Q58DM4 · ALKB2_BOVIN
- ProteinDNA oxidative demethylase ALKBH2
- GeneALKBH2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids278 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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).
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 + CO2This reaction proceeds in the forward direction.
- 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 + CO2This 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 + CO2This 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 + CO2This 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 + CO2This 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 + CO2This reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 Fe2+ ion per subunit.
Activity regulation
Activated by ascorbate and magnesium ions.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 101-103 | substrate | |||
Binding site | 121-123 | substrate | |||
Binding site | 158 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
Binding site | 160 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
Binding site | 170 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
Binding site | 170 | Fe cation (UniProtKB | ChEBI); catalytic | |||
Binding site | 172 | Fe cation (UniProtKB | ChEBI); catalytic | |||
Binding site | 173 | substrate | |||
Binding site | 235 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
Binding site | 235 | Fe cation (UniProtKB | ChEBI); catalytic | |||
Binding site | 247 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
Binding site | 251 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
Binding site | 253 | 2-oxoglutarate (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Molecular Function | broad specificity oxidative DNA demethylase activity | |
Molecular Function | cytosine C-5 DNA demethylase activity | |
Molecular Function | ferrous iron binding | |
Biological Process | DNA alkylation repair |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA oxidative demethylase ALKBH2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionQ58DM4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Relocates to the replication foci during S-phase.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000239274 | 1-278 | DNA 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 | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-49 | Disordered | |||
Motif | 3-7 | PCNA-binding | |||
Domain | 151-256 | Fe2OG 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 statusComplete
- Length278
- Mass (Da)31,053
- Last updated2005-04-26 v1
- MD5 ChecksumBCC0A69B93D47E2B97150055B509DB51
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAF7A4B6 | A0AAF7A4B6_BOVIN | ALKBH2 | 263 | ||
A0AAA9S941 | A0AAA9S941_BOVIN | ALKBH2 | 157 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BT021573 EMBL· GenBank· DDBJ | AAX46420.1 EMBL· GenBank· DDBJ | mRNA | ||
BC120178 EMBL· GenBank· DDBJ | AAI20179.1 EMBL· GenBank· DDBJ | mRNA |