P0CB42 · ALKB1_MOUSE
- ProteinNucleic acid dioxygenase ALKBH1
- GeneAlkbh1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids389 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
Catalytic activity
- 2-oxoglutarate + an N6-methyl-2'-deoxyadenosine in DNA + O2 = a 2'-deoxyadenosine in DNA + CO2 + formaldehyde + succinate
- 2-oxoglutarate + an N1-methyladenosine in tRNA + O2 = an adenosine in tRNA + CO2 + formaldehyde + succinate
- 2 2-oxoglutarate + 5-methylcytidine34 in mitochondrial tRNA(Met) + 2 O2 = 5-formylcytidine34 in mitochondrial tRNA(Met) + 2 CO2 + H2O + 2 succinate
- 2-oxoglutarate + an N3-methylcytidine in mRNA + O2 = a cytidine in mRNA + CO2 + formaldehyde + succinateThis reaction proceeds in the forward direction.
- 2-oxoglutarate + N1-methyladenosine58 in tRNA + O2 = adenosine58 in tRNA + CO2 + formaldehyde + succinate
Cofactor
Note: Binds 1 Fe2+ ion per subunit.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 144 | substrate | ||||
Sequence: W | ||||||
Binding site | 175-177 | substrate | ||||
Sequence: YHY | ||||||
Binding site | 220-222 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: NYY | ||||||
Binding site | 231 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 233 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 233 | substrate | ||||
Sequence: D | ||||||
Binding site | 287 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 338-344 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: RVNMTVR |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNucleic acid dioxygenase ALKBH1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP0CB42
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli.
Keywords
- Cellular component
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 233 | Loss of activity. | ||||
Sequence: D → A |
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.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000386453 | 1-389 | Nucleic acid dioxygenase ALKBH1 | |||
Sequence: MGKMAAAVASLATLAAEPREDAFRKLFRFYRQSRPGTADLGAVIDFSEAHLARSPKPGVPQVVRFPLNVSSVTERDAERVGLEPVSKWRAYGLEGYPGFIFIPNPFLPGCQRHWVKQCLKLYSQKPNVCNLDKHMTKEETQGLWEQSKEVLRSKEVTKRRPRSLLERLRWVTLGYHYNWDSKKYSADHYTPFPSDLAFLSEQVATACGFQGFQAEAGILNYYRLDSTLGIHVDRSELDHSKPLLSFSFGQSAIFLLGGLKRDEAPTAMFMHSGDIMVMSGFSRLLNHAVPRVLPHPDGECLPHCLETPLPAVLPSNSLVEPCSVEDWQVCATYLRTARVNMTVRQVLATGQDFPLEPVEETKRDIAADGLCHLHDPNSPVKRKRLNPNS |
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).
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).
Interacts with DNAJB6 (PubMed:18163532).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P0CB42 | Dnajb6 O54946-2 | 2 | EBI-13941048, EBI-13941040 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-127 | Interaction with DNAJB6 | ||||
Sequence: MGKMAAAVASLATLAAEPREDAFRKLFRFYRQSRPGTADLGAVIDFSEAHLARSPKPGVPQVVRFPLNVSSVTERDAERVGLEPVSKWRAYGLEGYPGFIFIPNPFLPGCQRHWVKQCLKLYSQKPN | ||||||
Region | 86-389 | tRNA-binding | ||||
Sequence: SKWRAYGLEGYPGFIFIPNPFLPGCQRHWVKQCLKLYSQKPNVCNLDKHMTKEETQGLWEQSKEVLRSKEVTKRRPRSLLERLRWVTLGYHYNWDSKKYSADHYTPFPSDLAFLSEQVATACGFQGFQAEAGILNYYRLDSTLGIHVDRSELDHSKPLLSFSFGQSAIFLLGGLKRDEAPTAMFMHSGDIMVMSGFSRLLNHAVPRVLPHPDGECLPHCLETPLPAVLPSNSLVEPCSVEDWQVCATYLRTARVNMTVRQVLATGQDFPLEPVEETKRDIAADGLCHLHDPNSPVKRKRLNPNS | ||||||
Domain | 213-347 | Fe2OG dioxygenase | ||||
Sequence: QAEAGILNYYRLDSTLGIHVDRSELDHSKPLLSFSFGQSAIFLLGGLKRDEAPTAMFMHSGDIMVMSGFSRLLNHAVPRVLPHPDGECLPHCLETPLPAVLPSNSLVEPCSVEDWQVCATYLRTARVNMTVRQVL |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length389
- Mass (Da)43,746
- Last updated2009-10-13 v1
- ChecksumD18C019F0CB9C0A5
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
CT030249 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |