Q8K1E6 · ALKB3_MOUSE
- ProteinAlpha-ketoglutarate-dependent dioxygenase alkB homolog 3
- GeneAlkbh3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids286 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A) (By similarity).
Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:16174769).
Has a strong preference for single-stranded DNA (PubMed:16174769).
Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3. Can repair exocyclic 3,N4-ethenocytosine adducs in single-stranded DNA. Also acts on RNA. Demethylates N1-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5'-untranslated regions (UTRs) and in the vicinity of start codons. Requires molecular oxygen, alpha-ketoglutarate and iron (By similarity).
Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:16174769).
Has a strong preference for single-stranded DNA (PubMed:16174769).
Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3. Can repair exocyclic 3,N4-ethenocytosine adducs in single-stranded DNA. Also acts on RNA. Demethylates N1-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5'-untranslated regions (UTRs) and in the vicinity of start codons. Requires molecular oxygen, alpha-ketoglutarate and iron (By similarity).
Catalytic activity
- 2-oxoglutarate + an N1-methyladenosine in mRNA + O2 = an adenosine in mRNA + CO2 + formaldehyde + succinate
- 2-oxoglutarate + an N1-methyl-2'-deoxyadenosine in single-stranded DNA + O2 = a 2'-deoxyadenosine in single-stranded DNA + CO2 + formaldehyde + H+ + succinateThis reaction proceeds in the forward direction.
- 2-oxoglutarate + an N3-methyl-2'-deoxycytidine in single-stranded DNA + O2 = a 2'-deoxycytidine in single-stranded DNA + CO2 + formaldehyde + H+ + succinateThis reaction proceeds in the forward direction.
- 2-oxoglutarate + a 3,N4-etheno-2'-deoxycytidine in single-stranded DNA + H2O + O2 = a 2'-deoxycytidine in single-stranded DNA + CO2 + glyoxal + succinateThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 Fe2+ ion per subunit.
Activity regulation
Activated by ascorbate.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 115 | substrate | ||||
Sequence: W | ||||||
Binding site | 141-143 | substrate | ||||
Sequence: YTY | ||||||
Binding site | 179-181 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: NFY | ||||||
Binding site | 191 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 193 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 194 | substrate | ||||
Sequence: D | ||||||
Binding site | 257 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 269-275 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: RVNLTFR | ||||||
Binding site | 275 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | 2-oxoglutarate-dependent dioxygenase activity | |
Molecular Function | broad specificity oxidative DNA demethylase activity | |
Molecular Function | cytosine C-5 DNA demethylase activity | |
Molecular Function | ferrous iron binding | |
Molecular Function | mRNA N1-methyladenosine dioxygenase activity | |
Molecular Function | oxidative RNA demethylase activity | |
Biological Process | cell population proliferation | |
Biological Process | DNA alkylation repair |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAlpha-ketoglutarate-dependent dioxygenase alkB homolog 3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8K1E6
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
No visible phenotype.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 193 | Loss of activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 257 | Reduced activity. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 16 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000239279 | 1-286 | Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 | |||
Sequence: MEDKRQRARVQGGWATPTKSQSATQPASPARSRLSQTAGPAWRSKEQQQCDRQFVFKEPQLVVRAAPEPRVIDREGVYEISLSPTGVSRVCLYPGFVDLKEADWILEQLCKDVPWKQRMGIREDVTYPQPRLTAWYGELPYTYSRITMEPNPHWLPVLWTLKSRIEENTSHTFNSLLCNFYRDEKDSVDWHSDDEPSLGSCPVIASLSFGATRTFEMRKKPPPEENGDYTYVERVKIPLDHGTLLIMEGATQADWQHRVPKEYHSRQPRVNLTFRTVYPDPRGAPR | ||||||
Modified residue | 177 | (4R)-5-hydroxyleucine; alternate | ||||
Sequence: L | ||||||
Modified residue | 177 | (4R)-5-oxoleucine; alternate | ||||
Sequence: L |
Post-translational modification
Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination. OTUD4 promotes USP7 and USP9X-dependent deubiquitination of 'Lys-48'-polyubiquitinated ALKBH3 promoting the repair of alkylated DNA lesions.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in testis, kidney, liver and heart.
Gene expression databases
Interaction
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-46 | Disordered | ||||
Sequence: MEDKRQRARVQGGWATPTKSQSATQPASPARSRLSQTAGPAWRSKE | ||||||
Compositional bias | 13-46 | Polar residues | ||||
Sequence: GWATPTKSQSATQPASPARSRLSQTAGPAWRSKE | ||||||
Domain | 172-278 | Fe2OG dioxygenase | ||||
Sequence: TFNSLLCNFYRDEKDSVDWHSDDEPSLGSCPVIASLSFGATRTFEMRKKPPPEENGDYTYVERVKIPLDHGTLLIMEGATQADWQHRVPKEYHSRQPRVNLTFRTVY |
Sequence similarities
Belongs to the alkB family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length286
- Mass (Da)33,061
- Last updated2002-10-01 v1
- Checksum2480D0D20A9893F4
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 13-46 | Polar residues | ||||
Sequence: GWATPTKSQSATQPASPARSRLSQTAGPAWRSKE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC018196 EMBL· GenBank· DDBJ | AAH18196.1 EMBL· GenBank· DDBJ | mRNA |