic acid dioxygenase ALKBH1

Proteomic databases

PTM databases

Expression

Tissue specificity

In adult organs, highly expressed in testis, eye, brain and kidney.

Developmental stage

Weak expression throughout the embryo at 8.5 dpc. As the cells migrate and differentiate during organogenesis, expressed in the spinal cord, forebrain and branchial arches at 9.5 dpc, and also in limb buds at 10.5 dpc. Peak expression at 11.5 dpc in the frontonasal process including telencephalon, maxillary, mandibular and hyoid arches, upper and lower limb buds and midbrain and rhombomere 1 roof plates. Expression decreases considerably from 11.5 dpc to 12.5 dpc (PubMed:21072209).
At 8.5 dpc is highly expressed in the chorion and the ectoplacental cone. At 10.5 dpc is highly expressed in multiple trophoblast lineages (spongiotrophoblasts, giant cell trophoblasts, glycogen cells, and labyrinthine trophoblasts). The highest placental level is at 9.5 dpc and subsequently decreases until parturition (PubMed:18163532).

Gene expression databases

Interaction

Subunit

Monomer (By similarity).
Interacts with DNAJB6 (PubMed:18163532).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P0CB42Dnajb6 O54946-22EBI-13941048, EBI-13941040

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region1-127Interaction with DNAJB6
Region86-389tRNA-binding
Domain213-347Fe2OG dioxygenase

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    389
  • Mass (Da)
    43,746
  • Last updated
    2009-10-13 v1
  • Checksum
    D18C019F0CB9C0A5
MGKMAAAVASLATLAAEPREDAFRKLFRFYRQSRPGTADLGAVIDFSEAHLARSPKPGVPQVVRFPLNVSSVTERDAERVGLEPVSKWRAYGLEGYPGFIFIPNPFLPGCQRHWVKQCLKLYSQKPNVCNLDKHMTKEETQGLWEQSKEVLRSKEVTKRRPRSLLERLRWVTLGYHYNWDSKKYSADHYTPFPSDLAFLSEQVATACGFQGFQAEAGILNYYRLDSTLGIHVDRSELDHSKPLLSFSFGQSAIFLLGGLKRDEAPTAMFMHSGDIMVMSGFSRLLNHAVPRVLPHPDGECLPHCLETPLPAVLPSNSLVEPCSVEDWQVCATYLRTARVNMTVRQVLATGQDFPLEPVEETKRDIAADGLCHLHDPNSPVKRKRLNPNS

Computationally mapped potential isoform sequences

There are 6 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q5XLJ1Q5XLJ1_MOUSEAlkbh1135
F6U5G1F6U5G1_MOUSEAlkbh1180
E0CZH7E0CZH7_MOUSEAlkbh178
E0CX46E0CX46_MOUSEAlkbh168
E0CY72E0CY72_MOUSEAlkbh1101
E0CYA7E0CYA7_MOUSEAlkbh1200

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
CT030249
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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