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Q58DM4 · ALKB2_BOVIN

  • Protein
    DNA oxidative demethylase ALKBH2
  • Gene
    ALKBH2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA (By similarity).
Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis (By similarity).
Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine (By similarity).
Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription (By similarity).
In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (By similarity).

Catalytic activity

  • a methylated nucleobase within DNA + 2-oxoglutarate + O2 = a nucleobase within DNA + formaldehyde + succinate + CO2
    This reaction proceeds in the forward direction.
    EC:1.14.11.33 (UniProtKB | ENZYME | Rhea)
  • an N1-methyl-2'-deoxyadenosine in double-stranded DNA + 2-oxoglutarate + O2 = a 2'-deoxyadenosine in double-stranded DNA + formaldehyde + succinate + CO2 + H+
    This reaction proceeds in the forward direction.
  • an N1-methyl-2'-deoxyadenosine in single-stranded DNA + 2-oxoglutarate + O2 = a 2'-deoxyadenosine in single-stranded DNA + formaldehyde + succinate + CO2 + H+
    This reaction proceeds in the forward direction.
  • an N3-methyl-2'-deoxycytidine in double-stranded DNA + 2-oxoglutarate + O2 = a 2'-deoxycytidine in double-stranded DNA + formaldehyde + succinate + CO2 + H+
    This reaction proceeds in the forward direction.
  • an N3-methyl-2'-deoxycytidine in single-stranded DNA + 2-oxoglutarate + O2 = a 2'-deoxycytidine in single-stranded DNA + formaldehyde + succinate + CO2 + H+
    This reaction proceeds in the forward direction.
  • a 1,N6-etheno-2'-deoxyadenosine in double-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2'-deoxyadenosine in double-stranded DNA + glyoxal + succinate + CO2
    This reaction proceeds in the forward direction.
  • a 1,N6-etheno-2'-deoxyadenosine in single-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2'-deoxyadenosine in single-stranded DNA + glyoxal + succinate + CO2
    This reaction proceeds in the forward direction.
  • a 3,N4-etheno-2'-deoxycytidine in double-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2'-deoxycytidine in double-stranded DNA + glyoxal + succinate + CO2
    This reaction proceeds in the forward direction.
  • a 3,N4-etheno-2'-deoxycytidine in single-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2'-deoxycytidine in single-stranded DNA + glyoxal + succinate + CO2
    This reaction proceeds in the forward direction.
  • a 1,N2-etheno-2'-deoxyguanosine in double-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2'-deoxyguanosine in double-stranded DNA + glyoxal + succinate + CO2
    This reaction proceeds in the forward direction.

Cofactor

Fe2+ (UniProtKB | Rhea| CHEBI:29033 )

Note: Binds 1 Fe2+ ion per subunit.

Activity regulation

Activated by ascorbate and magnesium ions.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site101-103substrate
Binding site121-123substrate
Binding site1582-oxoglutarate (UniProtKB | ChEBI)
Binding site1602-oxoglutarate (UniProtKB | ChEBI)
Binding site1702-oxoglutarate (UniProtKB | ChEBI)
Binding site170Fe cation (UniProtKB | ChEBI); catalytic
Binding site172Fe cation (UniProtKB | ChEBI); catalytic
Binding site173substrate
Binding site2352-oxoglutarate (UniProtKB | ChEBI)
Binding site235Fe cation (UniProtKB | ChEBI); catalytic
Binding site2472-oxoglutarate (UniProtKB | ChEBI)
Binding site2512-oxoglutarate (UniProtKB | ChEBI)
Binding site2532-oxoglutarate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentnucleolus
Cellular Componentnucleoplasm
Molecular Functionbroad specificity oxidative DNA demethylase activity
Molecular Functioncytosine C-5 DNA demethylase activity
Molecular Functionferrous iron binding
Biological ProcessDNA alkylation repair

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    DNA oxidative demethylase ALKBH2
  • EC number
  • Alternative names
    • Alkylated DNA repair protein alkB homolog 2
    • Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2

Gene names

    • Name
      ALKBH2
    • Synonyms
      ABH2

Organism names

  • Taxonomic identifier
  • Strain
    • Hereford
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos

Accessions

  • Primary accession
    Q58DM4
  • Secondary accessions
    • Q0VCG6

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Nucleus, nucleolus
Nucleus, nucleoplasm
Note: Relocates to the replication foci during S-phase.

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00002392741-278DNA oxidative demethylase ALKBH2

Proteomic databases

Expression

Gene expression databases

Interaction

Subunit

Interacts with PCNA homotrimer; this interaction is enhanced during the S-phase of the cell cycle. Interacts with nucleolar proteins NCL, UBTF and NPM1. Interacts with XRCC5-XRCC6 heterodimer.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, motif, domain.

Type
IDPosition(s)Description
Region1-49Disordered
Motif3-7PCNA-binding
Domain151-256Fe2OG dioxygenase

Domain

The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif, APIM), mediates the colocalization of ALKBH2 with PCNA at the replication foci, coordinating the repair of alkylated DNA damage with DNA replication.

Sequence similarities

Belongs to the alkB family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    278
  • Mass (Da)
    31,053
  • Last updated
    2005-04-26 v1
  • MD5 Checksum
    BCC0A69B93D47E2B97150055B509DB51
MDRFLVKGAVGSLKRRMEQEQTGGGPAGLAEEEGNSKKNPRRAAPGNGVDSAGLTWGRIRAEGLNCDYTILFGKAEADEIFQELEKEVEYFTGALARVQVFGKWHSVPRKQATYGDTGLTYTFSGLTLSPKPWIPVLERVRDRVSLVTGQTFNFVLINRYKDGQDHIGEHRDDERELALGSPIASVSFGACRDFVFRHKDSRGKHPSRRLEVVRLQLAHGSLLMMNHPTNTHWYHSLPVRKKVLAPRVNLTFRKILPTTKRTTLLTASASVGSFALHS

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0AAF7A4B6A0AAF7A4B6_BOVINALKBH2263
A0AAA9S941A0AAA9S941_BOVINALKBH2157

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
BT021573
EMBL· GenBank· DDBJ
AAX46420.1
EMBL· GenBank· DDBJ
mRNA
BC120178
EMBL· GenBank· DDBJ
AAI20179.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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